MDedge Endocrinology

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

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

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

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

Preventing a tsunami of heart disease

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

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

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

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

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

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

NYU Langone

Double down on screening

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

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

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

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

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

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

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

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

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

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

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

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

Preventing a tsunami of heart disease

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

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

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

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

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

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

NYU Langone

Double down on screening

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

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

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

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

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

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

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

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

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

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

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

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

Preventing a tsunami of heart disease

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

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

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

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

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

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

NYU Langone

Double down on screening

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

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

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

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

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

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

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

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

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

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

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

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

Blacks comprised 26% of SYMPLICITY HTN-3 trial

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

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

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

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

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

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

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

Renal denervation safe in Black and non-Black patients

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

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

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

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

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

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

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

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

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

Blacks comprised 26% of SYMPLICITY HTN-3 trial

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

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

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

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

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

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

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

Renal denervation safe in Black and non-Black patients

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

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

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

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

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

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

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

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

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

Blacks comprised 26% of SYMPLICITY HTN-3 trial

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

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

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

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

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

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

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

Renal denervation safe in Black and non-Black patients

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

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

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

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

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

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

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

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

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

Mitchel L. Zoler/MDedge News

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

The goal is getting patients on triple therapy

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

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

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

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

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

Effective interventions and the need for a champion

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

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

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

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

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

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

Research advances often don’t translate into management changes

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

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

Mitchel L. Zoler/MDedge News

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

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

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

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

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

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

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

Mitchel L. Zoler/MDedge News

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

The goal is getting patients on triple therapy

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

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

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

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

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

Effective interventions and the need for a champion

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

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

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

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

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

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

Research advances often don’t translate into management changes

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

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

Mitchel L. Zoler/MDedge News

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

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

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

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

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

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

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

Mitchel L. Zoler/MDedge News

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

The goal is getting patients on triple therapy

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

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

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

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

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

Effective interventions and the need for a champion

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

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

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

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

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

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

Research advances often don’t translate into management changes

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

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

Mitchel L. Zoler/MDedge News

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

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

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

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

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

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

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

Ted Bosworth/MDedge News

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

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

Causal AI trained on nearly 2 million patients

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

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

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

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

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

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

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

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

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

Treatments become understandable to patients

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

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

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

Causal AI trained on nearly 2 million patients

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

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

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

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

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

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

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

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

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

Treatments become understandable to patients

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

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

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

Causal AI trained on nearly 2 million patients

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

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

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

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

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

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

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

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

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

Treatments become understandable to patients

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

Brigham and Women’s Hospital

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

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

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

Study results

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

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

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

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

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

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

Results clarify which patients will benefit

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

Lundquist Institute

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

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

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

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

Dr. Budoff has no relevant disclosures.

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

Brigham and Women’s Hospital

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

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

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

Study results

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

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

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

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

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

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

Results clarify which patients will benefit

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

Lundquist Institute

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

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

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

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

Dr. Budoff has no relevant disclosures.

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

Brigham and Women’s Hospital

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

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

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

Study results

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

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

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

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

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

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

Results clarify which patients will benefit

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

Lundquist Institute

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

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

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

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

Dr. Budoff has no relevant disclosures.

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

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

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

Pix by Marti/Fotolia

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

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

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

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

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

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

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

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

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

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

‘Small but important effect’

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

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

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

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

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

First-of-its kind, nationwide pragmatic trial

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

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

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

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

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

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

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

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

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

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

These two strategies also improved vaccination rates across major subgroups.

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

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

Subanalysis in CVD

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

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

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

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

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

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

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

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

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

Pix by Marti/Fotolia

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

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

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

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

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

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

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

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

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

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

‘Small but important effect’

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

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

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

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

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

First-of-its kind, nationwide pragmatic trial

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

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

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

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

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

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

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

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

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

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

These two strategies also improved vaccination rates across major subgroups.

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

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

Subanalysis in CVD

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

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

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

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

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

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

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

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

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

Pix by Marti/Fotolia

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

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

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

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

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

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

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

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

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

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

‘Small but important effect’

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

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

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

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

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

First-of-its kind, nationwide pragmatic trial

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

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

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

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

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

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

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

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

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

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

These two strategies also improved vaccination rates across major subgroups.

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

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

Subanalysis in CVD

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

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

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

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

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

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