Cardiology

For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.

In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.

“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.

The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.

In this study, Dr. Hall and colleagues tested these two hypotheses head to head.

“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.

“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”

The study was published online Jan. 21, 2021 in Nature Medicine.
 

Pros and cons to both diets

For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m².

The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g⁻¹), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g⁻¹) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.

Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.

One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.

They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d⁻¹, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.

Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.

“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.

“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.

Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.

“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.

“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
 

Diet ‘tribes’

In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.

“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”

Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”

The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.

A version of this article first appeared on Medscape.com.

For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.

In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.

“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.

The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.

In this study, Dr. Hall and colleagues tested these two hypotheses head to head.

“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.

“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”

The study was published online Jan. 21, 2021 in Nature Medicine.
 

Pros and cons to both diets

For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m².

The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g⁻¹), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g⁻¹) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.

Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.

One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.

They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d⁻¹, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.

Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.

“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.

“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.

Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.

“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.

“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
 

Diet ‘tribes’

In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.

“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”

Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”

The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.

A version of this article first appeared on Medscape.com.

For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.

In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.

“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.

The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.

In this study, Dr. Hall and colleagues tested these two hypotheses head to head.

“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.

“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”

The study was published online Jan. 21, 2021 in Nature Medicine.
 

Pros and cons to both diets

For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m².

The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g⁻¹), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g⁻¹) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.

Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.

One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.

They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d⁻¹, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.

Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.

“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.

“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.

Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.

“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.

“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
 

Diet ‘tribes’

In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.

“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”

Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”

The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.

A version of this article first appeared on Medscape.com.

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.

Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.

Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.

Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.

Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.

Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.

Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.

In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.

The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
 

Timely treatment improves with algorithm

Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.

The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.

However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
 

Algorithm may reduce disparities

The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.

In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.

In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.

“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
 

Need to create culture of safety

“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.

The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.

“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”

The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.

In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.

Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.

Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.

Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.

In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.

The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
 

Timely treatment improves with algorithm

Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.

The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.

However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
 

Algorithm may reduce disparities

The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.

In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.

In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.

“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
 

Need to create culture of safety

“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.

The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.

“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”

The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.

In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.

Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.

Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.

Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.

In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.

The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
 

Timely treatment improves with algorithm

Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.

The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.

However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
 

Algorithm may reduce disparities

The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.

In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.

In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.

“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
 

Need to create culture of safety

“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.

The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.

“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”

The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.

In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

Physical activity mitigated the impact of high body mass index (BMI) on cardiovascular risk factors, but not overall cardiovascular disease risk, according to an observational study of half a million individuals.

Despite the historically high rates of overweight and obesity worldwide, some evidence suggests that cardiorespiratory fitness could reduce the effects of excess weight on cardiovascular disease risk, wrote Pedro L. Valenzuela, PhD, of the University of Alcalá, Madrid, and colleagues.

“To clarify the existence of the ‘fat-but-fit’ [or ‘elevated BMI but active’] paradox, in this observational study, we assessed the joint association between different BMI categories and physical activity levels, respectively, and the prevalence of major CVD risk factors,” they said.

In a population-based cohort study published in the European Journal of Preventive Cardiology, the researchers identified 527,662 adults aged 18-64 years who were insured by an occupational risk–prevention company and underwent annual medical exams as part of their coverage. The average age of the participants was 42 years, 32% were women, and the average BMI was 26.2 kg/m².

The participants were categorized as normal weight (42%), overweight (41%), and obese (18%), and their activity levels were categorized as inactive (64%), insufficiently active (12%), and regularly active (24%). In addition, 30% had hypercholesterolemia, 15% had hypertension, and 3% had diabetes.

Overall, compared with inactivity, insufficient activity or regular activity reduced CVD risk factors within each BMI category, and subgroups. “However, regular/insufficient PA did not compensate for the negative effects of overweight/obesity, as individuals with overweight/obesity were at greater CVD risk than their peers with normal weight, irrespective of PA levels,” the researchers said. Compared with active normal-weight men, the odds ratios for hypertension in active overweight men and active obese men were 1.98 and 4.93, respectively; the odds ratios for hypercholesterolemia were 1.61 and 2.03, respectively, and the odds ratios for diabetes were 1.33 and 3.62, respectively (P < .001 for all). Trends were similar for women.

The study results were limited by the cross-sectional design; inability to control for participants’ diet, and the reliance of self-reports of leisure-time physical activity. However, the findings were strengthened by the large sample size and “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight/obesity,” the researchers said.

Although increasing physical activity should remain a priority for health policies, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity,” they concluded.
 

Interpret findings with caution

“With the ever-increasing public health problem of overweight and obesity, it is useful to assess any measure or measures that can have a favorable or adverse effect on cardiometabolic risk factors and the risk of CVD” Prakash Deedwania, MD, of the University of California, San Francisco, said in an interview.

Dr. Deedwania said he was not entirely surprised by the study findings. “The investigators have correlated only the self-reported level of physical activity (which is not always reliable) to the presence of three cardiac risk factors: hypertension, hypercholesterolemia, and diabetes.”

The study “is not comparable to prior reports that had shown a favorable impact of carefully assessed cardiorespiratory fitness with the risk of CVD,” Dr. Deedwania noted. “However, this is one of the largest population-wide surveillance studies of more than a half million active workers across Spain, and it does show that, despite self-reported physical activity, overweight and obesity are associated with higher risks of hypertension, diabetes, and hypercholesterolemia,” he explained.

“The main message of these findings is that, although physical activity does have a dose-dependent favorable impact on CV risk, the main public health intervention to reduce the risk of CV risk should focus on weight loss in overweight and obese individuals,” Dr. Deedwania emphasized.

“Future studies should focus on comparing various levels of daily activities and routine exercise such as walking, bicycling, etc., with the beneficial impact on cardiometabolic risk factors in overweight and obese individuals,” he said.

Dr. Valenzuela disclosed support from the University of Alcalá. Research by corresponding author Dr. Lucia was funded by grants from Spanish Ministry of Science and Innovation and Fondos FEDER. Dr. Deedwania had no financial conflicts to disclose.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

A version of this article first appeared on Medscape.com.

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

A version of this article first appeared on Medscape.com.

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

A version of this article first appeared on Medscape.com.

Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.

AlexLMX/Getty Images

Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).

That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.

The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.

The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.

One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.

“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.

Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”

The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”

The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.

Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
 

Reassurance and concern

“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”

The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).

As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.

The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”

Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.

“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”

Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”

It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.

“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.

Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.

Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.

There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”

The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”

The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
 

Routine CMR for positive cases

The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.

The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.

All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.

Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.

The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.

They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.

The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.

The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.

At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.

“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”

Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.

A version of this article first appeared on Medscape.com.

Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.

AlexLMX/Getty Images

Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).

That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.

The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.

The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.

One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.

“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.

Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”

The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”

The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.

Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
 

Reassurance and concern

“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”

The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).

As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.

The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”

Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.

“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”

Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”

It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.

“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.

Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.

Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.

There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”

The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”

The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
 

Routine CMR for positive cases

The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.

The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.

All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.

Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.

The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.

They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.

The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.

The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.

At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.

“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”

Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.

A version of this article first appeared on Medscape.com.

Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.

AlexLMX/Getty Images

Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).

That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.

The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.

The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.

One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.

“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.

Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”

The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”

The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.

Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
 

Reassurance and concern

“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”

The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).

As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.

The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”

Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.

“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”

Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”

It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.

“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.

Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.

Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.

There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”

The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”

The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
 

Routine CMR for positive cases

The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.

The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.

All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.

Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.

The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.

They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.

The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.

The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.

At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.

“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”

Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.

A version of this article first appeared on Medscape.com.

From Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL.

Abstract

• Objective: To determine pharmacists’ preferences in bleed risk tool (BRT) usage and gastroprotection when bleed risk was lower than or equal to stroke risk in patients with nonvalvular atrial fibrillation and who were candidates for oral anticoagulation therapy (warfarin or direct oral anticoagulants [DOACs]).
• Methods: A survey consisting of 4 domains (demographics, clinical experience, BRT usage, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk) was developed. The anonymous survey was disseminated via REDCap software to members of the American College of Clinical Pharmacy ambulatory care and cardiology Practice-based Research Networks. Descriptive statistics were calculated for all study variables and inferential statistics were employed as necessary.
• Results: Of 165 BRT users, 97% preferred HAS-BLED. When bleed risk was lower than stroke risk, 151 respondents chose either DOACs (65%) or warfarin (35%); 15% added gastroprotection. When bleed risk was equal to stroke risk, 141 respondents chose DOACs (50%), warfarin (45%), or aspirin (5%); 40% added gastroprotection.
• Conclusion: In addition to BRT usage, pharmacists were judicious in their recommendation to add gastroprotection and would consider doing so if there was a specific indication. As more than 80% of extracranial bleeds are gastrointestinal bleeds and most BRTs are nonspecific for predicting these bleeds, randomized, prospective studies stratified by HAS-BLED and stroke risk scores are needed to provide further guidance on the efficacy and safety of oral anticoagulation therapy with or without gastroprotection.

Keywords: NVAF; gastroprotection; proton pump inhibitors; warfarin; oral anticoagulants.

Management of patients with nonvalvular atrial fibrillation (NVAF) with oral anticoagulation therapy (OACT) requires constant attention to maintain a balance between preventing strokes and minimizing bleeds. Several validated bleed risk tools (BRTs) available for use in NVAF patients include HAS-BLED, HEMORR₂HAGES, ATRIA, and mOBRI.^1,2 A high bleed risk score is not a contraindication to OACT, but, prior to and throughout therapy, bleed risk should be assessed and modifiable risk factors addressed.³ While intraluminal gastrointestinal (GI) bleeds are not considered a critical bleed site, they are a common complication of chronic OACT and can result in hemodynamic compromise and permanent discontinuation of therapy.^4,5 In 3233 patients with nonvariceal upper GI bleeds (2005-2016), the adjusted odds ratio of hospital admission, transfusion, and re-bleeding while on OACT (warfarin, heparin, or apixaban) was 3.48, 2.53, and 2.26, respectively.⁶ Addition of acid-suppressive therapy with a proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H₂RA) in NVAF patients at increased risk for upper GI bleeds and receiving OACT may result in fewer bleeds.^7,8

Pharmacists play an integral part in managing patients on warfarin,^9-11 and data on their role in managing patients receiving direct oral anticoagulants (DOACs) are increasing.^12-16 Inpatient pharmacists actively participate in multidisciplinary collaborative teams and use clinical decision-support systems or enhanced monitoring to ensure safe prescribing of high-risk medications.^12,15,16 Pharmacist-managed, outpatient-based anticoagulation services in patients on warfarin were associated with lower rates of bleeding and thromboembolic events and lower health care utilization versus routine care.¹⁷ However, it is unclear how pharmacists manage patients who are candidates for OACT but who may be at increased risk for upper GI bleeds. Using a US-based survey, the investigators sought to determine pharmacists’ preferences in BRT usage and gastroprotection when bleed risk was lower than or equal to stroke risk.

Methods

This cross-sectional study was conducted after receiving approval by Nova Southeastern University’s Institutional Review Board. The survey consisted of 16 items divided into 4 domains: demographics, clinical experience, use of BRTs, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk (Figure 1). Queries were multiple choice and allowed for free-text input when “Other” was selected. Licensed pharmacists ≥ 18 years of age who routinely provided care to patients with NVAF were eligible to participate in the study. Participants who reported using a BRT (users) completed all study domains, while participants who reported not using a BRT (nonusers) completed domains 1 through 3 only.

An invitation containing the survey link was sent to the American College of Clinical Pharmacy ambulatory care (n = 2237) and cardiology (n = 1318) pharmacists listed in the organization’s Practice-based Research Networks. The survey was administered in the United States between April and June 2016 via Research Electronic Data Capture (REDCap) software, a secure Web application for building and managing online surveys designed to support data collection for research studies.¹⁸

Survey responses were downloaded, and data were analyzed using NCSS 2019 Statistical Software, LLC (Kaysville, UT). Descriptive statistics were calculated for all study variables. Demographic and clinical experience data for the group that used a BRT versus the group that did not were compared using Pearson’s chi-square, ANOVA, or the Cochran-Armitage test for trends. Logistic regression with hierarchical forward selection with switching was used to identify predictors of drug selection and use of gastroprotection.

Results

Of 230 respondents who completed the survey (response rate 6.5%), 165 (72%) used a BRT and 65 (28%) did not. No significant differences were found for age, gender, duration in clinical practice, the percentage of time spent in patient care, or practice specialty between users and nonusers (Table). The median age of users was 32 years; 68% were females; the median duration in clinical practice was 6 years; 75% of their time was spent in clinical practice; and clinical settings included ambulatory care, cardiology, and internal medicine. A significant difference was found for practice region between users versus nonusers (P = 0.014). Respondents who managed more than 200 NVAF patients per year used a BRT more often than those who managed fewer than 100 NVAF patients per year (P = 0.001).

Of those who used a BRT, 97% utilized the HAS-BLED tool (n = 160). The remainder used HEMORR₂HAGES (n = 3), ATRIA (n = 1), and mOBRI (n = 1). Reasons for choosing HAS-BLED included “familiarity/ease-of-use,” “preference by institution/clinical team,” and the fact that it was a “validated tool for NVAF.”

When bleed risk was lower than stroke risk, 151 of 165 users (92%) chose a treatment option (Figure 2). Of those, 65% chose a DOAC and 35% chose warfarin. Fourteen respondents chose “other” and explained that they “would initiate OACT after weighing patient factors and preferences.” When a DOAC was selected, 9% (n = 9) chose PPI co-therapy and 4% (n = 4) chose a H₂RA. When warfarin was selected, 13% (n = 7) chose PPI co-therapy and 4% (n = 2) chose a H₂RA. Respondents who chose gastroprotection did not provide reasons for doing so, but those who did not add it explained that they “would add gastroprotection only if patient is also on an NSAID or has a history of GI bleed” or cited “patient preference.” Specific to warfarin, some respondents would not add gastroprotection, as anticoagulation with warfarin is “easily reversed.”

When bleed risk was equal to stroke risk, 141 of 165 users (85%) chose a treatment option (Figure 3). Fifty percent chose DOACs, 45% chose warfarin, and 5% chose aspirin. Logistic regression analysis (outcome DOAC versus warfarin area-under-ROC curve, 0.67) showed that as the number of NVAF patients seen in 12 months increased, respondents were more likely to select a DOAC over warfarin (odds ratio, 1.7; 95% CI, 1.1-2.5). Therefore, for every 50-patient increase per year, the probability of recommending a DOAC increased 1.7-fold.

Of respondents who selected either a DOAC or warfarin, 38% (n = 50) also added gastroprotection (Figure 3). When a DOAC was selected, 34% (n = 24) favored PPI co-therapy and 7% (n = 5) chose a H₂RA. When warfarin was selected, 19% (n = 12) favored PPI co-therapy, while 13% (n = 8) chose a H₂RA. Rationale for choosing gastroprotection, regardless of OACT selection, included “stroke is more devastating, so if patient wants to continue treatment, but knew risks of bleeding were similar, would recommend gastroprotection to help minimize bleeding risk” and “patient-specific consideration.” Rationales for not choosing gastroprotection included “would add gastroprotection only if patient is on dual antiplatelet therapy or has another indication”; “in most patients, stroke risk outweighs bleed risk so no need for gastroprotection unless there is a stated reason”; “would use apixaban as has lowest bleeding rate of all DOACs in clinical trials”; and “gastroprotection has not been shown to be beneficial in large scale trials.” 

Eight respondents chose aspirin because it was “easy and relatively low cost.” Twenty-four respondents chose “other” and explained that the choice of OACT depended on patient preference after they had discussed stroke and bleed risk with the patient and/or determined the etiology driving bleed risk.

Discussion

This is the first national survey exploring US pharmacists’ preferences in BRT usage and treatment based on bleed risk. Pharmacists preferred the HAS-BLED tool and considered patient-specific factors and evidence-based data when weighing the risk-benefit of OACT with or without gastroprotective therapy.

Similar to our findings, where three-quarters of pharmacists used a BRT, a recent Medscape/American College of Cardiology (ACC) survey reported that 74% of cardiologists used a BRT (eg, HAS-BLED) always/most of the time or sometimes to assess a patient’s overall risk of bleeding prior to initiating DOAC therapy; 27% never or rarely used a bleed risk score before prescribing DOACs.¹⁹ Although reasons for BRT preference were not provided, they may be similar to those reported by our respondents (ie, familiarity/ease-of-use). In both surveys, rationales for not using a BRT were not obtained, but possible reasons include lack of confidence with bleed risk calculators,²⁰ inconsistent implementation of comprehensive assessments (stroke risk, bleed risk, and medication-related issues prior to decision-making),²¹ and nonspecific guideline recommendations.²²

More recently, a network meta-analysis found that HAS-BLED and HEMORR₂HAGES had modest but balanced sensitivity (defined as the ratio between the number of major bleeding events in high-risk stratification and the total number of bleeding events) and specificity (defined as the ratio between the number of nonmajor bleeding events in the low-risk population and total nonbleeding events) for predicting major bleeding events.^2,3 Several respondents did comment that, although HAS-BLED was imprecise and only studied with warfarin, it was necessary to identify bleed risk in a patient starting a high-risk medication, and that the ACC anticoagulation application uses HAS-BLED with CHA₂DS₂VASc along with clinical trial data to estimate stroke risk and bleed risk, with projected risk reduction (strokes) and risk increases (bleeds) expected with each treatment (www.acc.org/tools-and-practice-support/mobile-resources/features/anticoag-evaluator). The 2019 AHA/ACC/HRS atrial fibrillation guideline recommends that HAS-BLED scores be used to assess bleed risk in patients for whom anticoagulation is being considered, and that the need for and choice of OACT should be periodically reevaluated to reassess stroke and bleed risks.²³

Although more than 80% of extracranial bleeds are GI bleeds,²⁴ most BRTs are nonspecific for predicting GI bleeds. Indeed, one respondent used a spreadsheet with several BRTs to maximize treatment guidance for patients with multiple risk factors for strokes and bleeds. A comprehensive approach to determining factors that increase bleed risk should be adopted. These factors include age (HAS-BLED, HEMORR₂HAGES, mOBRI, ATRIA); anemia (mOBRI, HEMORR₂HAGES, ATRIA); hepatic/renal disease (HAS-BLED, HEMORR₂HAGES, ATRIA, mOBRI); concomitant medications/alcohol use, including NSAIDs, corticosteroids, and antiplatelet therapy (HAS-BLED, HEMORR₂HAGES); bleed history/rebleeding risk (HEMORR₂HAGES, HAS-BLED, ATRIA); and GI bleeds (mOBRI).^1,2 Additional risk factors for GI bleeds include being a tobacco smoker and/or being infected with Helicobacter pylori. A prospective cohort study that analyzed data from questionnaires completed by 99,359 individuals from the Copenhagen General Population Study reported that the multivariable adjusted hazard ratio for current smokers versus never smokers was 2.20 (95% CI, 1.84-2.62) for GI bleeds.²⁵ Presence of H pylori should be investigated, with a subsequent eradication regimen implemented, as patients with warfarin-associated upper GI bleeds who were H pylori-positive had lower HAS-BLED scores versus those who were negative.²⁶

When bleed risk was lower than stroke risk (eg, HAS-BLED < 3, CHA₂DS₂VASc ≥ 1), respondents appropriately initiated therapy with an OAC (predominantly apixaban); a small proportion also added gastroprotection. If the patient did not have any other GI bleed risk factors (eg, a previous GI bleed or on chronic antiplatelet or NSAID therapy), the choice of OACT depended on the attributes of each OAC and patient preference.²⁷ Selection of warfarin was appropriate if cost, formulary restrictions, and availability of an inexpensive reversal agent were important concerns to patients and/or their health care providers. Rivaroxaban was selected because of its once-daily dosing and low risk for GI bleeding.

The recently published ARISTOPHANES study provides evidence that apixaban is an appropriate choice in patients with a HAS-BLED score < 3. In this retrospective observational study, more than 70% of patients received standard doses of DOACs (apixaban 5 mg, dabigatran 150 mg, or rivaroxaban 20 mg) and about 20% had a bleeding history, about 30% were on PPIs, less than 25% were on NSAIDs, and about 40% had a HAS-BLED score < 3. The study found that apixaban was more effective (reduced rates of ischemic or hemorrhagic strokes/systemic embolism) and safer (reduced rates of major GI bleed or intracranial bleed) than warfarin.²⁸ Dabigatran and rivaroxaban were also more effective than warfarin for stroke prevention and had a lower risk for major intracranial bleed risk; while the risk of major GI bleed was similar between dabigatran and warfarin, major GI bleed risk was higher for rivaroxaban. When compared with each other, the 3 DOACs were effective at stroke prevention, with apixaban more effective than dabigatran and rivaroxaban; similar efficacy was noted for dabigatran versus rivaroxaban. Apixaban was associated with fewer GI bleeds versus dabigatran and rivaroxaban, but with similar intracranial bleed risks; dabigatran was associated with fewer GI bleeds but similar intracranial bleed risks versus rivaroxaban.²⁸ Efficacy and safety findings from a subgroup analysis based on HAS-BLED scores < 3 and ≥ 3 were generally consistent with the main results.

When bleed risk was equal to stroke risk, the difficulty was determining how OACT in a patient at high stroke risk (CHA₂DS₂VASc score ≥ 2) and high bleed risk (HAS-BLED score ≥ 3) should be managed. Eight respondents chose aspirin and added gastroprotection with either a PPI or H₂RA; however, currently, aspirin is not recommended as the sole antithrombotic for patients with NVAF.²³ With the OACT, an interesting finding was that as the number of patients seen in 12 months increased, pharmacists were almost twice as likely to select a DOAC over warfarin. Moreover, pharmacists were judicious in their recommendation to add gastroprotection, and would consider doing so if there was a specific indication. At the time of our survey, several studies described DOAC-associated GI bleeds,^29-31 but data on the effectiveness of acid-suppressive therapy, specifically with PPIs, in the prevention of upper GI bleeds were sparse.^4,7,32 Respondents most likely were familiar with GI bleed risk factors and prevention strategies from various guidelines published between 2009 and 2010, which did not include DOACs.^33-35

Another important finding was pharmacists’ uncertainty as to the effectiveness of PPIs in preventing GI bleeds in combination with DOACs. The data are conflicting. A meta-analysis of older studies (2007-2015) showed that PPIs (but not H₂RAs) reduced the risk of upper GI bleeds in patients on warfarin but not for dabigatran.³⁶ A retrospective cohort study of Medicare beneficiaries on OACTs (2011-2015) showed the adjusted incidence of hospitalization for upper GI bleeds in patients on PPI co-therapy was significantly lower compared with patients not on PPI co-therapy (76 versus 115 per 10,000 person-years, respectively).⁸ Apixaban without PPI co-therapy was associated with the lowest risk of upper GI bleed hospitalizations (73/10,000 person-years), and PPI co-therapy further reduced this risk (49/10,000 person-years). Warfarin without PPI co-therapy was associated with the next lowest risk (113/10,000 person-years), followed by dabigatran (120/10,000 person-years) and rivaroxaban (144/10,000 person-years). PPI co-therapy significantly reduced the risk of upper GI bleed hospitalizations with all OACTs, but the incidence of upper GI bleed hospitalizations with rivaroxaban was significantly greater than with the other OACTs.⁸ Therefore, if there are concerns about the safety of PPIs,^37-39 or the patient is unable to tolerate a PPI, then apixaban may be the most appropriate DOAC for a patient with high bleed risk. Notably, a 2020 review of data from the PINNACLE registry (average age, 75-77 years; 31% on PPIs) found that the relative GI bleed safety advantage of apixaban and dabigatran versus warfarin was attenuated in patients ≥ 75 years.⁴⁰ Last, since the risk for lower GI bleeds is not reduced by PPIs,⁴¹ consideration of their use should be accompanied by an assessment to detect bleeds (eg, low hemoglobin/hematocrit, presence of bright red blood, hematochezia/melena, fecal occult testing), with prompt management as necessary.⁵

Limitations

Limitations of our survey included an overall low response rate, which can generate a biased sample if respondents are systematically different from nonrespondents. In addition, to maintain simplicity and reduce respondents’ time commitment, our survey did not include actual CHA₂DS₂VASc stroke risk scores, HAS-BLED bleed risk scores, or specific GI bleed risk factors when querying pharmacists about treatment options based on bleed risk. The addition of these variables would have improved the robustness of the data.

Conclusion

In addition to applying BRTs in the management of NVAF patients, pharmacists considered patient-specific variables, prescriber preferences, and evidence-based guidance when recommending OACT with or without gastroprotection. To avoid suboptimal patient management, busy pharmacists should be granted time to attend continuing education programs describing optimal OACT selection and formulation of individualized, evidence-based plans to address modifiable risk factors for bleeding, including the appropriate use of gastroprotection. Randomized, prospective, long-term studies stratified by HAS-BLED and CHA₂DS₂VASc scores are needed to further clarify efficacy, safety, and cost-effectiveness of OACT, with and without PPIs, in patients who may be at risk for upper GI bleeds.

Acknowledgments: The authors thank Robin J. Jacobs, PhD, MSW, MS, MPH, Patrick C. Hardigan, PhD, Steven Brettler, PharmD, MPH, Maria-Isabel A. Cabral, PharmD, and Reginald Gyapong, PharmD, for their participation in this project. The authors also sincerely thank Fabio Franco, BS Computer Science, who organized the database to enable efficient data management.

Corresponding author: Devada Singh-Franco, PharmD, CDE, Nova Southeastern University College of Pharmacy, 3200 S University Drive, Fort Lauderdale, FL 33328; singh@nova.edu

Disclosures: None.

Funding: The study was supported by Nova Southeastern University’s Health Professions Division Internal Research Grant.

From Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL.

Abstract

• Objective: To determine pharmacists’ preferences in bleed risk tool (BRT) usage and gastroprotection when bleed risk was lower than or equal to stroke risk in patients with nonvalvular atrial fibrillation and who were candidates for oral anticoagulation therapy (warfarin or direct oral anticoagulants [DOACs]).
• Methods: A survey consisting of 4 domains (demographics, clinical experience, BRT usage, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk) was developed. The anonymous survey was disseminated via REDCap software to members of the American College of Clinical Pharmacy ambulatory care and cardiology Practice-based Research Networks. Descriptive statistics were calculated for all study variables and inferential statistics were employed as necessary.
• Results: Of 165 BRT users, 97% preferred HAS-BLED. When bleed risk was lower than stroke risk, 151 respondents chose either DOACs (65%) or warfarin (35%); 15% added gastroprotection. When bleed risk was equal to stroke risk, 141 respondents chose DOACs (50%), warfarin (45%), or aspirin (5%); 40% added gastroprotection.
• Conclusion: In addition to BRT usage, pharmacists were judicious in their recommendation to add gastroprotection and would consider doing so if there was a specific indication. As more than 80% of extracranial bleeds are gastrointestinal bleeds and most BRTs are nonspecific for predicting these bleeds, randomized, prospective studies stratified by HAS-BLED and stroke risk scores are needed to provide further guidance on the efficacy and safety of oral anticoagulation therapy with or without gastroprotection.

Keywords: NVAF; gastroprotection; proton pump inhibitors; warfarin; oral anticoagulants.

Management of patients with nonvalvular atrial fibrillation (NVAF) with oral anticoagulation therapy (OACT) requires constant attention to maintain a balance between preventing strokes and minimizing bleeds. Several validated bleed risk tools (BRTs) available for use in NVAF patients include HAS-BLED, HEMORR₂HAGES, ATRIA, and mOBRI.^1,2 A high bleed risk score is not a contraindication to OACT, but, prior to and throughout therapy, bleed risk should be assessed and modifiable risk factors addressed.³ While intraluminal gastrointestinal (GI) bleeds are not considered a critical bleed site, they are a common complication of chronic OACT and can result in hemodynamic compromise and permanent discontinuation of therapy.^4,5 In 3233 patients with nonvariceal upper GI bleeds (2005-2016), the adjusted odds ratio of hospital admission, transfusion, and re-bleeding while on OACT (warfarin, heparin, or apixaban) was 3.48, 2.53, and 2.26, respectively.⁶ Addition of acid-suppressive therapy with a proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H₂RA) in NVAF patients at increased risk for upper GI bleeds and receiving OACT may result in fewer bleeds.^7,8

Pharmacists play an integral part in managing patients on warfarin,^9-11 and data on their role in managing patients receiving direct oral anticoagulants (DOACs) are increasing.^12-16 Inpatient pharmacists actively participate in multidisciplinary collaborative teams and use clinical decision-support systems or enhanced monitoring to ensure safe prescribing of high-risk medications.^12,15,16 Pharmacist-managed, outpatient-based anticoagulation services in patients on warfarin were associated with lower rates of bleeding and thromboembolic events and lower health care utilization versus routine care.¹⁷ However, it is unclear how pharmacists manage patients who are candidates for OACT but who may be at increased risk for upper GI bleeds. Using a US-based survey, the investigators sought to determine pharmacists’ preferences in BRT usage and gastroprotection when bleed risk was lower than or equal to stroke risk.

Methods

This cross-sectional study was conducted after receiving approval by Nova Southeastern University’s Institutional Review Board. The survey consisted of 16 items divided into 4 domains: demographics, clinical experience, use of BRTs, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk (Figure 1). Queries were multiple choice and allowed for free-text input when “Other” was selected. Licensed pharmacists ≥ 18 years of age who routinely provided care to patients with NVAF were eligible to participate in the study. Participants who reported using a BRT (users) completed all study domains, while participants who reported not using a BRT (nonusers) completed domains 1 through 3 only.

An invitation containing the survey link was sent to the American College of Clinical Pharmacy ambulatory care (n = 2237) and cardiology (n = 1318) pharmacists listed in the organization’s Practice-based Research Networks. The survey was administered in the United States between April and June 2016 via Research Electronic Data Capture (REDCap) software, a secure Web application for building and managing online surveys designed to support data collection for research studies.¹⁸

Survey responses were downloaded, and data were analyzed using NCSS 2019 Statistical Software, LLC (Kaysville, UT). Descriptive statistics were calculated for all study variables. Demographic and clinical experience data for the group that used a BRT versus the group that did not were compared using Pearson’s chi-square, ANOVA, or the Cochran-Armitage test for trends. Logistic regression with hierarchical forward selection with switching was used to identify predictors of drug selection and use of gastroprotection.

Results

Of 230 respondents who completed the survey (response rate 6.5%), 165 (72%) used a BRT and 65 (28%) did not. No significant differences were found for age, gender, duration in clinical practice, the percentage of time spent in patient care, or practice specialty between users and nonusers (Table). The median age of users was 32 years; 68% were females; the median duration in clinical practice was 6 years; 75% of their time was spent in clinical practice; and clinical settings included ambulatory care, cardiology, and internal medicine. A significant difference was found for practice region between users versus nonusers (P = 0.014). Respondents who managed more than 200 NVAF patients per year used a BRT more often than those who managed fewer than 100 NVAF patients per year (P = 0.001).

Of those who used a BRT, 97% utilized the HAS-BLED tool (n = 160). The remainder used HEMORR₂HAGES (n = 3), ATRIA (n = 1), and mOBRI (n = 1). Reasons for choosing HAS-BLED included “familiarity/ease-of-use,” “preference by institution/clinical team,” and the fact that it was a “validated tool for NVAF.”

When bleed risk was lower than stroke risk, 151 of 165 users (92%) chose a treatment option (Figure 2). Of those, 65% chose a DOAC and 35% chose warfarin. Fourteen respondents chose “other” and explained that they “would initiate OACT after weighing patient factors and preferences.” When a DOAC was selected, 9% (n = 9) chose PPI co-therapy and 4% (n = 4) chose a H₂RA. When warfarin was selected, 13% (n = 7) chose PPI co-therapy and 4% (n = 2) chose a H₂RA. Respondents who chose gastroprotection did not provide reasons for doing so, but those who did not add it explained that they “would add gastroprotection only if patient is also on an NSAID or has a history of GI bleed” or cited “patient preference.” Specific to warfarin, some respondents would not add gastroprotection, as anticoagulation with warfarin is “easily reversed.”

When bleed risk was equal to stroke risk, 141 of 165 users (85%) chose a treatment option (Figure 3). Fifty percent chose DOACs, 45% chose warfarin, and 5% chose aspirin. Logistic regression analysis (outcome DOAC versus warfarin area-under-ROC curve, 0.67) showed that as the number of NVAF patients seen in 12 months increased, respondents were more likely to select a DOAC over warfarin (odds ratio, 1.7; 95% CI, 1.1-2.5). Therefore, for every 50-patient increase per year, the probability of recommending a DOAC increased 1.7-fold.

Of respondents who selected either a DOAC or warfarin, 38% (n = 50) also added gastroprotection (Figure 3). When a DOAC was selected, 34% (n = 24) favored PPI co-therapy and 7% (n = 5) chose a H₂RA. When warfarin was selected, 19% (n = 12) favored PPI co-therapy, while 13% (n = 8) chose a H₂RA. Rationale for choosing gastroprotection, regardless of OACT selection, included “stroke is more devastating, so if patient wants to continue treatment, but knew risks of bleeding were similar, would recommend gastroprotection to help minimize bleeding risk” and “patient-specific consideration.” Rationales for not choosing gastroprotection included “would add gastroprotection only if patient is on dual antiplatelet therapy or has another indication”; “in most patients, stroke risk outweighs bleed risk so no need for gastroprotection unless there is a stated reason”; “would use apixaban as has lowest bleeding rate of all DOACs in clinical trials”; and “gastroprotection has not been shown to be beneficial in large scale trials.” 

Eight respondents chose aspirin because it was “easy and relatively low cost.” Twenty-four respondents chose “other” and explained that the choice of OACT depended on patient preference after they had discussed stroke and bleed risk with the patient and/or determined the etiology driving bleed risk.

Discussion

This is the first national survey exploring US pharmacists’ preferences in BRT usage and treatment based on bleed risk. Pharmacists preferred the HAS-BLED tool and considered patient-specific factors and evidence-based data when weighing the risk-benefit of OACT with or without gastroprotective therapy.

Similar to our findings, where three-quarters of pharmacists used a BRT, a recent Medscape/American College of Cardiology (ACC) survey reported that 74% of cardiologists used a BRT (eg, HAS-BLED) always/most of the time or sometimes to assess a patient’s overall risk of bleeding prior to initiating DOAC therapy; 27% never or rarely used a bleed risk score before prescribing DOACs.¹⁹ Although reasons for BRT preference were not provided, they may be similar to those reported by our respondents (ie, familiarity/ease-of-use). In both surveys, rationales for not using a BRT were not obtained, but possible reasons include lack of confidence with bleed risk calculators,²⁰ inconsistent implementation of comprehensive assessments (stroke risk, bleed risk, and medication-related issues prior to decision-making),²¹ and nonspecific guideline recommendations.²²

More recently, a network meta-analysis found that HAS-BLED and HEMORR₂HAGES had modest but balanced sensitivity (defined as the ratio between the number of major bleeding events in high-risk stratification and the total number of bleeding events) and specificity (defined as the ratio between the number of nonmajor bleeding events in the low-risk population and total nonbleeding events) for predicting major bleeding events.^2,3 Several respondents did comment that, although HAS-BLED was imprecise and only studied with warfarin, it was necessary to identify bleed risk in a patient starting a high-risk medication, and that the ACC anticoagulation application uses HAS-BLED with CHA₂DS₂VASc along with clinical trial data to estimate stroke risk and bleed risk, with projected risk reduction (strokes) and risk increases (bleeds) expected with each treatment (www.acc.org/tools-and-practice-support/mobile-resources/features/anticoag-evaluator). The 2019 AHA/ACC/HRS atrial fibrillation guideline recommends that HAS-BLED scores be used to assess bleed risk in patients for whom anticoagulation is being considered, and that the need for and choice of OACT should be periodically reevaluated to reassess stroke and bleed risks.²³

Although more than 80% of extracranial bleeds are GI bleeds,²⁴ most BRTs are nonspecific for predicting GI bleeds. Indeed, one respondent used a spreadsheet with several BRTs to maximize treatment guidance for patients with multiple risk factors for strokes and bleeds. A comprehensive approach to determining factors that increase bleed risk should be adopted. These factors include age (HAS-BLED, HEMORR₂HAGES, mOBRI, ATRIA); anemia (mOBRI, HEMORR₂HAGES, ATRIA); hepatic/renal disease (HAS-BLED, HEMORR₂HAGES, ATRIA, mOBRI); concomitant medications/alcohol use, including NSAIDs, corticosteroids, and antiplatelet therapy (HAS-BLED, HEMORR₂HAGES); bleed history/rebleeding risk (HEMORR₂HAGES, HAS-BLED, ATRIA); and GI bleeds (mOBRI).^1,2 Additional risk factors for GI bleeds include being a tobacco smoker and/or being infected with Helicobacter pylori. A prospective cohort study that analyzed data from questionnaires completed by 99,359 individuals from the Copenhagen General Population Study reported that the multivariable adjusted hazard ratio for current smokers versus never smokers was 2.20 (95% CI, 1.84-2.62) for GI bleeds.²⁵ Presence of H pylori should be investigated, with a subsequent eradication regimen implemented, as patients with warfarin-associated upper GI bleeds who were H pylori-positive had lower HAS-BLED scores versus those who were negative.²⁶

When bleed risk was lower than stroke risk (eg, HAS-BLED < 3, CHA₂DS₂VASc ≥ 1), respondents appropriately initiated therapy with an OAC (predominantly apixaban); a small proportion also added gastroprotection. If the patient did not have any other GI bleed risk factors (eg, a previous GI bleed or on chronic antiplatelet or NSAID therapy), the choice of OACT depended on the attributes of each OAC and patient preference.²⁷ Selection of warfarin was appropriate if cost, formulary restrictions, and availability of an inexpensive reversal agent were important concerns to patients and/or their health care providers. Rivaroxaban was selected because of its once-daily dosing and low risk for GI bleeding.

The recently published ARISTOPHANES study provides evidence that apixaban is an appropriate choice in patients with a HAS-BLED score < 3. In this retrospective observational study, more than 70% of patients received standard doses of DOACs (apixaban 5 mg, dabigatran 150 mg, or rivaroxaban 20 mg) and about 20% had a bleeding history, about 30% were on PPIs, less than 25% were on NSAIDs, and about 40% had a HAS-BLED score < 3. The study found that apixaban was more effective (reduced rates of ischemic or hemorrhagic strokes/systemic embolism) and safer (reduced rates of major GI bleed or intracranial bleed) than warfarin.²⁸ Dabigatran and rivaroxaban were also more effective than warfarin for stroke prevention and had a lower risk for major intracranial bleed risk; while the risk of major GI bleed was similar between dabigatran and warfarin, major GI bleed risk was higher for rivaroxaban. When compared with each other, the 3 DOACs were effective at stroke prevention, with apixaban more effective than dabigatran and rivaroxaban; similar efficacy was noted for dabigatran versus rivaroxaban. Apixaban was associated with fewer GI bleeds versus dabigatran and rivaroxaban, but with similar intracranial bleed risks; dabigatran was associated with fewer GI bleeds but similar intracranial bleed risks versus rivaroxaban.²⁸ Efficacy and safety findings from a subgroup analysis based on HAS-BLED scores < 3 and ≥ 3 were generally consistent with the main results.

When bleed risk was equal to stroke risk, the difficulty was determining how OACT in a patient at high stroke risk (CHA₂DS₂VASc score ≥ 2) and high bleed risk (HAS-BLED score ≥ 3) should be managed. Eight respondents chose aspirin and added gastroprotection with either a PPI or H₂RA; however, currently, aspirin is not recommended as the sole antithrombotic for patients with NVAF.²³ With the OACT, an interesting finding was that as the number of patients seen in 12 months increased, pharmacists were almost twice as likely to select a DOAC over warfarin. Moreover, pharmacists were judicious in their recommendation to add gastroprotection, and would consider doing so if there was a specific indication. At the time of our survey, several studies described DOAC-associated GI bleeds,^29-31 but data on the effectiveness of acid-suppressive therapy, specifically with PPIs, in the prevention of upper GI bleeds were sparse.^4,7,32 Respondents most likely were familiar with GI bleed risk factors and prevention strategies from various guidelines published between 2009 and 2010, which did not include DOACs.^33-35

Another important finding was pharmacists’ uncertainty as to the effectiveness of PPIs in preventing GI bleeds in combination with DOACs. The data are conflicting. A meta-analysis of older studies (2007-2015) showed that PPIs (but not H₂RAs) reduced the risk of upper GI bleeds in patients on warfarin but not for dabigatran.³⁶ A retrospective cohort study of Medicare beneficiaries on OACTs (2011-2015) showed the adjusted incidence of hospitalization for upper GI bleeds in patients on PPI co-therapy was significantly lower compared with patients not on PPI co-therapy (76 versus 115 per 10,000 person-years, respectively).⁸ Apixaban without PPI co-therapy was associated with the lowest risk of upper GI bleed hospitalizations (73/10,000 person-years), and PPI co-therapy further reduced this risk (49/10,000 person-years). Warfarin without PPI co-therapy was associated with the next lowest risk (113/10,000 person-years), followed by dabigatran (120/10,000 person-years) and rivaroxaban (144/10,000 person-years). PPI co-therapy significantly reduced the risk of upper GI bleed hospitalizations with all OACTs, but the incidence of upper GI bleed hospitalizations with rivaroxaban was significantly greater than with the other OACTs.⁸ Therefore, if there are concerns about the safety of PPIs,^37-39 or the patient is unable to tolerate a PPI, then apixaban may be the most appropriate DOAC for a patient with high bleed risk. Notably, a 2020 review of data from the PINNACLE registry (average age, 75-77 years; 31% on PPIs) found that the relative GI bleed safety advantage of apixaban and dabigatran versus warfarin was attenuated in patients ≥ 75 years.⁴⁰ Last, since the risk for lower GI bleeds is not reduced by PPIs,⁴¹ consideration of their use should be accompanied by an assessment to detect bleeds (eg, low hemoglobin/hematocrit, presence of bright red blood, hematochezia/melena, fecal occult testing), with prompt management as necessary.⁵

Limitations

Limitations of our survey included an overall low response rate, which can generate a biased sample if respondents are systematically different from nonrespondents. In addition, to maintain simplicity and reduce respondents’ time commitment, our survey did not include actual CHA₂DS₂VASc stroke risk scores, HAS-BLED bleed risk scores, or specific GI bleed risk factors when querying pharmacists about treatment options based on bleed risk. The addition of these variables would have improved the robustness of the data.

Conclusion

In addition to applying BRTs in the management of NVAF patients, pharmacists considered patient-specific variables, prescriber preferences, and evidence-based guidance when recommending OACT with or without gastroprotection. To avoid suboptimal patient management, busy pharmacists should be granted time to attend continuing education programs describing optimal OACT selection and formulation of individualized, evidence-based plans to address modifiable risk factors for bleeding, including the appropriate use of gastroprotection. Randomized, prospective, long-term studies stratified by HAS-BLED and CHA₂DS₂VASc scores are needed to further clarify efficacy, safety, and cost-effectiveness of OACT, with and without PPIs, in patients who may be at risk for upper GI bleeds.

Acknowledgments: The authors thank Robin J. Jacobs, PhD, MSW, MS, MPH, Patrick C. Hardigan, PhD, Steven Brettler, PharmD, MPH, Maria-Isabel A. Cabral, PharmD, and Reginald Gyapong, PharmD, for their participation in this project. The authors also sincerely thank Fabio Franco, BS Computer Science, who organized the database to enable efficient data management.

Corresponding author: Devada Singh-Franco, PharmD, CDE, Nova Southeastern University College of Pharmacy, 3200 S University Drive, Fort Lauderdale, FL 33328; singh@nova.edu

Disclosures: None.

Funding: The study was supported by Nova Southeastern University’s Health Professions Division Internal Research Grant.

From Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL.

Abstract

• Objective: To determine pharmacists’ preferences in bleed risk tool (BRT) usage and gastroprotection when bleed risk was lower than or equal to stroke risk in patients with nonvalvular atrial fibrillation and who were candidates for oral anticoagulation therapy (warfarin or direct oral anticoagulants [DOACs]).
• Methods: A survey consisting of 4 domains (demographics, clinical experience, BRT usage, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk) was developed. The anonymous survey was disseminated via REDCap software to members of the American College of Clinical Pharmacy ambulatory care and cardiology Practice-based Research Networks. Descriptive statistics were calculated for all study variables and inferential statistics were employed as necessary.
• Results: Of 165 BRT users, 97% preferred HAS-BLED. When bleed risk was lower than stroke risk, 151 respondents chose either DOACs (65%) or warfarin (35%); 15% added gastroprotection. When bleed risk was equal to stroke risk, 141 respondents chose DOACs (50%), warfarin (45%), or aspirin (5%); 40% added gastroprotection.
• Conclusion: In addition to BRT usage, pharmacists were judicious in their recommendation to add gastroprotection and would consider doing so if there was a specific indication. As more than 80% of extracranial bleeds are gastrointestinal bleeds and most BRTs are nonspecific for predicting these bleeds, randomized, prospective studies stratified by HAS-BLED and stroke risk scores are needed to provide further guidance on the efficacy and safety of oral anticoagulation therapy with or without gastroprotection.

Keywords: NVAF; gastroprotection; proton pump inhibitors; warfarin; oral anticoagulants.

Management of patients with nonvalvular atrial fibrillation (NVAF) with oral anticoagulation therapy (OACT) requires constant attention to maintain a balance between preventing strokes and minimizing bleeds. Several validated bleed risk tools (BRTs) available for use in NVAF patients include HAS-BLED, HEMORR₂HAGES, ATRIA, and mOBRI.^1,2 A high bleed risk score is not a contraindication to OACT, but, prior to and throughout therapy, bleed risk should be assessed and modifiable risk factors addressed.³ While intraluminal gastrointestinal (GI) bleeds are not considered a critical bleed site, they are a common complication of chronic OACT and can result in hemodynamic compromise and permanent discontinuation of therapy.^4,5 In 3233 patients with nonvariceal upper GI bleeds (2005-2016), the adjusted odds ratio of hospital admission, transfusion, and re-bleeding while on OACT (warfarin, heparin, or apixaban) was 3.48, 2.53, and 2.26, respectively.⁶ Addition of acid-suppressive therapy with a proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H₂RA) in NVAF patients at increased risk for upper GI bleeds and receiving OACT may result in fewer bleeds.^7,8

Pharmacists play an integral part in managing patients on warfarin,^9-11 and data on their role in managing patients receiving direct oral anticoagulants (DOACs) are increasing.^12-16 Inpatient pharmacists actively participate in multidisciplinary collaborative teams and use clinical decision-support systems or enhanced monitoring to ensure safe prescribing of high-risk medications.^12,15,16 Pharmacist-managed, outpatient-based anticoagulation services in patients on warfarin were associated with lower rates of bleeding and thromboembolic events and lower health care utilization versus routine care.¹⁷ However, it is unclear how pharmacists manage patients who are candidates for OACT but who may be at increased risk for upper GI bleeds. Using a US-based survey, the investigators sought to determine pharmacists’ preferences in BRT usage and gastroprotection when bleed risk was lower than or equal to stroke risk.

Methods

This cross-sectional study was conducted after receiving approval by Nova Southeastern University’s Institutional Review Board. The survey consisted of 16 items divided into 4 domains: demographics, clinical experience, use of BRTs, and treatment preferences based on cases where bleed risk was lower than or equal to stroke risk (Figure 1). Queries were multiple choice and allowed for free-text input when “Other” was selected. Licensed pharmacists ≥ 18 years of age who routinely provided care to patients with NVAF were eligible to participate in the study. Participants who reported using a BRT (users) completed all study domains, while participants who reported not using a BRT (nonusers) completed domains 1 through 3 only.

An invitation containing the survey link was sent to the American College of Clinical Pharmacy ambulatory care (n = 2237) and cardiology (n = 1318) pharmacists listed in the organization’s Practice-based Research Networks. The survey was administered in the United States between April and June 2016 via Research Electronic Data Capture (REDCap) software, a secure Web application for building and managing online surveys designed to support data collection for research studies.¹⁸

Survey responses were downloaded, and data were analyzed using NCSS 2019 Statistical Software, LLC (Kaysville, UT). Descriptive statistics were calculated for all study variables. Demographic and clinical experience data for the group that used a BRT versus the group that did not were compared using Pearson’s chi-square, ANOVA, or the Cochran-Armitage test for trends. Logistic regression with hierarchical forward selection with switching was used to identify predictors of drug selection and use of gastroprotection.

Results

Of 230 respondents who completed the survey (response rate 6.5%), 165 (72%) used a BRT and 65 (28%) did not. No significant differences were found for age, gender, duration in clinical practice, the percentage of time spent in patient care, or practice specialty between users and nonusers (Table). The median age of users was 32 years; 68% were females; the median duration in clinical practice was 6 years; 75% of their time was spent in clinical practice; and clinical settings included ambulatory care, cardiology, and internal medicine. A significant difference was found for practice region between users versus nonusers (P = 0.014). Respondents who managed more than 200 NVAF patients per year used a BRT more often than those who managed fewer than 100 NVAF patients per year (P = 0.001).

Of those who used a BRT, 97% utilized the HAS-BLED tool (n = 160). The remainder used HEMORR₂HAGES (n = 3), ATRIA (n = 1), and mOBRI (n = 1). Reasons for choosing HAS-BLED included “familiarity/ease-of-use,” “preference by institution/clinical team,” and the fact that it was a “validated tool for NVAF.”

When bleed risk was lower than stroke risk, 151 of 165 users (92%) chose a treatment option (Figure 2). Of those, 65% chose a DOAC and 35% chose warfarin. Fourteen respondents chose “other” and explained that they “would initiate OACT after weighing patient factors and preferences.” When a DOAC was selected, 9% (n = 9) chose PPI co-therapy and 4% (n = 4) chose a H₂RA. When warfarin was selected, 13% (n = 7) chose PPI co-therapy and 4% (n = 2) chose a H₂RA. Respondents who chose gastroprotection did not provide reasons for doing so, but those who did not add it explained that they “would add gastroprotection only if patient is also on an NSAID or has a history of GI bleed” or cited “patient preference.” Specific to warfarin, some respondents would not add gastroprotection, as anticoagulation with warfarin is “easily reversed.”

When bleed risk was equal to stroke risk, 141 of 165 users (85%) chose a treatment option (Figure 3). Fifty percent chose DOACs, 45% chose warfarin, and 5% chose aspirin. Logistic regression analysis (outcome DOAC versus warfarin area-under-ROC curve, 0.67) showed that as the number of NVAF patients seen in 12 months increased, respondents were more likely to select a DOAC over warfarin (odds ratio, 1.7; 95% CI, 1.1-2.5). Therefore, for every 50-patient increase per year, the probability of recommending a DOAC increased 1.7-fold.

Of respondents who selected either a DOAC or warfarin, 38% (n = 50) also added gastroprotection (Figure 3). When a DOAC was selected, 34% (n = 24) favored PPI co-therapy and 7% (n = 5) chose a H₂RA. When warfarin was selected, 19% (n = 12) favored PPI co-therapy, while 13% (n = 8) chose a H₂RA. Rationale for choosing gastroprotection, regardless of OACT selection, included “stroke is more devastating, so if patient wants to continue treatment, but knew risks of bleeding were similar, would recommend gastroprotection to help minimize bleeding risk” and “patient-specific consideration.” Rationales for not choosing gastroprotection included “would add gastroprotection only if patient is on dual antiplatelet therapy or has another indication”; “in most patients, stroke risk outweighs bleed risk so no need for gastroprotection unless there is a stated reason”; “would use apixaban as has lowest bleeding rate of all DOACs in clinical trials”; and “gastroprotection has not been shown to be beneficial in large scale trials.” 

Eight respondents chose aspirin because it was “easy and relatively low cost.” Twenty-four respondents chose “other” and explained that the choice of OACT depended on patient preference after they had discussed stroke and bleed risk with the patient and/or determined the etiology driving bleed risk.

Discussion

This is the first national survey exploring US pharmacists’ preferences in BRT usage and treatment based on bleed risk. Pharmacists preferred the HAS-BLED tool and considered patient-specific factors and evidence-based data when weighing the risk-benefit of OACT with or without gastroprotective therapy.

Similar to our findings, where three-quarters of pharmacists used a BRT, a recent Medscape/American College of Cardiology (ACC) survey reported that 74% of cardiologists used a BRT (eg, HAS-BLED) always/most of the time or sometimes to assess a patient’s overall risk of bleeding prior to initiating DOAC therapy; 27% never or rarely used a bleed risk score before prescribing DOACs.¹⁹ Although reasons for BRT preference were not provided, they may be similar to those reported by our respondents (ie, familiarity/ease-of-use). In both surveys, rationales for not using a BRT were not obtained, but possible reasons include lack of confidence with bleed risk calculators,²⁰ inconsistent implementation of comprehensive assessments (stroke risk, bleed risk, and medication-related issues prior to decision-making),²¹ and nonspecific guideline recommendations.²²

More recently, a network meta-analysis found that HAS-BLED and HEMORR₂HAGES had modest but balanced sensitivity (defined as the ratio between the number of major bleeding events in high-risk stratification and the total number of bleeding events) and specificity (defined as the ratio between the number of nonmajor bleeding events in the low-risk population and total nonbleeding events) for predicting major bleeding events.^2,3 Several respondents did comment that, although HAS-BLED was imprecise and only studied with warfarin, it was necessary to identify bleed risk in a patient starting a high-risk medication, and that the ACC anticoagulation application uses HAS-BLED with CHA₂DS₂VASc along with clinical trial data to estimate stroke risk and bleed risk, with projected risk reduction (strokes) and risk increases (bleeds) expected with each treatment (www.acc.org/tools-and-practice-support/mobile-resources/features/anticoag-evaluator). The 2019 AHA/ACC/HRS atrial fibrillation guideline recommends that HAS-BLED scores be used to assess bleed risk in patients for whom anticoagulation is being considered, and that the need for and choice of OACT should be periodically reevaluated to reassess stroke and bleed risks.²³

Although more than 80% of extracranial bleeds are GI bleeds,²⁴ most BRTs are nonspecific for predicting GI bleeds. Indeed, one respondent used a spreadsheet with several BRTs to maximize treatment guidance for patients with multiple risk factors for strokes and bleeds. A comprehensive approach to determining factors that increase bleed risk should be adopted. These factors include age (HAS-BLED, HEMORR₂HAGES, mOBRI, ATRIA); anemia (mOBRI, HEMORR₂HAGES, ATRIA); hepatic/renal disease (HAS-BLED, HEMORR₂HAGES, ATRIA, mOBRI); concomitant medications/alcohol use, including NSAIDs, corticosteroids, and antiplatelet therapy (HAS-BLED, HEMORR₂HAGES); bleed history/rebleeding risk (HEMORR₂HAGES, HAS-BLED, ATRIA); and GI bleeds (mOBRI).^1,2 Additional risk factors for GI bleeds include being a tobacco smoker and/or being infected with Helicobacter pylori. A prospective cohort study that analyzed data from questionnaires completed by 99,359 individuals from the Copenhagen General Population Study reported that the multivariable adjusted hazard ratio for current smokers versus never smokers was 2.20 (95% CI, 1.84-2.62) for GI bleeds.²⁵ Presence of H pylori should be investigated, with a subsequent eradication regimen implemented, as patients with warfarin-associated upper GI bleeds who were H pylori-positive had lower HAS-BLED scores versus those who were negative.²⁶

When bleed risk was lower than stroke risk (eg, HAS-BLED < 3, CHA₂DS₂VASc ≥ 1), respondents appropriately initiated therapy with an OAC (predominantly apixaban); a small proportion also added gastroprotection. If the patient did not have any other GI bleed risk factors (eg, a previous GI bleed or on chronic antiplatelet or NSAID therapy), the choice of OACT depended on the attributes of each OAC and patient preference.²⁷ Selection of warfarin was appropriate if cost, formulary restrictions, and availability of an inexpensive reversal agent were important concerns to patients and/or their health care providers. Rivaroxaban was selected because of its once-daily dosing and low risk for GI bleeding.

The recently published ARISTOPHANES study provides evidence that apixaban is an appropriate choice in patients with a HAS-BLED score < 3. In this retrospective observational study, more than 70% of patients received standard doses of DOACs (apixaban 5 mg, dabigatran 150 mg, or rivaroxaban 20 mg) and about 20% had a bleeding history, about 30% were on PPIs, less than 25% were on NSAIDs, and about 40% had a HAS-BLED score < 3. The study found that apixaban was more effective (reduced rates of ischemic or hemorrhagic strokes/systemic embolism) and safer (reduced rates of major GI bleed or intracranial bleed) than warfarin.²⁸ Dabigatran and rivaroxaban were also more effective than warfarin for stroke prevention and had a lower risk for major intracranial bleed risk; while the risk of major GI bleed was similar between dabigatran and warfarin, major GI bleed risk was higher for rivaroxaban. When compared with each other, the 3 DOACs were effective at stroke prevention, with apixaban more effective than dabigatran and rivaroxaban; similar efficacy was noted for dabigatran versus rivaroxaban. Apixaban was associated with fewer GI bleeds versus dabigatran and rivaroxaban, but with similar intracranial bleed risks; dabigatran was associated with fewer GI bleeds but similar intracranial bleed risks versus rivaroxaban.²⁸ Efficacy and safety findings from a subgroup analysis based on HAS-BLED scores < 3 and ≥ 3 were generally consistent with the main results.

When bleed risk was equal to stroke risk, the difficulty was determining how OACT in a patient at high stroke risk (CHA₂DS₂VASc score ≥ 2) and high bleed risk (HAS-BLED score ≥ 3) should be managed. Eight respondents chose aspirin and added gastroprotection with either a PPI or H₂RA; however, currently, aspirin is not recommended as the sole antithrombotic for patients with NVAF.²³ With the OACT, an interesting finding was that as the number of patients seen in 12 months increased, pharmacists were almost twice as likely to select a DOAC over warfarin. Moreover, pharmacists were judicious in their recommendation to add gastroprotection, and would consider doing so if there was a specific indication. At the time of our survey, several studies described DOAC-associated GI bleeds,^29-31 but data on the effectiveness of acid-suppressive therapy, specifically with PPIs, in the prevention of upper GI bleeds were sparse.^4,7,32 Respondents most likely were familiar with GI bleed risk factors and prevention strategies from various guidelines published between 2009 and 2010, which did not include DOACs.^33-35

Another important finding was pharmacists’ uncertainty as to the effectiveness of PPIs in preventing GI bleeds in combination with DOACs. The data are conflicting. A meta-analysis of older studies (2007-2015) showed that PPIs (but not H₂RAs) reduced the risk of upper GI bleeds in patients on warfarin but not for dabigatran.³⁶ A retrospective cohort study of Medicare beneficiaries on OACTs (2011-2015) showed the adjusted incidence of hospitalization for upper GI bleeds in patients on PPI co-therapy was significantly lower compared with patients not on PPI co-therapy (76 versus 115 per 10,000 person-years, respectively).⁸ Apixaban without PPI co-therapy was associated with the lowest risk of upper GI bleed hospitalizations (73/10,000 person-years), and PPI co-therapy further reduced this risk (49/10,000 person-years). Warfarin without PPI co-therapy was associated with the next lowest risk (113/10,000 person-years), followed by dabigatran (120/10,000 person-years) and rivaroxaban (144/10,000 person-years). PPI co-therapy significantly reduced the risk of upper GI bleed hospitalizations with all OACTs, but the incidence of upper GI bleed hospitalizations with rivaroxaban was significantly greater than with the other OACTs.⁸ Therefore, if there are concerns about the safety of PPIs,^37-39 or the patient is unable to tolerate a PPI, then apixaban may be the most appropriate DOAC for a patient with high bleed risk. Notably, a 2020 review of data from the PINNACLE registry (average age, 75-77 years; 31% on PPIs) found that the relative GI bleed safety advantage of apixaban and dabigatran versus warfarin was attenuated in patients ≥ 75 years.⁴⁰ Last, since the risk for lower GI bleeds is not reduced by PPIs,⁴¹ consideration of their use should be accompanied by an assessment to detect bleeds (eg, low hemoglobin/hematocrit, presence of bright red blood, hematochezia/melena, fecal occult testing), with prompt management as necessary.⁵

Limitations

Limitations of our survey included an overall low response rate, which can generate a biased sample if respondents are systematically different from nonrespondents. In addition, to maintain simplicity and reduce respondents’ time commitment, our survey did not include actual CHA₂DS₂VASc stroke risk scores, HAS-BLED bleed risk scores, or specific GI bleed risk factors when querying pharmacists about treatment options based on bleed risk. The addition of these variables would have improved the robustness of the data.

Conclusion

In addition to applying BRTs in the management of NVAF patients, pharmacists considered patient-specific variables, prescriber preferences, and evidence-based guidance when recommending OACT with or without gastroprotection. To avoid suboptimal patient management, busy pharmacists should be granted time to attend continuing education programs describing optimal OACT selection and formulation of individualized, evidence-based plans to address modifiable risk factors for bleeding, including the appropriate use of gastroprotection. Randomized, prospective, long-term studies stratified by HAS-BLED and CHA₂DS₂VASc scores are needed to further clarify efficacy, safety, and cost-effectiveness of OACT, with and without PPIs, in patients who may be at risk for upper GI bleeds.

Acknowledgments: The authors thank Robin J. Jacobs, PhD, MSW, MS, MPH, Patrick C. Hardigan, PhD, Steven Brettler, PharmD, MPH, Maria-Isabel A. Cabral, PharmD, and Reginald Gyapong, PharmD, for their participation in this project. The authors also sincerely thank Fabio Franco, BS Computer Science, who organized the database to enable efficient data management.

Corresponding author: Devada Singh-Franco, PharmD, CDE, Nova Southeastern University College of Pharmacy, 3200 S University Drive, Fort Lauderdale, FL 33328; singh@nova.edu

Disclosures: None.

Funding: The study was supported by Nova Southeastern University’s Health Professions Division Internal Research Grant.