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Do lipid labs need to be fasting?
When I worked as a scribe prior to starting medical school, it was commonplace for patients to have fasting labs. I always felt terrible for the patients we saw late in the afternoon that had somehow fasted all day. For many other patients, there was the challenge of finding a time when they could return to have fasting labs drawn.
However, I have still observed instances when patients need to have fasting labs. We can look at an example case to better understand when and why patients do and do not need to fast prior to having their lipids checked.
Case
A 57-year-old woman presents for an annual wellness visit. She has been healthy this past year with no new concerns. Her blood pressure has been well controlled, and she continues on a statin for hyperlipidemia. She is due for annual labs. She ate breakfast this morning. Which of the following do you recommend?
A. Obtain lipids with her other blood work now.
B. Have her return tomorrow to obtain fasting labs.
In this situation, A is the correct answer. The patient is due for routine screening labs and there are no current indications that fasting labs are necessary.
Studies of fasting vs. nonfasting lipids
Sidhu and Naugler performed a cross-sectional analysis comparing lipid values at fasting intervals of 1 hour to 16 hours.1 They found the mean total cholesterol and HDL cholesterol values differed by greater than 2%. For LDL cholesterol, the values differed by less than 10% and triglycerides values differed by less than 20%. With this information, the researchers concluded fasting for routine lipids is generally unnecessary.
Mora and colleagues performed a post hoc prospective follow-up of a randomized control
trial to assess if nonfasting lipid measurements could cause misclassification of cardiovascular risk assessment.2 Based on 8,270 participants, coronary events associated with fasting vs. nonfasting lipid values were similar when adjusted hazard ratios were compared. They also found an agreement of 94.8% when classifying participants into ASCVD risk categories for fasting and nonfasting lipid values. These outcomes led them to support the use of nonfasting lipid labs for routine cardiovascular risk assessment.
Rahman and colleagues performed a systematic review and found the use of nonfasting lipid values can reliably determine statin management in most situations.3 Circumstances where fasting labs should be used are if patients have a genetic dyslipidemia, if patients have severe hypertriglyceridemia (greater than 500 mg/dL), and if patients have pancreatitis. Triglyceride values fluctuate the most between the fasting and nonfasting state as seen above from Sidhu and Naugler. This could impact triglyceride disorder management and the accuracy of LDL cholesterol estimation (calculated by the Friedewald equation: LDL cholesterol = total cholesterol – HDL cholesterol – triglycerides/5 in mg/dL).3
Benefits of nonfasting lipid labs
There are many benefits of nonfasting labs. For the patients, they do not have to come to their appointments hungry, we can reduce the risk of hypoglycemia for those with diabetes, and they do not have to come back at a later date if they ate something earlier in the day.
For the lab, we can improve efficiency and decrease early morning congestion when patients typically come in for fasting labs.
Lastly, for the provider, nonfasting labs can improve workflow and help decrease the number of patients lost to follow-up who were unable to complete fasting labs the same day as their appointment.
Summary
Patients do not need to fast prior to having lipid levels drawn for routine screening. Fasting labs should be considered for patients who have a genetic dyslipidemia or if there is concern for hypertriglyceridemia.
Per the ACC/AHA guidelines, nonfasting lipids can be used to assess ASCVD risk and to establish a baseline LDL cholesterol in adults 20 years and older. If a patient has nonfasting triglycerides greater than 400 mg/dL, repeat fasting lipids should be drawn to assess fasting triglycerides and to establish a baseline LDL cholesterol.4
Ms. Ervin is a fourth-year medical student at the University of Washington, Seattle. She has no conflicts to disclose. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, and he serves as third-year medical student clerkship director at the university. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Rahman F et al. Curr Atheroscler Rep. 2018;20(3):14. Published 2018 Feb 17.
2. Mora S et al. JAMA Intern Med. 2019;179(7):898-905.
3. Sidhu D and Naugler C. Arch Intern Med. 2012;172(22):1707-10.
4. Hoover LE. Am Fam Physician. 2019 May 1;99(9):589-91.
When I worked as a scribe prior to starting medical school, it was commonplace for patients to have fasting labs. I always felt terrible for the patients we saw late in the afternoon that had somehow fasted all day. For many other patients, there was the challenge of finding a time when they could return to have fasting labs drawn.
However, I have still observed instances when patients need to have fasting labs. We can look at an example case to better understand when and why patients do and do not need to fast prior to having their lipids checked.
Case
A 57-year-old woman presents for an annual wellness visit. She has been healthy this past year with no new concerns. Her blood pressure has been well controlled, and she continues on a statin for hyperlipidemia. She is due for annual labs. She ate breakfast this morning. Which of the following do you recommend?
A. Obtain lipids with her other blood work now.
B. Have her return tomorrow to obtain fasting labs.
In this situation, A is the correct answer. The patient is due for routine screening labs and there are no current indications that fasting labs are necessary.
Studies of fasting vs. nonfasting lipids
Sidhu and Naugler performed a cross-sectional analysis comparing lipid values at fasting intervals of 1 hour to 16 hours.1 They found the mean total cholesterol and HDL cholesterol values differed by greater than 2%. For LDL cholesterol, the values differed by less than 10% and triglycerides values differed by less than 20%. With this information, the researchers concluded fasting for routine lipids is generally unnecessary.
Mora and colleagues performed a post hoc prospective follow-up of a randomized control
trial to assess if nonfasting lipid measurements could cause misclassification of cardiovascular risk assessment.2 Based on 8,270 participants, coronary events associated with fasting vs. nonfasting lipid values were similar when adjusted hazard ratios were compared. They also found an agreement of 94.8% when classifying participants into ASCVD risk categories for fasting and nonfasting lipid values. These outcomes led them to support the use of nonfasting lipid labs for routine cardiovascular risk assessment.
Rahman and colleagues performed a systematic review and found the use of nonfasting lipid values can reliably determine statin management in most situations.3 Circumstances where fasting labs should be used are if patients have a genetic dyslipidemia, if patients have severe hypertriglyceridemia (greater than 500 mg/dL), and if patients have pancreatitis. Triglyceride values fluctuate the most between the fasting and nonfasting state as seen above from Sidhu and Naugler. This could impact triglyceride disorder management and the accuracy of LDL cholesterol estimation (calculated by the Friedewald equation: LDL cholesterol = total cholesterol – HDL cholesterol – triglycerides/5 in mg/dL).3
Benefits of nonfasting lipid labs
There are many benefits of nonfasting labs. For the patients, they do not have to come to their appointments hungry, we can reduce the risk of hypoglycemia for those with diabetes, and they do not have to come back at a later date if they ate something earlier in the day.
For the lab, we can improve efficiency and decrease early morning congestion when patients typically come in for fasting labs.
Lastly, for the provider, nonfasting labs can improve workflow and help decrease the number of patients lost to follow-up who were unable to complete fasting labs the same day as their appointment.
Summary
Patients do not need to fast prior to having lipid levels drawn for routine screening. Fasting labs should be considered for patients who have a genetic dyslipidemia or if there is concern for hypertriglyceridemia.
Per the ACC/AHA guidelines, nonfasting lipids can be used to assess ASCVD risk and to establish a baseline LDL cholesterol in adults 20 years and older. If a patient has nonfasting triglycerides greater than 400 mg/dL, repeat fasting lipids should be drawn to assess fasting triglycerides and to establish a baseline LDL cholesterol.4
Ms. Ervin is a fourth-year medical student at the University of Washington, Seattle. She has no conflicts to disclose. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, and he serves as third-year medical student clerkship director at the university. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Rahman F et al. Curr Atheroscler Rep. 2018;20(3):14. Published 2018 Feb 17.
2. Mora S et al. JAMA Intern Med. 2019;179(7):898-905.
3. Sidhu D and Naugler C. Arch Intern Med. 2012;172(22):1707-10.
4. Hoover LE. Am Fam Physician. 2019 May 1;99(9):589-91.
When I worked as a scribe prior to starting medical school, it was commonplace for patients to have fasting labs. I always felt terrible for the patients we saw late in the afternoon that had somehow fasted all day. For many other patients, there was the challenge of finding a time when they could return to have fasting labs drawn.
However, I have still observed instances when patients need to have fasting labs. We can look at an example case to better understand when and why patients do and do not need to fast prior to having their lipids checked.
Case
A 57-year-old woman presents for an annual wellness visit. She has been healthy this past year with no new concerns. Her blood pressure has been well controlled, and she continues on a statin for hyperlipidemia. She is due for annual labs. She ate breakfast this morning. Which of the following do you recommend?
A. Obtain lipids with her other blood work now.
B. Have her return tomorrow to obtain fasting labs.
In this situation, A is the correct answer. The patient is due for routine screening labs and there are no current indications that fasting labs are necessary.
Studies of fasting vs. nonfasting lipids
Sidhu and Naugler performed a cross-sectional analysis comparing lipid values at fasting intervals of 1 hour to 16 hours.1 They found the mean total cholesterol and HDL cholesterol values differed by greater than 2%. For LDL cholesterol, the values differed by less than 10% and triglycerides values differed by less than 20%. With this information, the researchers concluded fasting for routine lipids is generally unnecessary.
Mora and colleagues performed a post hoc prospective follow-up of a randomized control
trial to assess if nonfasting lipid measurements could cause misclassification of cardiovascular risk assessment.2 Based on 8,270 participants, coronary events associated with fasting vs. nonfasting lipid values were similar when adjusted hazard ratios were compared. They also found an agreement of 94.8% when classifying participants into ASCVD risk categories for fasting and nonfasting lipid values. These outcomes led them to support the use of nonfasting lipid labs for routine cardiovascular risk assessment.
Rahman and colleagues performed a systematic review and found the use of nonfasting lipid values can reliably determine statin management in most situations.3 Circumstances where fasting labs should be used are if patients have a genetic dyslipidemia, if patients have severe hypertriglyceridemia (greater than 500 mg/dL), and if patients have pancreatitis. Triglyceride values fluctuate the most between the fasting and nonfasting state as seen above from Sidhu and Naugler. This could impact triglyceride disorder management and the accuracy of LDL cholesterol estimation (calculated by the Friedewald equation: LDL cholesterol = total cholesterol – HDL cholesterol – triglycerides/5 in mg/dL).3
Benefits of nonfasting lipid labs
There are many benefits of nonfasting labs. For the patients, they do not have to come to their appointments hungry, we can reduce the risk of hypoglycemia for those with diabetes, and they do not have to come back at a later date if they ate something earlier in the day.
For the lab, we can improve efficiency and decrease early morning congestion when patients typically come in for fasting labs.
Lastly, for the provider, nonfasting labs can improve workflow and help decrease the number of patients lost to follow-up who were unable to complete fasting labs the same day as their appointment.
Summary
Patients do not need to fast prior to having lipid levels drawn for routine screening. Fasting labs should be considered for patients who have a genetic dyslipidemia or if there is concern for hypertriglyceridemia.
Per the ACC/AHA guidelines, nonfasting lipids can be used to assess ASCVD risk and to establish a baseline LDL cholesterol in adults 20 years and older. If a patient has nonfasting triglycerides greater than 400 mg/dL, repeat fasting lipids should be drawn to assess fasting triglycerides and to establish a baseline LDL cholesterol.4
Ms. Ervin is a fourth-year medical student at the University of Washington, Seattle. She has no conflicts to disclose. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, and he serves as third-year medical student clerkship director at the university. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Rahman F et al. Curr Atheroscler Rep. 2018;20(3):14. Published 2018 Feb 17.
2. Mora S et al. JAMA Intern Med. 2019;179(7):898-905.
3. Sidhu D and Naugler C. Arch Intern Med. 2012;172(22):1707-10.
4. Hoover LE. Am Fam Physician. 2019 May 1;99(9):589-91.
Waist-hip ratio beats BMI for predicting obesity’s mortality risk
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
AT EASD 2022
‘Game changer’ semaglutide halves diabetes risk from obesity
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Two states aim to curb diet pill sales to minors
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Fish oil pills do not reduce fractures in healthy seniors: VITAL
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASMBR 2022
Dietary change tops for reducing CVD risk in stage 1 hypertension
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
When do we stop using BMI to diagnose obesity?
“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.
As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
BMI: From observational measurement to clinical use
Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.
The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.
Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.
In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.
By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
BMI as a tool to diagnose obesity
We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.
Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.
Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.
This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.
Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
Is it time to phase out BMI?
The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:
- Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
- Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
- Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.
The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.
Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.
Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.
Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.
A version of this article first appeared on Medscape.com.
“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.
As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
BMI: From observational measurement to clinical use
Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.
The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.
Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.
In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.
By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
BMI as a tool to diagnose obesity
We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.
Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.
Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.
This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.
Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
Is it time to phase out BMI?
The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:
- Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
- Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
- Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.
The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.
Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.
Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.
Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.
A version of this article first appeared on Medscape.com.
“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.
As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
BMI: From observational measurement to clinical use
Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.
The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.
Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.
In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.
By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
BMI as a tool to diagnose obesity
We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.
Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.
Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.
This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.
Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
Is it time to phase out BMI?
The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:
- Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
- Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
- Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.
The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.
Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.
Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.
Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.
A version of this article first appeared on Medscape.com.
‘Spectacular’ polypill results also puzzle docs
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
Test Lp(a) levels to inform ASCVD management: NLA statement
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
No invasive strategy benefit at 5 years in ISCHEMIA-CKD extension study
A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.
The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.
Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.
Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.
Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.
Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.
REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.
ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.
“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”
A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.
“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.
At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.
The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).
In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.
Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.
For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”
But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”
ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.
A version of this article first appeared on Medscape.com.
A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.
The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.
Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.
Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.
Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.
Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.
REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.
ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.
“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”
A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.
“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.
At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.
The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).
In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.
Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.
For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”
But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”
ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.
A version of this article first appeared on Medscape.com.
A trip to the cath lab for possible revascularization after a positive stress test, compared with a wait-and-see approach backed by optimal medications, did not improve 5-year survival for patients with advanced chronic kidney disease (CKD) in the ISCHEMIA-CKD trial’s extension study, ISCHEMIA-CKD EXTEND.
The long-term results, from the same 777 patients followed for an average of 2.2 years in the main trial, are consistent with the overall findings of no survival advantage with an initially invasive strategy, compared with one that is initially conservative. The finding applies to patients like those in the trial who had moderate to severe ischemia at stress testing and whose CKD put them in an especially high-risk and little-studied coronary artery disease (CAD) category.
Indeed, in a reflection of that high-risk status, 5-year all-cause mortality reached about 40% and cardiovascular (CV) mortality approached 30%, with no significant differences between patients in the invasive- and conservative-strategy groups.
Those numbers arguably put CKD’s effect on CAD survival in about the same league as an ejection fraction (EF) of 35% or less. For context, all-cause mortality over 3-4 years was about 32% in the REVIVED-BCIS2 trial of such patients with ischemic reduced-EF cardiomyopathy, whether or not they were revascularized, observed Sripal Bangalore, MD, MHA.
Yet in ISCHEMIA-CKD EXTEND, “you’re seeing in a group of patients, with largely preserved EF but advanced CKD, a mortality rate close to 40% at 5 years,” said Dr. Bangalore of New York University.
Although the study doesn’t show benefit from the initially invasive approach in CKD patients with stable CAD, for those with acute coronary syndromes (ACS), it seems to suggest that “at least the invasive strategy is safe,” Dr. Bangalore said during a press conference preceding his presentation of the study Aug. 29 at the annual congress of the European Society of Cardiology, held in Barcelona.
REVIVED-BCIS2 was also presented at the ESC sessions on Aug. 27, as reported by this news organization.
ISCHEMIA-CKD EXTEND “is a large trial and a very well-done trial. The results are robust, and they should influence clinical practice,” Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said as the invited discussant after Dr. Bangalore’s presentation.
“The main message here, really, is don’t just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization,” Dr. Bhatt said. “The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.”
A caveat, he said, is that the trial’s results don’t apply to the types of patients excluded from it, including those with recent ACS and those who are highly symptomatic or have an EF of less than 35%.
“Those CKD patients likely benefit from an invasive strategy with anatomically appropriate revascularization,” whether percutaneous coronary intervention (PCI) or coronary bypass surgery, Dr. Bhatt said.
At a median follow-up of 5 years in the extension study, the rates of death from any cause were 40.6% for patients in the invasive-strategy group and 37.4% for those in the conservative-strategy group. That yielded a hazard ratio of 1.12 (95% confidence interval, 0.89-1.41; P = .32) after adjustment for age, sex, diabetes status, EF, dialysis status, and – for patients not on dialysis – baseline estimated glomerular filtration rate.
The rates of CV death were 29% for patients managed invasively and 27% for those initially managed conservatively, for a similarly adjusted HR of 1.04 (95% CI, 0.80-1.37; P = .75).
In subgroup analyses, Dr. Bangalore reported, there were no significant differences in all-cause or CV mortality by diabetes status, by severity of baseline ischemia, or by whether the patient had recently experienced new or more frequent angina at study entry, was on guideline-directed medical therapy at baseline, or was on dialysis.
Among the contributions of ISCHEMIA-CKD and its 5-year extension study, Dr. Bangalore told this news organization, is that the relative safety of revascularization they showed may help to counter “renalism,” that is, the aversion to invasive intervention in patients with advanced CKD in clinical practice.
For example, if a patient with advanced CKD presents with an acute myocardial infarction, “people are hesitant to take them to the cath lab,” Dr. Bangalore said. But “if you follow protocols, if you follow strategies to minimize the risk, you can safely go ahead and do it.”
But in patients with stable CAD, as the ISCHEMIA-CKD studies show, “routinely revascularizing them may not have significant benefits.”
ISCHEMIC-CKD and its extension study were funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore discloses receiving research grants from NHLBI and serving as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Amgen, Pfizer, Merck, and Reata. Dr. Bhatt has disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022