Cardiology

Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.

But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.

enot-poloskun/Getty Images

• 1.31 (95% CI, 1.30-1.33) for heart failure
• 1.40 (95% CI, 1.37-1.43) for stroke
• 1.59 (95% CI, 1.43-1.75) for systemic embolism
• 1.14 (95% CI, 1.13-1.16) for major bleeding  
• 0.81 (95% CI, 0.79-0.82) for MI

Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).

The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.

For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.

“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”

Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.

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

Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.

But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.

enot-poloskun/Getty Images

• 1.31 (95% CI, 1.30-1.33) for heart failure
• 1.40 (95% CI, 1.37-1.43) for stroke
• 1.59 (95% CI, 1.43-1.75) for systemic embolism
• 1.14 (95% CI, 1.13-1.16) for major bleeding  
• 0.81 (95% CI, 0.79-0.82) for MI

Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).

The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.

For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.

“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”

Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.

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

Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.

But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.

enot-poloskun/Getty Images

• 1.31 (95% CI, 1.30-1.33) for heart failure
• 1.40 (95% CI, 1.37-1.43) for stroke
• 1.59 (95% CI, 1.43-1.75) for systemic embolism
• 1.14 (95% CI, 1.13-1.16) for major bleeding  
• 0.81 (95% CI, 0.79-0.82) for MI

Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).

The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.

For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.

“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”

Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.

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

Hypertensive disorders of pregnancy (HDP) are associated with a greater than twofold risk of developing hypertension a decade later, new research suggests.

Investigators prospectively studied patients who had and who had not experienced HDP 10 years earlier; most self-identified as Black. They found that those with a history of HDP had a 2.4-fold higher risk for new hypertension than those without such a history.

Patients who developed hypertension showed greater left ventricular (LV) remodeling (including greater relative wall thickness), worse diastolic function, more abnormal longitudinal strain, and higher effective arterial elastance than those without hypertension, regardless of the presence or absence of an HDP history.

“We know that patients with preeclampsia are at a higher risk for heart disease later in life, and it seems to be driven by the development of new hypertension,” lead author Lisa Levine, MD, MSCE, director, pregnancy and heart disease program, Hospital of the University of Pennsylvania, Philadelphia, told this news organization.

It is critically important to “study a more diverse population, including a larger percentage of Black patients, since HDP and CVD both disproportionately affect Black women,” Dr. Levine said. “And it is important to screen patients for hypertension, getting them into primary care for visits, getting them diagnosed sooner, and treating them early for hypertension.”

The study was published in the Journal of the American College of Cardiology.
 

Understudied population

HDP includes gestational hypertension and preeclampsia, Dr. Levine explained. “We already know that patients who have had preeclampsia are at higher risk for stroke, heart failure [HF], and myocardial infarction later in life,” she said. The goal of this study was to see whether, instead of waiting 20-30 years, they could look only 10 years later to see which patients would be at highest risk for future heart disease, Dr. Levine said.

In particular, it’s known that cardiovascular disease (CVD) and HDP “disproportionately affect Black women,” Dr. Levine continued. “What makes our study different from other studies is that we focused predominantly on the Black African American population, since it’s understudied and also at highest risk for preeclampsia and heart disease,” she said.

They set out to “evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier,” the authors state.

To investigate the question, the researchers performed a prospective, cross-sectional study between April 2016 and December 2019 of patients with and without a diagnosis of HDP during a previous pregnancy at least 10 years earlier (from 2005 to 2007). Patients were drawn from a parent cohort in a previously performed observational study of patients with preeclampsia or HDP and normotensive control subjects.

The current study focused on 135 patients (85% Black), 84 with a history of HDP and 51 without. Of the Black patients, 91.7% had a history of HDP, compared with 8.3% of the White patients.

During an in-person visit, the researchers assessed participants’ blood pressure and other clinical risk factors for CVD, including fasting glucose and lipids. They also used noninvasive means to measure cardiac and vascular structure and function.
 

Importance of routine screening

The risk for new hypertension was 2.4 times higher in patients with a history of HDP than in those without HDP, with stage 2 hypertension noted in 56.0% of patients with and in 23.5% without HDP (P < .001). This equates to a relative risk of 2.4 (95% confidence interval, 1.39-4.14), even after adjustment for race, maternal age, body mass index, and history of preterm birth.

“Importantly, 18% of patients with a history of HDP met criteria for a new diagnosis of hypertension identified through the study visit,” the authors report.

There were no differences in many cardiac measures (left ventricular (LV) structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function) between patients with and without a history of HDP.

However, patients with chronic hypertension (CHTN), regardless of HDP history, had other cardiac abnormalities, including greater LV remodeling, worse diastolic function, and higher effective arterial elastance.

“The data regarding increased risk of hypertension after HDP is not a novel finding, however our cohort is unique in the high baseline rate of stage 2 hypertension, even among patients without a history of HDP,” the authors comment.

In fact, when they looked at the diagnosis of either stage 1 or stage 2 hypertension, they found that more than 80% of patients with and 60% of patients without a history of HDP had hypertension. Notably, among patients with a history of HDP, only 39% had a formal diagnosis of either stage 1 or stage 2 hypertension, further highlighting “the importance of routine screening for CHTN in this population,” they state.

“Further studies should evaluate the optimal time period to screen for postpartum hypertension and a monitoring plan for these at-risk women,” Dr. Levine added.
 

‘Opportunity of a lifetime’

Commenting for this news organization, Malamo Countouris, MD, MS, assistant professor of medicine and codirector, postpartum hypertension program, University of Pittsburgh Medical Center, said hypertension is “underrecognized and undertreated among young, premenopausal, Black women.”

Pregnancy “gives us a clue, through HDP, as to who is high risk to develop chronic hypertension and subsequent subclinical structural cardiac changes in the decade after delivery,” said Dr. Countouris, who was not involved with the study.

“The jury is still out on whether HDP contributes independently to cardiovascular changes in the years after delivery. Ongoing research is needed to clarify the unique or compounding contributions of pregnancy complications and hypertension,” she added.

In an accompanying editorial , Josephine Chou, MD, MS, director of cardio-obstetrics and codirector of maternal cardiology, Yale University, New Haven, Conn., called the study a “laudable contribution to understanding of HDP and hypertension within the first decade after pregnancy,” saying that it “paves the way for future efforts to improve postpartum CV care, enabling us to grasp this opportunity of a lifetime to ultimately reduce maternal and pregnancy-related morbidity and mortality.”

This study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute, and the American Association of Obstetricians and Gynecologists Foundation. Dr. Levine reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Countouris reports receiving funding from the American Heart Association. Dr. Chou reports no relevant financial relationships.

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

Hypertensive disorders of pregnancy (HDP) are associated with a greater than twofold risk of developing hypertension a decade later, new research suggests.

Investigators prospectively studied patients who had and who had not experienced HDP 10 years earlier; most self-identified as Black. They found that those with a history of HDP had a 2.4-fold higher risk for new hypertension than those without such a history.

Patients who developed hypertension showed greater left ventricular (LV) remodeling (including greater relative wall thickness), worse diastolic function, more abnormal longitudinal strain, and higher effective arterial elastance than those without hypertension, regardless of the presence or absence of an HDP history.

“We know that patients with preeclampsia are at a higher risk for heart disease later in life, and it seems to be driven by the development of new hypertension,” lead author Lisa Levine, MD, MSCE, director, pregnancy and heart disease program, Hospital of the University of Pennsylvania, Philadelphia, told this news organization.

It is critically important to “study a more diverse population, including a larger percentage of Black patients, since HDP and CVD both disproportionately affect Black women,” Dr. Levine said. “And it is important to screen patients for hypertension, getting them into primary care for visits, getting them diagnosed sooner, and treating them early for hypertension.”

The study was published in the Journal of the American College of Cardiology.
 

Understudied population

HDP includes gestational hypertension and preeclampsia, Dr. Levine explained. “We already know that patients who have had preeclampsia are at higher risk for stroke, heart failure [HF], and myocardial infarction later in life,” she said. The goal of this study was to see whether, instead of waiting 20-30 years, they could look only 10 years later to see which patients would be at highest risk for future heart disease, Dr. Levine said.

In particular, it’s known that cardiovascular disease (CVD) and HDP “disproportionately affect Black women,” Dr. Levine continued. “What makes our study different from other studies is that we focused predominantly on the Black African American population, since it’s understudied and also at highest risk for preeclampsia and heart disease,” she said.

They set out to “evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier,” the authors state.

To investigate the question, the researchers performed a prospective, cross-sectional study between April 2016 and December 2019 of patients with and without a diagnosis of HDP during a previous pregnancy at least 10 years earlier (from 2005 to 2007). Patients were drawn from a parent cohort in a previously performed observational study of patients with preeclampsia or HDP and normotensive control subjects.

The current study focused on 135 patients (85% Black), 84 with a history of HDP and 51 without. Of the Black patients, 91.7% had a history of HDP, compared with 8.3% of the White patients.

During an in-person visit, the researchers assessed participants’ blood pressure and other clinical risk factors for CVD, including fasting glucose and lipids. They also used noninvasive means to measure cardiac and vascular structure and function.
 

Importance of routine screening

The risk for new hypertension was 2.4 times higher in patients with a history of HDP than in those without HDP, with stage 2 hypertension noted in 56.0% of patients with and in 23.5% without HDP (P < .001). This equates to a relative risk of 2.4 (95% confidence interval, 1.39-4.14), even after adjustment for race, maternal age, body mass index, and history of preterm birth.

“Importantly, 18% of patients with a history of HDP met criteria for a new diagnosis of hypertension identified through the study visit,” the authors report.

There were no differences in many cardiac measures (left ventricular (LV) structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function) between patients with and without a history of HDP.

However, patients with chronic hypertension (CHTN), regardless of HDP history, had other cardiac abnormalities, including greater LV remodeling, worse diastolic function, and higher effective arterial elastance.

“The data regarding increased risk of hypertension after HDP is not a novel finding, however our cohort is unique in the high baseline rate of stage 2 hypertension, even among patients without a history of HDP,” the authors comment.

In fact, when they looked at the diagnosis of either stage 1 or stage 2 hypertension, they found that more than 80% of patients with and 60% of patients without a history of HDP had hypertension. Notably, among patients with a history of HDP, only 39% had a formal diagnosis of either stage 1 or stage 2 hypertension, further highlighting “the importance of routine screening for CHTN in this population,” they state.

“Further studies should evaluate the optimal time period to screen for postpartum hypertension and a monitoring plan for these at-risk women,” Dr. Levine added.
 

‘Opportunity of a lifetime’

Commenting for this news organization, Malamo Countouris, MD, MS, assistant professor of medicine and codirector, postpartum hypertension program, University of Pittsburgh Medical Center, said hypertension is “underrecognized and undertreated among young, premenopausal, Black women.”

Pregnancy “gives us a clue, through HDP, as to who is high risk to develop chronic hypertension and subsequent subclinical structural cardiac changes in the decade after delivery,” said Dr. Countouris, who was not involved with the study.

“The jury is still out on whether HDP contributes independently to cardiovascular changes in the years after delivery. Ongoing research is needed to clarify the unique or compounding contributions of pregnancy complications and hypertension,” she added.

In an accompanying editorial , Josephine Chou, MD, MS, director of cardio-obstetrics and codirector of maternal cardiology, Yale University, New Haven, Conn., called the study a “laudable contribution to understanding of HDP and hypertension within the first decade after pregnancy,” saying that it “paves the way for future efforts to improve postpartum CV care, enabling us to grasp this opportunity of a lifetime to ultimately reduce maternal and pregnancy-related morbidity and mortality.”

This study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute, and the American Association of Obstetricians and Gynecologists Foundation. Dr. Levine reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Countouris reports receiving funding from the American Heart Association. Dr. Chou reports no relevant financial relationships.

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

Hypertensive disorders of pregnancy (HDP) are associated with a greater than twofold risk of developing hypertension a decade later, new research suggests.

Investigators prospectively studied patients who had and who had not experienced HDP 10 years earlier; most self-identified as Black. They found that those with a history of HDP had a 2.4-fold higher risk for new hypertension than those without such a history.

Patients who developed hypertension showed greater left ventricular (LV) remodeling (including greater relative wall thickness), worse diastolic function, more abnormal longitudinal strain, and higher effective arterial elastance than those without hypertension, regardless of the presence or absence of an HDP history.

“We know that patients with preeclampsia are at a higher risk for heart disease later in life, and it seems to be driven by the development of new hypertension,” lead author Lisa Levine, MD, MSCE, director, pregnancy and heart disease program, Hospital of the University of Pennsylvania, Philadelphia, told this news organization.

It is critically important to “study a more diverse population, including a larger percentage of Black patients, since HDP and CVD both disproportionately affect Black women,” Dr. Levine said. “And it is important to screen patients for hypertension, getting them into primary care for visits, getting them diagnosed sooner, and treating them early for hypertension.”

The study was published in the Journal of the American College of Cardiology.
 

Understudied population

HDP includes gestational hypertension and preeclampsia, Dr. Levine explained. “We already know that patients who have had preeclampsia are at higher risk for stroke, heart failure [HF], and myocardial infarction later in life,” she said. The goal of this study was to see whether, instead of waiting 20-30 years, they could look only 10 years later to see which patients would be at highest risk for future heart disease, Dr. Levine said.

In particular, it’s known that cardiovascular disease (CVD) and HDP “disproportionately affect Black women,” Dr. Levine continued. “What makes our study different from other studies is that we focused predominantly on the Black African American population, since it’s understudied and also at highest risk for preeclampsia and heart disease,” she said.

They set out to “evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier,” the authors state.

To investigate the question, the researchers performed a prospective, cross-sectional study between April 2016 and December 2019 of patients with and without a diagnosis of HDP during a previous pregnancy at least 10 years earlier (from 2005 to 2007). Patients were drawn from a parent cohort in a previously performed observational study of patients with preeclampsia or HDP and normotensive control subjects.

The current study focused on 135 patients (85% Black), 84 with a history of HDP and 51 without. Of the Black patients, 91.7% had a history of HDP, compared with 8.3% of the White patients.

During an in-person visit, the researchers assessed participants’ blood pressure and other clinical risk factors for CVD, including fasting glucose and lipids. They also used noninvasive means to measure cardiac and vascular structure and function.
 

Importance of routine screening

The risk for new hypertension was 2.4 times higher in patients with a history of HDP than in those without HDP, with stage 2 hypertension noted in 56.0% of patients with and in 23.5% without HDP (P < .001). This equates to a relative risk of 2.4 (95% confidence interval, 1.39-4.14), even after adjustment for race, maternal age, body mass index, and history of preterm birth.

“Importantly, 18% of patients with a history of HDP met criteria for a new diagnosis of hypertension identified through the study visit,” the authors report.

There were no differences in many cardiac measures (left ventricular (LV) structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function) between patients with and without a history of HDP.

However, patients with chronic hypertension (CHTN), regardless of HDP history, had other cardiac abnormalities, including greater LV remodeling, worse diastolic function, and higher effective arterial elastance.

“The data regarding increased risk of hypertension after HDP is not a novel finding, however our cohort is unique in the high baseline rate of stage 2 hypertension, even among patients without a history of HDP,” the authors comment.

In fact, when they looked at the diagnosis of either stage 1 or stage 2 hypertension, they found that more than 80% of patients with and 60% of patients without a history of HDP had hypertension. Notably, among patients with a history of HDP, only 39% had a formal diagnosis of either stage 1 or stage 2 hypertension, further highlighting “the importance of routine screening for CHTN in this population,” they state.

“Further studies should evaluate the optimal time period to screen for postpartum hypertension and a monitoring plan for these at-risk women,” Dr. Levine added.
 

‘Opportunity of a lifetime’

Commenting for this news organization, Malamo Countouris, MD, MS, assistant professor of medicine and codirector, postpartum hypertension program, University of Pittsburgh Medical Center, said hypertension is “underrecognized and undertreated among young, premenopausal, Black women.”

Pregnancy “gives us a clue, through HDP, as to who is high risk to develop chronic hypertension and subsequent subclinical structural cardiac changes in the decade after delivery,” said Dr. Countouris, who was not involved with the study.

“The jury is still out on whether HDP contributes independently to cardiovascular changes in the years after delivery. Ongoing research is needed to clarify the unique or compounding contributions of pregnancy complications and hypertension,” she added.

In an accompanying editorial , Josephine Chou, MD, MS, director of cardio-obstetrics and codirector of maternal cardiology, Yale University, New Haven, Conn., called the study a “laudable contribution to understanding of HDP and hypertension within the first decade after pregnancy,” saying that it “paves the way for future efforts to improve postpartum CV care, enabling us to grasp this opportunity of a lifetime to ultimately reduce maternal and pregnancy-related morbidity and mortality.”

This study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute, and the American Association of Obstetricians and Gynecologists Foundation. Dr. Levine reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Countouris reports receiving funding from the American Heart Association. Dr. Chou reports no relevant financial relationships.

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

It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.

The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents

At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.

But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.

Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.

So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.

The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents

At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.

But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.

Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.

So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.

The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents

At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.

But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.

Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.

So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The social behavior associated with the COVID-19 pandemic may have reduced the incidence of Kawasaki disease, according to results of a cohort study of nearly 4,000 children.

The incidence of Kawasaki disease in the United States declined by 28.2% between 2018 and 2020, possibly as a result of factors including school closures, mask mandates, and reduced ambient pollution that might reduce exposure to Kawasaki disease (KD) in the environment, but a potential association has not been explored, wrote Jennifer A. Burney, PhD, of the University of California, San Diego, and colleagues.

KD received greater attention in the public and medical communities because of the emergence of multisystem inflammatory syndrome in children (MIS-C), which is similar to, but distinct from, KD, and because of the noticeable drop in KD cases during the pandemic, the researchers said.

In a multicenter cohort study published in JAMA Network Open , the researchers reviewed data from 2,461 consecutive patients with KD who were diagnosed between Jan. 1, 2018, and Dec. 31, 2020. They conducted a detailed analysis of analysis of 1,461 children with KD who were diagnosed between Jan. 1, 2002, and Nov. 15, 2021, at Rady Children’s Hospital San Diego (RCHSD), using data from before, during, and after the height of the pandemic. The median age of the children in the RCHSD analysis was 2.8 years, 62% were male, and 35% were Hispanic.

Overall, the prevalence of KD declined from 894 in 2018 to 646 in 2020, across the United States, but the decline was uneven, the researchers noted.

In the RCHSD cohort in San Diego, KD cases in children aged 1-5 years decreased significantly from 2020 to 2021 compared to the mean number of cases in previous years (22 vs. 44.9, P = .02). KD cases also decreased significantly among males and Asian children.

Notably, the occurrence of the KD clinical features of strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation decreased during 2020 compared with the baseline period, although only strawberry tongue reached statistical significance (39% vs. 63%, P = .04). The prevalence of patients with an enlarged lymph node was 21% in 2020 vs. 32% prior to the pandemic (P = .09); the prevalence of periungual desquamation during these periods was 47% vs. 58%, P = .16).

The researchers also used data from Census Block Groups (CBGs) to assess the impact of mobility metrics and environmental exposures on KD during the pandemic for the San Diego patient cohort. They found that KD cases during the pandemic were more likely to occur in neighborhoods of higher socioeconomic status, and that neighborhoods with lower levels of nitrous oxides had fewer KD cases.

Overall, “The reduction in KD case numbers coincided with masking, school closures, reduced circulation of respiratory viruses, and reduced air pollution,” the researchers wrote in their discussion of the findings. “A rebound in KD case numbers to prepandemic levels coincided with the lifting of mask mandates and, subsequently, the return to in-person schooling,” they wrote.

The study findings were limited by several factors including the small sample sizes, which also limit the interpretation of mobility and pollution data, the researchers noted. Other limitations include the high interannual variability of KD and the inclusion of 2021 rebound data from the San Diego region only.

“Although our original hypothesis was that shelter-in-place measures would track with reduced KD cases, this was not borne out by the San Diego region data. Instead, the San Diego case occurrence data suggest that exposures that triggered KD were more likely to occur in the home, with a shift toward households with higher SES during the pandemic,” the researchers noted. However, “The results presented here are consistent with a respiratory portal of entry for the trigger(s) of KD,” they said.
 

Study fails to validate its conclusions

“This study attempts to test the hypothesis that various social restrictions were associated with a decrease in rate of diagnosed Kawasaki disease cases during portions of the SARS-CoV-2 pandemic,” Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, said in an interview.

“However, it appears that it fails to achieve this conclusion and I disagree with the findings,” said Dr. Gorelik, who was not involved in the study but served as first author on an updated Kawasaki disease treatment guideline published earlier this spring in Arthritis & Rheumatology.

“The study does not find statistically significant associations either with shelter in place orders or with cell phone mobility data, as stated in the conclusion, directly contradicting its own claim,” Dr. Gorelik said. “Secondly, the study makes an assumption that various methods, especially the wearing of masks by children and school closures, had a significant effect on the spread of respiratory viruses. There are no prospective, population based, controlled real world studies that validate this claim, and two prospective controlled real-world studies that dispute this,” he emphasized. “Cloth masks and surgical masks, which were the types of masks worn by school students, are also known to have a nonsignificant and paltry – in the latter, certainly less than 50%, and perhaps as little as 10% – effect on the reduction of respiratory viral spread,” he added.

“Mechanistic studies on mask wearing may suggest some mask efficacy, but these studies are as valid as mechanistic studies showing the effect of various antifungal pharmaceuticals on the replication of SARS-CoV-2 virus in culture, meaning only valid as hypothesis generating, and ultimately the latter hypothesis failed to bear out,” Dr. Gorelik explained. “We do not know the reason why other respiratory viruses and non-SARS-CoV-2 coronaviruses declined during the pandemic, but we do know that despite this, the SARS-CoV-2 coronavirus itself did not appear to suffer the same fate. Thus, it is very possible that another factor was at work, and we know that during other viral pandemics, typically circulating viruses decline, potentially due to induction of interferon responses in hosts, in a general effect known as ‘viral interference,’ ” he said.

“Overall, we must have robust evidence to support benefits of hypotheses that have demonstrated clear damage to children during this pandemic (such as school closures), and this study fails to live up to that requirement,” Dr. Gorelik said.  

The study was supported by the Gordon and Marilyn Macklin Foundation and the Patient-Centered Outcomes Research Institute. Dr. Burney and Dr. Gorelik had no financial conflicts to disclose.

The social behavior associated with the COVID-19 pandemic may have reduced the incidence of Kawasaki disease, according to results of a cohort study of nearly 4,000 children.

The incidence of Kawasaki disease in the United States declined by 28.2% between 2018 and 2020, possibly as a result of factors including school closures, mask mandates, and reduced ambient pollution that might reduce exposure to Kawasaki disease (KD) in the environment, but a potential association has not been explored, wrote Jennifer A. Burney, PhD, of the University of California, San Diego, and colleagues.

KD received greater attention in the public and medical communities because of the emergence of multisystem inflammatory syndrome in children (MIS-C), which is similar to, but distinct from, KD, and because of the noticeable drop in KD cases during the pandemic, the researchers said.

In a multicenter cohort study published in JAMA Network Open , the researchers reviewed data from 2,461 consecutive patients with KD who were diagnosed between Jan. 1, 2018, and Dec. 31, 2020. They conducted a detailed analysis of analysis of 1,461 children with KD who were diagnosed between Jan. 1, 2002, and Nov. 15, 2021, at Rady Children’s Hospital San Diego (RCHSD), using data from before, during, and after the height of the pandemic. The median age of the children in the RCHSD analysis was 2.8 years, 62% were male, and 35% were Hispanic.

Overall, the prevalence of KD declined from 894 in 2018 to 646 in 2020, across the United States, but the decline was uneven, the researchers noted.

In the RCHSD cohort in San Diego, KD cases in children aged 1-5 years decreased significantly from 2020 to 2021 compared to the mean number of cases in previous years (22 vs. 44.9, P = .02). KD cases also decreased significantly among males and Asian children.

Notably, the occurrence of the KD clinical features of strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation decreased during 2020 compared with the baseline period, although only strawberry tongue reached statistical significance (39% vs. 63%, P = .04). The prevalence of patients with an enlarged lymph node was 21% in 2020 vs. 32% prior to the pandemic (P = .09); the prevalence of periungual desquamation during these periods was 47% vs. 58%, P = .16).

The researchers also used data from Census Block Groups (CBGs) to assess the impact of mobility metrics and environmental exposures on KD during the pandemic for the San Diego patient cohort. They found that KD cases during the pandemic were more likely to occur in neighborhoods of higher socioeconomic status, and that neighborhoods with lower levels of nitrous oxides had fewer KD cases.

Overall, “The reduction in KD case numbers coincided with masking, school closures, reduced circulation of respiratory viruses, and reduced air pollution,” the researchers wrote in their discussion of the findings. “A rebound in KD case numbers to prepandemic levels coincided with the lifting of mask mandates and, subsequently, the return to in-person schooling,” they wrote.

The study findings were limited by several factors including the small sample sizes, which also limit the interpretation of mobility and pollution data, the researchers noted. Other limitations include the high interannual variability of KD and the inclusion of 2021 rebound data from the San Diego region only.

“Although our original hypothesis was that shelter-in-place measures would track with reduced KD cases, this was not borne out by the San Diego region data. Instead, the San Diego case occurrence data suggest that exposures that triggered KD were more likely to occur in the home, with a shift toward households with higher SES during the pandemic,” the researchers noted. However, “The results presented here are consistent with a respiratory portal of entry for the trigger(s) of KD,” they said.
 

Study fails to validate its conclusions

“This study attempts to test the hypothesis that various social restrictions were associated with a decrease in rate of diagnosed Kawasaki disease cases during portions of the SARS-CoV-2 pandemic,” Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, said in an interview.

“However, it appears that it fails to achieve this conclusion and I disagree with the findings,” said Dr. Gorelik, who was not involved in the study but served as first author on an updated Kawasaki disease treatment guideline published earlier this spring in Arthritis & Rheumatology.

“The study does not find statistically significant associations either with shelter in place orders or with cell phone mobility data, as stated in the conclusion, directly contradicting its own claim,” Dr. Gorelik said. “Secondly, the study makes an assumption that various methods, especially the wearing of masks by children and school closures, had a significant effect on the spread of respiratory viruses. There are no prospective, population based, controlled real world studies that validate this claim, and two prospective controlled real-world studies that dispute this,” he emphasized. “Cloth masks and surgical masks, which were the types of masks worn by school students, are also known to have a nonsignificant and paltry – in the latter, certainly less than 50%, and perhaps as little as 10% – effect on the reduction of respiratory viral spread,” he added.

“Mechanistic studies on mask wearing may suggest some mask efficacy, but these studies are as valid as mechanistic studies showing the effect of various antifungal pharmaceuticals on the replication of SARS-CoV-2 virus in culture, meaning only valid as hypothesis generating, and ultimately the latter hypothesis failed to bear out,” Dr. Gorelik explained. “We do not know the reason why other respiratory viruses and non-SARS-CoV-2 coronaviruses declined during the pandemic, but we do know that despite this, the SARS-CoV-2 coronavirus itself did not appear to suffer the same fate. Thus, it is very possible that another factor was at work, and we know that during other viral pandemics, typically circulating viruses decline, potentially due to induction of interferon responses in hosts, in a general effect known as ‘viral interference,’ ” he said.

“Overall, we must have robust evidence to support benefits of hypotheses that have demonstrated clear damage to children during this pandemic (such as school closures), and this study fails to live up to that requirement,” Dr. Gorelik said.  

The study was supported by the Gordon and Marilyn Macklin Foundation and the Patient-Centered Outcomes Research Institute. Dr. Burney and Dr. Gorelik had no financial conflicts to disclose.

The social behavior associated with the COVID-19 pandemic may have reduced the incidence of Kawasaki disease, according to results of a cohort study of nearly 4,000 children.

The incidence of Kawasaki disease in the United States declined by 28.2% between 2018 and 2020, possibly as a result of factors including school closures, mask mandates, and reduced ambient pollution that might reduce exposure to Kawasaki disease (KD) in the environment, but a potential association has not been explored, wrote Jennifer A. Burney, PhD, of the University of California, San Diego, and colleagues.

KD received greater attention in the public and medical communities because of the emergence of multisystem inflammatory syndrome in children (MIS-C), which is similar to, but distinct from, KD, and because of the noticeable drop in KD cases during the pandemic, the researchers said.

In a multicenter cohort study published in JAMA Network Open , the researchers reviewed data from 2,461 consecutive patients with KD who were diagnosed between Jan. 1, 2018, and Dec. 31, 2020. They conducted a detailed analysis of analysis of 1,461 children with KD who were diagnosed between Jan. 1, 2002, and Nov. 15, 2021, at Rady Children’s Hospital San Diego (RCHSD), using data from before, during, and after the height of the pandemic. The median age of the children in the RCHSD analysis was 2.8 years, 62% were male, and 35% were Hispanic.

Overall, the prevalence of KD declined from 894 in 2018 to 646 in 2020, across the United States, but the decline was uneven, the researchers noted.

In the RCHSD cohort in San Diego, KD cases in children aged 1-5 years decreased significantly from 2020 to 2021 compared to the mean number of cases in previous years (22 vs. 44.9, P = .02). KD cases also decreased significantly among males and Asian children.

Notably, the occurrence of the KD clinical features of strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation decreased during 2020 compared with the baseline period, although only strawberry tongue reached statistical significance (39% vs. 63%, P = .04). The prevalence of patients with an enlarged lymph node was 21% in 2020 vs. 32% prior to the pandemic (P = .09); the prevalence of periungual desquamation during these periods was 47% vs. 58%, P = .16).

The researchers also used data from Census Block Groups (CBGs) to assess the impact of mobility metrics and environmental exposures on KD during the pandemic for the San Diego patient cohort. They found that KD cases during the pandemic were more likely to occur in neighborhoods of higher socioeconomic status, and that neighborhoods with lower levels of nitrous oxides had fewer KD cases.

Overall, “The reduction in KD case numbers coincided with masking, school closures, reduced circulation of respiratory viruses, and reduced air pollution,” the researchers wrote in their discussion of the findings. “A rebound in KD case numbers to prepandemic levels coincided with the lifting of mask mandates and, subsequently, the return to in-person schooling,” they wrote.

The study findings were limited by several factors including the small sample sizes, which also limit the interpretation of mobility and pollution data, the researchers noted. Other limitations include the high interannual variability of KD and the inclusion of 2021 rebound data from the San Diego region only.

“Although our original hypothesis was that shelter-in-place measures would track with reduced KD cases, this was not borne out by the San Diego region data. Instead, the San Diego case occurrence data suggest that exposures that triggered KD were more likely to occur in the home, with a shift toward households with higher SES during the pandemic,” the researchers noted. However, “The results presented here are consistent with a respiratory portal of entry for the trigger(s) of KD,” they said.
 

Study fails to validate its conclusions

“This study attempts to test the hypothesis that various social restrictions were associated with a decrease in rate of diagnosed Kawasaki disease cases during portions of the SARS-CoV-2 pandemic,” Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, said in an interview.

“However, it appears that it fails to achieve this conclusion and I disagree with the findings,” said Dr. Gorelik, who was not involved in the study but served as first author on an updated Kawasaki disease treatment guideline published earlier this spring in Arthritis & Rheumatology.

“The study does not find statistically significant associations either with shelter in place orders or with cell phone mobility data, as stated in the conclusion, directly contradicting its own claim,” Dr. Gorelik said. “Secondly, the study makes an assumption that various methods, especially the wearing of masks by children and school closures, had a significant effect on the spread of respiratory viruses. There are no prospective, population based, controlled real world studies that validate this claim, and two prospective controlled real-world studies that dispute this,” he emphasized. “Cloth masks and surgical masks, which were the types of masks worn by school students, are also known to have a nonsignificant and paltry – in the latter, certainly less than 50%, and perhaps as little as 10% – effect on the reduction of respiratory viral spread,” he added.

“Mechanistic studies on mask wearing may suggest some mask efficacy, but these studies are as valid as mechanistic studies showing the effect of various antifungal pharmaceuticals on the replication of SARS-CoV-2 virus in culture, meaning only valid as hypothesis generating, and ultimately the latter hypothesis failed to bear out,” Dr. Gorelik explained. “We do not know the reason why other respiratory viruses and non-SARS-CoV-2 coronaviruses declined during the pandemic, but we do know that despite this, the SARS-CoV-2 coronavirus itself did not appear to suffer the same fate. Thus, it is very possible that another factor was at work, and we know that during other viral pandemics, typically circulating viruses decline, potentially due to induction of interferon responses in hosts, in a general effect known as ‘viral interference,’ ” he said.

“Overall, we must have robust evidence to support benefits of hypotheses that have demonstrated clear damage to children during this pandemic (such as school closures), and this study fails to live up to that requirement,” Dr. Gorelik said.  

The study was supported by the Gordon and Marilyn Macklin Foundation and the Patient-Centered Outcomes Research Institute. Dr. Burney and Dr. Gorelik had no financial conflicts to disclose.

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

The following highlights are a brief overview of guideline updates, drug approvals, and diagnostics relevant to geriatric medicine from June 2021 to April 2022, some of which were discussed at the American Geriatrics Society conference in May. I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).

Aspirin for primary prevention

It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.¹

The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.

While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.²

Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
 

Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia

One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.

Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.⁴

Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.

Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.⁵

Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.

In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.⁶
 

Overdiagnosis of CKD in older adults

The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m² for adults aged 65 and older.⁷

The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.⁸ In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.

A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.

These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
 

Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.

References

1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.

2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.

3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.

4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.

5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.

6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.

7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.

8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.

The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.

Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.

Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).

The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.

“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.

Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.

Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.

Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.

“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
 

First safety meta-analysis

The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.

Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.

Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).

The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.

Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.

As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).

Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.

Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.

Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
 

A big step forward

Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.

“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.

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

Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.

The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.

Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.

Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).

The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.

“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.

Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.

Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.

Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.

“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
 

First safety meta-analysis

The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.

Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.

Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).

The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.

Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.

As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).

Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.

Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.

Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
 

A big step forward

Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.

“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.

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

Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.

The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.

Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.

Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).

The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.

“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.

Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.

Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.

Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.

“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
 

First safety meta-analysis

The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.

Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.

Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).

The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.

Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.

As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).

Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.

Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.

Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
 

A big step forward

Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.

“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.

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

Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.

“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.

For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.

Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.

Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.

“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .

Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”

Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.

Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.

Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.

Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.

“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.

For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.

Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.

Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.

“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .

Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”

Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.

Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.

Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.

Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.

“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.

For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.

Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.

Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.

“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .

Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”

Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.

Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.

Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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