CAD & Atherosclerosis

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

In an analysis of randomized trials, the Mediterranean diet and low-fat diets were linked to reduced risks of all-cause mortality and nonfatal MI over 3 years in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also showed lower risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

“These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change,” wrote the authors, led by Giorgio Karam, a medical student at the University of Manitoba, Winnipeg.

The results were published online in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors noted.

For this study, Mr. Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of “moderate” certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1,000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1,000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1,000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not “convincingly” superior to a low-fat diet for mortality or nonfatal MI, the authors noted.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1,000 over 5 years.

The five other dietary programs generally had “little or no benefit” compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet.

The group acknowledges the findings may not entirely apply to a non-Danish population.


 

A screening role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for this news organization.

Brigham and Women&#039;s Hospital

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Dr. Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two-thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write Dr. McDermott and Dr. Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.
 

Graded risk

The analysis included 9,533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one-third of the coronary tree was considered extensive and less than one-third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk for MI, compared with those without coronary atherosclerosis, was:

• 7.65 (95% confidence interval, 3.53-16.57) overall in patients with extensive disease.
• 8.28 (95% CI, 3.75-18.32) in those with obstructive but nonextensive disease.
• 9.19 (95% CI, 4.49-18.82) overall in those with obstructive disease.
• 12.48 (95% CI, 5.50-28.12) in those with or obstructive and extensive disease.

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:

• 2.70 (95% CI, 1.72-4.25) in those with extensive but nonobstructive disease.
• 3.15 (95% CI, 2.05-4.83) in those with extensive and obstructive disease.

“It’s one thing to show that the more plaque, the higher the risk,” Dr. Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about 6,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor, and SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Dr. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Dr. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for Dr. McDermott and Dr. Newby, who are SCOT-HEART 2 investigators, can be found here.

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

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.

“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”

“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”

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

CRF up, mortality risk down

Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.

Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.

The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.

CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.

Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.

Conversely, medication use was progressively higher among those in low CRF categories.

After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.

For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).

Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.

A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.

The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”

“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”

“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”

If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
 

CRF impact “woefully underestimated”

Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.

“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”

Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:

• Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
• At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
• Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
• Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
• Fit people who undergo elective or emergent surgical procedures have better outcomes.
• Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.

Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”

“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.

“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”

In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”

“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.

No funding or relevant financial relationships were disclosed.

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

Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.

“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”

“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”

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

CRF up, mortality risk down

Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.

Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.

The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.

CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.

Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.

Conversely, medication use was progressively higher among those in low CRF categories.

After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.

For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).

Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.

A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.

The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”

“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”

“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”

If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
 

CRF impact “woefully underestimated”

Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.

“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”

Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:

• Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
• At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
• Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
• Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
• Fit people who undergo elective or emergent surgical procedures have better outcomes.
• Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.

Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”

“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.

“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”

In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”

“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.

No funding or relevant financial relationships were disclosed.

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

Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.

“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”

“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”

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

CRF up, mortality risk down

Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.

Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.

The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.

CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.

Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.

Conversely, medication use was progressively higher among those in low CRF categories.

After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.

For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).

Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.

A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.

The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”

“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”

“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”

If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
 

CRF impact “woefully underestimated”

Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.

“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”

Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:

• Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
• At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
• Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
• Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
• Fit people who undergo elective or emergent surgical procedures have better outcomes.
• Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.

Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”

“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.

“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”

In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”

“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.

No funding or relevant financial relationships were disclosed.

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

The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.

Olivier Le Moal/Getty Images

The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.

The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.

Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.

The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.

“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.

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

The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.

Olivier Le Moal/Getty Images

The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.

The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.

Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.

The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.

“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.

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

The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.

Olivier Le Moal/Getty Images

The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.

The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.

Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.

The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.

“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

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

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

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

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

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

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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

Providing care for individuals with both cardiovascular disease (CVD) and obesity necessitates addressing both conditions at the same time, say the authors of a new state-of-the-art review.

“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.

The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.

And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.

Obesity can also alter drug pharmacokinetics and pharmacodynamics.

Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”

They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
 

Excess fat acts as filter and can skew diagnostic results

“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.

The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.

Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m². In interventional radiology, there may be poor visualization of target areas.

“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
 

Therapeutic challenges: Drugs may work differently

A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.

Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.

Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.

Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
 

Cardiac rehabilitation is an intervention opportunity

Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.

But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.

“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.

The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”

Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.

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