Hypertension

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

At age 57, a senior scientific researcher in Santa Barbara, California, complained of chronic erectile dysfunction (ED) in what had been a sexually active marriage. “I just couldn’t get an erection, let alone sustain one. Apart from that, I maybe felt a bit tired but generally okay,” he said. Though seemingly well otherwise, 18 months later he was dead of a hereditary right-sided colon cancer.

While not all cases of ED are associated with a dire outcome, the genitourinary signals of ED and lower urinary tract symptoms (LUTS), especially nocturia, serve as sentinel indicators of the presence of, or risk factors for, serious chronic conditions. These commonly include cardiovascular disease (CVD), diabetes, and metabolic syndrome and are associated with obesity, depression, and obstructive sleep apnea.

Sometimes these serious conditions may stay under the radar until men seek help for ED or LUTS.

“We know that among men who had a heart attack, 50% had some degree of ED within 3 years of their cardiac event,” Sam Tafari, MBBS, of the Endocrine and Metabolic Unit at Royal Adelaide Hospital in Adelaide, South Australia, said in an interview.

That’s the bad news. The good news is that these two problems may specifically incentivize men to seek timely care for serious conditions they might otherwise not get, according to Dr. Tafari. And primary care doctors are ideally positioned to get men early multifaceted care. He recently coauthored a call to action on this issue in a review appearing in the Journal of Men’s Health.

In Dr. Tafari’s experience, most patients seeking urological care are unaware of the multiple conditions linked to ED and LUTS. “Many consider these to be due to issues like low testosterone, which actually make up a very small proportion of cases of ED,” he said. Aging, obesity, inactivity, smoking, alcohol abuse, and prescription and street drugs can also contribute to the development of ED.

In most affected men, ED is of vascular etiology, with endothelial dysfunction of the inner lining of blood vessels and smooth muscle the common denominator.

This dysfunction causes inadequate blood supply to both the coronary and the penile arteries, so ED and CVD are considered different manifestations of the same systemic disorder. Because the tumescence-controlling cavernosal vessels of the penis are considerably smaller, the same level of arteriopathy causes a more severe reduction in blood in the erectile tissue. As a result, ED often precedes CVD and presents an early opportunity to screen men for CVD.

As to the mechanisms behind LUTS, Peter N. Tsambarlis, MD, a urologist at Northwestern Medicine in Chicago, subscribes to the inflammation theory. “Suboptimal health issues such as high [blood] pressure, blood lipids, and blood glucose lead to chronic widespread inflammation, which makes the bladder less flexible as a storage vessel,” he explained. “It’s not able to stretch adequately overnight to hold the urine until morning.”
 

Ask Early, Ask Often

Jeffrey P. Weiss, MD, PhD, chair of the Department of Urology at SUNY Downstate Health Sciences University in Brooklyn, New York, has done research that uncovered a relationship between structural cardiac disease and nocturia. “So if you had to ask a patient a single question that would point to a global health issue, it would be ‘Do you have frequent nighttime urination,’ ” he said.

It’s never too soon to ask men about these symptoms, said Dr. Tsambarlis. The best time to raise issues of ED and LUTS is when a man enters primary care — regardless of age or absence of symptoms. “That way you have a baseline and can watch for changes and do early intervention as needed. Men don’t usually want to bring up sexual dysfunction or urinary health, but asking doesn’t need to dominate the visit,” he said.

Dr. Tafari recommends that primary care physicians adopt a targeted approach using ED and nocturia as entry points for engaging men in their healthcare. While acknowledging that primary care physicians have an ever-growing checklist of questions to ask patients and hardly need one more thing to screen for, he suggests asking two quick, and easy “before you go” genitourinary queries:

• Are you having trouble with erections or having sex?
• Are you getting up at night to pass urine more than once?

“The men really appreciate being asked,” he said. “But what worries me is all the men we don’t see who have these symptoms but don’t know they’re important, and no one is asking about them.”

Gideon Richards, MD, a urologist at the Northwell Health Physician Partners Smith Institute for Urology at Garden City, and director of Men’s Health, Central Region, for Northwell Health in New Hyde Park, both in New York, said erectile problems should not wait for specialty care. By the time men with ED are referred to urology, they may already have failed treatment with first-line phosphodiesterase 5 inhibitor therapy, he said. “A significant proportion will have arteriogenic erectile dysfunction, a measurable decrease in the amount of blood flow into the erectile bodies.”

Addressing the Issue

Addressing genitourinary-signaled issues has the double benefit of easing ED and LUTS and improving men’s health and longevity and may help narrow the worldwide gender gap in life expectancy. As a recent global analysis found, there’s a 5-year longevity disparity favoring women over men. Biology aside, men do not access healthcare as often as women, who consult their general practitioners regularly throughout their lifespan for multiple reasons, including reproductive care, and more screening programs are aimed at women.

Added Dr. Tsambarlis, “Men should know that losing weight and switching to a healthy lifestyle can improve sexual function about half as much as phosphodiesterase 5 inhibitors such as sildenafil [Viagra] or tadalafil [Cialis].”

“Many, however, would prefer just to take drugs rather than change their lifestyle and lose weight. There are certainly effective options available, but these are not uniformly effective,” said Dr. Weiss.

Dr. Tafari’s group is designing a short, simple, culturally acceptable screening tool for use in primary care practice and will monitor its impact on physician prescribing habits and overall men’s health outcomes.

Dr. Tafari received funding from the Hospital Research Foundation and Freemasons Centre for Male Health and Wellbeing in Adelaide, South Australia. Dr. Tafari, Dr. Tsambarlis, Dr. Weiss, and Dr. Richards had no relevant conflicts of interest to declare.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Updated guidelines for the management of atrial fibrillation released by the European Society of Cardiology are revamping the approach to care for this complex, multifactorial disease.

The identification and treatment of comorbidities and risk factors are the initial and central components of patient management, and are crucial for all other aspects of care for patients with atrial fibrillation (AF), Isabelle Van Gelder, MD, PhD, professor of cardiology at the University Medical Center in Groningen, the Netherlands, explained at the European Society of Cardiology (ESC) Congress.

It is not just appropriate to place the same emphasis on the control of comorbidities as on the rhythm disturbance, it is critical, said Dr. Van Gelder, who served as chair of the ESC-AF guidelines task force.

Comorbidities are the drivers of both the onset and recurrence of atrial fibrillation, and a dynamic approach to comorbidities is “central for the success of AF management.”
 

Class I Recommendation

In fact, on the basis of overwhelming evidence, a class I recommendation has been issued for a large number of goals in the comorbidity and risk factor management step of atrial fibrillation management, including those for hypertension, components of heart failure, obesity, diabetes, alcohol consumption, and exercise.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors “should be offered to all patients with AF,” according to Dr. Van Gelder, who identified this as a new class I recommendation.

Patients who are not managed aggressively for the listed comorbidities ultimately face “treatment failure, poor patient outcomes, and a waste of healthcare resources,” she said.

Control of sleep apnea is also noted as a key target, although Van Gelder acknowledged that the supporting evidence only allows for a class IIb recommendation.

Control of comorbidities is not a new idea. In the 2023 joint guideline, led by a consortium of professional groups, including the American Heart Association (AHA) and the American College of Cardiology (ACC), the control of comorbidities, including most of those identified in the new ESC guidelines, was second in a list of 10 key take-home messages.

However, the new ESC guidelines have prioritized comorbidity management by listing it first in each of the specific patient-care pathways developed to define optimized care. 

These pathways, defined in algorithms for newly diagnosed AF, paroxysmal AF, and persistent AF, always start with the assessment of comorbidities, followed by step A — avoiding stroke — largely with anticoagulation.

Direct oral anticoagulants should be used, “except in those with a mechanical valve or mitral stenosis,” Dr. Van Gelder said. This includes, essentially, all patients with a CHA2DS2-VASc score of 2 or greater, and it should be “considered” in those with a score of 1. 

The ESC framework has been identified with the acronym AF-CARE, in which the C stands for comorbidities.

In the A step of the framework, identifying and treating all modifiable bleeding risk factors in AF patients is a class I recommendation. On the basis of a class III recommendation, she cautioned against withholding anticoagulants because of CHA2DS2-VASc risk factors alone. Rather, Dr. Van Gelder called the decision to administer or withhold anticoagulation — like all decisions — one that should be individualized in consultation with the patient.

For reducing AF symptoms and rhythm control, the specific pathways diverge for newly diagnosed AF, paroxysmal AF, and persistent AF. Like all of the guidelines, the specific options for symptom management and AF ablation are color coded, with green signifying level 1 evidence.

The evaluation and dynamic reassessment step refers to the need to periodically assess patients for new modifiable risk factors related to comorbidities, risk for stroke, risk for bleeding, and risk for AF. 

The management of risk factors for AF has long been emphasized in guidelines, but a previous focus on AF with attention to comorbidities has been replaced by a focus on comorbidities with an expectation of more durable AF control. The success of this pivot is based on multidisciplinary care, chosen in collaboration with the patient, to reduce or eliminate the triggers of AF and the risks of its complications.
 

Pathways Are Appropriate for All Patients

A very important recommendation — and this is new — is “to treat all our patients with atrial fibrillation, whether they are young or old, men or women, Black or White, or at high or low risk, according to our patient-centered integrated AF-CARE approach,” Dr. Van Gelder said.

The changes reflect a shared appreciation for the tight relation between the control of comorbidities and the control of AF, according to José A. Joglar, MD, professor of cardiac electrophysiologic research at the University of Texas Southwestern Medical Center in Dallas. Dr. Joglar was chair of the writing committee for the joint 2023 AF guidelines released by the AHA, ACC, the American College of Clinical Pharmacy, and the Heart Rhythm Society.

“It is increasingly clear that AF in many cases is the consequence of underlying risk factors and comorbidities, which cannot be separated from AF alone,” Dr. Joglar explained in an interview.

This was placed first “to emphasize the importance of viewing AFib as a complex disease that requires a holistic, multidisciplinary approach to care, as opposed to being viewed just as a rhythm abnormality,” he said.
 

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

LONDON — Simplified and more aggressive targets are among the significant changes to the updated hypertension guidelines released by the European Society of Cardiology.

For most treated patients, the new systolic blood pressure goal is a target of 120 mm Hg to 129 mm Hg, which is a move away from the previous two-step recommendation.

Although the updated guidelines, presented here at the ESC Congress, continue to define hypertension as a systolic BP of at least 140 mm Hg and a diastolic BP of at least 90 mm Hg, there is a new category — elevated BP. This is defined as a systolic BP of 120 mm Hg to 139 mm Hg or a diastolic BP of 70 mm Hg to 89 mm Hg, and cardiovascular risk assessment is advised to guide treatment, particularly in patients with a BP of at least 130/80 mm Hg.

The guidelines also introduce new recommendations for lifestyle options to help lower BP, including changes to exercise advice and the addition of potassium supplementation. And for the first time, the ESC guidelines provide recommendations for the use of renal denervation to treat hypertension in certain circumstances.

The guidelines were produced by an international panel, led by Bill McEvoy, MB BCh, from the University of Galway, Ireland, and Rhian Touyz, MB BCh, PhD, from McGill University in Montreal.
 

Three Categories of Blood Pressure

There are now three categories for BP classification — non-elevated (< 120/70 mm Hg), elevated (120 mm Hg to139 mm Hg/70 mm Hg to 89 mm Hg), and hypertension (≥ 140/90 mm Hg) — Dr. McEvoy reported during a session on the new guidelines here at ESC.

The emphasis on out-of-office BP measurement is stronger than in previous guidelines, but office measurement will still be used, he said.

All patients in the hypertension category qualify for treatment, whereas those in the new elevated BP category will be subject to cardiovascular risk stratification before a treatment decision is made.

Patients in the elevated BP category who also have moderate or severe chronic kidney disease, established cardiovascular disease, diabetes, or familial hypercholesterolemia are among those considered at increased risk for cardiovascular disease, as are patients with an estimated 10-year cardiovascular risk of 10% or higher. In such patients with a confirmed BP of at least 130/80 mm Hg, after 3 months of lifestyle intervention, pharmacologic treatment is recommended.

“This new category of elevated blood pressure recognizes that people do not go from normal blood pressure to hypertensive overnight,” Dr. McEvoy said. “It is, in most cases, a steady gradient of change, and different subgroups of patients — for example, those at a higher risk of developing cardiovascular disease — could benefit from more intensive treatment before their blood pressure reaches the traditional threshold of hypertension.”
 

New Lower Target

The major change in target pressures in these guidelines is based on new clinical trial data that confirm that lower pressures lead to lower cardiovascular event rates, resulting in the new systolic BP target of 120 mm Hg to 129 mm Hg for most patients receiving antihypertensive medications.

This systolic target represents a major change from previous European guidelines, Dr. McEvoy said, which have generally recommended that patients be treated to a target of less than 140/90 mm Hg and, only after that has been reached, then treated to a target of less than 130/80 mm Hg (a two-step approach).

“This change is driven by new trial evidence confirming that more intensive blood pressure treatment targets reduce cardiovascular outcomes across a broad spectrum of eligible patients,” Dr. McEvoy said.

There are, however, several caveats to this recommendation, including the requirement that treatment to this target be well tolerated; more lenient targets can be considered in people with symptomatic orthostatic hypotension, those 85 years and older, and those with moderate to severe frailty or a limited life expectancy. For these patients, the guidelines recommend a target “that is as low as reasonably achievable.”
 

More in Line With US Guidelines

The new European guidelines are now more in line with the American guidelines, said Eugene Yang, MD, from the University of Washington in Seattle, who is chair of the Hypertension Writing Group at the American College of Cardiology.

“These new European guidelines have thoughtfully used the latest study data to simplify recommendations for a specific lower blood pressure target. This is a step forward. There is now a greater alignment of European and US guidelines. This is good to reduce confusion and build consensus across the world,” he said.

Both sets of guidelines now recommend a BP target of less than 130/80 mm Hg for most people. 

“I think the Europeans have now embraced this more aggressive target because there are many more studies now showing that these lower blood pressure levels do lead to a reduction in cardiovascular events,” Dr. Yang explained. “When the last European guidelines came out, there was only SPRINT. Now there are several more studies showing similar results.”
 

New Lifestyle Advice

The updated recommendation of 75 minutes of vigorous-intensity aerobic exercise per week has been added as an alternative to the previous recommendation of at least 2.5 hours per week of moderate-intensity aerobic exercise. This should be complemented with low- or moderate-intensity dynamic or isometric resistance training two to three times a week. 

It is also recommended that people with hypertension, but without moderate or advanced chronic kidney disease, increase potassium intake with salt substitutes or diets rich in fruits and vegetables.
 

Renal Denervation Included for First Time 

For the first time, the guidelines include the option of renal denervation for the treatment of hypertension — at medium- to high-volume centers — for patients with resistant hypertension that is uncontrolled despite a three-drug combination.

However, renal denervation is not recommended as a first-line treatment because of the lack of evidence of a benefit in cardiovascular outcomes. It is also not recommended for patients with highly impaired renal function or secondary causes of hypertension.

Dr. Yang said he approves of the inclusion of a frailty assessment in the new guidelines and less aggressive targets for people who are in poor health and older than age 85 years, but added that, “on the whole, they have less age-specific stratification than before, which is a significant change, and a good one in my view.” 

Again, this is like the American guidelines, which have no age cutoffs and a target of less than 130/80 mm Hg for all, with the caveat that clinical judgment may be needed for individuals who are institutionalized, he added.

Dr. Yang said he was not as keen on the requirement for a cardiovascular risk assessment to guide treatment decisions for people with a systolic BP in the 130 mm Hg to 139 mm Hg range, although this is also included in the current American guidelines.

“As a clinician, I think this complicates things a bit too much and, as such, will be a barrier to treatment. In my view, blood pressure treatment recommendations need to be as simple as possible, so I think we still have some work to do there,” he said.

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

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.