Hypertension

New research shows that supine orthostatic hypotension is more common and better predicts falls and orthostatic symptoms than seated OH, supporting a supine OH protocol in clinical practice, the researchers say.

“Older adults at risk for falls undergoing assessment for OH should lie supine rather than sitting prior to standing to get the most informative OH assessment,” study author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, said in an interview.

“The findings call for a change in current practice,” Dr. Juraschek said.

He presented the study Sept. 29 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The seated position for detecting OH is “commonly used for convenience. Since many clinics already perform a seated blood pressure, it saves time for people to stand shortly afterward,” he explained.

“It has also been thought that the two are interchangeable [i.e., the change in blood pressure from seated to standing was just a lower magnitude than the change from supine to standing]. However, we showed that the physiology is on average quite different, questioning prior perspectives on the interchangeability of the two protocols,” he added.

The researchers studied 522 adults (mean age, 76 years; 42% women) at high risk for falls and with vitamin D levels in the insufficient/deficient range participating in the Study to Understand Fall Reduction and Vitamin D (STURDY).

The study showed that vitamin D supplementation was not associated with OH or the main study outcome of falls.

The study used two different OH assessment protocols – seated to standing and supine to standing – and Dr. Juraschek’s team used the data to gauge the impact of supine and seated positions on OH prevalence and its relation with fall risk and orthostatic symptoms.

OH was defined as a drop in systolic BP of at least 20 mm Hg or diastolic BP of at least 10 mm Hg.

At baseline, mean BP was 129/68 mm Hg. Mean BP increased 3.4/2.6 mm Hg after sitting, but decreased 3.7/0.7 mm Hg after lying supine.

Of the 953 OH assessments (supine and seated), OH was detected in 14.8% of the supine measurements but in only 2.2% of the seated measures.

Supine OH better predicted falls (hazard ratio, 1.60; 95% CI, 0.98-2.61; P = .06) than seated OH (HR, 0.70; 95% CI, 0.30-1.60; P = .39).

Although both were nonsignificant, “potentially due to power,” the association with falls was stronger for supine OH than for seated OH, Dr. Juraschek said.

In addition, seated OH was not associated with orthostatic symptoms, whereas supine OH was significantly associated with a greater risk of fainting, blacking out, seeing spots, room spinning, and headache in the previous month (P = .048-.002).
 

Useful study confirms anecdotal evidence

This is a “useful study” from a “reputable” group, “and the results reveal what I would have expected,” Robert Carey, MD, University of Virginia, Charlottesville, who wasn’t involved in the study, said in an interview.

The findings, Dr. Carey said, show that measuring supine, compared with standing, “actually correlates much better with the untoward effects of orthostatic hypotension which are falls and symptoms such as dizziness and spots before your eyes.”

“Seated BP is mostly used for convenience and a little bit shorter protocol. Most clinical trials do seated orthostatic hypotension measurements. I’ve always taught my medical students and others to use the supine to standing because I’ve just anecdotally felt that this was a much better way of detecting true orthostatic hypotension and that’s how we do it at the University of Virginia Hospital,” Dr. Carey said.

The study had no funding. Dr. Juraschek and Dr. Carey have no relevant conflicts of interest.

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

New research shows that supine orthostatic hypotension is more common and better predicts falls and orthostatic symptoms than seated OH, supporting a supine OH protocol in clinical practice, the researchers say.

“Older adults at risk for falls undergoing assessment for OH should lie supine rather than sitting prior to standing to get the most informative OH assessment,” study author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, said in an interview.

“The findings call for a change in current practice,” Dr. Juraschek said.

He presented the study Sept. 29 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The seated position for detecting OH is “commonly used for convenience. Since many clinics already perform a seated blood pressure, it saves time for people to stand shortly afterward,” he explained.

“It has also been thought that the two are interchangeable [i.e., the change in blood pressure from seated to standing was just a lower magnitude than the change from supine to standing]. However, we showed that the physiology is on average quite different, questioning prior perspectives on the interchangeability of the two protocols,” he added.

The researchers studied 522 adults (mean age, 76 years; 42% women) at high risk for falls and with vitamin D levels in the insufficient/deficient range participating in the Study to Understand Fall Reduction and Vitamin D (STURDY).

The study showed that vitamin D supplementation was not associated with OH or the main study outcome of falls.

The study used two different OH assessment protocols – seated to standing and supine to standing – and Dr. Juraschek’s team used the data to gauge the impact of supine and seated positions on OH prevalence and its relation with fall risk and orthostatic symptoms.

OH was defined as a drop in systolic BP of at least 20 mm Hg or diastolic BP of at least 10 mm Hg.

At baseline, mean BP was 129/68 mm Hg. Mean BP increased 3.4/2.6 mm Hg after sitting, but decreased 3.7/0.7 mm Hg after lying supine.

Of the 953 OH assessments (supine and seated), OH was detected in 14.8% of the supine measurements but in only 2.2% of the seated measures.

Supine OH better predicted falls (hazard ratio, 1.60; 95% CI, 0.98-2.61; P = .06) than seated OH (HR, 0.70; 95% CI, 0.30-1.60; P = .39).

Although both were nonsignificant, “potentially due to power,” the association with falls was stronger for supine OH than for seated OH, Dr. Juraschek said.

In addition, seated OH was not associated with orthostatic symptoms, whereas supine OH was significantly associated with a greater risk of fainting, blacking out, seeing spots, room spinning, and headache in the previous month (P = .048-.002).
 

Useful study confirms anecdotal evidence

This is a “useful study” from a “reputable” group, “and the results reveal what I would have expected,” Robert Carey, MD, University of Virginia, Charlottesville, who wasn’t involved in the study, said in an interview.

The findings, Dr. Carey said, show that measuring supine, compared with standing, “actually correlates much better with the untoward effects of orthostatic hypotension which are falls and symptoms such as dizziness and spots before your eyes.”

“Seated BP is mostly used for convenience and a little bit shorter protocol. Most clinical trials do seated orthostatic hypotension measurements. I’ve always taught my medical students and others to use the supine to standing because I’ve just anecdotally felt that this was a much better way of detecting true orthostatic hypotension and that’s how we do it at the University of Virginia Hospital,” Dr. Carey said.

The study had no funding. Dr. Juraschek and Dr. Carey have no relevant conflicts of interest.

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

New research shows that supine orthostatic hypotension is more common and better predicts falls and orthostatic symptoms than seated OH, supporting a supine OH protocol in clinical practice, the researchers say.

“Older adults at risk for falls undergoing assessment for OH should lie supine rather than sitting prior to standing to get the most informative OH assessment,” study author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, said in an interview.

“The findings call for a change in current practice,” Dr. Juraschek said.

He presented the study Sept. 29 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The seated position for detecting OH is “commonly used for convenience. Since many clinics already perform a seated blood pressure, it saves time for people to stand shortly afterward,” he explained.

“It has also been thought that the two are interchangeable [i.e., the change in blood pressure from seated to standing was just a lower magnitude than the change from supine to standing]. However, we showed that the physiology is on average quite different, questioning prior perspectives on the interchangeability of the two protocols,” he added.

The researchers studied 522 adults (mean age, 76 years; 42% women) at high risk for falls and with vitamin D levels in the insufficient/deficient range participating in the Study to Understand Fall Reduction and Vitamin D (STURDY).

The study showed that vitamin D supplementation was not associated with OH or the main study outcome of falls.

The study used two different OH assessment protocols – seated to standing and supine to standing – and Dr. Juraschek’s team used the data to gauge the impact of supine and seated positions on OH prevalence and its relation with fall risk and orthostatic symptoms.

OH was defined as a drop in systolic BP of at least 20 mm Hg or diastolic BP of at least 10 mm Hg.

At baseline, mean BP was 129/68 mm Hg. Mean BP increased 3.4/2.6 mm Hg after sitting, but decreased 3.7/0.7 mm Hg after lying supine.

Of the 953 OH assessments (supine and seated), OH was detected in 14.8% of the supine measurements but in only 2.2% of the seated measures.

Supine OH better predicted falls (hazard ratio, 1.60; 95% CI, 0.98-2.61; P = .06) than seated OH (HR, 0.70; 95% CI, 0.30-1.60; P = .39).

Although both were nonsignificant, “potentially due to power,” the association with falls was stronger for supine OH than for seated OH, Dr. Juraschek said.

In addition, seated OH was not associated with orthostatic symptoms, whereas supine OH was significantly associated with a greater risk of fainting, blacking out, seeing spots, room spinning, and headache in the previous month (P = .048-.002).
 

Useful study confirms anecdotal evidence

This is a “useful study” from a “reputable” group, “and the results reveal what I would have expected,” Robert Carey, MD, University of Virginia, Charlottesville, who wasn’t involved in the study, said in an interview.

The findings, Dr. Carey said, show that measuring supine, compared with standing, “actually correlates much better with the untoward effects of orthostatic hypotension which are falls and symptoms such as dizziness and spots before your eyes.”

“Seated BP is mostly used for convenience and a little bit shorter protocol. Most clinical trials do seated orthostatic hypotension measurements. I’ve always taught my medical students and others to use the supine to standing because I’ve just anecdotally felt that this was a much better way of detecting true orthostatic hypotension and that’s how we do it at the University of Virginia Hospital,” Dr. Carey said.

The study had no funding. Dr. Juraschek and Dr. Carey have no relevant conflicts of interest.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults who need to track their blood pressure to find out if they have hypertension prefer to do it at home rather than at a clinic or kiosk or with 24-hour ambulatory BP monitoring (ABPM), according to a new study.

“From a patient-centered perspective, home BP monitoring is the most acceptable method for diagnosing hypertension, although participants were willing to complete ABPM and appreciated its accuracy,” said Beverly Green, MD, MPH, of Kaiser Permanente Washington, Seattle.

Dr. Green presented the study Sept. 29 during the virtual American Heart Association Hypertension Scientific Sessions 2021.

“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr. Green said in an AHA news release.

“Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure, and cardiovascular death,” she added.
 

Convenience is key

The BP-CHECK study was a three-group, randomized, controlled diagnostic study that tested the accuracy and acceptability of office, home, and kiosk BP monitoring against the gold-standard – ABPM – for diagnosing hypertension. Dr. Green presented the results on patient adherence and acceptability of these methods.

Those assigned to clinic measurements were asked to return to the clinic for at least one additional BP check, as is routine in diagnosing hypertension in clinical practice.

Those in the home group were given and trained to use a Bluetooth/web-enabled home BP monitor and were asked to take their BP twice a day (morning and evening, with two measurements each time) for 5 days.

Those in the kiosk group were trained to use a BP kiosk with a smart card and were asked to return to the kiosk (or a nearby pharmacy with the same kiosk) on 3 separate days and measure their BP three times at each visit.

All participants were asked to complete their group-assigned diagnostic regimens in 3 weeks and then to complete 24-hour ABPM.

The trial enrolled 510 adults who presented to Kaiser Permanente Washington primary care clinics with elevated BP (mean, 150/88 mm Hg) but who had not yet been diagnosed with hypertension. Their mean age was 59 years, 80% of the study participants were White, and 51% were male.

Adherence to the monitoring regimen was highest in the home BP group (90.6%), followed by the clinic group (87.2%), and lowest in the kiosk group (67.9%). Adherence to ABPM among all participants was 91.6%.

Overall, acceptability was highest for the home BP group, followed by the clinic and kiosk groups; 24-hour ABPM monitoring was the least acceptable option.

Home was the “overwhelming” stated preference when asked before randomization and after, Dr. Green said.

The findings come as no surprise to Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee. “Patients will do what’s most convenient for them,” he told this news organization.

“We know from other studies that really all you need to do is measure the blood pressure twice a day for 3 days. That will give you a good idea what that patient’s blood pressure is as it relates to future cardiac events,” said Dr. Lawrence, who wasn’t involved in the study.

“We should really begin to focus more on these home, self-measured blood pressures using validated devices, and that’s important because a lot of the devices out there aren’t validated,” he explained.

“Patients with hypertension should have a blood pressure monitor at home that is validated and should be instructed in how to use it properly,” Dr. Lawrence concluded.

Funding for the study was provided by the Patient-Centered Outcomes Research Institute. Dr. Green and Dr. Lawrence have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Adults with diabetes whose blood pressure does not drop as expected at night (nondipping), or whose BP increases during the night (reverse dipping) are at higher risk of dying than peers with normal nighttime BP patterns, a longitudinal study has shown.

“Reverse dippers have more than double the risk of death for any cause over 20 years, irrespective of blood pressure control,” study investigator Martina Chiriacò, MD, University of Pisa (Italy), said in an interview.

“Primary physicians and diabetologists should look for abnormal blood pressure dipping patterns in patients with diabetes through 24-hour ambulatory blood pressure monitoring,” she added.

Dr. Chiriacò presented the research Sept. 28 at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Scarce data

Previous studies have shown that a nondipping BP pattern is linked to renal and cardiovascular disease, both in healthy individuals and in patients with hypertension or diabetes.

“Nevertheless, the long-term effect of nondipping on mortality in diabetes is still unclear; in particular, data on reverse dippers are extremely scarce,” Dr. Chiriacò explained.

To investigate, the researchers analyzed data on 349 adults with diabetes (81% type 2 diabetes) who were followed for more than 2 decades as part of the CHAMPION study, all with available 24-hour ambulatory BP monitoring (ABPM) and heart rate variability monitoring.

Dipping, nondipping, and reverse dipping were defined as a decline of at least 10%, a decline of less than 10%, and an increase of at least 0.1% in average night-time systolic BP, compared with average daytime SBP, respectively.

The cohort involved 166 (47.6%) dippers, 144 (41.2%) nondippers, and 39 (11.2%) reverse dippers.

Compared with dippers, nondippers and reverse dippers showed a progressively higher prevalence of cardiac autonomic neuropathy, low heart rate variability, 24-hour hypertension, isolated nocturnal hypertension, postural hypotension, and lower prevalence of white-coat hypertension.

During a median follow-up of 21 years, 136 patients died (39%). 

Compared with dippers, reverse dippers and nondippers had an average reduction in survival of 2.5 years and 1.1 years, respectively, Dr. Chiriacò reported.

During follow-up, risk for all-cause mortality was about twofold higher for reverse dippers than for dippers (adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8; P = .003) and than for nondippers (adjusted HR, 1.8; 95% CI, 1.1-2.9; P = .34).

There was no significant difference in all-cause mortality risk between dippers and nondippers.

Notably, said Dr. Chiriacò, the one in five patients with isolated nocturnal hypertension had a reduction in survival similar to that seen in individuals with 24-hour sustained hypertension (average, 1.2 years).

Individuals with low heart rate variability over 24 hours had an average reduction in survival of 1.8 years.
 

Important underused diagnostic tool

“We believe that our study is important since it is the only available study with a follow-up longer than 20 years that explores the role of blood pressure patterns and heart rate variability as risk factors for all-cause mortality in diabetes,” Dr. Chiriacò said in an interview.

There are some available strategies to reduce BP during the night, she added. “The most tested and effective is the administration of anti-hypertensive medications in the evening rather than in the morning.”

Weighing in on the study, Maryann McLaughlin, MD, cardiologist at Mount Sinai Hospital, New York, said: “Interestingly, most physicians do not do 24-hour ambulatory blood pressure monitoring when they’re making the diagnosis of hypertension.”

“And really, the correct way to make a diagnosis of hypertension and rule out white-coat hypertension is either with a 24-hour ambulatory blood pressure monitor or use of home blood pressure monitors,” she said in an interview.

“The 24-hour ambulatory blood pressure monitor is an important diagnostic tool and a great way to really look at this issue of dipping, which is a very important physiologic parameter,” Dr. McLaughlin said.

“In our offices, we offer the 24-hour home ambulatory blood pressure monitor routinely. Most patients are receptive to it and they usually tolerate it pretty well,” Dr. McLaughlin said.

The study was funded by the University of Pisa. Dr. Chiriacò and Dr. McLaughlin have no relevant disclosures.

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

Sexual harassment or assault during military service among young and middle-aged veterans is associated with an increased risk for hypertension, a new study suggests.

“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.

“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Lasting impact on physical health

Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017. 

All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.

During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).

Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).

After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).

When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.

“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.

“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.

Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
 

Social determinants of health

Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”

“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.

“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.

Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.

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

Sexual harassment or assault during military service among young and middle-aged veterans is associated with an increased risk for hypertension, a new study suggests.

“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.

“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Lasting impact on physical health

Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017. 

All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.

During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).

Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).

After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).

When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.

“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.

“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.

Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
 

Social determinants of health

Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”

“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.

“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.

Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.

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

Sexual harassment or assault during military service among young and middle-aged veterans is associated with an increased risk for hypertension, a new study suggests.

“Understanding a patient’s trauma history is invaluable for treating the whole person,” Allison E. Gaffey, PhD, Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, told this news organization.

“Assessing men and women’s history of trauma, including sexual trauma, is critical for recognizing nontraditional factors that contribute to their cardiovascular risk and to gain a more comprehensive understanding of their mental and physical health,” Dr. Gaffey added.

She presented her research at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
 

Lasting impact on physical health

Dr. Gaffey and colleagues analyzed data from the VA for roughly 1.2 million veterans (mean age, 30.2 years; 12% female) who were discharged from the military after Sept. 30, 2001, and who received health care services at VA medical centers from 2001 to 2017. 

All were screened for sexual harassment and assault, known as military sexual trauma (MST), when they first began receiving VA care.

During 16 years of follow-up, 33,881 veterans screened positive for MST (65% women), and 307,332 developed hypertension (15% women).

Overall, MST was associated with a 30% increase in risk for incident hypertension in unadjusted models (hazard ratio, 1.30; 95% confidence interval, 1.28-1.33; P < .001).

After adjustment for demographic characteristics, lifestyle factors, cardiovascular comorbidities, PTSD, anxiety, and depression, MST remained significantly associated with hypertension (adjusted HR, 1.10; 95% CI, 1.08-1.12; P < .001).

When women and men were examined separately, the link between MST and risk for hypertension remained for both groups, but was slightly stronger among women.

“Sexual trauma has been associated with autonomic dysfunction, inflammation, and dysregulation in the hypothalamic pituitary adrenal axis and renin-angiotensin-aldosterone system, which could lead to elevations in BP over time,” Dr. Gaffey told this news organization.

“These findings show that even many years after being discharged from military service, exposure to military sexual trauma can continue to significantly influence veterans’ physical health,” she added.

Dr. Gaffey said it will be important to determine if early treatment of MST improves hypertension risk, particularly among those showing elevated blood pressure or stage 1 hypertension.
 

Social determinants of health

Willie Lawrence Jr., MD, head of the AHA National Hypertension Control Initiative oversight committee, said the findings in this study are “in line with what we know about the impact of social determinants of health on high blood pressure.”

“There are studies that suggest that things that we historically don’t look at as risk factors for hypertension – lifelong racism, crime, mental health status – do in fact predict your risk of developing hypertension,” Dr. Lawrence, from Spectrum Health in Benton Harbor, Mich., told this news organization.

“It’s not just your genetics that will determine your health, and there are a lot of things that will affect your blood pressure. Your blood pressure is really just a barometer of everything that’s going on in your life and some of the things that have gone on in your life in the past,” added Dr. Lawrence, who wasn’t involved in the study.

Funding for the study was provided by the Department of Veterans Affairs. Dr. Gaffey and Dr. Lawrence have no relevant disclosures.

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

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

New evidence suggests a drug used to lower blood sugar levels may also help extend the duration of preterm pregnancies in women with preeclampsia.

The findings from a small clinical trial, published Sept. 23 in the BMJ, showed that pregnant women who received the diabetes medication metformin prolonged their pregnancy by a week compared to those who received a placebo. Although this finding was not statistically significant, researchers said they are “cautiously optimistic” about the treatment of preterm preeclampsia.

“We hope that it will encourage others to test not only metformin but also other promising therapeutic candidates to treat and prevent preeclampsia,” study author Catherine Cluver, MBChB, FCOG, PhD, associate professor in the department of obstetrics and gynecology at Stellenbosch University in South Africa, said in an interview.

Preeclampsia, a condition that occurs about 1 in 25 pregnancies in the United States, happens when a woman develops high blood pressure and protein in her urine, according to the Centers for Disease Control and Prevention.

Preterm preeclampsia is a severe variant affecting 0.5% of all pregnancies, or 10% of those with preeclampsia, researchers wrote in the study. The condition is associated with more maternal and neonatal death and increases their risks of developing an illness.

Dr. Cluver said that when a mother develops preeclampsia, the lining of her blood vessels, or the endothelium, is affected and there are specific proteins in the blood that increase. Dr. Cluver’s preclinical study found that metformin improved endothelial function and decreased these biomarkers in laboratory work.

“We therefore set out to see if metformin could be used to prolong gestation in preterm preeclampsia,” she said.

For the study, Dr. Cluver and colleagues performed a double-blind, placebo-controlled clinical trial to compare the prolongation of pregnancies among women who were at least 26 months pregnant with preterm preeclampsia. They were treated with either 3 grams of extended-release metformin (90 women), or a matching placebo (90 women).*

In the treatment group, the average time from the start of the study to delivery was 17.7 days, compared to 10.1 days in the placebo group. The median difference was 7.6 days.

The researchers also found that 40% of women in the metformin group reached 34 weeks’ gestation compared with 28% of those in the placebo group. Fewer women in the metformin group delivered because of fetal indications such as fetal distress or other issues – 33% vs. 44%. However, the researchers said those results were not statistically significant.

They said they were cautiously optimistic when they found that the median time for prolongation of pregnancy in the metformin group was 17.5 days compared with 7.9 days in the placebo group, findings that were statistically significant.

Some adverse effects participants experienced while taking metformin during their pregnancy included diarrhea and an increase in nausea.

Although the study is important in maternal-fetal medicine and is a novel approach to preterm preeclampsia, the findings weren’t strong enough, but they point to the need for further study, said Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy who was not involved in the study.

“Even though they did have an improved outcome, it wasn’t strong enough. It wasn’t long enough to prove that the medicine was useful or efficacious,” said Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, New York.

Metformin is also used to treat gestational diabetes, which is an “advantage of repurposing the drug is that it is likely to be safe,” the researchers wrote. They said longer term follow-up data might be worthwhile in future trials.

None of the experts had conflicts of interest to disclose.

*This story was updated on 10/6/2021.

New evidence suggests a drug used to lower blood sugar levels may also help extend the duration of preterm pregnancies in women with preeclampsia.

The findings from a small clinical trial, published Sept. 23 in the BMJ, showed that pregnant women who received the diabetes medication metformin prolonged their pregnancy by a week compared to those who received a placebo. Although this finding was not statistically significant, researchers said they are “cautiously optimistic” about the treatment of preterm preeclampsia.

“We hope that it will encourage others to test not only metformin but also other promising therapeutic candidates to treat and prevent preeclampsia,” study author Catherine Cluver, MBChB, FCOG, PhD, associate professor in the department of obstetrics and gynecology at Stellenbosch University in South Africa, said in an interview.

Preeclampsia, a condition that occurs about 1 in 25 pregnancies in the United States, happens when a woman develops high blood pressure and protein in her urine, according to the Centers for Disease Control and Prevention.

Preterm preeclampsia is a severe variant affecting 0.5% of all pregnancies, or 10% of those with preeclampsia, researchers wrote in the study. The condition is associated with more maternal and neonatal death and increases their risks of developing an illness.

Dr. Cluver said that when a mother develops preeclampsia, the lining of her blood vessels, or the endothelium, is affected and there are specific proteins in the blood that increase. Dr. Cluver’s preclinical study found that metformin improved endothelial function and decreased these biomarkers in laboratory work.

“We therefore set out to see if metformin could be used to prolong gestation in preterm preeclampsia,” she said.

For the study, Dr. Cluver and colleagues performed a double-blind, placebo-controlled clinical trial to compare the prolongation of pregnancies among women who were at least 26 months pregnant with preterm preeclampsia. They were treated with either 3 grams of extended-release metformin (90 women), or a matching placebo (90 women).*

In the treatment group, the average time from the start of the study to delivery was 17.7 days, compared to 10.1 days in the placebo group. The median difference was 7.6 days.

The researchers also found that 40% of women in the metformin group reached 34 weeks’ gestation compared with 28% of those in the placebo group. Fewer women in the metformin group delivered because of fetal indications such as fetal distress or other issues – 33% vs. 44%. However, the researchers said those results were not statistically significant.

They said they were cautiously optimistic when they found that the median time for prolongation of pregnancy in the metformin group was 17.5 days compared with 7.9 days in the placebo group, findings that were statistically significant.

Some adverse effects participants experienced while taking metformin during their pregnancy included diarrhea and an increase in nausea.

Although the study is important in maternal-fetal medicine and is a novel approach to preterm preeclampsia, the findings weren’t strong enough, but they point to the need for further study, said Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy who was not involved in the study.

“Even though they did have an improved outcome, it wasn’t strong enough. It wasn’t long enough to prove that the medicine was useful or efficacious,” said Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, New York.

Metformin is also used to treat gestational diabetes, which is an “advantage of repurposing the drug is that it is likely to be safe,” the researchers wrote. They said longer term follow-up data might be worthwhile in future trials.

None of the experts had conflicts of interest to disclose.

*This story was updated on 10/6/2021.

New evidence suggests a drug used to lower blood sugar levels may also help extend the duration of preterm pregnancies in women with preeclampsia.

The findings from a small clinical trial, published Sept. 23 in the BMJ, showed that pregnant women who received the diabetes medication metformin prolonged their pregnancy by a week compared to those who received a placebo. Although this finding was not statistically significant, researchers said they are “cautiously optimistic” about the treatment of preterm preeclampsia.

“We hope that it will encourage others to test not only metformin but also other promising therapeutic candidates to treat and prevent preeclampsia,” study author Catherine Cluver, MBChB, FCOG, PhD, associate professor in the department of obstetrics and gynecology at Stellenbosch University in South Africa, said in an interview.

Preeclampsia, a condition that occurs about 1 in 25 pregnancies in the United States, happens when a woman develops high blood pressure and protein in her urine, according to the Centers for Disease Control and Prevention.

Preterm preeclampsia is a severe variant affecting 0.5% of all pregnancies, or 10% of those with preeclampsia, researchers wrote in the study. The condition is associated with more maternal and neonatal death and increases their risks of developing an illness.

Dr. Cluver said that when a mother develops preeclampsia, the lining of her blood vessels, or the endothelium, is affected and there are specific proteins in the blood that increase. Dr. Cluver’s preclinical study found that metformin improved endothelial function and decreased these biomarkers in laboratory work.

“We therefore set out to see if metformin could be used to prolong gestation in preterm preeclampsia,” she said.

For the study, Dr. Cluver and colleagues performed a double-blind, placebo-controlled clinical trial to compare the prolongation of pregnancies among women who were at least 26 months pregnant with preterm preeclampsia. They were treated with either 3 grams of extended-release metformin (90 women), or a matching placebo (90 women).*

In the treatment group, the average time from the start of the study to delivery was 17.7 days, compared to 10.1 days in the placebo group. The median difference was 7.6 days.

The researchers also found that 40% of women in the metformin group reached 34 weeks’ gestation compared with 28% of those in the placebo group. Fewer women in the metformin group delivered because of fetal indications such as fetal distress or other issues – 33% vs. 44%. However, the researchers said those results were not statistically significant.

They said they were cautiously optimistic when they found that the median time for prolongation of pregnancy in the metformin group was 17.5 days compared with 7.9 days in the placebo group, findings that were statistically significant.

Some adverse effects participants experienced while taking metformin during their pregnancy included diarrhea and an increase in nausea.

Although the study is important in maternal-fetal medicine and is a novel approach to preterm preeclampsia, the findings weren’t strong enough, but they point to the need for further study, said Victor Klein, MD, MBA, CPHRM, a specialist in high-risk pregnancy who was not involved in the study.

“Even though they did have an improved outcome, it wasn’t strong enough. It wasn’t long enough to prove that the medicine was useful or efficacious,” said Dr. Klein, vice chairman of obstetrics and gynecology at North Shore University Hospital, New York.

Metformin is also used to treat gestational diabetes, which is an “advantage of repurposing the drug is that it is likely to be safe,” the researchers wrote. They said longer term follow-up data might be worthwhile in future trials.

None of the experts had conflicts of interest to disclose.

*This story was updated on 10/6/2021.

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Bariatric surgery is associated with a reduction in risk of major adverse cardiac events (MACE), and Roux-en-Y gastric bypass (RYGB) is linked to a greater reduction than sleeve gastrectomy (SG).

Those are the key findings of a retrospective analysis of a large group of patients who received care at the Cleveland Clinic between 1998 and 2017. MACE is defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality.

“I think what it tells us is that, in making these choices and in counseling patients about the potential advantages of undergoing bariatric surgery for their obesity and diabetes, that they should know that they’re more likely to be protected by a Roux-en-Y gastric bypass, although certainly sleeve gastrectomy is effective,” said study coauthor Steven E. Nissen, MD, who is the chief academic officer of the Heart and Vascular Institute at the Cleveland Clinic.

Previous studies have shown a benefit to metabolic surgery in patients with type 2 diabetes and obesity, improving diabetes control and altering cardiometabolic risk factors. Others have shown a link between surgery and reduced mortality. Most studies examined the impact of RYGB. SG is a newer procedure, but its relative simplicity and lower complication rate have helped it become the most commonly performed metabolic surgery in the world.

“There was no study to compare gastric bypass and sleeve gastrectomy head to head in terms of reduction in risk of cardiovascular disease. There are studies comparing these two procedures for diabetes control and weight loss, but not specifically in terms of effects on their risk of developing cardiovascular disease. That’s the unique feature of this study,” said lead author Ali Aminian, MD, who is director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

The researchers included 2,287 adults with type 2 diabetes and a body mass index of at least 30 kg/m², with no history of solid organ transplant, severe heart failure, or active cancer. 1,362 underwent RYGB, and 693 SG. Outcomes were compared with 11,435 matched nonsurgical patients.

At 5 years, 13.7% of the RYGB group experienced a MACE (95% confidence interval, 11.4-15.9), compared with 24.7% of the SG group for a relative reduction of 33% (95% CI, 19.0-30.0; adjusted hazard ratio, 0.77; P = .035). The nonsurgical group had a 5-year MACE incidence of 30.4% (95% CI, 29.4-31.5). Compared with usual care, the risk of MACE was lower in both the RYGB group (HR, 0.53; P < .001) and the SG group (HR, 0.69; P < .001). The researchers also analyzed the cumulative incidence of all-cause mortality, myocardial infarction, and ischemic stroke (three-component MACE) at 5 years. The cumulative incidence of three-component MACE at 5 years was 15.5% in the usual care group, 6.4% in the RYGB group (HR, 0.53 versus usual care; P < .001) and 11.8% in the SG group (HR vs. usual care, 0.65; P = .006).

The RYGB group had less nephropathy at 5 years (2.8% vs. 8.3%; HR, 0.47; P = .005), and experienced a greater reduction in weight, glycated hemoglobin, and diabetes and cardiovascular medication use. At 5 years, RYGB was associated with a higher frequency of upper endoscopy (45.8% vs. 35.6%, P < .001) and abdominal surgical procedures (10.8% vs. 5.4%, P = .001), compared with SG.

“Both procedures are extremely safe and extremely effective,” said Dr. Aminian. He pointed out the need to consider multiple factors when choosing between the procedures, including overall health, weight, comorbidities, and the patient’s values and goals.

A few factors may be contraindicated for one procedure or another. The sleeve may worsen severe reflux disease, while the gastric bypass may interfere more with absorption of psychiatric medications. Some patients may have multiple comorbidities that could point to a less risky procedure. “Decision-making should not be solely based on findings of this study. All these conditions need to be considered when patients and surgeons make a final decision about the most appropriate procedure,” said Dr. Aminian.

Dr. Nissen noted that the associations were wide ranging, including classic outcomes like death, stroke, and heart failure, but also extending to heart failure, coronary events, cerebral vascular events, nephropathy, and atrial fibrillation. “I found the nephropathy results to be amongst the most striking, that Roux-en-Y really dramatically reduced the risk of neuropathy,” he added. That’s a particularly important point because end-stage renal disease is a common cause of diabetes mortality.

Dr. Nissen acknowledged the limitations of the retrospective nature of the study, though he feels confident that the relationships are causal. “Bariatric surgery desperately needs a randomized, controlled trial, where both groups get intensive dietary and lifestyle counseling, but one group gets metabolic surgery and the other doesn’t. Given the dramatic effects in diabetic patients of reducing their hemoglobin A1c in a sustained way, reducing their body weight. We think these are very strong data to suggest that we have a major reduction in all the endpoints. If we’re right about this, the randomized controlled trial will show that dramatic effect, and will convince even the skeptics that metabolic surgery is the best way to go.”

Bariatric surgery is associated with a reduction in risk of major adverse cardiac events (MACE), and Roux-en-Y gastric bypass (RYGB) is linked to a greater reduction than sleeve gastrectomy (SG).

Those are the key findings of a retrospective analysis of a large group of patients who received care at the Cleveland Clinic between 1998 and 2017. MACE is defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality.

“I think what it tells us is that, in making these choices and in counseling patients about the potential advantages of undergoing bariatric surgery for their obesity and diabetes, that they should know that they’re more likely to be protected by a Roux-en-Y gastric bypass, although certainly sleeve gastrectomy is effective,” said study coauthor Steven E. Nissen, MD, who is the chief academic officer of the Heart and Vascular Institute at the Cleveland Clinic.

Previous studies have shown a benefit to metabolic surgery in patients with type 2 diabetes and obesity, improving diabetes control and altering cardiometabolic risk factors. Others have shown a link between surgery and reduced mortality. Most studies examined the impact of RYGB. SG is a newer procedure, but its relative simplicity and lower complication rate have helped it become the most commonly performed metabolic surgery in the world.

“There was no study to compare gastric bypass and sleeve gastrectomy head to head in terms of reduction in risk of cardiovascular disease. There are studies comparing these two procedures for diabetes control and weight loss, but not specifically in terms of effects on their risk of developing cardiovascular disease. That’s the unique feature of this study,” said lead author Ali Aminian, MD, who is director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

The researchers included 2,287 adults with type 2 diabetes and a body mass index of at least 30 kg/m², with no history of solid organ transplant, severe heart failure, or active cancer. 1,362 underwent RYGB, and 693 SG. Outcomes were compared with 11,435 matched nonsurgical patients.

At 5 years, 13.7% of the RYGB group experienced a MACE (95% confidence interval, 11.4-15.9), compared with 24.7% of the SG group for a relative reduction of 33% (95% CI, 19.0-30.0; adjusted hazard ratio, 0.77; P = .035). The nonsurgical group had a 5-year MACE incidence of 30.4% (95% CI, 29.4-31.5). Compared with usual care, the risk of MACE was lower in both the RYGB group (HR, 0.53; P < .001) and the SG group (HR, 0.69; P < .001). The researchers also analyzed the cumulative incidence of all-cause mortality, myocardial infarction, and ischemic stroke (three-component MACE) at 5 years. The cumulative incidence of three-component MACE at 5 years was 15.5% in the usual care group, 6.4% in the RYGB group (HR, 0.53 versus usual care; P < .001) and 11.8% in the SG group (HR vs. usual care, 0.65; P = .006).

The RYGB group had less nephropathy at 5 years (2.8% vs. 8.3%; HR, 0.47; P = .005), and experienced a greater reduction in weight, glycated hemoglobin, and diabetes and cardiovascular medication use. At 5 years, RYGB was associated with a higher frequency of upper endoscopy (45.8% vs. 35.6%, P < .001) and abdominal surgical procedures (10.8% vs. 5.4%, P = .001), compared with SG.

“Both procedures are extremely safe and extremely effective,” said Dr. Aminian. He pointed out the need to consider multiple factors when choosing between the procedures, including overall health, weight, comorbidities, and the patient’s values and goals.

A few factors may be contraindicated for one procedure or another. The sleeve may worsen severe reflux disease, while the gastric bypass may interfere more with absorption of psychiatric medications. Some patients may have multiple comorbidities that could point to a less risky procedure. “Decision-making should not be solely based on findings of this study. All these conditions need to be considered when patients and surgeons make a final decision about the most appropriate procedure,” said Dr. Aminian.

Dr. Nissen noted that the associations were wide ranging, including classic outcomes like death, stroke, and heart failure, but also extending to heart failure, coronary events, cerebral vascular events, nephropathy, and atrial fibrillation. “I found the nephropathy results to be amongst the most striking, that Roux-en-Y really dramatically reduced the risk of neuropathy,” he added. That’s a particularly important point because end-stage renal disease is a common cause of diabetes mortality.

Dr. Nissen acknowledged the limitations of the retrospective nature of the study, though he feels confident that the relationships are causal. “Bariatric surgery desperately needs a randomized, controlled trial, where both groups get intensive dietary and lifestyle counseling, but one group gets metabolic surgery and the other doesn’t. Given the dramatic effects in diabetic patients of reducing their hemoglobin A1c in a sustained way, reducing their body weight. We think these are very strong data to suggest that we have a major reduction in all the endpoints. If we’re right about this, the randomized controlled trial will show that dramatic effect, and will convince even the skeptics that metabolic surgery is the best way to go.”

Bariatric surgery is associated with a reduction in risk of major adverse cardiac events (MACE), and Roux-en-Y gastric bypass (RYGB) is linked to a greater reduction than sleeve gastrectomy (SG).

Those are the key findings of a retrospective analysis of a large group of patients who received care at the Cleveland Clinic between 1998 and 2017. MACE is defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality.

“I think what it tells us is that, in making these choices and in counseling patients about the potential advantages of undergoing bariatric surgery for their obesity and diabetes, that they should know that they’re more likely to be protected by a Roux-en-Y gastric bypass, although certainly sleeve gastrectomy is effective,” said study coauthor Steven E. Nissen, MD, who is the chief academic officer of the Heart and Vascular Institute at the Cleveland Clinic.

Previous studies have shown a benefit to metabolic surgery in patients with type 2 diabetes and obesity, improving diabetes control and altering cardiometabolic risk factors. Others have shown a link between surgery and reduced mortality. Most studies examined the impact of RYGB. SG is a newer procedure, but its relative simplicity and lower complication rate have helped it become the most commonly performed metabolic surgery in the world.

“There was no study to compare gastric bypass and sleeve gastrectomy head to head in terms of reduction in risk of cardiovascular disease. There are studies comparing these two procedures for diabetes control and weight loss, but not specifically in terms of effects on their risk of developing cardiovascular disease. That’s the unique feature of this study,” said lead author Ali Aminian, MD, who is director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

The researchers included 2,287 adults with type 2 diabetes and a body mass index of at least 30 kg/m², with no history of solid organ transplant, severe heart failure, or active cancer. 1,362 underwent RYGB, and 693 SG. Outcomes were compared with 11,435 matched nonsurgical patients.

At 5 years, 13.7% of the RYGB group experienced a MACE (95% confidence interval, 11.4-15.9), compared with 24.7% of the SG group for a relative reduction of 33% (95% CI, 19.0-30.0; adjusted hazard ratio, 0.77; P = .035). The nonsurgical group had a 5-year MACE incidence of 30.4% (95% CI, 29.4-31.5). Compared with usual care, the risk of MACE was lower in both the RYGB group (HR, 0.53; P < .001) and the SG group (HR, 0.69; P < .001). The researchers also analyzed the cumulative incidence of all-cause mortality, myocardial infarction, and ischemic stroke (three-component MACE) at 5 years. The cumulative incidence of three-component MACE at 5 years was 15.5% in the usual care group, 6.4% in the RYGB group (HR, 0.53 versus usual care; P < .001) and 11.8% in the SG group (HR vs. usual care, 0.65; P = .006).

The RYGB group had less nephropathy at 5 years (2.8% vs. 8.3%; HR, 0.47; P = .005), and experienced a greater reduction in weight, glycated hemoglobin, and diabetes and cardiovascular medication use. At 5 years, RYGB was associated with a higher frequency of upper endoscopy (45.8% vs. 35.6%, P < .001) and abdominal surgical procedures (10.8% vs. 5.4%, P = .001), compared with SG.

“Both procedures are extremely safe and extremely effective,” said Dr. Aminian. He pointed out the need to consider multiple factors when choosing between the procedures, including overall health, weight, comorbidities, and the patient’s values and goals.

A few factors may be contraindicated for one procedure or another. The sleeve may worsen severe reflux disease, while the gastric bypass may interfere more with absorption of psychiatric medications. Some patients may have multiple comorbidities that could point to a less risky procedure. “Decision-making should not be solely based on findings of this study. All these conditions need to be considered when patients and surgeons make a final decision about the most appropriate procedure,” said Dr. Aminian.

Dr. Nissen noted that the associations were wide ranging, including classic outcomes like death, stroke, and heart failure, but also extending to heart failure, coronary events, cerebral vascular events, nephropathy, and atrial fibrillation. “I found the nephropathy results to be amongst the most striking, that Roux-en-Y really dramatically reduced the risk of neuropathy,” he added. That’s a particularly important point because end-stage renal disease is a common cause of diabetes mortality.

Dr. Nissen acknowledged the limitations of the retrospective nature of the study, though he feels confident that the relationships are causal. “Bariatric surgery desperately needs a randomized, controlled trial, where both groups get intensive dietary and lifestyle counseling, but one group gets metabolic surgery and the other doesn’t. Given the dramatic effects in diabetic patients of reducing their hemoglobin A1c in a sustained way, reducing their body weight. We think these are very strong data to suggest that we have a major reduction in all the endpoints. If we’re right about this, the randomized controlled trial will show that dramatic effect, and will convince even the skeptics that metabolic surgery is the best way to go.”

The new guideline on management of heart failure (HF) from the European Society of Cardiology seemed to bear an asterisk or footnote even before its full unveiling in the early hours of ESC Congress 2021.

frankpeters/Getty Images

The document would offer little new in the arena of HF with preserved ejection fraction (HFpEF), so understandably the fast-approaching presentation of a major HFpEF trial – arguably the conference’s marquee event – would feel to some like the elephant in the room.

“I’d like to highlight this unfortunate timing of the guideline, because it’s an hour or 2 before we hear the full story from EMPEROR-Preserved, which I’m sure will change the guidelines,” Faiez Zannad, MD, PhD, University of Lorraine, Vandoeuvre-Les-Nancy, France, said wryly.

Anticipation of the trial’s full presentation was intense as the ESC congress got underway, in part because the top-line and incomplete message from EMPEROR-Preserved had already been released: Patients with HFpEF treated with the sodium-glucose cotransporter 2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) showed a significant benefit for the primary endpoint of cardiovascular (CV) death or HF hospitalization.

Although empagliflozin is the first medication to achieve that status in a major HFpEF trial, conspicuously absent from the early announcement were the magnitude of “benefit” and any data. Still, the tantalizing top-line results mean that technically, at least, “we have a drug which is effective in reduced and preserved ejection fraction,” Dr. Zannad said.

But the new guideline, published online Aug. 27, 2021, in the European Heart Journal and comprehensively described that day at the congress, was never really expected to consider results from EMPEROR-Reduced. “These new indications do need to go through the regulatory authorities,” such as the European Medicines Agency and the U.S. Food and Drug Administration, observed Carlos Aguiar, MD, Hospital Santa Cruz, Carnaxide, Portugal.

“It does take some time for the whole process to be concluded and, finally, as physicians, being able to implement it in clinical practice,” Dr. Aguiar said as moderator of press briefing prior to the ESC congress.

The ESC guideline’s next iteration or update could well include an SGLT2 inhibitor recommendation that applies beyond the ejection fraction limits of HFrEF. Still, the document summarized that day reflects a number of pivotal concepts with profound treatment implications. Among them are the field’s latest paradigm for medical therapy of HFrEF and the increasingly accepted division of traditional HFpEF into two entities: HF with mildly reduced ejection fraction (HFmrEF); and HFpEF, with its left ventricular ejection fraction (LVEF) threshold raised to 50%.

In fact, HFmrEF in the new document is a drug-therapy indication that barely existed a few years ago but grew in prominence after secondary findings from trials like TOPCAT for spironolactone and PARAGON-HF for sacubitril-valsartan (Entresto, Novartis), an angiotensin-receptor/neprilysin inhibitor (ARNI). Still, the HFmrEF recommendations come with different class and level-of-evidence designations.

Those new guideline features and others in the realm of pharmacologic therapy were summarized by the document’s authors at the 2021 Heart Failure Association of the European Society of Cardiology (ESC-HFA) meeting, and covered at the time by this news organization

The ‘fantastic four’

One of the document’s central recommendations specifies which contemporary drug classes should be initiated, and when, in patients with HFrEF. An ACE inhibitor or ARNI, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor collectively earned a class I recommendation, “given the importance of these key HFrEF therapies, some of which have been shown to improve outcomes within a month of initiation,” observed Roy S. Gardner, MBChB, MD.

An agent from each of the four classes is to be “commenced and up-titrated as quickly and as safely as possible, whilst using the lowest effective dose of loop diuretic to relieve congestion,” said Dr. Gardner, from Golden Jubilee National Hospital, Clydebank, Scotland, when presenting the full HFrEF portion of the guidelines.

The oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo, Merck), which recently emerged from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization, gained a class IIb recommendation.

The document’s “simplified algorithm” for managing such patients overall and the advent of SGLT2 inhibitors are new twists in ESC guidelines for HF. But the way the four drug classes are started in patients is key and could take some practitioners time to get used to. There is no prespecified order of initiation.

“We’ve left the door open for clinicians to evaluate the evidence to make sure these four drugs are started, and to tailor how to do it according to the patient,” based on clinical considerations such as blood pressure or renal function, said Theresa A. McDonagh, MD, King’s College London, cochair of the guideline task force.

“The SGLT2 inhibitor trials were done on top of therapy with ACE inhibitors or ARNI, beta-blockers, and MRAs, so some people no doubt will choose to follow a sequenced approach,” Dr. McDonagh said. Other practitioners will consider each patient and attempt to get all four started “as quickly and safely as possible based on the phenotype.”

Importantly, clinicians “should not wait for weeks, months, or years until you have the four drugs in the patient, but you should do this within weeks,” cautioned Johann Bauersachs, MD, Hannover (Germany) Medical School, a discussant for the guideline presentation who is listed as a reviewer on the document.

Although angiotensin-receptor blockers (ARBs) and ACE inhibitors are sometimes thought of as interchangeable, the new guideline does not give them the same weight. “The angiotensin-receptor blocker valsartan is a constituent of the ARNI,” Dr. McDonagh noted. “So, the place of ARBs in heart failure has been downgraded in HFrEF. They are really for those who are intolerant of an ACE inhibitor or an ARNI.”

In practice, ARBs are likely to be used as first-line therapy in some circumstances, observed Dr. Bauersachs. They are “the default option in, unfortunately, many low-income countries that may not afford sacubitril-valsartan. And I know that there are many of them.”
 

Tweaks to device recommendations

The new document contains several new wrinkles in the recommendations for HF device therapy, which should usually be considered only if still appropriate after at least 3 months of optimal medical therapy, Dr. Gardner said.

For example, use of an implantable cardioverter-defibrillator (ICD) has been demoted from its previous class I recommendation to class II, level of evidence A, in patients with nonischemic cardiomyopathy “in light of the data from the DANISH study,” Dr. Gardner said.

The 2016 DANISH trial was noteworthy for questioning the survival benefits of ICDs in patients with nonischemic cardiomyopathy, whether or not they were also receiving cardiac resynchronization therapy (CRT).

The new document also puts greater emphasis on a range of specific CRT patient-selection criteria. Beyond the conventional recommended standards of an LVEF of 35% or less, QRS of at least 150 ms, and left-bundle-branch block on optimal meds, consideration can be given to CRT if the QRS is only 130 ms or greater. “And where it’s appropriate to do so, an ICD could be an option,” Dr. Gardner said.

It also recommends CRT as a replacement for right ventricular pacing in patients with high-degree atrioventricular block. “And this, for the first time, includes patients with atrial fibrillation,” he said. “The previous indications for CRT were in individuals in sinus rhythm.”

The new document recommends that HF in any patient be classified as HFrEF, defined by an LVEF of ≤40%; HFmrEF, defined by an LVEF of 41%-49%; or HFpEF, defined by an LVEF of at least 50%. “Importantly, for all forms, the presence of the clinical syndrome of heart failure is a prerequisite,” observed Carolyn S.P. Lam, MBBS, PhD, Duke-NUS Graduate Medical School, Singapore, at the presentation.

In a critical update from previous guidelines, the term HF with “mid-range” ejection fraction was replaced by the term specifying “mildly reduced” ejection fraction, Dr. Lam noted. The shift retains the acronym but now reflects growing appreciation that HFmrEF patients can benefit from treatments also used in HFrEF, including ACE inhibitors, ARBs, beta-blockers, MRAs, and sacubitril-valsartan, she said.

Support for that relationship comes largely from post hoc subgroup analyses of trials that featured some patients with LVEF 40%-49%. That includes most HFpEF trials represented in the guideline document, but also EMPEROR-Preserved, which saw gains for the primary outcome across the entire range of LVEF above 40%.

The LVEF-based definitions are consistent with a recent HF classification proposal endorsed by the ESC and subspecialty societies in Europe, North America, Japan, India, Australia, New Zealand, and China.

The document doesn’t update recommendations for HFpEF, in which “no treatment has been shown to convincingly reduce mortality or morbidity,” Dr. Lam observed. Still, she noted, the guideline task force “acknowledges that treatment options for HFpEF are being revised even as the guidelines have been published.”

That could be a reference to empagliflozin in EMPEROR-Preserved, but it also refers to the strikingly broad wording of an expanded indication for sacubitril-valsartan in the United States – “to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure” – without specific restrictions on the basis of LVEF. The new indication was announced in early 2021, too late to be considered in the new guidelines.
 

Whither LVEF-based definitions?

During discussion after the guideline presentation, Dr. Zannad speculated on the future of HF classifications based on ventricular function, given trial evidence in recent years that some agents – notably spironolactone, sacubitril-valsartan, and now, apparently, empagliflozin – might be effective in HFpEF as well as HFrEF.

Will the field continue with “LVEF-centric” distinctions across the range of HF, or transition to “some definition in which drug therapies can be used independently across the full spectrum of ejection fraction?” Dr. Zannad posed.

“I think we need to wait and see what some of these trials with the SGLT2 inhibitors are going to show in heart failure with preserved ejection fraction,” Dr. McDonagh replied. “And I think that will be a step for the next guideline, completely redefining heart failure.”

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

The new guideline on management of heart failure (HF) from the European Society of Cardiology seemed to bear an asterisk or footnote even before its full unveiling in the early hours of ESC Congress 2021.

frankpeters/Getty Images

The document would offer little new in the arena of HF with preserved ejection fraction (HFpEF), so understandably the fast-approaching presentation of a major HFpEF trial – arguably the conference’s marquee event – would feel to some like the elephant in the room.

“I’d like to highlight this unfortunate timing of the guideline, because it’s an hour or 2 before we hear the full story from EMPEROR-Preserved, which I’m sure will change the guidelines,” Faiez Zannad, MD, PhD, University of Lorraine, Vandoeuvre-Les-Nancy, France, said wryly.

Anticipation of the trial’s full presentation was intense as the ESC congress got underway, in part because the top-line and incomplete message from EMPEROR-Preserved had already been released: Patients with HFpEF treated with the sodium-glucose cotransporter 2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) showed a significant benefit for the primary endpoint of cardiovascular (CV) death or HF hospitalization.

Although empagliflozin is the first medication to achieve that status in a major HFpEF trial, conspicuously absent from the early announcement were the magnitude of “benefit” and any data. Still, the tantalizing top-line results mean that technically, at least, “we have a drug which is effective in reduced and preserved ejection fraction,” Dr. Zannad said.

But the new guideline, published online Aug. 27, 2021, in the European Heart Journal and comprehensively described that day at the congress, was never really expected to consider results from EMPEROR-Reduced. “These new indications do need to go through the regulatory authorities,” such as the European Medicines Agency and the U.S. Food and Drug Administration, observed Carlos Aguiar, MD, Hospital Santa Cruz, Carnaxide, Portugal.

“It does take some time for the whole process to be concluded and, finally, as physicians, being able to implement it in clinical practice,” Dr. Aguiar said as moderator of press briefing prior to the ESC congress.

The ESC guideline’s next iteration or update could well include an SGLT2 inhibitor recommendation that applies beyond the ejection fraction limits of HFrEF. Still, the document summarized that day reflects a number of pivotal concepts with profound treatment implications. Among them are the field’s latest paradigm for medical therapy of HFrEF and the increasingly accepted division of traditional HFpEF into two entities: HF with mildly reduced ejection fraction (HFmrEF); and HFpEF, with its left ventricular ejection fraction (LVEF) threshold raised to 50%.

In fact, HFmrEF in the new document is a drug-therapy indication that barely existed a few years ago but grew in prominence after secondary findings from trials like TOPCAT for spironolactone and PARAGON-HF for sacubitril-valsartan (Entresto, Novartis), an angiotensin-receptor/neprilysin inhibitor (ARNI). Still, the HFmrEF recommendations come with different class and level-of-evidence designations.

Those new guideline features and others in the realm of pharmacologic therapy were summarized by the document’s authors at the 2021 Heart Failure Association of the European Society of Cardiology (ESC-HFA) meeting, and covered at the time by this news organization

The ‘fantastic four’

One of the document’s central recommendations specifies which contemporary drug classes should be initiated, and when, in patients with HFrEF. An ACE inhibitor or ARNI, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor collectively earned a class I recommendation, “given the importance of these key HFrEF therapies, some of which have been shown to improve outcomes within a month of initiation,” observed Roy S. Gardner, MBChB, MD.

An agent from each of the four classes is to be “commenced and up-titrated as quickly and as safely as possible, whilst using the lowest effective dose of loop diuretic to relieve congestion,” said Dr. Gardner, from Golden Jubilee National Hospital, Clydebank, Scotland, when presenting the full HFrEF portion of the guidelines.

The oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo, Merck), which recently emerged from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization, gained a class IIb recommendation.

The document’s “simplified algorithm” for managing such patients overall and the advent of SGLT2 inhibitors are new twists in ESC guidelines for HF. But the way the four drug classes are started in patients is key and could take some practitioners time to get used to. There is no prespecified order of initiation.

“We’ve left the door open for clinicians to evaluate the evidence to make sure these four drugs are started, and to tailor how to do it according to the patient,” based on clinical considerations such as blood pressure or renal function, said Theresa A. McDonagh, MD, King’s College London, cochair of the guideline task force.

“The SGLT2 inhibitor trials were done on top of therapy with ACE inhibitors or ARNI, beta-blockers, and MRAs, so some people no doubt will choose to follow a sequenced approach,” Dr. McDonagh said. Other practitioners will consider each patient and attempt to get all four started “as quickly and safely as possible based on the phenotype.”

Importantly, clinicians “should not wait for weeks, months, or years until you have the four drugs in the patient, but you should do this within weeks,” cautioned Johann Bauersachs, MD, Hannover (Germany) Medical School, a discussant for the guideline presentation who is listed as a reviewer on the document.

Although angiotensin-receptor blockers (ARBs) and ACE inhibitors are sometimes thought of as interchangeable, the new guideline does not give them the same weight. “The angiotensin-receptor blocker valsartan is a constituent of the ARNI,” Dr. McDonagh noted. “So, the place of ARBs in heart failure has been downgraded in HFrEF. They are really for those who are intolerant of an ACE inhibitor or an ARNI.”

In practice, ARBs are likely to be used as first-line therapy in some circumstances, observed Dr. Bauersachs. They are “the default option in, unfortunately, many low-income countries that may not afford sacubitril-valsartan. And I know that there are many of them.”
 

Tweaks to device recommendations

The new document contains several new wrinkles in the recommendations for HF device therapy, which should usually be considered only if still appropriate after at least 3 months of optimal medical therapy, Dr. Gardner said.

For example, use of an implantable cardioverter-defibrillator (ICD) has been demoted from its previous class I recommendation to class II, level of evidence A, in patients with nonischemic cardiomyopathy “in light of the data from the DANISH study,” Dr. Gardner said.

The 2016 DANISH trial was noteworthy for questioning the survival benefits of ICDs in patients with nonischemic cardiomyopathy, whether or not they were also receiving cardiac resynchronization therapy (CRT).

The new document also puts greater emphasis on a range of specific CRT patient-selection criteria. Beyond the conventional recommended standards of an LVEF of 35% or less, QRS of at least 150 ms, and left-bundle-branch block on optimal meds, consideration can be given to CRT if the QRS is only 130 ms or greater. “And where it’s appropriate to do so, an ICD could be an option,” Dr. Gardner said.

It also recommends CRT as a replacement for right ventricular pacing in patients with high-degree atrioventricular block. “And this, for the first time, includes patients with atrial fibrillation,” he said. “The previous indications for CRT were in individuals in sinus rhythm.”

The new document recommends that HF in any patient be classified as HFrEF, defined by an LVEF of ≤40%; HFmrEF, defined by an LVEF of 41%-49%; or HFpEF, defined by an LVEF of at least 50%. “Importantly, for all forms, the presence of the clinical syndrome of heart failure is a prerequisite,” observed Carolyn S.P. Lam, MBBS, PhD, Duke-NUS Graduate Medical School, Singapore, at the presentation.

In a critical update from previous guidelines, the term HF with “mid-range” ejection fraction was replaced by the term specifying “mildly reduced” ejection fraction, Dr. Lam noted. The shift retains the acronym but now reflects growing appreciation that HFmrEF patients can benefit from treatments also used in HFrEF, including ACE inhibitors, ARBs, beta-blockers, MRAs, and sacubitril-valsartan, she said.

Support for that relationship comes largely from post hoc subgroup analyses of trials that featured some patients with LVEF 40%-49%. That includes most HFpEF trials represented in the guideline document, but also EMPEROR-Preserved, which saw gains for the primary outcome across the entire range of LVEF above 40%.

The LVEF-based definitions are consistent with a recent HF classification proposal endorsed by the ESC and subspecialty societies in Europe, North America, Japan, India, Australia, New Zealand, and China.

The document doesn’t update recommendations for HFpEF, in which “no treatment has been shown to convincingly reduce mortality or morbidity,” Dr. Lam observed. Still, she noted, the guideline task force “acknowledges that treatment options for HFpEF are being revised even as the guidelines have been published.”

That could be a reference to empagliflozin in EMPEROR-Preserved, but it also refers to the strikingly broad wording of an expanded indication for sacubitril-valsartan in the United States – “to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure” – without specific restrictions on the basis of LVEF. The new indication was announced in early 2021, too late to be considered in the new guidelines.
 

Whither LVEF-based definitions?

During discussion after the guideline presentation, Dr. Zannad speculated on the future of HF classifications based on ventricular function, given trial evidence in recent years that some agents – notably spironolactone, sacubitril-valsartan, and now, apparently, empagliflozin – might be effective in HFpEF as well as HFrEF.

Will the field continue with “LVEF-centric” distinctions across the range of HF, or transition to “some definition in which drug therapies can be used independently across the full spectrum of ejection fraction?” Dr. Zannad posed.

“I think we need to wait and see what some of these trials with the SGLT2 inhibitors are going to show in heart failure with preserved ejection fraction,” Dr. McDonagh replied. “And I think that will be a step for the next guideline, completely redefining heart failure.”

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

The new guideline on management of heart failure (HF) from the European Society of Cardiology seemed to bear an asterisk or footnote even before its full unveiling in the early hours of ESC Congress 2021.

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The document would offer little new in the arena of HF with preserved ejection fraction (HFpEF), so understandably the fast-approaching presentation of a major HFpEF trial – arguably the conference’s marquee event – would feel to some like the elephant in the room.

“I’d like to highlight this unfortunate timing of the guideline, because it’s an hour or 2 before we hear the full story from EMPEROR-Preserved, which I’m sure will change the guidelines,” Faiez Zannad, MD, PhD, University of Lorraine, Vandoeuvre-Les-Nancy, France, said wryly.

Anticipation of the trial’s full presentation was intense as the ESC congress got underway, in part because the top-line and incomplete message from EMPEROR-Preserved had already been released: Patients with HFpEF treated with the sodium-glucose cotransporter 2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) showed a significant benefit for the primary endpoint of cardiovascular (CV) death or HF hospitalization.

Although empagliflozin is the first medication to achieve that status in a major HFpEF trial, conspicuously absent from the early announcement were the magnitude of “benefit” and any data. Still, the tantalizing top-line results mean that technically, at least, “we have a drug which is effective in reduced and preserved ejection fraction,” Dr. Zannad said.

But the new guideline, published online Aug. 27, 2021, in the European Heart Journal and comprehensively described that day at the congress, was never really expected to consider results from EMPEROR-Reduced. “These new indications do need to go through the regulatory authorities,” such as the European Medicines Agency and the U.S. Food and Drug Administration, observed Carlos Aguiar, MD, Hospital Santa Cruz, Carnaxide, Portugal.

“It does take some time for the whole process to be concluded and, finally, as physicians, being able to implement it in clinical practice,” Dr. Aguiar said as moderator of press briefing prior to the ESC congress.

The ESC guideline’s next iteration or update could well include an SGLT2 inhibitor recommendation that applies beyond the ejection fraction limits of HFrEF. Still, the document summarized that day reflects a number of pivotal concepts with profound treatment implications. Among them are the field’s latest paradigm for medical therapy of HFrEF and the increasingly accepted division of traditional HFpEF into two entities: HF with mildly reduced ejection fraction (HFmrEF); and HFpEF, with its left ventricular ejection fraction (LVEF) threshold raised to 50%.

In fact, HFmrEF in the new document is a drug-therapy indication that barely existed a few years ago but grew in prominence after secondary findings from trials like TOPCAT for spironolactone and PARAGON-HF for sacubitril-valsartan (Entresto, Novartis), an angiotensin-receptor/neprilysin inhibitor (ARNI). Still, the HFmrEF recommendations come with different class and level-of-evidence designations.

Those new guideline features and others in the realm of pharmacologic therapy were summarized by the document’s authors at the 2021 Heart Failure Association of the European Society of Cardiology (ESC-HFA) meeting, and covered at the time by this news organization

The ‘fantastic four’

One of the document’s central recommendations specifies which contemporary drug classes should be initiated, and when, in patients with HFrEF. An ACE inhibitor or ARNI, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor collectively earned a class I recommendation, “given the importance of these key HFrEF therapies, some of which have been shown to improve outcomes within a month of initiation,” observed Roy S. Gardner, MBChB, MD.

An agent from each of the four classes is to be “commenced and up-titrated as quickly and as safely as possible, whilst using the lowest effective dose of loop diuretic to relieve congestion,” said Dr. Gardner, from Golden Jubilee National Hospital, Clydebank, Scotland, when presenting the full HFrEF portion of the guidelines.

The oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo, Merck), which recently emerged from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization, gained a class IIb recommendation.

The document’s “simplified algorithm” for managing such patients overall and the advent of SGLT2 inhibitors are new twists in ESC guidelines for HF. But the way the four drug classes are started in patients is key and could take some practitioners time to get used to. There is no prespecified order of initiation.

“We’ve left the door open for clinicians to evaluate the evidence to make sure these four drugs are started, and to tailor how to do it according to the patient,” based on clinical considerations such as blood pressure or renal function, said Theresa A. McDonagh, MD, King’s College London, cochair of the guideline task force.

“The SGLT2 inhibitor trials were done on top of therapy with ACE inhibitors or ARNI, beta-blockers, and MRAs, so some people no doubt will choose to follow a sequenced approach,” Dr. McDonagh said. Other practitioners will consider each patient and attempt to get all four started “as quickly and safely as possible based on the phenotype.”

Importantly, clinicians “should not wait for weeks, months, or years until you have the four drugs in the patient, but you should do this within weeks,” cautioned Johann Bauersachs, MD, Hannover (Germany) Medical School, a discussant for the guideline presentation who is listed as a reviewer on the document.

Although angiotensin-receptor blockers (ARBs) and ACE inhibitors are sometimes thought of as interchangeable, the new guideline does not give them the same weight. “The angiotensin-receptor blocker valsartan is a constituent of the ARNI,” Dr. McDonagh noted. “So, the place of ARBs in heart failure has been downgraded in HFrEF. They are really for those who are intolerant of an ACE inhibitor or an ARNI.”

In practice, ARBs are likely to be used as first-line therapy in some circumstances, observed Dr. Bauersachs. They are “the default option in, unfortunately, many low-income countries that may not afford sacubitril-valsartan. And I know that there are many of them.”
 

Tweaks to device recommendations

The new document contains several new wrinkles in the recommendations for HF device therapy, which should usually be considered only if still appropriate after at least 3 months of optimal medical therapy, Dr. Gardner said.

For example, use of an implantable cardioverter-defibrillator (ICD) has been demoted from its previous class I recommendation to class II, level of evidence A, in patients with nonischemic cardiomyopathy “in light of the data from the DANISH study,” Dr. Gardner said.

The 2016 DANISH trial was noteworthy for questioning the survival benefits of ICDs in patients with nonischemic cardiomyopathy, whether or not they were also receiving cardiac resynchronization therapy (CRT).

The new document also puts greater emphasis on a range of specific CRT patient-selection criteria. Beyond the conventional recommended standards of an LVEF of 35% or less, QRS of at least 150 ms, and left-bundle-branch block on optimal meds, consideration can be given to CRT if the QRS is only 130 ms or greater. “And where it’s appropriate to do so, an ICD could be an option,” Dr. Gardner said.

It also recommends CRT as a replacement for right ventricular pacing in patients with high-degree atrioventricular block. “And this, for the first time, includes patients with atrial fibrillation,” he said. “The previous indications for CRT were in individuals in sinus rhythm.”

The new document recommends that HF in any patient be classified as HFrEF, defined by an LVEF of ≤40%; HFmrEF, defined by an LVEF of 41%-49%; or HFpEF, defined by an LVEF of at least 50%. “Importantly, for all forms, the presence of the clinical syndrome of heart failure is a prerequisite,” observed Carolyn S.P. Lam, MBBS, PhD, Duke-NUS Graduate Medical School, Singapore, at the presentation.

In a critical update from previous guidelines, the term HF with “mid-range” ejection fraction was replaced by the term specifying “mildly reduced” ejection fraction, Dr. Lam noted. The shift retains the acronym but now reflects growing appreciation that HFmrEF patients can benefit from treatments also used in HFrEF, including ACE inhibitors, ARBs, beta-blockers, MRAs, and sacubitril-valsartan, she said.

Support for that relationship comes largely from post hoc subgroup analyses of trials that featured some patients with LVEF 40%-49%. That includes most HFpEF trials represented in the guideline document, but also EMPEROR-Preserved, which saw gains for the primary outcome across the entire range of LVEF above 40%.

The LVEF-based definitions are consistent with a recent HF classification proposal endorsed by the ESC and subspecialty societies in Europe, North America, Japan, India, Australia, New Zealand, and China.

The document doesn’t update recommendations for HFpEF, in which “no treatment has been shown to convincingly reduce mortality or morbidity,” Dr. Lam observed. Still, she noted, the guideline task force “acknowledges that treatment options for HFpEF are being revised even as the guidelines have been published.”

That could be a reference to empagliflozin in EMPEROR-Preserved, but it also refers to the strikingly broad wording of an expanded indication for sacubitril-valsartan in the United States – “to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure” – without specific restrictions on the basis of LVEF. The new indication was announced in early 2021, too late to be considered in the new guidelines.
 

Whither LVEF-based definitions?

During discussion after the guideline presentation, Dr. Zannad speculated on the future of HF classifications based on ventricular function, given trial evidence in recent years that some agents – notably spironolactone, sacubitril-valsartan, and now, apparently, empagliflozin – might be effective in HFpEF as well as HFrEF.

Will the field continue with “LVEF-centric” distinctions across the range of HF, or transition to “some definition in which drug therapies can be used independently across the full spectrum of ejection fraction?” Dr. Zannad posed.

“I think we need to wait and see what some of these trials with the SGLT2 inhibitors are going to show in heart failure with preserved ejection fraction,” Dr. McDonagh replied. “And I think that will be a step for the next guideline, completely redefining heart failure.”

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