Hypertension

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

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..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

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..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Current guidelines recommend a 5-minute rest period before a blood pressure screening measurement, but that might not be necessary for all patients.

In a prospective crossover study, average differences in blood pressure measurements obtained after 0 or 2 minutes of rest were not significantly different than readings obtained after the recommended 5 minutes of rest in adults with systolic blood pressure below 140 mm Hg.

“The average differences in BP by rest period were small, and BPs obtained after shorter rest periods were noninferior to those obtained after 5 minutes when SBP is below 140,” Tammy M. Brady, MD, PhD, Johns Hopkins University, Baltimore, said in an interview.

“This suggests shorter rest times, even 0 minutes, may be reasonable for screening when the initial SBP is below 140,” said Brady.

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..
 

A challenging recommendation

The 5-minute rest period is “challenging” to implement in busy clinical settings, Dr. Brady said. The researchers therefore set out to determine the effect of no rest and the effect of a shorter rest period (2 minutes) on blood pressure screening.

They recruited 113 adults (mean age, 55; 64% women, 74% Black) with SBP that ranged from below 115 mm Hg to above 145 mm Hg and with diastolic BP that ranged from below 75 mm Hg to above 105 mm Hg. About one-quarter (28%) had SBP in the stage 2 hypertension range (at least 140 mm Hg).

They obtained four sets of automated BP measurements after 5, 2, or 0 minutes of rest. All participants had their BP measured after a second 5-minute rest period as their last measurement to estimate repeatability.

Overall, there was no significant difference in the average BP obtained at any of the rest periods.

After the first and second 5-minute rest period, BPs were 127.5/74.7 mm Hg and 127.0/75.6 mm Hg, respectively. After 2 and 0 minutes of rest, BPs were 126.8/73.7 mm Hg and 126.5/74.0 mm Hg.

When looking just at adults with SBP below 140 mm Hg, there was no more than an average difference of ±2 mm Hg between BPs obtained at the 5-minute resting periods, compared with the shorter resting periods.

However, in those with SBP below 140 mm Hg, BP values were significantly different (defined as more than ±2 mm Hg) with shorter rest periods, “suggesting that shorter rest periods were in fact inferior to resting for 5 minutes in these patients,” Dr. Brady said.
 

More efficient, economic

“Economics play a significant role in blood pressure screenings, as clinics not as well-funded may find it especially challenging to implement a uniform, 5-minute rest period before testing, which could ultimately reduce the number of patients able to be screened,” Dr. Brady added in a conference statement.

“While our study sample was small, a reasonable approach based on these findings would be to measure blood pressure after minimal to no rest, and then repeat the measurements after 5 minutes only if a patient is found to have elevated blood pressure,” she said.

Weighing in on the results, Karen A. Griffin, MD, who chairs the AHA council on hypertension, said that “reducing the rest period to screen an individual for hypertension may result in faster throughput in the clinic and confer a cost savings.”

“At the present time, in order to maintain the clinic flow, some clinics use a single, often times ‘nonrested’ BP measurement as a screen, reserving the 5-minute rest automated-office BP measurement for patients found to have an elevated screening BP,” noted Dr. Griffin, professor of medicine, Loyola University Medical Center, Maywood, Ill.

“Nevertheless, even if limiting the use of automated-office BP to those who fail the initial screening BP, a cost savings would still be realized by reducing the currently recommended 5-minute rest to 2 minutes and have the most impact in very busy, less well-funded clinics,” said Dr. Griffin.

She cautioned, however, that further studies in a larger population will be needed before making a change to current clinical practice guidelines.

The study had no specific funding. Dr. Brady and Dr. Griffin have no relevant disclosures.

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.

The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .

“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said. 

“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”

These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.

“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
 

Brain changes

Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.  

“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.

Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.

For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.

For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.

For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.

This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.

Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.

Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).

“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.

Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.

“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested. 
 

Impact of CV risk factors

Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”

The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.

“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.

“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.

Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.

SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.

This article originally appeared on Medscape.com .

The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.

The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .

“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said. 

“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”

These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.

“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
 

Brain changes

Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.  

“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.

Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.

For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.

For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.

For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.

This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.

Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.

Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).

“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.

Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.

“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested. 
 

Impact of CV risk factors

Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”

The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.

“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.

“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.

Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.

SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.

This article originally appeared on Medscape.com .

The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.

The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .

“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said. 

“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”

These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.

“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
 

Brain changes

Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.  

“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.

Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.

For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.

For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.

For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.

This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.

Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.

Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).

“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.

Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.

“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested. 
 

Impact of CV risk factors

Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”

The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.

“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.

“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.

Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.

SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.

This article originally appeared on Medscape.com .

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

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

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

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

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?

1. Coenzyme Q10 160 mg twice a day

2. Vitamin D 2,000 IU daily

3. Vitamin E 400 IU daily

4. Vitamin B₁₂ 1,000 mcg daily

Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.

Vitamin D has been implicated in the prevention of many disease processes, including acute respiratory infections. Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.

In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.¹

yulka3ice/Getty Images

Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.²

These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.³ The recommended upper level of intake is 4,000 IU/day.
 

Too much of a good thing?

Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.⁴ Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.

Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.⁵ Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
 

Other benefits

Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).⁶

A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.⁷

Pearl

Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.

Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.

2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583

3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.

4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953

5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.

6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.

7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
 

Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?

1. Coenzyme Q10 160 mg twice a day

2. Vitamin D 2,000 IU daily

3. Vitamin E 400 IU daily

4. Vitamin B₁₂ 1,000 mcg daily

Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.

Vitamin D has been implicated in the prevention of many disease processes, including acute respiratory infections. Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.

In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.¹

yulka3ice/Getty Images

Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.²

These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.³ The recommended upper level of intake is 4,000 IU/day.
 

Too much of a good thing?

Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.⁴ Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.

Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.⁵ Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
 

Other benefits

Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).⁶

A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.⁷

Pearl

Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.

Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.

2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583

3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.

4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953

5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.

6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.

7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
 

Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?

1. Coenzyme Q10 160 mg twice a day

2. Vitamin D 2,000 IU daily

3. Vitamin E 400 IU daily

4. Vitamin B₁₂ 1,000 mcg daily

Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.

Vitamin D has been implicated in the prevention of many disease processes, including acute respiratory infections. Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.

In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.¹

yulka3ice/Getty Images

Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.²

These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.³ The recommended upper level of intake is 4,000 IU/day.
 

Too much of a good thing?

Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.⁴ Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.

Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.⁵ Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
 

Other benefits

Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).⁶

A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.⁷

Pearl

Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.

Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.

2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583

3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.

4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953

5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.

6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.

7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
 

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

Hydrochlorothiazide (HCTZ) is associated with an increased risk of nonmelanoma skin cancer, and patients who take the drug should limit sun exposure and undergo regular skin cancer screening, according to updates to the medication’s label.

The skin cancer risk is small, however, and patients should continue taking HCTZ, a commonly used diuretic and antihypertensive drug, unless their doctor says otherwise, according to a U.S. Food and Drug Administration announcement about the labeling changes, which the agency approved on Aug. 20.

HCTZ, first approved in 1959, is associated with photosensitivity. Researchers identified a relationship between HCTZ and nonmelanoma skin cancer in postmarketing studies. Investigators have described dose-response patterns for basal cell carcinoma and squamous cell carcinoma (SCC).

An FDA analysis found that the risk mostly was increased for SCC. The drug was associated with approximately one additional case of SCC per 16,000 patients per year. For white patients who received a cumulative dose of 50,000 mg or more, the risk was greater. In this patient population, HCTZ was associated with about one additional case of SCC per 6,700 patients per year, according to the label.

Reliably estimating the frequency of nonmelanoma skin cancer and establishing a causal relationship to drug exposure is not possible with the available postmarketing data, the label notes

“Treatment for nonmelanoma skin cancer is typically local and successful, with very low rates of death,” the FDA said. “Meanwhile, the risks of uncontrolled blood pressure can be severe and include life-threatening heart attacks or stroke. Given this information, patients should continue to use HCTZ and take protective skin care measures to reduce their risk of nonmelanoma skin cancer, unless directed otherwise from their health care provider.”

Patients can reduce sun exposure by using broad-spectrum sunscreens with a sun protection factor value of at least 15, limiting time in the sun, and wearing protective clothing, the agency advised.

[email protected]

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]