Lipid Disorders

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

PHILADELPHIA – In two studies run in parallel fashion to test different strategies, one that employed automatic referral to a pharmacist appeared to be superior to one using alerts from the electronic health record (EHR) in increasing the number of at-risk patients receiving a prescription for statins.

When outcomes were compared across these related studies, the pharmacist referrals had a greater positive impact on statin prescriptions while also increasing the proportion of patients on an appropriate statin dose, reported Alexander C. Faranoff, MD, assistant professor of cardiovascular medicine at Penn Medicine, Philadelphia.

The parallel studies were part of the SUPER LIPID program, created to generate evidence-based strategies for increasing the proportion of at-risk patients on statins. Dr. Faranoff said current data show that at least 50% of patients indicated for high-intensity statins in the United States are not taking them.

The two studies were presented together in a late breaking presentation at the American Heart Association scientific sessions.
 

EHR algorithm identifies statin candidates

The candidates for statin therapy were identified through an EHR algorithm for both studies. Both compared the impact of the intervention against a baseline period of usual care, although the study of EHR alerts also randomized physicians to provide usual care for 3 months or 6 months prior to intervention.

Dr. Faranoff described these interventions as non–visit related and visit related.

In the study of the non–visit-related strategy, referrals were generated by EHR and sent directly to the pharmacist. Upon receipt, the pharmacist verified the order was appropriate and called the patient directly to discuss starting therapy. Patients agreeing to start a statin were provided with a prescription and followed by the pharmacist.

In the study of the patient-visit approach, physicians seeing EHR-identified candidates received interruptive pop-up alerts during patient encounters. The physicians were randomized to provide usual care for 3 or 6 months before they began receiving alerts. The alerts recommended referral to a pharmacist.

During usual care in the non–visit-related study, only 15.2% of the 975 candidates for statins received a prescription. During the intervention period, the rate climbed to 31.6%. Statistically, the intervention more than doubled the odds ratio (OR) of receiving a statin prescription relative to usual care (OR 2.22; 95% confidence interval [CI] 1.47-3.37).

In addition, the proportion of patients receiving an appropriate dose of statins climbed from 7.7% in the period of usual care to 24.8% in the intervention period (OR 6.79; 95% CI 4.00-11.53).
 

Visit-based study also randomized

In the study evaluating a visit-based intervention, 16 physicians were randomized to deliver usual care for 3 or 6 months. Of physicians randomized to 3 months, 970 candidates for statins were treated during the 6-month intervention period. The physicians randomized to usual care for 6 months treated 672 candidates for statins during a 3-month intervention period,

More than 3,000 alerts were sent to both groups of physicians over the intervention period. Only 165 (4.6%) were associated with a prescription.

For the group randomized to 3 months of usual care, the proportion of candidates for statins who received a prescription rose from 14.9% during the period of usual care to 17.6% in the first 3 months of intervention and then fell slightly to 15.5% in the second 3 months.

For the group randomized to usual care for 6 months, the proportion of candidates for statins who received a prescription rose from about 11% during the period of usual care to 14.6%. Combining data from both arms, the small gain in prescriptions was significant but modest (OR 1.43; 95% CI 1.02-2.00).

In addition, the visit-based EHR notifications failed to yield a significant gain in the proportion of patients on an appropriate statin dose. During the intervention period, this proportion was only about 9% of patients treated by either of the two groups of randomized physicians,

The SUPER LIPID program involved 11 internal medicine and family medicine clinics in rural Pennsylvania. In the visit-based intervention, 16 primary care physicians (PCPs) were randomized. In the asynchronous intervention, 10 primary care practices participated. The EHR identified a total of 1,950 candidates for a statin.

Although the gain in statin prescriptions was disappointing for the visit-based intervention, the strategy of using the EHR to refer statin-eligible patients to pharmacists “could be an effective adjunct to visit-based clinical interactions in increasing statin prescribing for high-risk patients,” Dr. Faranoff maintained.
 

Overcoming clinical inertia a challenge

The greater efficacy of a pharmacist-based approach did not surprise the AHA-invited discussant, Benjamin M. Scirica, MD, associate professor of medicine at Harvard Medical School, Boston.

Pointing out that the pharmacist-based strategy of increasing statin prescriptions is more complicated and more costly, he said, “You get what you pay for.” In his opinion, simple solutions are unlikely ever to be effective due to the complex reasons for clinical inertia. Overall, he thinks a multifaceted approach to placing more patients who need statins on therapy is essential.

“Implementation science is hard,” Dr. Scirica said. Even though the referral-to-a-pharmacist approach ended up putting more patients on statins and putting them on an appropriate dose, he said even this more effective strategy “is still not getting to the majority of patients.”

This does not mean that this approach is without merit or should not be one of many strategies employed, but Dr. Scirica said “there is so much more to be done,” and that it should be employed along with other initiatives.

Faranoff reports no potential conflicts of interest. Dr. Scirica reports financial relationships with AbbVie, Aktiia, AstraZeneca, Better Therapeutics, Boehringer-Ingelheim, Eisai, GlaxoSmithKline, Hanmi, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi.

In an early phase multicenter clinical study, large reductions in lipoprotein(a), or Lp(a), were achieved with a well-tolerated small interfering RNA (siRNA) therapeutic, lepodisiran.

The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.

Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
 

Lp(a) strongly associated with CV risk

Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.

Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.

So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.

By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.

Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.

Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.

The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.

They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m²), or tobacco use (> 10 cigarettes/day).

Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
 

Safety profile is placebo-like

The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.

The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.

These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.

Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
 

Lp(a) not responsive to lifestyle changes

Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.

The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.

“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.

Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.

“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.

Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.

Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”

Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.

“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.

Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.

Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.

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

In an early phase multicenter clinical study, large reductions in lipoprotein(a), or Lp(a), were achieved with a well-tolerated small interfering RNA (siRNA) therapeutic, lepodisiran.

The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.

Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
 

Lp(a) strongly associated with CV risk

Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.

Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.

So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.

By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.

Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.

Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.

The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.

They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m²), or tobacco use (> 10 cigarettes/day).

Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
 

Safety profile is placebo-like

The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.

The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.

These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.

Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
 

Lp(a) not responsive to lifestyle changes

Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.

The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.

“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.

Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.

“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.

Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.

Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”

Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.

“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.

Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.

Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.

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

In an early phase multicenter clinical study, large reductions in lipoprotein(a), or Lp(a), were achieved with a well-tolerated small interfering RNA (siRNA) therapeutic, lepodisiran.

The reductions in serum Lp(a) in patients receiving lepodisiran were dose dependent but adverse events were not, said Steven E. Nissen, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine.

Rather, drug-related adverse events “were uncommon and generally similar across all lepodisiran doses and the placebo group,” reported Dr. Nissen, who pointed out that safety and tolerability were the primary endpoints and purpose of this phase 1 study.
 

Lp(a) strongly associated with CV risk

Similar to LDL cholesterol (LDL-C), elevated levels of serum Lp(a) have been associated with major adverse cardiac events (MACE). In a 2022 review article that summarized pathophysiological, observational, and genetic studies, Lp(a) was found to be implicated in vascular inflammation, atherogenesis, calcification, and thrombosis.

Furthermore, Lp(a) has been associated with residual risk of cardiovascular (CV) events even after tight control of other risk factors, including elevated LDL-C, Dr. Nissen said.

So far, no well-tolerated therapy has been found to be effective for reducing Lp(a), but siRNA is a novel and attractive approach, according to Dr. Nissen, who presented these results at the annual scientific sessions of the American Heart Association. They were also published online in JAMA.

By silencing target genes, siRNA therapies can inhibit a basic step in a given pathological process. In this case, lepodisiran silences the LPA gene to halt encoding of apolipoprotein(a), which plays a key role in Lp(a) production.

Lepodisiran is not the only treatment in development for Lp(a), noted the AHA-invited discussant Michelle L. O’Donoghue, MD, chair in cardiology, Brigham and Women’s Hospital, Boston. She mentioned several other siRNA therapies, including olpasiran that was effective in a phase 2 trial she led and published in the New England Journal of Medicine.

Drugs with different mechanisms, such as the antisense oligonucleotide pelacarsen, showed activity when tested earlier this year in a phase 1 study. No study has yet been conducted to link reductions in Lp(a) with CV event risk reduction.

The current study with lepodisiran was conducted with the participation of five clinical research sites in the United States and Singapore. Participants between the ages of 18 and 65 years were enrolled if they had a serum Lp(a) of at least 75 nmol/L (30 mg/dL), which is considered moderately elevated.

They were excluded if they had CV disease or significant risk factors, including a blood pressure greater than 160/40 mm Hg, impaired renal function (eGFR < 60 mL/min per 1.73 m²), or tobacco use (> 10 cigarettes/day).

Of 340 candidates screened, 48 were randomly assigned to one placebo or six lepodisiran groups. There were 12 participants in the placebo group and 6 in each of the lepodisiran dosing groups (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, and 608 mg). All doses and placebo were administered subcutaneously one time with a planned follow-up of up to 48 weeks.
 

Safety profile is placebo-like

The single most common adverse event, shared by those randomly assigned to placebo, was injection-site reaction. There were no adverse events, including laboratory abnormalities, that were persistent and clearly different for those assigned to any dose of lepodisiran relative to placebo.

The maximum median percentage change in serum Lp(a) out to day 337 of follow-up was 5% reduction in the placebo group. In the active treatment groups, the reductions were 41% on 4 mg, 59% on 12 mg, 76% on 32 mg, 96% on 304 mg, and 97% on 608 mg.

These reductions were generally sustained for as long as therapy was maintained. Maximal reductions were reached at day 85 in the 4-mg group but were achieved by day 29 in the 605-mg group, Dr. Nissen reported. In fact, serum Lp(a) was undetectable in the 605-mg group at day 29 and remained so until day 281.

Currently, there is no practical treatment for Lp(a). The only potential exception, apheresis, is “cumbersome” to perform and must be repeated for sustained reductions. Niacin and PCSK9 inhibitors are known to provide modest reductions in Lp(a), but Dr. Nissen said they are too modest to expect a meaningful clinical benefit.
 

Lp(a) not responsive to lifestyle changes

Statins as well as all lifestyle modifications, including diet, have been shown to have “little or no effect,” Dr. Nissen said.

The safety and the evidence so far of sustained Lp(a) lowering has already led to a phase 2 trial, according to Dr. Nissen, but the more important test for the future of lepodisiran will be studies powered to confirm reductions in MACE. Lepodisiran may finally allow that hypothesis to be tested.

“I think a lot of us have been waiting a long time for evidence that we can reliably reduce Lp(a),” said Karol Watson, MD, PhD, who has a research interest in lipids and is a professor of medicine at the University of California, Los Angeles.

Although she conceded that the overwhelming evidence that Lp(a) is a risk factor does not ensure that any specific Lp(a)-lowering therapy will be clinically viable, she suggested this drug is a promising candidate to move this field forward.

“At the highest doses, lepodisiran is not just lowering Lp(a), it appears to be getting rid of it,” she said.

Dr. O’Donoghue said that the phase 1 results suggest lepodisiran might have a somewhat longer duration of action than other siRNA therapies studied for Lp(a) so far, but said larger trials are needed to determine whether the growing number of drugs in this class differ in ways that are clinically meaningful.

Overall, the excitement in this field is probably mostly driven by the fact that there are so many promising therapies for Lp(a) that address the target in so many unique ways. Dr. O’Donoghue cited, as an example, a gene-editing therapy called CTX320 that showed impressive effects in an animal study presented at the AHA meeting as a poster. She called the pipeline for treating Lp(a) “rich.”

Elevated Lp(a) is genetically determined, so levels do not generally change over time, said Donald Lloyd-Jones, MD, chair of the department of preventive medicine, Northwestern Medicine, Chicago.

“It is not affected by your diet. It is not affected by your exercise. What your level is will be the level you will have for the rest of your life,” he said. Generally, it is recommended to have Lp(a) measured just once to more accurately calculate cardiovascular risk, but Dr. Lloyd-Jones predicted that this lipid subfraction might be measured more frequently to verify control if a therapeutic becomes available.

Dr. Nissen agreed. Estimating that 64 million people in the United States have significantly elevated Lp(a), he expects this risk to be addressed as a specific and independent target in CV risk management when and if it becomes treatable.

Dr. Nissen reported financial relationships with Novartis, Silence Therapeutics, and Eli Lilly, which provided funding for this trial. Dr. Watson reported financial relationships with Amgen, Boehringer Ingelheim, Lilly, and Novartis. Dr. Lloyd-Jones disclosed no relevant financial relationships.

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

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

Clinicians are well aware of the benefits of physical activity and the consequences of inactivity. 

Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers. 

But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.

That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.

But here’s the thing: Doctors are in a unique position to change things.

Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.

“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”

Conveniently, just like exercise, the best way to get started is to ... get started.

Here’s how to break down the process into steps.
 

1. Ask patients about their physical activity

Think of this as taking any kind of patient history, only for physical activity.

Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?

“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
 

2. Write an actual prescription

By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.

Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
 

3. Measure what they do

Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.

With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.

For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
 

4. Refer out when necessary

This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”

For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.

If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
 

5. Follow up

Ask about physical activity during every contact, either in person or online. 

Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.

“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
 

What NOT to say to patients about exercise

This might surprise you: 

“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”

It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards. 

“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”

And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”

You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.

Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class. 

Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
 

How to motivate patients to move

New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.

Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be. 

As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”

They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling. 

For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life. 

For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
 

Reducing resistance to resistance training

A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.  

“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”

Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands. 

Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.” 

And yet, “a common suggestion ... from health care providers was to join a gym.”

Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.

He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.

Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.

One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
 

Practicing, preaching, and checking privilege

When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach. 

Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD. 

Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)

But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.

“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”

That leads to this advice for his fellow physicians:

“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says. 

Understanding that is crucial for assessing your patient’s needs and providing the right help.

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

Clinicians are well aware of the benefits of physical activity and the consequences of inactivity. 

Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers. 

But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.

That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.

But here’s the thing: Doctors are in a unique position to change things.

Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.

“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”

Conveniently, just like exercise, the best way to get started is to ... get started.

Here’s how to break down the process into steps.
 

1. Ask patients about their physical activity

Think of this as taking any kind of patient history, only for physical activity.

Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?

“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
 

2. Write an actual prescription

By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.

Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
 

3. Measure what they do

Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.

With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.

For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
 

4. Refer out when necessary

This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”

For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.

If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
 

5. Follow up

Ask about physical activity during every contact, either in person or online. 

Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.

“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
 

What NOT to say to patients about exercise

This might surprise you: 

“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”

It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards. 

“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”

And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”

You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.

Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class. 

Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
 

How to motivate patients to move

New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.

Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be. 

As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”

They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling. 

For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life. 

For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
 

Reducing resistance to resistance training

A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.  

“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”

Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands. 

Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.” 

And yet, “a common suggestion ... from health care providers was to join a gym.”

Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.

He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.

Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.

One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
 

Practicing, preaching, and checking privilege

When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach. 

Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD. 

Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)

But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.

“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”

That leads to this advice for his fellow physicians:

“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says. 

Understanding that is crucial for assessing your patient’s needs and providing the right help.

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

Clinicians are well aware of the benefits of physical activity and the consequences of inactivity. 

Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers. 

But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.

That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.

But here’s the thing: Doctors are in a unique position to change things.

Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.

“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”

Conveniently, just like exercise, the best way to get started is to ... get started.

Here’s how to break down the process into steps.
 

1. Ask patients about their physical activity

Think of this as taking any kind of patient history, only for physical activity.

Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?

“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
 

2. Write an actual prescription

By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.

Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
 

3. Measure what they do

Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.

With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.

For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
 

4. Refer out when necessary

This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”

For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.

If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
 

5. Follow up

Ask about physical activity during every contact, either in person or online. 

Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.

“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
 

What NOT to say to patients about exercise

This might surprise you: 

“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”

It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards. 

“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”

And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”

You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.

Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class. 

Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
 

How to motivate patients to move

New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.

Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be. 

As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”

They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling. 

For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life. 

For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
 

Reducing resistance to resistance training

A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.  

“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”

Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands. 

Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.” 

And yet, “a common suggestion ... from health care providers was to join a gym.”

Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.

He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.

Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.

One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
 

Practicing, preaching, and checking privilege

When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach. 

Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD. 

Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)

But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.

“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”

That leads to this advice for his fellow physicians:

“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says. 

Understanding that is crucial for assessing your patient’s needs and providing the right help.

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

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.