Cardiology

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Eugene Yang, MD, often confronts the complexities of weighing various medical interventions for high blood pressure. Among these is when to scale back antihypertensive drugs or stop them completely.

He considers a patient’s comorbidities, severity of symptoms, and risk factors for heart attack and stroke, among other variables. Central to this calculus is the recognition of age as a pivotal determinant of quality of life, according to Dr. Yang, the chair of the Prevention of Cardiovascular Disease Council at the American College of Cardiology.

For older adults, for example, the variance in functional status can be striking. One octogenarian may be bedbound due to severe dementia, while another might be playing pickleball three times a week.

“This happens to me in my practice all the time. I have patients who are restricted in mobility and have severe memory loss: Their functionality is quite poor,” Dr. Yang said. “In a patient where we have a limited life expectancy, where they have limited function or core memory, the goal is not to prolong life: It’s to make them more comfortable.”

Knowing when to deprescribe blood pressure medications is crucial. For some, lifestyle changes can do the trick. For others, particularly older patients, their comorbid conditions and medication regimens need to be considered.

“There’s a recognition that we need to move to a new paradigm where we need to decide when to be aggressive and when to be less aggressive,” Dr. Yang said.

The American Heart Association and the American College of Cardiology most recently released guidelines in 2017, changing the cutoff for diagnosis from 140/90 to 130/80 mm Hg. The groups have issued no updates since then, leaving primary care physicians and their colleagues to navigate this territory with caution, balancing the benefits of reduction with the potential harms of undertreatment.

One example of an area that needs updating is the consideration of the age, currently missing from current guidance on hypertension management from government and medical bodies in the United States. However, European Society of Hypertension guidelines, updated in June 2023, recommend adults over age 80 or those classified as frail should be treated when their systolic blood pressure exceeds 160.

“For the first time, we have a chapter in the guidelines on hypertension and management in older people,” Reinhold Kreutz, MD, PhD, immediate past-president of the European Society of Hypertension, said. “If a patient has low blood pressure and symptoms such as dizziness or frailty, a reduction in medication should be considered.”

High blood pressure does not always present with noticeable symptoms, and patients do not always show up for an office visit in time for early intervention. It can pave the way for severe health complications including heart failure, stroke, kidney disease, heart attack, and, ultimately, death.

Grim statistics reveal its toll: Hypertension was a primary or contributing cause of nearly 700,000 deaths in the United States in 2021, and nearly half of adults have the condition. Only about one in four adults have their high blood pressure under control.
 

New Research Provides Insight

A recent study may provide needed insights for primary care clinicians: Gradually reducing hypertensive medication may not induce the feared fluctuations in blood pressure, contrary to prior concerns.

Researchers in Seoul, South Korea, analyzed the blood pressure of 83 patients diagnosed with hypertension who reduced their use of medication. They found that the use of less medication was associated with an increase in blood pressure readings taken at home but not in the clinic nor did it appear to influence blood pressure variability. The mean age of participants was 66 years.

Research shows systolic blood pressure variability is an important predictor of cardiovascular outcomes, as well as the risk for dementia.

When crafting treatment plans, clinicians should recognize the diverse factors at play for a particular patient, particularly concerning other health conditions.

Obesity, diabetes, and hyperlipidemia are among the common comorbidities often intertwined with hypertension. Because additional conditions come with more symptoms to consider and various medications, these health profiles demand tailored approaches to hypertension treatment.

Clinicians can recommend lifestyle modifications like dietary changes and regular exercise as first steps for patients who are diagnosed with grade 1 hypertension but who do not have cardiovascular disease, chronic kidney disease, diabetes, or organ damage. However, in cases where comorbidities are present or hypertension escalates to grade 2, clinicians should turn to medications for management, according to the International Society of Hypertension.

Patients with heart failure and reduced ejection fraction have unique challenges, according to Keith C. Ferdinand, MD, the Gereld S. Berenson Endowed Chair in Preventative Cardiology at the Tulane School of Medicine in New Orleans, Louisiana.

“Patients who have heart disease, they get a pump so the blood pressure comes down — but medicine is often needed to prevent further heart failure,” Dr. Ferdinand said.

Dr. Ferdinand stressed the importance of continuous medication to stave off further cardiac deterioration. He advocated for a cautious approach, emphasizing the continued use of medications like sacubitril/valsartan, beta-blockers, or sodium-glucose transport protein inhibitors to safeguard against heart failure progression.

Patients should also self-monitor blood pressure at home and be taught how to properly fit a cuff to enable accurate measurements. This approach empowers patients to actively engage in their health management and detect any deviations that warrant further attention, he said.
 

Medications for Hypertension

The use of any of the five major drug classes — angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium blockers, and thiazide/thiazide-like diuretics — and their combinations are recommended as the basis of antihypertensive treatment strategies.

Dr. Yang said primary care clinicians must be careful to decrease doses slowly. Central-acting medications such as clonidine and beta-blockers ultimately reduce heart rate and dilate blood vessels.

Decreasing the dose too quickly can create a rebound effect, and medication should be means reduced and closely monitored over the course of several weeks, Dr. Yang said.

“You cannot just withdraw abruptly with certain medications — you have to wean off slowly,” because patients may experience high blood pressure again, Dr. Yang said.

A version of this article appeared on Medscape.com.

Eugene Yang, MD, often confronts the complexities of weighing various medical interventions for high blood pressure. Among these is when to scale back antihypertensive drugs or stop them completely.

He considers a patient’s comorbidities, severity of symptoms, and risk factors for heart attack and stroke, among other variables. Central to this calculus is the recognition of age as a pivotal determinant of quality of life, according to Dr. Yang, the chair of the Prevention of Cardiovascular Disease Council at the American College of Cardiology.

For older adults, for example, the variance in functional status can be striking. One octogenarian may be bedbound due to severe dementia, while another might be playing pickleball three times a week.

“This happens to me in my practice all the time. I have patients who are restricted in mobility and have severe memory loss: Their functionality is quite poor,” Dr. Yang said. “In a patient where we have a limited life expectancy, where they have limited function or core memory, the goal is not to prolong life: It’s to make them more comfortable.”

Knowing when to deprescribe blood pressure medications is crucial. For some, lifestyle changes can do the trick. For others, particularly older patients, their comorbid conditions and medication regimens need to be considered.

“There’s a recognition that we need to move to a new paradigm where we need to decide when to be aggressive and when to be less aggressive,” Dr. Yang said.

The American Heart Association and the American College of Cardiology most recently released guidelines in 2017, changing the cutoff for diagnosis from 140/90 to 130/80 mm Hg. The groups have issued no updates since then, leaving primary care physicians and their colleagues to navigate this territory with caution, balancing the benefits of reduction with the potential harms of undertreatment.

One example of an area that needs updating is the consideration of the age, currently missing from current guidance on hypertension management from government and medical bodies in the United States. However, European Society of Hypertension guidelines, updated in June 2023, recommend adults over age 80 or those classified as frail should be treated when their systolic blood pressure exceeds 160.

“For the first time, we have a chapter in the guidelines on hypertension and management in older people,” Reinhold Kreutz, MD, PhD, immediate past-president of the European Society of Hypertension, said. “If a patient has low blood pressure and symptoms such as dizziness or frailty, a reduction in medication should be considered.”

High blood pressure does not always present with noticeable symptoms, and patients do not always show up for an office visit in time for early intervention. It can pave the way for severe health complications including heart failure, stroke, kidney disease, heart attack, and, ultimately, death.

Grim statistics reveal its toll: Hypertension was a primary or contributing cause of nearly 700,000 deaths in the United States in 2021, and nearly half of adults have the condition. Only about one in four adults have their high blood pressure under control.
 

New Research Provides Insight

A recent study may provide needed insights for primary care clinicians: Gradually reducing hypertensive medication may not induce the feared fluctuations in blood pressure, contrary to prior concerns.

Researchers in Seoul, South Korea, analyzed the blood pressure of 83 patients diagnosed with hypertension who reduced their use of medication. They found that the use of less medication was associated with an increase in blood pressure readings taken at home but not in the clinic nor did it appear to influence blood pressure variability. The mean age of participants was 66 years.

Research shows systolic blood pressure variability is an important predictor of cardiovascular outcomes, as well as the risk for dementia.

When crafting treatment plans, clinicians should recognize the diverse factors at play for a particular patient, particularly concerning other health conditions.

Obesity, diabetes, and hyperlipidemia are among the common comorbidities often intertwined with hypertension. Because additional conditions come with more symptoms to consider and various medications, these health profiles demand tailored approaches to hypertension treatment.

Clinicians can recommend lifestyle modifications like dietary changes and regular exercise as first steps for patients who are diagnosed with grade 1 hypertension but who do not have cardiovascular disease, chronic kidney disease, diabetes, or organ damage. However, in cases where comorbidities are present or hypertension escalates to grade 2, clinicians should turn to medications for management, according to the International Society of Hypertension.

Patients with heart failure and reduced ejection fraction have unique challenges, according to Keith C. Ferdinand, MD, the Gereld S. Berenson Endowed Chair in Preventative Cardiology at the Tulane School of Medicine in New Orleans, Louisiana.

“Patients who have heart disease, they get a pump so the blood pressure comes down — but medicine is often needed to prevent further heart failure,” Dr. Ferdinand said.

Dr. Ferdinand stressed the importance of continuous medication to stave off further cardiac deterioration. He advocated for a cautious approach, emphasizing the continued use of medications like sacubitril/valsartan, beta-blockers, or sodium-glucose transport protein inhibitors to safeguard against heart failure progression.

Patients should also self-monitor blood pressure at home and be taught how to properly fit a cuff to enable accurate measurements. This approach empowers patients to actively engage in their health management and detect any deviations that warrant further attention, he said.
 

Medications for Hypertension

The use of any of the five major drug classes — angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium blockers, and thiazide/thiazide-like diuretics — and their combinations are recommended as the basis of antihypertensive treatment strategies.

Dr. Yang said primary care clinicians must be careful to decrease doses slowly. Central-acting medications such as clonidine and beta-blockers ultimately reduce heart rate and dilate blood vessels.

Decreasing the dose too quickly can create a rebound effect, and medication should be means reduced and closely monitored over the course of several weeks, Dr. Yang said.

“You cannot just withdraw abruptly with certain medications — you have to wean off slowly,” because patients may experience high blood pressure again, Dr. Yang said.

A version of this article appeared on Medscape.com.

Eugene Yang, MD, often confronts the complexities of weighing various medical interventions for high blood pressure. Among these is when to scale back antihypertensive drugs or stop them completely.

He considers a patient’s comorbidities, severity of symptoms, and risk factors for heart attack and stroke, among other variables. Central to this calculus is the recognition of age as a pivotal determinant of quality of life, according to Dr. Yang, the chair of the Prevention of Cardiovascular Disease Council at the American College of Cardiology.

For older adults, for example, the variance in functional status can be striking. One octogenarian may be bedbound due to severe dementia, while another might be playing pickleball three times a week.

“This happens to me in my practice all the time. I have patients who are restricted in mobility and have severe memory loss: Their functionality is quite poor,” Dr. Yang said. “In a patient where we have a limited life expectancy, where they have limited function or core memory, the goal is not to prolong life: It’s to make them more comfortable.”

Knowing when to deprescribe blood pressure medications is crucial. For some, lifestyle changes can do the trick. For others, particularly older patients, their comorbid conditions and medication regimens need to be considered.

“There’s a recognition that we need to move to a new paradigm where we need to decide when to be aggressive and when to be less aggressive,” Dr. Yang said.

The American Heart Association and the American College of Cardiology most recently released guidelines in 2017, changing the cutoff for diagnosis from 140/90 to 130/80 mm Hg. The groups have issued no updates since then, leaving primary care physicians and their colleagues to navigate this territory with caution, balancing the benefits of reduction with the potential harms of undertreatment.

One example of an area that needs updating is the consideration of the age, currently missing from current guidance on hypertension management from government and medical bodies in the United States. However, European Society of Hypertension guidelines, updated in June 2023, recommend adults over age 80 or those classified as frail should be treated when their systolic blood pressure exceeds 160.

“For the first time, we have a chapter in the guidelines on hypertension and management in older people,” Reinhold Kreutz, MD, PhD, immediate past-president of the European Society of Hypertension, said. “If a patient has low blood pressure and symptoms such as dizziness or frailty, a reduction in medication should be considered.”

High blood pressure does not always present with noticeable symptoms, and patients do not always show up for an office visit in time for early intervention. It can pave the way for severe health complications including heart failure, stroke, kidney disease, heart attack, and, ultimately, death.

Grim statistics reveal its toll: Hypertension was a primary or contributing cause of nearly 700,000 deaths in the United States in 2021, and nearly half of adults have the condition. Only about one in four adults have their high blood pressure under control.
 

New Research Provides Insight

A recent study may provide needed insights for primary care clinicians: Gradually reducing hypertensive medication may not induce the feared fluctuations in blood pressure, contrary to prior concerns.

Researchers in Seoul, South Korea, analyzed the blood pressure of 83 patients diagnosed with hypertension who reduced their use of medication. They found that the use of less medication was associated with an increase in blood pressure readings taken at home but not in the clinic nor did it appear to influence blood pressure variability. The mean age of participants was 66 years.

Research shows systolic blood pressure variability is an important predictor of cardiovascular outcomes, as well as the risk for dementia.

When crafting treatment plans, clinicians should recognize the diverse factors at play for a particular patient, particularly concerning other health conditions.

Obesity, diabetes, and hyperlipidemia are among the common comorbidities often intertwined with hypertension. Because additional conditions come with more symptoms to consider and various medications, these health profiles demand tailored approaches to hypertension treatment.

Clinicians can recommend lifestyle modifications like dietary changes and regular exercise as first steps for patients who are diagnosed with grade 1 hypertension but who do not have cardiovascular disease, chronic kidney disease, diabetes, or organ damage. However, in cases where comorbidities are present or hypertension escalates to grade 2, clinicians should turn to medications for management, according to the International Society of Hypertension.

Patients with heart failure and reduced ejection fraction have unique challenges, according to Keith C. Ferdinand, MD, the Gereld S. Berenson Endowed Chair in Preventative Cardiology at the Tulane School of Medicine in New Orleans, Louisiana.

“Patients who have heart disease, they get a pump so the blood pressure comes down — but medicine is often needed to prevent further heart failure,” Dr. Ferdinand said.

Dr. Ferdinand stressed the importance of continuous medication to stave off further cardiac deterioration. He advocated for a cautious approach, emphasizing the continued use of medications like sacubitril/valsartan, beta-blockers, or sodium-glucose transport protein inhibitors to safeguard against heart failure progression.

Patients should also self-monitor blood pressure at home and be taught how to properly fit a cuff to enable accurate measurements. This approach empowers patients to actively engage in their health management and detect any deviations that warrant further attention, he said.
 

Medications for Hypertension

The use of any of the five major drug classes — angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium blockers, and thiazide/thiazide-like diuretics — and their combinations are recommended as the basis of antihypertensive treatment strategies.

Dr. Yang said primary care clinicians must be careful to decrease doses slowly. Central-acting medications such as clonidine and beta-blockers ultimately reduce heart rate and dilate blood vessels.

Decreasing the dose too quickly can create a rebound effect, and medication should be means reduced and closely monitored over the course of several weeks, Dr. Yang said.

“You cannot just withdraw abruptly with certain medications — you have to wean off slowly,” because patients may experience high blood pressure again, Dr. Yang said.

A version of this article appeared on Medscape.com.

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.