Cardiology

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

A Pesco-Mediterranean diet consisting of plants, legumes, nuts, whole grains, extra-virgin olive oil (EVOO), moderate amounts of dairy products, and fish and/or seafood, together with intermittent fasting (also called time-restricted eating), can reduce risk for cardiovascular disease (CVD), according to a new review.

The authors presented the research and conceptual underpinnings of this approach, which “proposes that following a Pesco-Mediterranean diet with time-restricted eating is evidence-based and ideal for reducing cardiovascular risk,” study coauthor Sarah Smith, PhD, RN, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview.

The review was published online September 14 in the Journal of the American College of Cardiology.
 

‘Omnivore’s dilemma’

A host of epidemiologic studies and randomized clinical trials support an association between the traditional Mediterranean diet and lower risk for all-cause and CVD mortality, coronary heart disease, metabolic syndrome, neurodegenerative diseases, and other adverse outcome. The diet has been subsequently endorsed by several sets of guidelines, including those from the Department of Health & Human Services and the Department of Agriculture, and the 2019 American Heart Association/American College of Cardiology primary prevention guidelines.

“Although humans are omnivores and can subsist on a myriad of foods, the ideal diet for health remains a dilemma for many people,” lead author James H. O’Keefe, MD, director of preventive cardiology at Saint Luke’s, said in a news release.

“Plant-rich diets reduce CVD risk; however, veganism is difficult to follow and can result in important nutrient deficiencies,” he stated.

On the other hand, “the standard American diet is high in red meat, especially processed meat from animals raised in inhumane conditions, fed unnatural foods, and often treated with hormones and antibiotics,” the authors pointed out.

Together with overconsumption of red meat, sugar and processed food contribute to poor health outcomes, Dr. Smith noted.

The review was designed to present the Pesco-Mediterranean diet as “a solution to the ‘omnivore’s dilemma’ about what to eat,” said Dr. O’Keefe.

Study coauthor Ibrahim M. Saeed, MD, a cardiologist at Saint Luke’s, added that the research “attempts to emphasize the results of landmark prospective trials that highlight good, healthy eating options rather than just [foods that people would] want to avoid.”
 

Key components

The traditional Mediterranean diet includes “unrestricted use of EVOO,” but the quality of the olive oil is “crucial” and it must be unrefined and cold pressed, the authors emphasized.

The “highly bioactive” polyphenols likely “underlie EVOO’s numerous cardiometabolic benefits,” the researchers wrote, noting that the 2014 PREDIMED trial provided “first-level scientific evidence of [EVOO’s] cardioprotective effects [if used] within the context of the Mediterranean diet.”

The authors recommend “generous use” of EVOO in salad dressings and vegetable dishes, pasta, rice, fish, sauces, or legumes.

They also review the role of tree nuts, noting that they are “nutrient-dense foods rich in unsaturated fats, fiber, protein, polyphenols, phytosterols, tocopherols, and nonsodium minerals” and have been shown beneficial in CVD prevention.

Legumes play a “central role” in the Mediterranean diet and are an “excellent source” of vegetable protein, folate, magnesium, and fiber. Legume consumption is associated with lowered risk for CVD, as well as improved blood glucose, cholesterol, blood pressure, and body weight, the authors stated.

Whole grains like barley, whole oats, brown rice, and quinoa are likewise central components of the traditional Mediterranean diet. The authors warned that refined grain products and commercial precooked pasta or pizza should be “consumed only in small amounts.”
 

Window of time

In time-restricted eating (which is one type of intermittent fasting), the daily intake of food is limited to a window of time, usually 6-12 hours each day, the authors explained.

When done regularly, this type of eating has been shown to both decrease intra-abdominal adipose tissue and reduce free-radical production. Additionally, it “elicits powerful cellular responses” that may reduce risks for systemic inflammation, diabetes, CVD, cancer, and neurodegenerative diseases.

However, the authors warned, the evidence supporting time-restricted eating is still preliminary.
 

‘Let food be thy medicine’

Andrew Freeman, MD, cochair of the ACC’s nutrition & lifestyle work group, cautioned that many American plant-based Mediterranean diets often include large amount of feta cheese and lamb and foods are often “heavily doused” in olive oil, while the traditional Mediterranean diet consists primarily of greens and lentils and is plant based.

“The goal would be to have a whole grain and leafy vegetables as the center of the meal, and – if an animal product such as fish is included – it should be limited to as little as possible and used as the garnish rather than the main dish,” he stated.

Moreover, fish are often exposed to large amount of toxins, heavy metals, and microplastics, so “don’t overdo eating fish,” he advised.

Dr. Freeman said that intermittent fasting “has a lot of promise and no harm” and concentrating food consumption during a shorter period in the day instead of “grazing throughout the day” will reduce constant snacking. “But don’t gorge yourself during those hours,” he warned.

Dr. Freeman concluded by citing the guidance of Hippocrates: “Let food be thy medicine.

“There’s some real truth to that,” he added.

No source of funding was listed. Dr. Smith and Dr. Freeman disclosed no relevant financial relationships. Dr. O’Keefe has a major ownership interest in CardioTabs, a supplement company that sells some products containing omega-3 fatty acids.

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

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

The risk for death goes up for patients with atrial fibrillation (AFib) who are put on direct oral anticoagulants (DOAC) at dosages other than those approved for stroke prevention, whether higher or lower than doses specified in the labeling, suggests a large registry study.

A quarter of more than 10,000 patients in the registry took the drugs at such nonrecommended higher or lower dosages. Overwhelmingly it was the latter, perhaps reflecting caution on the part of some practitioners looking to minimize the risk of bleeding complications.

The risk of major bleeding indeed dropped sharply for those taking DOACs at lower-than-recommended levels, but at the cost of a 25% jump in all-cause mortality over 2 years, report investigators from their analysis of patients in the GARFIELD-AF registry published Sept. 14 in the Journal of the American College of Cardiology.

Risks of major bleeding and of stroke or systemic embolism didn’t climb significantly for patients either under- or overdosed.

In general, “physicians are worried about giving too much anticoagulant, and they tend to favor erring on the low-dose side,” lead author A. John Camm, MD, St. George’s University of London, said in an interview. That’s how it was when an oral anticoagulation meant a vitamin K antagonist (VKA) and underdosing was frequent; and it remains an issue in the DOAC era. “It’s not just a little problem. It’s a very big problem.”

Today, clinicians may prescribe DOACs similar to how they prescribed VKAs, by cautiously choosing a lower dosage for selected patients based on their risk profile, Dr. Camm observed. But in contrast to the VKAs, the DOACs “were studied with different dose-reduction strategies, and their labeling requires them to be prescribed according to different parameters.”

They variously base dosage reductions on age, body weight, renal function, or drug-drug interactions, for example, but some clinicians “tend to think that all of those factors should be applied in every instance, with every drug,” he said.

“So I think there’s some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality,” Dr. Camm said. “But by reducing the dose, they expose their patients to these other major cardiovascular events.”

Numerically, the excess mortality among underdosed patients appeared to be driven by death from heart failure or myocardial infarction. There was little or no contribution from sudden death, fatal strokes, or noncardiovascular death.

The findings “remind clinicians to dose DOACs properly and that there are consequences of dosing errors,” observes Gerald V. Naccarelli, MD, of Penn State University and the Milton S. Hershey Medical Center, Hershey, in an accompanying editorial.

Based on the major clinical trials that established the drugs as mainstream stroke-preventive therapy in AFib, as well as extensive regulatory review, each DOAC’s label-recommended dosing “is a guidance of the truth to achieve the highest efficacy and most safety in our patients,” Dr. Naccarelli wrote. “As clinicians are risk adverse, underdosing might result in lower major bleeding rates, and physicians are blamed for bleeding but not necessarily for allowing embolic strokes to occur. These data raise the issue that underdosing is associated with worse patient outcomes.”

The GARFIELD-AF analysis covered 10,426 adults with nonvalvular AFib in 35 countries who initiated a DOAC from 2013 to 2016. The drugs were prescribed at dosages consistent with recommendations in each respective country’s labeling for stroke prevention in AFib in 72.9% of the cohort. Most full and adjusted dose levels approved by the European Medicines Agency, Food and Drug Administration, and regulators in Japan were the same or similar.

But there were a few exceptions. All dosing criteria across the three regulatory domains were the same for apixaban (Eliquis). But variations included lower dosage options for rivaroxaban (Xarelto) and edoxaban (Savaysa, Lixiana) in Japan, and a uniquely low dabigatran (Pradaxa) dosage option in the United States.

The DOAC used least often was the one most frequently underdosed. More than half of patients prescribed edoxaban were given it at a lower-than-recommended dosage.

The adjusted hazard ratio for all-cause mortality at 2 years for DOAC under- or overdosing, compared with dosing at recommended levels, was 1.24 (95% confidence interval, 1.04-1.48). The difference was driven by underdosing, for which the HR was 1.25 (95% CI, 1.04-1.50). The HR for over-dosing was only 1.19 (95% CI, 0.83-1.71).

Multivariate adjustment accounted for age, sex, and ethnicity; type of AFib; diabetes; hypertension; history of bleeding; prior stroke, transient ischemic attack, or systemic embolism; heart failure; vascular disease; smoking; and heavy alcohol consumption.

The risk of stroke or systemic embolism didn’t go up or down significantly for either overdosed or underdosed patients. Neither group showed an increased risk for major bleeding; however, the HR for major bleeding in underdosed patients fell to 0.50 (95% CI, 0.28-0.88).

Underdosing was more common in some world regions than others. The rate exceeded 30% in all Latin American countries except Argentina, the report stated, and in all Asian countries except Singapore.

Japanese patients have long received oral anticoagulation at lower dosages than are used in the West, Dr. Camm observed. When VKAs were the only choice, for example, international normalized ratio targets were consistently a bit lower in Japan than in, for example, North America or Europe.

“And when [novel] OACs were developed, again, the Japanese took the view that their patients are more vulnerable to bleeding, and therefore a lower dose would be appropriate. In some instances, lower-dose regimens have been specifically studied in the Japanese,” Dr. Camm said. “Having said that, this concept of bleeding being more problematic in Asian patients has expanded well beyond Japan, and therefore in many Asian communities, lower doses of [novel] OACs are chosen.”

Many other factors may contribute to DOAC underdosing, including differences in dosing strategies between primary care practitioners and specialists, or between hospital-based and office-based clinicians, for example.

“It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care,” Dr. Camm proposed. “Therefore you could have increased mortality due to other cardiovascular causes, or even noncardiovascular events, through absence of good quality care. Our study did not address that specifically. But it might be the case, speculatively.”

The study was supported by a grant from Bayer to the Thrombosis Research Institute, “which sponsors the GARFIELD-AF registry.” Dr. Camm discloses receiving grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, and Daiichi Sankyo. Disclosures for the other authors are in the report. Dr. Naccarelli disclosed consulting and participating in research for Janssen and serving as a consultant for Milestone, Sanofi, Omeicos, and Acesion Pharma.

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

A new study using cardiac magnetic resonance (CMR) imaging to examine the effects of novel coronavirus infection on the heart showed signs suggestive of myocarditis in 4 out of 26 competitive athletes who recovered from asymptomatic or mild cases of COVID-19.

While these and other similar findings are concerning, commentators are saying the results are preliminary and do not indicate widespread CMR screening is appropriate.

Two of the 4 patients showing signs of myocarditis in this series had no symptoms of COVID-19 but tested positive on routine testing. An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (30.8%) had LGE without T2 elevation suggestive of prior myocardial injury.

An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (31%) had LGE without T2 elevation suggestive of prior myocardial injury.

This finding, said Saurabh Rajpal, MBBS, MD, the study’s lead author, “could suggest prior myocardial injury or it could suggest athletic myocardial adaptation.”

In a research letter published in JAMA Cardiology, Rajpal and colleagues at Ohio State University in Columbus, described the findings of comprehensive CMR examinations in competitive athletes referred to the sport medicine clinic after testing positive for COVID-19 on reverse transcriptase-polymerase chain reaction between June and August 2020.

The university had made the decision in the spring to use CMR imaging as a screening tool for return to play, said Dr. Rajpal. While CMR is being used for research purposes, the American College of Cardiology’s recent “consensus expert opinion” statement on resumption of sport and exercise after COVID-19 infection does not require CMR imaging for resumption of competitive activity (JAMA Cardiol. 2020 May 13. doi:10.1001/jamacardio.2020.2136).

None of the athletes required hospitalization for their illness, and only 27% reported mild symptoms during the short-term infection, including sore throat, shortness of breath, myalgia, and fever.

On the day of CMR imaging, ECG and transthoracic echocardiography were performed, and serum troponin I was measured. There were no diagnostic ST/T wave changes, ventricular function and volumes were normal, and no athletes showed elevated serum troponin levels.

The updated Lake Louise Criteria were used to assess CMR findings consistent with myocarditis.

“I don’t think this is a COVID-specific issue. We have seen myocarditis after other viral infections; it’s just that COVID-19 is the most studied thus far, and with strenuous activity, inflammation in the heart can be risky,” Dr. Rajpal said in an interview. He added that more long-term and larger studies with control populations are needed.

His group is continuing to follow these athletes and has suggested that CMR “may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation.”
 

Significance still unknown

Matthew Martinez, MD, the director of sports cardiology at Atlantic Health – Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, urged caution in making too much of the findings of this small study.

“We know that viruses cause myocardial damage and myocarditis. What we don’t know is how important these findings are. And in terms of risk, would we find the same phenomenon if we did this, say, in flu patients or in other age groups?” Dr. Martinez said in an interview.

“I haven’t seen all the images, but what I’d want to know is are these very subtle findings? Are these overt findings? Is this part of an active individual with symptoms? I need to know a little more data before I can tell if this influences the increased risk of sudden cardiac death that we often associate with myocarditis. I’m not sure how this should influence making decisions with regards to return to play.”

Dr. Martinez, who is the ACC’s chair of Sports and Exercise but was not an author of their recent guidance on return to sport, said that he is not routinely using CMR to assess athletes post-infection, as per the ACC’s recommendations.

“My approach is to evaluate anybody with a history of COVID infection and, first, determine whether it was an important infection with significant symptoms or not. And then, if they’re participating at a high level or are professional athletes, I would suggest an ECG, echo, and troponin. That’s our recommendation for the last several months and is still an appropriate way to evaluate that group.”

“In the presence of an abnormality or ongoing symptoms, I would ask for an MRI at that point,” said Dr. Martinez.

“We just don’t have much data on athletes with no symptoms to use to interpret these CMR findings and the study didn’t offer any controls. We don’t even know if these findings are new findings or old findings that have just been identified now,” he added.

New, updated recommendations from the ACC are coming soon, said Dr. Martinez. “I do not expect them to include CMR as first line.”
 

Cardiologists concerned about misinformation

This is at least the fourth study showing myocardial damage post-COVID-19 infection and there is concern in the medical community that the media has overstated the risks of heart damage, especially in athletes, and at the same time overstated the benefits of CMR.

In particular, Puntmann et al reported in July a 100-patient study that showed evidence of myocardial inflammation by CMR in 78% of patients recently recovered from a bout of COVID-19 (JAMA Cardiol. 2020 Jul 27; doi:10.1001/jamacardio.2020.3557).

“That paper is completely problematic,” John Mandrola, MD, of Baptists Medical Associates, Louisville, Ky., said in an interview. “It has the same overarching weaknesses [of other studies] that it’s observational and retrospective, but there were also numerical issues. So to me that paper is an interesting observation, but utterly unconvincing and preliminary,” said Dr. Mandrola.

Those limitations didn’t stop the study from garnering media attention, however. The Altmetric score (an attention score that tracks all mentions of an article in the media and on social media) for the Puntmann et al paper is approaching 13,000, including coverage from 276 news outlets and more than 19,000 tweets, putting it in the 99th percentile of all research outputs tracked by Altmetric to date.

To counter this, an “open letter” posted online just days before the Rajpal study published urging professional societies to “offer clear guidance discouraging CMR screening for COVID-19 related heart abnormalities in asymptomatic members of the general public.” The letter was signed by 51 clinicians, researchers, and imaging specialists from around the world.

Dr. Mandrola, one of the signatories, said: “This topic really scares people, and when it gets in the media like this, I think the leaders of these societies need to come out and say something really clear on major news networks letting people know that it’s just way too premature to start doing CMRs on every athlete that’s gotten this virus.”

“I understand that the current guidelines may be clear that CMR is not a first-line test for this indication, but when the media coverage is so extensive and so overblown, I wonder how much impact the guidelines will have in countering this fear that’s in the community,” he added.

Asked to comment on the letter, Dr. Rajpal said he agrees with the signatories that asymptomatic people from general population do not need routine cardiac MRI. “However, competitive athletes are a different story. Testing depends on risk assessment in specific population and competitive athletes as per our protocol will get enhanced cardiac workup including CMR for responsible and safe start of competitive sports. ... In the present scenario, while we get more data including control data, we will continue with our current protocol.”

Dr. Mandrola is Medscape Cardiology’s Chief Cardiology Consultant. MDedge is part of the Medscape Professional Network.

This article first appeared on Medscape.com.

A new study using cardiac magnetic resonance (CMR) imaging to examine the effects of novel coronavirus infection on the heart showed signs suggestive of myocarditis in 4 out of 26 competitive athletes who recovered from asymptomatic or mild cases of COVID-19.

While these and other similar findings are concerning, commentators are saying the results are preliminary and do not indicate widespread CMR screening is appropriate.

Two of the 4 patients showing signs of myocarditis in this series had no symptoms of COVID-19 but tested positive on routine testing. An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (30.8%) had LGE without T2 elevation suggestive of prior myocardial injury.

An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (31%) had LGE without T2 elevation suggestive of prior myocardial injury.

This finding, said Saurabh Rajpal, MBBS, MD, the study’s lead author, “could suggest prior myocardial injury or it could suggest athletic myocardial adaptation.”

In a research letter published in JAMA Cardiology, Rajpal and colleagues at Ohio State University in Columbus, described the findings of comprehensive CMR examinations in competitive athletes referred to the sport medicine clinic after testing positive for COVID-19 on reverse transcriptase-polymerase chain reaction between June and August 2020.

The university had made the decision in the spring to use CMR imaging as a screening tool for return to play, said Dr. Rajpal. While CMR is being used for research purposes, the American College of Cardiology’s recent “consensus expert opinion” statement on resumption of sport and exercise after COVID-19 infection does not require CMR imaging for resumption of competitive activity (JAMA Cardiol. 2020 May 13. doi:10.1001/jamacardio.2020.2136).

None of the athletes required hospitalization for their illness, and only 27% reported mild symptoms during the short-term infection, including sore throat, shortness of breath, myalgia, and fever.

On the day of CMR imaging, ECG and transthoracic echocardiography were performed, and serum troponin I was measured. There were no diagnostic ST/T wave changes, ventricular function and volumes were normal, and no athletes showed elevated serum troponin levels.

The updated Lake Louise Criteria were used to assess CMR findings consistent with myocarditis.

“I don’t think this is a COVID-specific issue. We have seen myocarditis after other viral infections; it’s just that COVID-19 is the most studied thus far, and with strenuous activity, inflammation in the heart can be risky,” Dr. Rajpal said in an interview. He added that more long-term and larger studies with control populations are needed.

His group is continuing to follow these athletes and has suggested that CMR “may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation.”
 

Significance still unknown

Matthew Martinez, MD, the director of sports cardiology at Atlantic Health – Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, urged caution in making too much of the findings of this small study.

“We know that viruses cause myocardial damage and myocarditis. What we don’t know is how important these findings are. And in terms of risk, would we find the same phenomenon if we did this, say, in flu patients or in other age groups?” Dr. Martinez said in an interview.

“I haven’t seen all the images, but what I’d want to know is are these very subtle findings? Are these overt findings? Is this part of an active individual with symptoms? I need to know a little more data before I can tell if this influences the increased risk of sudden cardiac death that we often associate with myocarditis. I’m not sure how this should influence making decisions with regards to return to play.”

Dr. Martinez, who is the ACC’s chair of Sports and Exercise but was not an author of their recent guidance on return to sport, said that he is not routinely using CMR to assess athletes post-infection, as per the ACC’s recommendations.

“My approach is to evaluate anybody with a history of COVID infection and, first, determine whether it was an important infection with significant symptoms or not. And then, if they’re participating at a high level or are professional athletes, I would suggest an ECG, echo, and troponin. That’s our recommendation for the last several months and is still an appropriate way to evaluate that group.”

“In the presence of an abnormality or ongoing symptoms, I would ask for an MRI at that point,” said Dr. Martinez.

“We just don’t have much data on athletes with no symptoms to use to interpret these CMR findings and the study didn’t offer any controls. We don’t even know if these findings are new findings or old findings that have just been identified now,” he added.

New, updated recommendations from the ACC are coming soon, said Dr. Martinez. “I do not expect them to include CMR as first line.”
 

Cardiologists concerned about misinformation

This is at least the fourth study showing myocardial damage post-COVID-19 infection and there is concern in the medical community that the media has overstated the risks of heart damage, especially in athletes, and at the same time overstated the benefits of CMR.

In particular, Puntmann et al reported in July a 100-patient study that showed evidence of myocardial inflammation by CMR in 78% of patients recently recovered from a bout of COVID-19 (JAMA Cardiol. 2020 Jul 27; doi:10.1001/jamacardio.2020.3557).

“That paper is completely problematic,” John Mandrola, MD, of Baptists Medical Associates, Louisville, Ky., said in an interview. “It has the same overarching weaknesses [of other studies] that it’s observational and retrospective, but there were also numerical issues. So to me that paper is an interesting observation, but utterly unconvincing and preliminary,” said Dr. Mandrola.

Those limitations didn’t stop the study from garnering media attention, however. The Altmetric score (an attention score that tracks all mentions of an article in the media and on social media) for the Puntmann et al paper is approaching 13,000, including coverage from 276 news outlets and more than 19,000 tweets, putting it in the 99th percentile of all research outputs tracked by Altmetric to date.

To counter this, an “open letter” posted online just days before the Rajpal study published urging professional societies to “offer clear guidance discouraging CMR screening for COVID-19 related heart abnormalities in asymptomatic members of the general public.” The letter was signed by 51 clinicians, researchers, and imaging specialists from around the world.

Dr. Mandrola, one of the signatories, said: “This topic really scares people, and when it gets in the media like this, I think the leaders of these societies need to come out and say something really clear on major news networks letting people know that it’s just way too premature to start doing CMRs on every athlete that’s gotten this virus.”

“I understand that the current guidelines may be clear that CMR is not a first-line test for this indication, but when the media coverage is so extensive and so overblown, I wonder how much impact the guidelines will have in countering this fear that’s in the community,” he added.

Asked to comment on the letter, Dr. Rajpal said he agrees with the signatories that asymptomatic people from general population do not need routine cardiac MRI. “However, competitive athletes are a different story. Testing depends on risk assessment in specific population and competitive athletes as per our protocol will get enhanced cardiac workup including CMR for responsible and safe start of competitive sports. ... In the present scenario, while we get more data including control data, we will continue with our current protocol.”

Dr. Mandrola is Medscape Cardiology’s Chief Cardiology Consultant. MDedge is part of the Medscape Professional Network.

This article first appeared on Medscape.com.

A new study using cardiac magnetic resonance (CMR) imaging to examine the effects of novel coronavirus infection on the heart showed signs suggestive of myocarditis in 4 out of 26 competitive athletes who recovered from asymptomatic or mild cases of COVID-19.

While these and other similar findings are concerning, commentators are saying the results are preliminary and do not indicate widespread CMR screening is appropriate.

Two of the 4 patients showing signs of myocarditis in this series had no symptoms of COVID-19 but tested positive on routine testing. An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (30.8%) had LGE without T2 elevation suggestive of prior myocardial injury.

An additional 12 student athletes (46%) showed late gadolinium enhancement (LGE), of whom 8 (31%) had LGE without T2 elevation suggestive of prior myocardial injury.

This finding, said Saurabh Rajpal, MBBS, MD, the study’s lead author, “could suggest prior myocardial injury or it could suggest athletic myocardial adaptation.”

In a research letter published in JAMA Cardiology, Rajpal and colleagues at Ohio State University in Columbus, described the findings of comprehensive CMR examinations in competitive athletes referred to the sport medicine clinic after testing positive for COVID-19 on reverse transcriptase-polymerase chain reaction between June and August 2020.

The university had made the decision in the spring to use CMR imaging as a screening tool for return to play, said Dr. Rajpal. While CMR is being used for research purposes, the American College of Cardiology’s recent “consensus expert opinion” statement on resumption of sport and exercise after COVID-19 infection does not require CMR imaging for resumption of competitive activity (JAMA Cardiol. 2020 May 13. doi:10.1001/jamacardio.2020.2136).

None of the athletes required hospitalization for their illness, and only 27% reported mild symptoms during the short-term infection, including sore throat, shortness of breath, myalgia, and fever.

On the day of CMR imaging, ECG and transthoracic echocardiography were performed, and serum troponin I was measured. There were no diagnostic ST/T wave changes, ventricular function and volumes were normal, and no athletes showed elevated serum troponin levels.

The updated Lake Louise Criteria were used to assess CMR findings consistent with myocarditis.

“I don’t think this is a COVID-specific issue. We have seen myocarditis after other viral infections; it’s just that COVID-19 is the most studied thus far, and with strenuous activity, inflammation in the heart can be risky,” Dr. Rajpal said in an interview. He added that more long-term and larger studies with control populations are needed.

His group is continuing to follow these athletes and has suggested that CMR “may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation.”
 

Significance still unknown

Matthew Martinez, MD, the director of sports cardiology at Atlantic Health – Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, urged caution in making too much of the findings of this small study.

“We know that viruses cause myocardial damage and myocarditis. What we don’t know is how important these findings are. And in terms of risk, would we find the same phenomenon if we did this, say, in flu patients or in other age groups?” Dr. Martinez said in an interview.

“I haven’t seen all the images, but what I’d want to know is are these very subtle findings? Are these overt findings? Is this part of an active individual with symptoms? I need to know a little more data before I can tell if this influences the increased risk of sudden cardiac death that we often associate with myocarditis. I’m not sure how this should influence making decisions with regards to return to play.”

Dr. Martinez, who is the ACC’s chair of Sports and Exercise but was not an author of their recent guidance on return to sport, said that he is not routinely using CMR to assess athletes post-infection, as per the ACC’s recommendations.

“My approach is to evaluate anybody with a history of COVID infection and, first, determine whether it was an important infection with significant symptoms or not. And then, if they’re participating at a high level or are professional athletes, I would suggest an ECG, echo, and troponin. That’s our recommendation for the last several months and is still an appropriate way to evaluate that group.”

“In the presence of an abnormality or ongoing symptoms, I would ask for an MRI at that point,” said Dr. Martinez.

“We just don’t have much data on athletes with no symptoms to use to interpret these CMR findings and the study didn’t offer any controls. We don’t even know if these findings are new findings or old findings that have just been identified now,” he added.

New, updated recommendations from the ACC are coming soon, said Dr. Martinez. “I do not expect them to include CMR as first line.”
 

Cardiologists concerned about misinformation

This is at least the fourth study showing myocardial damage post-COVID-19 infection and there is concern in the medical community that the media has overstated the risks of heart damage, especially in athletes, and at the same time overstated the benefits of CMR.

In particular, Puntmann et al reported in July a 100-patient study that showed evidence of myocardial inflammation by CMR in 78% of patients recently recovered from a bout of COVID-19 (JAMA Cardiol. 2020 Jul 27; doi:10.1001/jamacardio.2020.3557).

“That paper is completely problematic,” John Mandrola, MD, of Baptists Medical Associates, Louisville, Ky., said in an interview. “It has the same overarching weaknesses [of other studies] that it’s observational and retrospective, but there were also numerical issues. So to me that paper is an interesting observation, but utterly unconvincing and preliminary,” said Dr. Mandrola.

Those limitations didn’t stop the study from garnering media attention, however. The Altmetric score (an attention score that tracks all mentions of an article in the media and on social media) for the Puntmann et al paper is approaching 13,000, including coverage from 276 news outlets and more than 19,000 tweets, putting it in the 99th percentile of all research outputs tracked by Altmetric to date.

To counter this, an “open letter” posted online just days before the Rajpal study published urging professional societies to “offer clear guidance discouraging CMR screening for COVID-19 related heart abnormalities in asymptomatic members of the general public.” The letter was signed by 51 clinicians, researchers, and imaging specialists from around the world.

Dr. Mandrola, one of the signatories, said: “This topic really scares people, and when it gets in the media like this, I think the leaders of these societies need to come out and say something really clear on major news networks letting people know that it’s just way too premature to start doing CMRs on every athlete that’s gotten this virus.”

“I understand that the current guidelines may be clear that CMR is not a first-line test for this indication, but when the media coverage is so extensive and so overblown, I wonder how much impact the guidelines will have in countering this fear that’s in the community,” he added.

Asked to comment on the letter, Dr. Rajpal said he agrees with the signatories that asymptomatic people from general population do not need routine cardiac MRI. “However, competitive athletes are a different story. Testing depends on risk assessment in specific population and competitive athletes as per our protocol will get enhanced cardiac workup including CMR for responsible and safe start of competitive sports. ... In the present scenario, while we get more data including control data, we will continue with our current protocol.”

Dr. Mandrola is Medscape Cardiology’s Chief Cardiology Consultant. MDedge is part of the Medscape Professional Network.

This article first appeared on Medscape.com.

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

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

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

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

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

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

A challenging recommendation

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

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

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

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

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

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

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

More efficient, economic

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

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

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

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

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

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

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

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

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

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

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

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

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

A challenging recommendation

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

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

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

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

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

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

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

More efficient, economic

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

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

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

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

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

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

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

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

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

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

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

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

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

A challenging recommendation

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

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

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

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

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

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

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

More efficient, economic

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

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

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

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

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

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

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

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

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

New guidelines on sports cardiology from the European Society of Cardiology break fresh ground by green-lighting participation in vigorous competitive sports by selected patients with stable coronary artery disease, heart failure, or mild arrhythmias.

These liberalized guidelines, released at the virtual annual congress of the European Society of Cardiology, thus move well beyond the standard exercise advice to engage in about 150 minutes per week of moderate physical activity, typically defined as brisk walking or its equivalent.

The guidelines reflect a conviction that exercise is powerful medicine for patients with cardiovascular disease and also affords a means to help curb the epidemics of diabetes and obesity that drive cardiovascular risk, according to Antonio Pelliccia, MD, who cochaired the 24-member task force of European and American experts that developed the guidelines.

In a session highlighting the new sports cardiology guidelines, Mats Borjesson, MD, head of the Center for Health and Performance at Gothenburg (Sweden) University, summarized the section devoted to patients with stable coronary artery disease: “If you have established CAD and a low risk of adverse events during exercise, you are eligible for high-intensity exercise and competitive sports. But if you have persistent ischemia despite medical treatment, or symptoms, then you’re only eligible for leisure-time subthreshold activity.”

Dr. Pelliccia put this new recommendation into context.

“We are not talking anymore in this particular disease just about cardiac rehabilitation or leisure-time activity, but we are also opening the border and talking about competitive sports activity in selected patients where you have the evidence for low risk of exercise-induced adverse events. This is a major achievement now for what is the major disease in our adult population,” said Dr. Pelliccia, chief of cardiology at the Institute of Sports Medicine and Science at the Italian National Olympic Committee and professor of sports cardiology at La Sapienza University of Rome.

The recommendation for individualized consideration of all types of exercise, even including vigorous competitive sports, in low-risk patients with CAD gets a class IIa, level of evidence (LOE) C recommendation in the new guidelines. That’s a big step down from a ringing class Ia endorsement, but since sports cardiology is a relatively young field with little evidence that’s based on randomized trials, the guidelines are rife with many other class IIa, LOE C recommendations as well.

“The level of evidence is rather low, so these guidelines are very much the personal perspective of the expert panel,” explained Martin Halle, MD, professor and head of the department of prevention, rehabilitation, and sports cardiology at Technical University of Munich.

The high-risk features for exercise-induced cardiac adverse events in patients with longstanding stable CAD, as cited in the guidelines, include a critical coronary stenosis, defined as a more than 70% lesion in a major coronary artery or a greater than 50% stenosis in the left main, and/or a fractional flow reserve score of less than 0.8; a left ventricular ejection fraction of 50% or less with wall-motion abnormalities; inducible myocardial ischemia on maximal exercise testing; nonsustained ventricular tachycardia; polymorphic or very frequent ventricular premature beats at rest and during maximum stress; and a recent acute coronary syndrome (ACS). These features call for an exercise prescription tailored to remain below the patient’s angina and ischemia thresholds.

“It’s important for cardiologists out there to understand that we definitely need a maximal exercise test. In somebody who is running and has an ACS and then wants to start running again, 200 watts on an ergometer is too low. We have to push them up to the end, and then if everything is okay – left ventricular function is okay, no ischemia, no arrhythmias under exercise testing – then it’s fine,” Dr. Halle said.

Dr. Pelliccia added that close follow-up is needed, because this is an evolving disease.”
 

Exercise and heart failure

Massimo F. Piepoli, MD, PhD, noted that the guidelines give a class IIb, LOE C recommendation for consideration of high-intensity recreational endurance and power sports in patients with heart failure with either midrange or preserved ejection fraction, provided they are stable, asymptomatic, on optimal guideline-directed medical therapy, and without abnormalities on a maximal exercise stress test.

European Society of Cardiology

However, such intense physical activity is not recommended in patients with heart failure with reduced ejection fraction, regardless of their symptom status, added Dr. Piepoli of Guglielmo da Saliceto Hospital in Placenza, Italy.

“We’re talking here, I think for the first time, about possible competitive sports participation in individuals with heart failure, depending on their clinical condition. We are really opening the barriers to sports participation, even in these patients in whom we never thought of it before,” Dr. Pelliccia observed.

Valvular heart disease and exercise

Guidelines panelist Sabiha Gati, MRCP, PhD, said asymptomatic individuals with mild valvular abnormalities can participate in all recreational and competitive sports; that’s a class I, LOE C recommendation.

European Society of Cardiology

“Moderate regurgitant lesions are better tolerated than stenotic lesions, and those with preserved systolic function, good functional capacity, without any exercise-induced arrhythmias or ischemia or abnormal hemodynamic response are considered to be low risk and can participate in all sports,” added Dr. Gati, a cardiologist at Royal Brompton Hospital, London.

The two most common valvular abnormalities encountered in clinical practice are bicuspid aortic valve and mitral valve prolapse. Dr. Gati noted that, while mitral valve prolapse has a benign prognosis in the great majority of affected individuals, the presence of specific features indicative of increased risk for sudden cardiac death precludes participation in strenuous exercise. These include T-wave inversion in the inferior leads on a 12-lead ECG, long QT, bileaflet mitral valve prolapse, basal inferolateral wall fibrosis, severe mitral regurgitation, or a family history of sudden cardiac death.

Bicuspid aortic valve has a prevalence of 1%-2% in the general population. It can be associated with aortic stenosis, aortic regurgitation, and increased risk of ascending aortic aneurysm and dissection. Since it remains unclear whether intensive exercise accelerates aortic dilatation, a cautious approach to sports participation is recommended in patients with an ascending aorta above the normal limit of 40 mm, she said.

The 80-page ESC sports cardiology guidelines, published online simultaneously with their presentation, cover a broad range of additional topics, including exercise recommendations for the general public, for the elderly, as well as for patients with cardiomyopathies, adult congenital heart disease, arrhythmias, and channelopathies. Gaps in evidence are also highlighted.

[email protected]

SOURCE: Pelliccia A. ESC 2020 and Eur Heart J. 2020 Aug 29. doi: 10.1093/eurheartj/ehaa605.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

Biologics used as treatment for psoriasis may also help reduce lipid-rich necrotic core (LRNC), a high-risk plaque associated with cardiovascular events, recent research from a prospective, observational study suggests.

Waldemarus/Thinkstock

Cardiac CT scans performed on patients with psoriasis 1 year after starting biologic therapy revealed a reduction in LRNC, compared with patients who were not receiving biologics, according to Harry Choi, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health and colleagues. The association with reduction in LRNC and biologic therapy remained significant when adjusted for type of biologic. “These findings demonstrate that LRNC may be modulated by the control of systemic inflammation,” the researchers wrote in their study, published Sept. 15 in Circulation: Cardiovascular Imaging.

Dr. Choi and colleagues evaluated 289 patients with psoriasis within the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative cohort. The patients had a mean age of 50 years and a mean body mass index of 29.4 kg/m², as well as a mean Psoriasis Area and Severity Index (PASI) score of 6.0. At baseline, 29% of patients had hypertension, 41% had hyperlipidemia, their mean Framingham risk score was 1.9, and a three-quarters (212 of 289) had mild to moderate psoriasis.

Changes in LRNC were observed at 1 year, compared with baseline prior to and after receiving biologic therapy (124 patients) in comparison with patients who did not undergo biologic therapy (85 patients). Biologic therapies were grouped by type, which included anti–tumor necrosis factor (anti-TNF), anti–interleukin (IL)–12/23, and anti–IL-17 biologics.

There were a significant associations between LRNC and Framingham risk score (standardized beta coefficient, 0.12; 95% confidence interval, 0.00-0.15; P = .045) and severity of psoriasis (beta, 0.13; 95% CI, 0.01-0.26; P = .029) at baseline.
 

Key findings

The researchers found a significant reduction in LRNC 1 year after patients began biologic therapy (median, 2.97 mm²; interquartile range, 1.99-4.66), compared with baseline (median, 3.12 mm²; IQR, 1.84-4.35) (P = .028), while patients who did not receive biologic therapy had nonsignificantly higher LRNC after 1 year (median, 3.12 mm²; IQR, 1.82-4.60), compared with baseline measurements (median, 3.34 mm²; IQR, 2.04–4.74) (P = .06).

The results remained significant after the researchers adjusted for psoriasis severity, Framingham risk score, BMI, use of statins (beta, −0.09; 95% CI, −0.01 to −0.18; P = .033). Significant reductions in LRNC also remained when analyzing patients receiving anti-TNF, anti–IL-12/23, and anti–IL-17 biologics independently, and there were no significant between-group differences in reduction of LRNC.
 

The potential of biologics for improving vascular health

Discussing the study results in a press release from the American Heart Association, senior author Nehal N. Mehta, MD, MSCE, FAHA, chief of the Lab of Inflammation and Cardiometabolic Diseases at the NHLBI at NIH, compared the effect biologic therapy had on coronary plaque reduction with that of statins.

“There is approximately 6%-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries,” Dr. Mehta said in the release.

In an interview, Nieca Goldberg, MD, medical director of NYU Women’s Heart Program at NYU Langone Health, echoed Dr. Mehta’s commments and said psoriasis carries the “potential to treat two conditions with the same drug.”

“We know conditions such as psoriatic arthritis and rheumatoid arthritis cause chronic inflammation. Chronic inflammation causes injury to blood vessels and high-risk coronary plaque. Individuals with these inflammatory conditions are at high risk for heart attack,” she said. “This study shows that biologic treatment for psoriatic arthritis can reduce the presence of high-risk plaque. It shows the potential to treat chronic inflammation and high-risk coronary plaque.”

While the results show an association between use of biologics and LRNC reduction, the study design was observational and patients had a short follow-up period. Dr. Goldberg noted more studies are needed to evaluate the effect of biologics on reducing cardiovascular events such as a myocardial infarction.

“We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health,” Dr. Mehta said in the press release. “Imagine if we can treat both psoriasis and coronary heart disease with one therapy – that is the question to be asked in future studies.”

This study was funded with support from the NHLBI Intramural Research Program and the NIH Medical Research Scholars Program at the National Institutes of Health. One investigator reports financial relationships with numerous pharmaceutical companies. The other authors report no relevant conflicts of interest. Dr. Mehta also reports numerous such relationships. Dr. Goldberg reports no relevant conflicts of interest.

SOURCE: Choi H et al. Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

More people with diffuse idiopathic skeletal hyperostosis (DISH) develop cardiovascular disease (CVD) than is predicted by the Framingham Risk Score, results of an observational study have shown.

Atherosclerosis. 2019;287:24-9 (CC BY 4.0)

Notably, a higher rate of myocardial infarction (MI) was seen in those with DISH than in those without DISH over the 10-year follow-up period (24.4% vs. 4.3%; P = .0055).

“We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and as a result, earlier and more aggressive preventive medical interventions instituted,” corresponding author Reuven Mader, MD, and associates wrote in Arthritis Research & Therapy.

“What Mader’s study is pointing out is that it’s worth the radiologist reporting [DISH],” Elizabeth A. Regan, MD, PhD, from the National Jewish Health Center in Denver, said in an interview.

DISH on a chest x-ray or CT scan should be another “red flag to be even more attentive to cardiovascular risk,” she added, particularly because studies have shown that people with DISH tend to be obese, have metabolic syndrome, or diabetes – all of which independently increase their risk for cardiovascular disease.
 

An old condition often found by accident

Physicians have known about DISH for many years, Dr. Mader of Ha’Emek Medical Center in Afula, Israel, observed in an interview. Historical evidence suggests it was present more than a thousand years ago, but it wasn’t until the 1950s that it gained scientific interest. Originally coined Forestier’s disease, it was renamed DISH in the late 1960s following the realization that it was not limited to the spine.

“It is a condition which is characterized by new bone formation,” Dr. Mader explained. This new bone formation has some predilection for the entheses – the tendons, ligaments, or joint capsules, that attach to the bone.

“Diagnosis of the disease is based mainly on radiographs, especially of the thoracic spine, and it requires the formation of bridges that connect at least four contiguous vertebra,” he continued.

“The bridges are usually right-sided and usually the intervertebral spaces are spared. Classically there is no involvement of the sacroiliac joints, although there are some changes that might involve the sacroiliac joints but in a different manner than in inflammatory sacroiliitis.”

DISH was originally thought to be a pain syndrome, which has “not played out,” Dr. Regan noted in her interview. While there may be people who experience pain as a result of DISH, most cases are asymptomatic and usually picked up incidentally on a chest x-ray or CT scan.

“It’s something that’s not obvious,” she said. One of the main problems it can cause is stiffness and lack of mobility in the spine and this can lead to quite severe fractures in some cases, such as during a car accident. Hence spinal surgeons and other orthopedic specialists, such as Dr. Regan, have also taken an interest in the condition.

“Apart from the thoracic spine, DISH may also involve the cervical spine; there have been many reports about difficulty in swallowing, breathing, and in the lumbar spine, spinal stenosis and so forth,” Dr. Mader said. The differential diagnosis includes ankylosing spondylitis, although there is some evidence that the two can coexist.

“The diagnosis depends on the alertness of the examining physician,” he added, noting that rheumatologists and other specialists would be “very aware of this condition” and “sensitive to changes that we see when we examine these patients.”
 

DISH and heightened cardiovascular risk

Previous work by Dr. Mader and associates has shown that people with DISH are more often affected by the metabolic syndrome than are those without DISH. The cross-sectional study had excluded those with preexisting CVD and found that people with DISH had a significantly higher Framingham Risk Score, compared with a control group of people with osteoarthritis and no DISH (P = .004), which in turn meant they had a significantly (P = .007) higher 10-year risk for developing CVD.

The aim of their most recent study was to compare the actual rate of CV events in 2016 versus those predicted by the Framingham Risk Score in 2006. To do this, they compared the available electronic medical records of 45 individuals with DISH and 47 without it.

The results showed that almost 39% of people with DISH had developed CVD, whereas the Framingham Risk Score had estimated that just under 27% would develop CVD.

For every 1% increase in the CVD risk calculated by the Framingham Risk Score, the odds of CVD increased by 4% in the DISH group versus the control group (P = .02).

While there was a significant (P < .003) difference in the Framingham Risk Score between the DISH and control groups in 2006 (28.6% vs. 17.8%), there was no overall statistical difference (P = .2) in the composite CVD outcome (38.8% vs. 25.5%) 10 years later, as calculated by the revised Framingham Risk Score, which included MI, cerebrovascular accident, transient ischemic attack, peripheral artery disease, and heart failure with preserved ejection fraction.

“We are dealing with patients who are in their 70s. So, it is expected that this group of patients will be more often affected by cardiovascular disease” than younger individuals, Dr. Mader observed. That said, the study’s findings “confirm the theory that patients with DISH have a high likelihood of developing cardiovascular disease,” he added, acknowledging that it was only the risk for MI that was statistically significantly higher in people with DISH than in the controls.
 

DISH and coronary artery calcification

“It might be even more interesting to have a different control population that had no osteoarthritis,” Dr. Regan observed.

As the associate director of the COPDGene study, Dr. Regan has access to data collected from a large cohort of people with chronic obstructive pulmonary disease (COPD; n = 2,728), around 13% of whom were identified as having DISH in one recent study.

In that study, the presence of DISH versus no DISH was associated with a 37% higher risk for having coronary artery calcification (CAC) – a marker for atherosclerosis and cardiovascular disease. Two-thirds of people with DISH had CAC, compared with 46.9% of those without DISH (P < .001). The prevalence of DISH was 8.8% in those without CAC, 12.8% in those with a CAC score of 1-100, 20% in those with a CAC score of 100-400, and 24.7% in those with a CAC score of more than 400, which is associated with a very high risk for coronary artery disease.

Dr. Regan observed that information on heart attacks and strokes were collected within the COPDGene study, so it would be possible to look at cardiovascular risk in their patients with DISH and confirm the findings of Mader and colleagues.

“I think the most important thing is recognizing that there are things going on in the spine that are important to people’s general health,” Dr. Regan said.

Dr. Mader noted: “It makes sense that patients with DISH should be more meticulously followed for at least the traditional risk factors and better treated because they are at a higher risk for these events.”

The study received no financial support. Neither Dr. Mader nor Dr. Regan had any conflicts of interest to disclose.

SOURCE: Glick K et al. Arthritis Res Ther. 2020. doi: 10.1186/s13075-020-02278-w.

More people with diffuse idiopathic skeletal hyperostosis (DISH) develop cardiovascular disease (CVD) than is predicted by the Framingham Risk Score, results of an observational study have shown.

Atherosclerosis. 2019;287:24-9 (CC BY 4.0)

Notably, a higher rate of myocardial infarction (MI) was seen in those with DISH than in those without DISH over the 10-year follow-up period (24.4% vs. 4.3%; P = .0055).

“We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and as a result, earlier and more aggressive preventive medical interventions instituted,” corresponding author Reuven Mader, MD, and associates wrote in Arthritis Research & Therapy.

“What Mader’s study is pointing out is that it’s worth the radiologist reporting [DISH],” Elizabeth A. Regan, MD, PhD, from the National Jewish Health Center in Denver, said in an interview.

DISH on a chest x-ray or CT scan should be another “red flag to be even more attentive to cardiovascular risk,” she added, particularly because studies have shown that people with DISH tend to be obese, have metabolic syndrome, or diabetes – all of which independently increase their risk for cardiovascular disease.
 

An old condition often found by accident

Physicians have known about DISH for many years, Dr. Mader of Ha’Emek Medical Center in Afula, Israel, observed in an interview. Historical evidence suggests it was present more than a thousand years ago, but it wasn’t until the 1950s that it gained scientific interest. Originally coined Forestier’s disease, it was renamed DISH in the late 1960s following the realization that it was not limited to the spine.

“It is a condition which is characterized by new bone formation,” Dr. Mader explained. This new bone formation has some predilection for the entheses – the tendons, ligaments, or joint capsules, that attach to the bone.

“Diagnosis of the disease is based mainly on radiographs, especially of the thoracic spine, and it requires the formation of bridges that connect at least four contiguous vertebra,” he continued.

“The bridges are usually right-sided and usually the intervertebral spaces are spared. Classically there is no involvement of the sacroiliac joints, although there are some changes that might involve the sacroiliac joints but in a different manner than in inflammatory sacroiliitis.”

DISH was originally thought to be a pain syndrome, which has “not played out,” Dr. Regan noted in her interview. While there may be people who experience pain as a result of DISH, most cases are asymptomatic and usually picked up incidentally on a chest x-ray or CT scan.

“It’s something that’s not obvious,” she said. One of the main problems it can cause is stiffness and lack of mobility in the spine and this can lead to quite severe fractures in some cases, such as during a car accident. Hence spinal surgeons and other orthopedic specialists, such as Dr. Regan, have also taken an interest in the condition.

“Apart from the thoracic spine, DISH may also involve the cervical spine; there have been many reports about difficulty in swallowing, breathing, and in the lumbar spine, spinal stenosis and so forth,” Dr. Mader said. The differential diagnosis includes ankylosing spondylitis, although there is some evidence that the two can coexist.

“The diagnosis depends on the alertness of the examining physician,” he added, noting that rheumatologists and other specialists would be “very aware of this condition” and “sensitive to changes that we see when we examine these patients.”
 

DISH and heightened cardiovascular risk

Previous work by Dr. Mader and associates has shown that people with DISH are more often affected by the metabolic syndrome than are those without DISH. The cross-sectional study had excluded those with preexisting CVD and found that people with DISH had a significantly higher Framingham Risk Score, compared with a control group of people with osteoarthritis and no DISH (P = .004), which in turn meant they had a significantly (P = .007) higher 10-year risk for developing CVD.

The aim of their most recent study was to compare the actual rate of CV events in 2016 versus those predicted by the Framingham Risk Score in 2006. To do this, they compared the available electronic medical records of 45 individuals with DISH and 47 without it.

The results showed that almost 39% of people with DISH had developed CVD, whereas the Framingham Risk Score had estimated that just under 27% would develop CVD.

For every 1% increase in the CVD risk calculated by the Framingham Risk Score, the odds of CVD increased by 4% in the DISH group versus the control group (P = .02).

While there was a significant (P < .003) difference in the Framingham Risk Score between the DISH and control groups in 2006 (28.6% vs. 17.8%), there was no overall statistical difference (P = .2) in the composite CVD outcome (38.8% vs. 25.5%) 10 years later, as calculated by the revised Framingham Risk Score, which included MI, cerebrovascular accident, transient ischemic attack, peripheral artery disease, and heart failure with preserved ejection fraction.

“We are dealing with patients who are in their 70s. So, it is expected that this group of patients will be more often affected by cardiovascular disease” than younger individuals, Dr. Mader observed. That said, the study’s findings “confirm the theory that patients with DISH have a high likelihood of developing cardiovascular disease,” he added, acknowledging that it was only the risk for MI that was statistically significantly higher in people with DISH than in the controls.
 

DISH and coronary artery calcification

“It might be even more interesting to have a different control population that had no osteoarthritis,” Dr. Regan observed.

As the associate director of the COPDGene study, Dr. Regan has access to data collected from a large cohort of people with chronic obstructive pulmonary disease (COPD; n = 2,728), around 13% of whom were identified as having DISH in one recent study.

In that study, the presence of DISH versus no DISH was associated with a 37% higher risk for having coronary artery calcification (CAC) – a marker for atherosclerosis and cardiovascular disease. Two-thirds of people with DISH had CAC, compared with 46.9% of those without DISH (P < .001). The prevalence of DISH was 8.8% in those without CAC, 12.8% in those with a CAC score of 1-100, 20% in those with a CAC score of 100-400, and 24.7% in those with a CAC score of more than 400, which is associated with a very high risk for coronary artery disease.

Dr. Regan observed that information on heart attacks and strokes were collected within the COPDGene study, so it would be possible to look at cardiovascular risk in their patients with DISH and confirm the findings of Mader and colleagues.

“I think the most important thing is recognizing that there are things going on in the spine that are important to people’s general health,” Dr. Regan said.

Dr. Mader noted: “It makes sense that patients with DISH should be more meticulously followed for at least the traditional risk factors and better treated because they are at a higher risk for these events.”

The study received no financial support. Neither Dr. Mader nor Dr. Regan had any conflicts of interest to disclose.

SOURCE: Glick K et al. Arthritis Res Ther. 2020. doi: 10.1186/s13075-020-02278-w.

More people with diffuse idiopathic skeletal hyperostosis (DISH) develop cardiovascular disease (CVD) than is predicted by the Framingham Risk Score, results of an observational study have shown.

Atherosclerosis. 2019;287:24-9 (CC BY 4.0)

Notably, a higher rate of myocardial infarction (MI) was seen in those with DISH than in those without DISH over the 10-year follow-up period (24.4% vs. 4.3%; P = .0055).

“We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and as a result, earlier and more aggressive preventive medical interventions instituted,” corresponding author Reuven Mader, MD, and associates wrote in Arthritis Research & Therapy.

“What Mader’s study is pointing out is that it’s worth the radiologist reporting [DISH],” Elizabeth A. Regan, MD, PhD, from the National Jewish Health Center in Denver, said in an interview.

DISH on a chest x-ray or CT scan should be another “red flag to be even more attentive to cardiovascular risk,” she added, particularly because studies have shown that people with DISH tend to be obese, have metabolic syndrome, or diabetes – all of which independently increase their risk for cardiovascular disease.
 

An old condition often found by accident

Physicians have known about DISH for many years, Dr. Mader of Ha’Emek Medical Center in Afula, Israel, observed in an interview. Historical evidence suggests it was present more than a thousand years ago, but it wasn’t until the 1950s that it gained scientific interest. Originally coined Forestier’s disease, it was renamed DISH in the late 1960s following the realization that it was not limited to the spine.

“It is a condition which is characterized by new bone formation,” Dr. Mader explained. This new bone formation has some predilection for the entheses – the tendons, ligaments, or joint capsules, that attach to the bone.

“Diagnosis of the disease is based mainly on radiographs, especially of the thoracic spine, and it requires the formation of bridges that connect at least four contiguous vertebra,” he continued.

“The bridges are usually right-sided and usually the intervertebral spaces are spared. Classically there is no involvement of the sacroiliac joints, although there are some changes that might involve the sacroiliac joints but in a different manner than in inflammatory sacroiliitis.”

DISH was originally thought to be a pain syndrome, which has “not played out,” Dr. Regan noted in her interview. While there may be people who experience pain as a result of DISH, most cases are asymptomatic and usually picked up incidentally on a chest x-ray or CT scan.

“It’s something that’s not obvious,” she said. One of the main problems it can cause is stiffness and lack of mobility in the spine and this can lead to quite severe fractures in some cases, such as during a car accident. Hence spinal surgeons and other orthopedic specialists, such as Dr. Regan, have also taken an interest in the condition.

“Apart from the thoracic spine, DISH may also involve the cervical spine; there have been many reports about difficulty in swallowing, breathing, and in the lumbar spine, spinal stenosis and so forth,” Dr. Mader said. The differential diagnosis includes ankylosing spondylitis, although there is some evidence that the two can coexist.

“The diagnosis depends on the alertness of the examining physician,” he added, noting that rheumatologists and other specialists would be “very aware of this condition” and “sensitive to changes that we see when we examine these patients.”
 

DISH and heightened cardiovascular risk

Previous work by Dr. Mader and associates has shown that people with DISH are more often affected by the metabolic syndrome than are those without DISH. The cross-sectional study had excluded those with preexisting CVD and found that people with DISH had a significantly higher Framingham Risk Score, compared with a control group of people with osteoarthritis and no DISH (P = .004), which in turn meant they had a significantly (P = .007) higher 10-year risk for developing CVD.

The aim of their most recent study was to compare the actual rate of CV events in 2016 versus those predicted by the Framingham Risk Score in 2006. To do this, they compared the available electronic medical records of 45 individuals with DISH and 47 without it.

The results showed that almost 39% of people with DISH had developed CVD, whereas the Framingham Risk Score had estimated that just under 27% would develop CVD.

For every 1% increase in the CVD risk calculated by the Framingham Risk Score, the odds of CVD increased by 4% in the DISH group versus the control group (P = .02).

While there was a significant (P < .003) difference in the Framingham Risk Score between the DISH and control groups in 2006 (28.6% vs. 17.8%), there was no overall statistical difference (P = .2) in the composite CVD outcome (38.8% vs. 25.5%) 10 years later, as calculated by the revised Framingham Risk Score, which included MI, cerebrovascular accident, transient ischemic attack, peripheral artery disease, and heart failure with preserved ejection fraction.

“We are dealing with patients who are in their 70s. So, it is expected that this group of patients will be more often affected by cardiovascular disease” than younger individuals, Dr. Mader observed. That said, the study’s findings “confirm the theory that patients with DISH have a high likelihood of developing cardiovascular disease,” he added, acknowledging that it was only the risk for MI that was statistically significantly higher in people with DISH than in the controls.
 

DISH and coronary artery calcification

“It might be even more interesting to have a different control population that had no osteoarthritis,” Dr. Regan observed.

As the associate director of the COPDGene study, Dr. Regan has access to data collected from a large cohort of people with chronic obstructive pulmonary disease (COPD; n = 2,728), around 13% of whom were identified as having DISH in one recent study.

In that study, the presence of DISH versus no DISH was associated with a 37% higher risk for having coronary artery calcification (CAC) – a marker for atherosclerosis and cardiovascular disease. Two-thirds of people with DISH had CAC, compared with 46.9% of those without DISH (P < .001). The prevalence of DISH was 8.8% in those without CAC, 12.8% in those with a CAC score of 1-100, 20% in those with a CAC score of 100-400, and 24.7% in those with a CAC score of more than 400, which is associated with a very high risk for coronary artery disease.

Dr. Regan observed that information on heart attacks and strokes were collected within the COPDGene study, so it would be possible to look at cardiovascular risk in their patients with DISH and confirm the findings of Mader and colleagues.

“I think the most important thing is recognizing that there are things going on in the spine that are important to people’s general health,” Dr. Regan said.

Dr. Mader noted: “It makes sense that patients with DISH should be more meticulously followed for at least the traditional risk factors and better treated because they are at a higher risk for these events.”

The study received no financial support. Neither Dr. Mader nor Dr. Regan had any conflicts of interest to disclose.

SOURCE: Glick K et al. Arthritis Res Ther. 2020. doi: 10.1186/s13075-020-02278-w.