Cardiology

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

a_namenko/Getty Images

“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

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

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

a_namenko/Getty Images

“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

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

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

a_namenko/Getty Images

“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

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

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
 

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
 

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
 

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

THE CASE

A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).

However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.

About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.

The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.

THE DIAGNOSIS

The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.

The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.

As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.

Continue to: DISCUSSION

 

 

DISCUSSION

Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.¹ Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.² However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.

Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.^3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.⁶ Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.⁷

The severe worsening of this patient’s LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD.

Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al⁸ posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.

A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.

Our patient was started on a post­operative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuva­statin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.

THE TAKEAWAY

Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.

CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; sbcdickmann@ufl.edu

THE CASE

A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).

However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.

About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.

The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.

THE DIAGNOSIS

The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.

The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.

As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.

Continue to: DISCUSSION

 

 

DISCUSSION

Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.¹ Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.² However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.

Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.^3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.⁶ Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.⁷

The severe worsening of this patient’s LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD.

Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al⁸ posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.

A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.

Our patient was started on a post­operative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuva­statin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.

THE TAKEAWAY

Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.

CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; sbcdickmann@ufl.edu

THE CASE

A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).

However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.

About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.

The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.

THE DIAGNOSIS

The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.

The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.

As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.

Continue to: DISCUSSION

 

 

DISCUSSION

Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.¹ Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.² However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.

Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.^3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.⁶ Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.⁷

The severe worsening of this patient’s LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD.

Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al⁸ posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.

A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.

Our patient was started on a post­operative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuva­statin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.

THE TAKEAWAY

Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.

CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; sbcdickmann@ufl.edu

WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.

Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
 

Blacks comprised 26% of SYMPLICITY HTN-3 trial

In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.

In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.

Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.

In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.

In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.

For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).

The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.

Renal denervation safe in Black and non-Black patients

Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.

While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.

“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.

This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.

“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.

Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.

WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.

Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
 

Blacks comprised 26% of SYMPLICITY HTN-3 trial

In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.

In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.

Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.

In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.

In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.

For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).

The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.

Renal denervation safe in Black and non-Black patients

Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.

While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.

“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.

This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.

“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.

Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.

WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.

Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
 

Blacks comprised 26% of SYMPLICITY HTN-3 trial

In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.

In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.

Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.

In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.

In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.

For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).

The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.

Renal denervation safe in Black and non-Black patients

Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.

While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.

“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.

This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.

“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.

Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).

Ted Bosworth/MDedge News

Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.

The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
 

Causal AI trained on nearly 2 million patients

This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.

To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.

When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.

Providing examples, Dr. Ference explained that a PGS in the 80^th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80^th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.

Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80^th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.

Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.

Even though family history is equivalent to having PGS above the 95^th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.

Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.

According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
 

Treatments become understandable to patients

“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.

A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.

Ted Bosworth/MDedge News

Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.

By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.

With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.

She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.

Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.

NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).

Ted Bosworth/MDedge News

Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.

The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
 

Causal AI trained on nearly 2 million patients

This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.

To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.

When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.

Providing examples, Dr. Ference explained that a PGS in the 80^th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80^th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.

Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80^th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.

Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.

Even though family history is equivalent to having PGS above the 95^th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.

Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.

According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
 

Treatments become understandable to patients

“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.

A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.

Ted Bosworth/MDedge News

Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.

By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.

With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.

She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.

Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.

NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).

Ted Bosworth/MDedge News

Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.

The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
 

Causal AI trained on nearly 2 million patients

This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.

To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.

When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.

Providing examples, Dr. Ference explained that a PGS in the 80^th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80^th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.

Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80^th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.

Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.

Even though family history is equivalent to having PGS above the 95^th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.

Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.

According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
 

Treatments become understandable to patients

“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.

A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.

Ted Bosworth/MDedge News

Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.

By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.

With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.

She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.

Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

A secondary analysis of a large landmark clinical trial of how the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin effects cardiovascular risk has identified two biomarkers that can help better determine which patients with type 2 diabetes (T2D) and cardiovascular disease risk would derive the most benefit from the drug.

Brigham and Women’s Hospital

The researchers found that N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels helped identify a subset of T2D patients at higher risk of major adverse cardiovascular events who would benefit most from dapagliflozin.

“We’ve shown previously that these two biomarkers are very robust risk indicators for cardiovascular death and heart failure events,” senior study author David A. Morrow, MD, of Harvard University, Boston, said in an interview. “In this study, we now show that the two biomarkers also yield important prognostic information for MACE [major adverse cardiovascular events].”

Although NT-proBNP is typically measured to diagnose heart failure, and hsTnT to diagnose acute MI, Dr. Morrow pointed out that this analysis demonstrated the potential for using the two tests to evaluate risks in T2D patients.
 

Study results

The secondary analysis included 14,565 patients in the DECLARE-TIMI 58 trial. The patients had T2D and multiple risk factors for atherosclerotic cardiovascular disease (about 60%) or established ASCVD (about 40%). All patients had available blood samples and the data were collected from May 2013 to September 2018. The primary outcome was MACE, a composite of MI, ischemic stroke, and cardiovascular death. The results were reported online in JAMA Cardiology.

The analysis found that higher baseline concentrations of NT-proBNP increased MACE risks by 62% (95% confidence interval, 1.49-1.76) and hsTnT elevated those risks by 59% (95% CI, 1.46-1.74).

Among placebo patients, when divided into risk quartiles, those in the highest quartile had significantly higher risk with both elevated NT-proBNP and hsTnT, compared with those with low concentrations. For example, patients with established ASCVD had a 22.9% risk vs. 9.5% with elevated NT-proBNP (P < .001) and a 24.2% vs. 7.2% risk with elevated hsTnT (P < .001). The gap was similar for patients with multiple risk factors.

Dr. Morrow noted that the main DECLARE-TIMI 58 trial showed that dapagliflozin reduced the rates of cardiovascular death or hospitalization for heart failure in patients with T2D, when compared to placebo, but didn’t reach statistical significance for MACE (N Engl J Med. 2019;380:347-57).

“We have previously shown that among patients with T2D who have high risk indicators, such as prior MI or long-standing diabetes, dapagliflozin also appeared to reduce MACE,” Dr. Morrow said. “In this study, we find that these two widely available biomarkers also identify a high-risk group who may have even more potential benefits from treatment with an SGLT2i.”

Dr. Morrow noted that the study design – a nested prospective biomarker study within a randomized, double-blind, placebo-controlled clinical trial – “is a particular strength.”
 

Results clarify which patients will benefit

This secondary analysis of DECLARE-TIMI 58 brings more clarity to the types of T2D patients who will get the most cardiovascular benefits from dapagliflozin, said Matthew J. Budoff, MD, professor of medicine at University of California, Los Angeles, and Endowed Chair of Preventive Cardiology at the Lundquist Institute in Torrance, Calif.

Lundquist Institute

“The big picture is, we’ve known for some time from epidemiologic studies that these biomarkers, when they’re elevated, mean that the patient is at higher risk of having a cardiovascular event,” he said, “but I think what it helps us with is in knowing in whom to use dapagliflozin for prevention of ASCVD. The effect in the DECLARE-TIMI 58 trial was quite modest, but if you can subgroup it, in these high-risk people there’s a more profound effect. It helps in risk stratification because the absolute benefit is larger.”

The specific biomarkers, NT-proBNP and hsTnT, “haven’t been explored very much in clinical trials,” Dr. Budoff said, “so I do think that it’s nice that in a randomized trial it plays out the way we might expect.”

He added that “for many clinicians this is novel, because I don’t think they were aware of the biomarker data, so I think that this does add some clinical benefit in that context.” The findings also strengthen the case to get T2D patients with higher ASCVD risk onto SGLT2 inhibitors if they’re not already, he said.

Dr. Morrow disclosed relationships with AstraZeneca, Roche Diagnostics, Abbott Laboratories, Anthos Therapeutics, ARCA Biopharma, Merck, Novartis, Pfizer, Regeneron, Siemens, and InCarda outside the reported work.

Dr. Budoff has no relevant disclosures.

Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.

And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.

The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older.  

Pix by Marti/Fotolia

Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet

The subanalysis in patients with CVD was published online March 5 in Circulation.

“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”  

They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.

Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.

In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.

Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”

“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”

“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.

“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.

‘Small but important effect’

In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”

A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”

Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes. 

However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.

Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.

First-of-its kind, nationwide pragmatic trial

The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.

They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.

This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.

Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:

• Standard electronic letter
• Standard electronic letter sent at randomization and again 14 days later (repeated letter)
• Depersonalized letter without the recipient’s name
• Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
• Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
• Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)  
• Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
• Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
• Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)

The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.

All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022. 

The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.

The analyses were done in one randomly selected individual per household.

Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).

These two strategies also improved vaccination rates across major subgroups.

The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.

The seven other letter strategies did not increase flu shot uptake.

Subanalysis in CVD

In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).

The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).

Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”

Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”

NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.

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

Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.

And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.

The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older.  

Pix by Marti/Fotolia

Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet

The subanalysis in patients with CVD was published online March 5 in Circulation.

“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”  

They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.

Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.

In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.

Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”

“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”

“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.

“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.

‘Small but important effect’

In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”

A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”

Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes. 

However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.

Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.

First-of-its kind, nationwide pragmatic trial

The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.

They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.

This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.

Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:

• Standard electronic letter
• Standard electronic letter sent at randomization and again 14 days later (repeated letter)
• Depersonalized letter without the recipient’s name
• Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
• Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
• Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)  
• Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
• Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
• Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)

The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.

All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022. 

The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.

The analyses were done in one randomly selected individual per household.

Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).

These two strategies also improved vaccination rates across major subgroups.

The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.

The seven other letter strategies did not increase flu shot uptake.

Subanalysis in CVD

In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).

The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).

Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”

Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”

NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.

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

Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.

And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.

The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older.  

Pix by Marti/Fotolia

Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet

The subanalysis in patients with CVD was published online March 5 in Circulation.

“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”  

They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.

Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.

In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.

Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”

“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”

“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.

“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.

‘Small but important effect’

In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”

A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”

Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes. 

However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.

Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.

First-of-its kind, nationwide pragmatic trial

The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.

They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.

This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.

Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:

• Standard electronic letter
• Standard electronic letter sent at randomization and again 14 days later (repeated letter)
• Depersonalized letter without the recipient’s name
• Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
• Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
• Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)  
• Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
• Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
• Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)

The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.

All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022. 

The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.

The analyses were done in one randomly selected individual per household.

Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).

These two strategies also improved vaccination rates across major subgroups.

The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.

The seven other letter strategies did not increase flu shot uptake.

Subanalysis in CVD

In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).

The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).

Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”

Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”

NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.

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