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Screening finds high rates of CVD in diabetes, COPD patients
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AT ESC CONGRESS 2023
ESC backs SGLT2 inhibitor plus GLP-1 in diabetes with high CVD risk
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AT ESC CONGRESS 2023
Low-dose colchicine for ASCVD: Your questions answered
This transcript has been edited for clarity.
Dr. O’Donoghue: We’re going to discuss a very important and emerging topic, which is the use of low-dose colchicine. I think there’s much interest in the use of this drug, which now has a Food and Drug Administration indication, which we’ll talk about further, and it’s also been written into both European and American guidelines that have been recently released.
who’s been at the forefront of research into anti-inflammatory therapeutics.
Lifestyle lipid-lowering paramount
Dr. O’Donoghue: As we think about the concept behind the use of colchicine, we’ve obviously done a large amount of research into lipid-lowering drugs, but where does colchicine now fit in?
Dr. Ridker: Let’s make sure we get the basics down. Anti-inflammatory therapy is going to be added on top of quality other care. This is not a replacement for lipids; it’s not a change in diet, exercise, and smoking cessation. The new data are really telling us that a patient who’s aggressively treated to guideline-recommended levels can still do much better in terms of preventing heart attack, stroke, cardiovascular death, and revascularization by adding low-dose colchicine as the first proven anti-inflammatory therapy for atherosclerotic disease.
I have to say, Michelle, for me, it’s been a wonderful end of a journey in many ways. This story starts almost 30 years ago for quite a few of us, thinking about inflammation and atherosclerosis. The whole C-reactive protein (CRP) story is still an ongoing one. We recently showed, for example, that residual inflammatory risk in some 30,000 patients, all taking a statin, was a far better predictor of the likelihood of more cardiovascular events, in particular cardiovascular death, than was residual cholesterol risk.
Think about that. We’re all aggressively giving second lipid-lowering drugs in our very sick patients, but that means inflammation is really the untapped piece of this.
The two clinical trials we have in front of us, the COLCOT trial and the LoDoCo2 trial – both New England Journal of Medicine papers, both with roughly 5,000 patients – provide very clear evidence that following a relatively recent myocardial infarction (that’s COLCOT) in chronic stable atherosclerosis (that’s LoDoCo2), we’re getting 25%-30% relative risk reductions in major adverse cardiovascular events (MACEs) on top of aggressive statin therapy. That’s a big deal. It’s safe, it works, and it’s fully consistent with all the information we have about inflammation being part and parcel of atherosclerosis. It’s a pretty exciting time.
Inflammatory pathway
Dr. O’Donoghue: It beautifully proves the inflammatory hypothesis in many ways. You led CANTOS, and that was a much more specific target. Here, in terms of the effects of colchicine, what do we know about how it may work on the inflammatory cascade?
Dr. Ridker: Our CANTOS trial was proof of principle that you could directly target, with a very specific monoclonal antibody, a specific piece of this innate immune cascade and lower cardiovascular event rates.
Colchicine is a more broad-spectrum drug. It does have a number of antineutrophil effects – that’s important, by the way. Neutrophils are really becoming very important in atherosclerotic disease progression. It’s an indirect inhibitor of the so-called NLRP3 inflammasome, which is where both interleukin-1 (that’s the target for canakinumab) and IL-6 are up-regulated. As you know, it’s been used to treat gout and pericarditis in high doses in short, little bursts.
The change here is this use of low-dose colchicine, that’s 0.5 mg once a day for years to treat chronic, stable atherosclerosis. It is very much like using a statin. The idea here is to prevent the progression of the disease by slowing down and maybe stabilizing the plaque so we have fewer heart attacks and strokes down the road.
It’s entering the armamentarium – at least my armamentarium – as chronic, stable secondary prevention. That’s where the new American College of Cardiology/American Heart Association guidelines also put it. It’s really in as a treatment for chronic, stable atherosclerosis. I think that’s where it belongs.
When to start colchicine, and in whom?
Dr. O’Donoghue: To that point, as we think about the efficacy, I think it’s nice, as you outlined, that we have two complementary trials that are both showing a consistent reduction in MACEs, one in the post–acute coronary syndrome (ACS) state and one for more chronic patients.
At what point do you think would be the appropriate time to start therapy, and who would you be starting it for?
Dr. Ridker: Michelle, that’s a great question. There’s a very interesting analysis that just came out from the LoDoCo2 investigators. It’s kind of a landmark analysis. What they show is that 1 year, 2 years, 3 years, and 4 years since the initiating myocardial infarction, the drug is very effective.
In fact, you could think about starting this drug at your clinic in patients with chronic, stable atherosclerotic disease. That’s just like we would start a statin in people who had a heart attack some time ago, and that’s absolutely fine.
I’m using it for what I call my frequent fliers, those patients who just keep coming back. They’re already on aggressive lipid-lowering therapy. I have them on beta-blockers, aspirin, and all the usual things. I say, look, I can get a large risk reduction by starting them on this drug.
There are a few caveats, Michelle. Like all drugs, colchicine comes with some adverse effects. Most of them are pretty rare, but there are some patients I would not give this drug to, just to be very clear. Colchicine is cleared by the kidney and by the liver. Patients who have severe chronic kidney disease and severe liver disease – this is a no-go for those patients. We should talk about where patients in that realm might want to go.
Then there are some unusual drugs. Colchicine is metabolized by the CYP3A4 and the P-glycoprotein pathway. There are a few drugs, such as ketoconazole, fluconazole, and cyclosporine, that if your primary care doctor or internist is going to start for a short term, you probably want to stop your colchicine for a week or two.
In people with familial Mediterranean fever, for whom colchicine is lifesaving and life-changing and who take it for 20, 30, or 40 years, there’s been no increase in risk for cancer. There have been very few adverse effects. I think it’s interesting that we, who practice in North America, basically never see familial Mediterranean fever. If we were practicing in Lebanon, Israel, or North Africa, this would be a very common therapy that we’d all be extremely familiar with.
Dr. O’Donoghue: To that point, it’s interesting to hear that colchicine was even used by the ancient Greeks and ancient Egyptians. It’s a drug that’s been around for a long time.
In terms of its safety, some people have been talking about the fact that an increase in noncardiovascular death was seen in LoDoCo2. What are your thoughts on that? Is that anything that we should be concerned about?
Colchicine safety and contraindications
Dr. Ridker: First, to set the record straight, a meta-analysis has been done of all-cause mortality in the various colchicine trials, and the hazard ratio is 1.04. I’ll remind you, and all of us know, that the hazard ratios for all-cause mortality in the PCSK9 trials, the bempedoic acid trials, and the ezetimibe trials are also essentially neutral. We’re in a state where we don’t let these trials roll long enough to see benefits necessarily on all-cause mortality. Some of us think we probably should, but that’s just the reality of trials.
One of most interesting things that was part of the FDA review, I suspect, was that there was no specific cause of any of this. It was not like there was a set of particular issues. I suspect that most people think this is probably the play of chance and with time, things will get better.
Again, I do want to emphasize this is not a drug for severe chronic kidney disease and severe liver disease, because those patients will get in trouble with this. The other thing that’s worth knowing is when you start a patient on low-dose colchicine – that’s 0.5 mg/d – there will be some patients who get some short-term gastrointestinal upset. That’s very common when you start colchicine at the much higher doses you might use to treat acute gout or pericarditis. In these trials, the vast majority of patients treated through that, and there were very few episodes long-term. I think it’s generally safe. That’s where we’re at.
Dr. O’Donoghue: Paul, you’ve been a leader, certainly, at looking at CRP as a marker of inflammation. Do you, in your practice, consider CRP levels when making a decision about who is appropriate for this therapy?
Dr. Ridker: That’s another terrific question. I do, because I’m trying to distinguish in my own mind patients who have residual inflammatory risk, in whom the high-sensitivity CRP (hsCRP) level remains high despite being on statins versus those with residual cholesterol risk, in whom I’m really predominantly worried about LDL cholesterol, that I haven’t brought it down far enough.
I do measure it, and if the CRP remains high and the LDL cholesterol is low, to me, that’s residual inflammatory risk and that’s the patient I would target this to. Conversely, if the LDL cholesterol was still, say, above some threshold of 75-100 and I’m worried about that, even if the CRP is low, I’ll probably add a second lipid-lowering drug.
The complexity of this, however, is that CRP was not measured in either LoDoCo2 or COLCOT. That’s mostly because they didn’t have much funding. These trials were done really on a shoestring. They were not sponsored by major pharma at all. We know that the median hsCRP in these trials was probably around 3.5-4 mg/L so I’m pretty comfortable doing that. Others have just advocated giving it to many patients. I must say I like to use biomarkers to think through the biology and who might have the best benefit-to-risk ratio. In my practice, I am doing it that way.
Inpatient vs. outpatient initiation
Dr. O’Donoghue: This is perhaps my last question for you before we wrap up. I know you talked about use of low-dose colchicine for patients with more chronic, stable coronary disease. Now obviously, COLCOT studied patients who were early post ACS, and there we certainly think about the anti-inflammatory effects as potentially having more benefit. What are your thoughts about early initiation of colchicine in that setting, the acute hospitalized setting? Do you think it’s more appropriate for an outpatient start?
Dr. Ridker: Today, I think this is all about chronic, stable atherosclerosis. Yes, COLCOT enrolled their patients within 30 days of a recent myocardial infarction, but as we all know, that’s a pretty stable phase. The vast majority were enrolled after 15 days. There were a small number enrolled within 3 days or something like that, but the benefit is about the same in all these patients.
Conversely, there’s been a small number of trials looking at colchicine in acute coronary ischemia and they’ve not been terribly promising. That makes some sense, though, right? We want to get an artery open. In acute ischemia, that’s about revascularization. It’s about oxygenation. It’s about reperfusion injury. My guess is that 3, 4, 5, or 6 days later, when it becomes a stable situation, is when the drug is probably effective.
Again, there will be some ongoing true intervention trials with large sample sizes for acute coronary ischemia. We don’t have those yet. Right now, I think it’s a therapy for chronic, stable angina. That’s many of our patients.
I would say that if you compare the relative benefit in these trials of adding ezetimibe to a statin, that’s a 5% or 6% benefit. For PCSK9 inhibitors – we all use them – it’s about a 15% benefit. These are 25%-30% risk reductions. If we’re going to think about what’s the next drug to give on top of the statin, serious consideration should be given to low-dose colchicine.
Let me also emphasize that this is not an either/or situation. This is about the fact that we now understand atherosclerosis to be a disorder both of lipid accumulation and a proinflammatory systemic response. We can give these drugs together. I suspect that the best patient care is going to be very aggressive lipid-lowering combined with pretty aggressive inflammation inhibition. I suspect that, down the road, that’s where all of us are going to be.
Dr. O’Donoghue: Thank you so much, Paul, for walking us through that today. I think it was a very nice, succinct review of the evidence, and then also just getting our minds more accustomed to the concept that we can now start to target more orthogonal axes that really get at the pathobiology of what’s going on in the atherosclerotic plaque. I think it’s an important topic.
Dr. O’Donoghue is an associate professor of medicine at Harvard Medical School and an associate physician at Brigham and Women’s Hospital, both in Boston. Dr. Ridker is director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. Both Dr. O’Donoghue and Dr. Ridker reported numerous conflicts of interest.
This transcript has been edited for clarity.
Dr. O’Donoghue: We’re going to discuss a very important and emerging topic, which is the use of low-dose colchicine. I think there’s much interest in the use of this drug, which now has a Food and Drug Administration indication, which we’ll talk about further, and it’s also been written into both European and American guidelines that have been recently released.
who’s been at the forefront of research into anti-inflammatory therapeutics.
Lifestyle lipid-lowering paramount
Dr. O’Donoghue: As we think about the concept behind the use of colchicine, we’ve obviously done a large amount of research into lipid-lowering drugs, but where does colchicine now fit in?
Dr. Ridker: Let’s make sure we get the basics down. Anti-inflammatory therapy is going to be added on top of quality other care. This is not a replacement for lipids; it’s not a change in diet, exercise, and smoking cessation. The new data are really telling us that a patient who’s aggressively treated to guideline-recommended levels can still do much better in terms of preventing heart attack, stroke, cardiovascular death, and revascularization by adding low-dose colchicine as the first proven anti-inflammatory therapy for atherosclerotic disease.
I have to say, Michelle, for me, it’s been a wonderful end of a journey in many ways. This story starts almost 30 years ago for quite a few of us, thinking about inflammation and atherosclerosis. The whole C-reactive protein (CRP) story is still an ongoing one. We recently showed, for example, that residual inflammatory risk in some 30,000 patients, all taking a statin, was a far better predictor of the likelihood of more cardiovascular events, in particular cardiovascular death, than was residual cholesterol risk.
Think about that. We’re all aggressively giving second lipid-lowering drugs in our very sick patients, but that means inflammation is really the untapped piece of this.
The two clinical trials we have in front of us, the COLCOT trial and the LoDoCo2 trial – both New England Journal of Medicine papers, both with roughly 5,000 patients – provide very clear evidence that following a relatively recent myocardial infarction (that’s COLCOT) in chronic stable atherosclerosis (that’s LoDoCo2), we’re getting 25%-30% relative risk reductions in major adverse cardiovascular events (MACEs) on top of aggressive statin therapy. That’s a big deal. It’s safe, it works, and it’s fully consistent with all the information we have about inflammation being part and parcel of atherosclerosis. It’s a pretty exciting time.
Inflammatory pathway
Dr. O’Donoghue: It beautifully proves the inflammatory hypothesis in many ways. You led CANTOS, and that was a much more specific target. Here, in terms of the effects of colchicine, what do we know about how it may work on the inflammatory cascade?
Dr. Ridker: Our CANTOS trial was proof of principle that you could directly target, with a very specific monoclonal antibody, a specific piece of this innate immune cascade and lower cardiovascular event rates.
Colchicine is a more broad-spectrum drug. It does have a number of antineutrophil effects – that’s important, by the way. Neutrophils are really becoming very important in atherosclerotic disease progression. It’s an indirect inhibitor of the so-called NLRP3 inflammasome, which is where both interleukin-1 (that’s the target for canakinumab) and IL-6 are up-regulated. As you know, it’s been used to treat gout and pericarditis in high doses in short, little bursts.
The change here is this use of low-dose colchicine, that’s 0.5 mg once a day for years to treat chronic, stable atherosclerosis. It is very much like using a statin. The idea here is to prevent the progression of the disease by slowing down and maybe stabilizing the plaque so we have fewer heart attacks and strokes down the road.
It’s entering the armamentarium – at least my armamentarium – as chronic, stable secondary prevention. That’s where the new American College of Cardiology/American Heart Association guidelines also put it. It’s really in as a treatment for chronic, stable atherosclerosis. I think that’s where it belongs.
When to start colchicine, and in whom?
Dr. O’Donoghue: To that point, as we think about the efficacy, I think it’s nice, as you outlined, that we have two complementary trials that are both showing a consistent reduction in MACEs, one in the post–acute coronary syndrome (ACS) state and one for more chronic patients.
At what point do you think would be the appropriate time to start therapy, and who would you be starting it for?
Dr. Ridker: Michelle, that’s a great question. There’s a very interesting analysis that just came out from the LoDoCo2 investigators. It’s kind of a landmark analysis. What they show is that 1 year, 2 years, 3 years, and 4 years since the initiating myocardial infarction, the drug is very effective.
In fact, you could think about starting this drug at your clinic in patients with chronic, stable atherosclerotic disease. That’s just like we would start a statin in people who had a heart attack some time ago, and that’s absolutely fine.
I’m using it for what I call my frequent fliers, those patients who just keep coming back. They’re already on aggressive lipid-lowering therapy. I have them on beta-blockers, aspirin, and all the usual things. I say, look, I can get a large risk reduction by starting them on this drug.
There are a few caveats, Michelle. Like all drugs, colchicine comes with some adverse effects. Most of them are pretty rare, but there are some patients I would not give this drug to, just to be very clear. Colchicine is cleared by the kidney and by the liver. Patients who have severe chronic kidney disease and severe liver disease – this is a no-go for those patients. We should talk about where patients in that realm might want to go.
Then there are some unusual drugs. Colchicine is metabolized by the CYP3A4 and the P-glycoprotein pathway. There are a few drugs, such as ketoconazole, fluconazole, and cyclosporine, that if your primary care doctor or internist is going to start for a short term, you probably want to stop your colchicine for a week or two.
In people with familial Mediterranean fever, for whom colchicine is lifesaving and life-changing and who take it for 20, 30, or 40 years, there’s been no increase in risk for cancer. There have been very few adverse effects. I think it’s interesting that we, who practice in North America, basically never see familial Mediterranean fever. If we were practicing in Lebanon, Israel, or North Africa, this would be a very common therapy that we’d all be extremely familiar with.
Dr. O’Donoghue: To that point, it’s interesting to hear that colchicine was even used by the ancient Greeks and ancient Egyptians. It’s a drug that’s been around for a long time.
In terms of its safety, some people have been talking about the fact that an increase in noncardiovascular death was seen in LoDoCo2. What are your thoughts on that? Is that anything that we should be concerned about?
Colchicine safety and contraindications
Dr. Ridker: First, to set the record straight, a meta-analysis has been done of all-cause mortality in the various colchicine trials, and the hazard ratio is 1.04. I’ll remind you, and all of us know, that the hazard ratios for all-cause mortality in the PCSK9 trials, the bempedoic acid trials, and the ezetimibe trials are also essentially neutral. We’re in a state where we don’t let these trials roll long enough to see benefits necessarily on all-cause mortality. Some of us think we probably should, but that’s just the reality of trials.
One of most interesting things that was part of the FDA review, I suspect, was that there was no specific cause of any of this. It was not like there was a set of particular issues. I suspect that most people think this is probably the play of chance and with time, things will get better.
Again, I do want to emphasize this is not a drug for severe chronic kidney disease and severe liver disease, because those patients will get in trouble with this. The other thing that’s worth knowing is when you start a patient on low-dose colchicine – that’s 0.5 mg/d – there will be some patients who get some short-term gastrointestinal upset. That’s very common when you start colchicine at the much higher doses you might use to treat acute gout or pericarditis. In these trials, the vast majority of patients treated through that, and there were very few episodes long-term. I think it’s generally safe. That’s where we’re at.
Dr. O’Donoghue: Paul, you’ve been a leader, certainly, at looking at CRP as a marker of inflammation. Do you, in your practice, consider CRP levels when making a decision about who is appropriate for this therapy?
Dr. Ridker: That’s another terrific question. I do, because I’m trying to distinguish in my own mind patients who have residual inflammatory risk, in whom the high-sensitivity CRP (hsCRP) level remains high despite being on statins versus those with residual cholesterol risk, in whom I’m really predominantly worried about LDL cholesterol, that I haven’t brought it down far enough.
I do measure it, and if the CRP remains high and the LDL cholesterol is low, to me, that’s residual inflammatory risk and that’s the patient I would target this to. Conversely, if the LDL cholesterol was still, say, above some threshold of 75-100 and I’m worried about that, even if the CRP is low, I’ll probably add a second lipid-lowering drug.
The complexity of this, however, is that CRP was not measured in either LoDoCo2 or COLCOT. That’s mostly because they didn’t have much funding. These trials were done really on a shoestring. They were not sponsored by major pharma at all. We know that the median hsCRP in these trials was probably around 3.5-4 mg/L so I’m pretty comfortable doing that. Others have just advocated giving it to many patients. I must say I like to use biomarkers to think through the biology and who might have the best benefit-to-risk ratio. In my practice, I am doing it that way.
Inpatient vs. outpatient initiation
Dr. O’Donoghue: This is perhaps my last question for you before we wrap up. I know you talked about use of low-dose colchicine for patients with more chronic, stable coronary disease. Now obviously, COLCOT studied patients who were early post ACS, and there we certainly think about the anti-inflammatory effects as potentially having more benefit. What are your thoughts about early initiation of colchicine in that setting, the acute hospitalized setting? Do you think it’s more appropriate for an outpatient start?
Dr. Ridker: Today, I think this is all about chronic, stable atherosclerosis. Yes, COLCOT enrolled their patients within 30 days of a recent myocardial infarction, but as we all know, that’s a pretty stable phase. The vast majority were enrolled after 15 days. There were a small number enrolled within 3 days or something like that, but the benefit is about the same in all these patients.
Conversely, there’s been a small number of trials looking at colchicine in acute coronary ischemia and they’ve not been terribly promising. That makes some sense, though, right? We want to get an artery open. In acute ischemia, that’s about revascularization. It’s about oxygenation. It’s about reperfusion injury. My guess is that 3, 4, 5, or 6 days later, when it becomes a stable situation, is when the drug is probably effective.
Again, there will be some ongoing true intervention trials with large sample sizes for acute coronary ischemia. We don’t have those yet. Right now, I think it’s a therapy for chronic, stable angina. That’s many of our patients.
I would say that if you compare the relative benefit in these trials of adding ezetimibe to a statin, that’s a 5% or 6% benefit. For PCSK9 inhibitors – we all use them – it’s about a 15% benefit. These are 25%-30% risk reductions. If we’re going to think about what’s the next drug to give on top of the statin, serious consideration should be given to low-dose colchicine.
Let me also emphasize that this is not an either/or situation. This is about the fact that we now understand atherosclerosis to be a disorder both of lipid accumulation and a proinflammatory systemic response. We can give these drugs together. I suspect that the best patient care is going to be very aggressive lipid-lowering combined with pretty aggressive inflammation inhibition. I suspect that, down the road, that’s where all of us are going to be.
Dr. O’Donoghue: Thank you so much, Paul, for walking us through that today. I think it was a very nice, succinct review of the evidence, and then also just getting our minds more accustomed to the concept that we can now start to target more orthogonal axes that really get at the pathobiology of what’s going on in the atherosclerotic plaque. I think it’s an important topic.
Dr. O’Donoghue is an associate professor of medicine at Harvard Medical School and an associate physician at Brigham and Women’s Hospital, both in Boston. Dr. Ridker is director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. Both Dr. O’Donoghue and Dr. Ridker reported numerous conflicts of interest.
This transcript has been edited for clarity.
Dr. O’Donoghue: We’re going to discuss a very important and emerging topic, which is the use of low-dose colchicine. I think there’s much interest in the use of this drug, which now has a Food and Drug Administration indication, which we’ll talk about further, and it’s also been written into both European and American guidelines that have been recently released.
who’s been at the forefront of research into anti-inflammatory therapeutics.
Lifestyle lipid-lowering paramount
Dr. O’Donoghue: As we think about the concept behind the use of colchicine, we’ve obviously done a large amount of research into lipid-lowering drugs, but where does colchicine now fit in?
Dr. Ridker: Let’s make sure we get the basics down. Anti-inflammatory therapy is going to be added on top of quality other care. This is not a replacement for lipids; it’s not a change in diet, exercise, and smoking cessation. The new data are really telling us that a patient who’s aggressively treated to guideline-recommended levels can still do much better in terms of preventing heart attack, stroke, cardiovascular death, and revascularization by adding low-dose colchicine as the first proven anti-inflammatory therapy for atherosclerotic disease.
I have to say, Michelle, for me, it’s been a wonderful end of a journey in many ways. This story starts almost 30 years ago for quite a few of us, thinking about inflammation and atherosclerosis. The whole C-reactive protein (CRP) story is still an ongoing one. We recently showed, for example, that residual inflammatory risk in some 30,000 patients, all taking a statin, was a far better predictor of the likelihood of more cardiovascular events, in particular cardiovascular death, than was residual cholesterol risk.
Think about that. We’re all aggressively giving second lipid-lowering drugs in our very sick patients, but that means inflammation is really the untapped piece of this.
The two clinical trials we have in front of us, the COLCOT trial and the LoDoCo2 trial – both New England Journal of Medicine papers, both with roughly 5,000 patients – provide very clear evidence that following a relatively recent myocardial infarction (that’s COLCOT) in chronic stable atherosclerosis (that’s LoDoCo2), we’re getting 25%-30% relative risk reductions in major adverse cardiovascular events (MACEs) on top of aggressive statin therapy. That’s a big deal. It’s safe, it works, and it’s fully consistent with all the information we have about inflammation being part and parcel of atherosclerosis. It’s a pretty exciting time.
Inflammatory pathway
Dr. O’Donoghue: It beautifully proves the inflammatory hypothesis in many ways. You led CANTOS, and that was a much more specific target. Here, in terms of the effects of colchicine, what do we know about how it may work on the inflammatory cascade?
Dr. Ridker: Our CANTOS trial was proof of principle that you could directly target, with a very specific monoclonal antibody, a specific piece of this innate immune cascade and lower cardiovascular event rates.
Colchicine is a more broad-spectrum drug. It does have a number of antineutrophil effects – that’s important, by the way. Neutrophils are really becoming very important in atherosclerotic disease progression. It’s an indirect inhibitor of the so-called NLRP3 inflammasome, which is where both interleukin-1 (that’s the target for canakinumab) and IL-6 are up-regulated. As you know, it’s been used to treat gout and pericarditis in high doses in short, little bursts.
The change here is this use of low-dose colchicine, that’s 0.5 mg once a day for years to treat chronic, stable atherosclerosis. It is very much like using a statin. The idea here is to prevent the progression of the disease by slowing down and maybe stabilizing the plaque so we have fewer heart attacks and strokes down the road.
It’s entering the armamentarium – at least my armamentarium – as chronic, stable secondary prevention. That’s where the new American College of Cardiology/American Heart Association guidelines also put it. It’s really in as a treatment for chronic, stable atherosclerosis. I think that’s where it belongs.
When to start colchicine, and in whom?
Dr. O’Donoghue: To that point, as we think about the efficacy, I think it’s nice, as you outlined, that we have two complementary trials that are both showing a consistent reduction in MACEs, one in the post–acute coronary syndrome (ACS) state and one for more chronic patients.
At what point do you think would be the appropriate time to start therapy, and who would you be starting it for?
Dr. Ridker: Michelle, that’s a great question. There’s a very interesting analysis that just came out from the LoDoCo2 investigators. It’s kind of a landmark analysis. What they show is that 1 year, 2 years, 3 years, and 4 years since the initiating myocardial infarction, the drug is very effective.
In fact, you could think about starting this drug at your clinic in patients with chronic, stable atherosclerotic disease. That’s just like we would start a statin in people who had a heart attack some time ago, and that’s absolutely fine.
I’m using it for what I call my frequent fliers, those patients who just keep coming back. They’re already on aggressive lipid-lowering therapy. I have them on beta-blockers, aspirin, and all the usual things. I say, look, I can get a large risk reduction by starting them on this drug.
There are a few caveats, Michelle. Like all drugs, colchicine comes with some adverse effects. Most of them are pretty rare, but there are some patients I would not give this drug to, just to be very clear. Colchicine is cleared by the kidney and by the liver. Patients who have severe chronic kidney disease and severe liver disease – this is a no-go for those patients. We should talk about where patients in that realm might want to go.
Then there are some unusual drugs. Colchicine is metabolized by the CYP3A4 and the P-glycoprotein pathway. There are a few drugs, such as ketoconazole, fluconazole, and cyclosporine, that if your primary care doctor or internist is going to start for a short term, you probably want to stop your colchicine for a week or two.
In people with familial Mediterranean fever, for whom colchicine is lifesaving and life-changing and who take it for 20, 30, or 40 years, there’s been no increase in risk for cancer. There have been very few adverse effects. I think it’s interesting that we, who practice in North America, basically never see familial Mediterranean fever. If we were practicing in Lebanon, Israel, or North Africa, this would be a very common therapy that we’d all be extremely familiar with.
Dr. O’Donoghue: To that point, it’s interesting to hear that colchicine was even used by the ancient Greeks and ancient Egyptians. It’s a drug that’s been around for a long time.
In terms of its safety, some people have been talking about the fact that an increase in noncardiovascular death was seen in LoDoCo2. What are your thoughts on that? Is that anything that we should be concerned about?
Colchicine safety and contraindications
Dr. Ridker: First, to set the record straight, a meta-analysis has been done of all-cause mortality in the various colchicine trials, and the hazard ratio is 1.04. I’ll remind you, and all of us know, that the hazard ratios for all-cause mortality in the PCSK9 trials, the bempedoic acid trials, and the ezetimibe trials are also essentially neutral. We’re in a state where we don’t let these trials roll long enough to see benefits necessarily on all-cause mortality. Some of us think we probably should, but that’s just the reality of trials.
One of most interesting things that was part of the FDA review, I suspect, was that there was no specific cause of any of this. It was not like there was a set of particular issues. I suspect that most people think this is probably the play of chance and with time, things will get better.
Again, I do want to emphasize this is not a drug for severe chronic kidney disease and severe liver disease, because those patients will get in trouble with this. The other thing that’s worth knowing is when you start a patient on low-dose colchicine – that’s 0.5 mg/d – there will be some patients who get some short-term gastrointestinal upset. That’s very common when you start colchicine at the much higher doses you might use to treat acute gout or pericarditis. In these trials, the vast majority of patients treated through that, and there were very few episodes long-term. I think it’s generally safe. That’s where we’re at.
Dr. O’Donoghue: Paul, you’ve been a leader, certainly, at looking at CRP as a marker of inflammation. Do you, in your practice, consider CRP levels when making a decision about who is appropriate for this therapy?
Dr. Ridker: That’s another terrific question. I do, because I’m trying to distinguish in my own mind patients who have residual inflammatory risk, in whom the high-sensitivity CRP (hsCRP) level remains high despite being on statins versus those with residual cholesterol risk, in whom I’m really predominantly worried about LDL cholesterol, that I haven’t brought it down far enough.
I do measure it, and if the CRP remains high and the LDL cholesterol is low, to me, that’s residual inflammatory risk and that’s the patient I would target this to. Conversely, if the LDL cholesterol was still, say, above some threshold of 75-100 and I’m worried about that, even if the CRP is low, I’ll probably add a second lipid-lowering drug.
The complexity of this, however, is that CRP was not measured in either LoDoCo2 or COLCOT. That’s mostly because they didn’t have much funding. These trials were done really on a shoestring. They were not sponsored by major pharma at all. We know that the median hsCRP in these trials was probably around 3.5-4 mg/L so I’m pretty comfortable doing that. Others have just advocated giving it to many patients. I must say I like to use biomarkers to think through the biology and who might have the best benefit-to-risk ratio. In my practice, I am doing it that way.
Inpatient vs. outpatient initiation
Dr. O’Donoghue: This is perhaps my last question for you before we wrap up. I know you talked about use of low-dose colchicine for patients with more chronic, stable coronary disease. Now obviously, COLCOT studied patients who were early post ACS, and there we certainly think about the anti-inflammatory effects as potentially having more benefit. What are your thoughts about early initiation of colchicine in that setting, the acute hospitalized setting? Do you think it’s more appropriate for an outpatient start?
Dr. Ridker: Today, I think this is all about chronic, stable atherosclerosis. Yes, COLCOT enrolled their patients within 30 days of a recent myocardial infarction, but as we all know, that’s a pretty stable phase. The vast majority were enrolled after 15 days. There were a small number enrolled within 3 days or something like that, but the benefit is about the same in all these patients.
Conversely, there’s been a small number of trials looking at colchicine in acute coronary ischemia and they’ve not been terribly promising. That makes some sense, though, right? We want to get an artery open. In acute ischemia, that’s about revascularization. It’s about oxygenation. It’s about reperfusion injury. My guess is that 3, 4, 5, or 6 days later, when it becomes a stable situation, is when the drug is probably effective.
Again, there will be some ongoing true intervention trials with large sample sizes for acute coronary ischemia. We don’t have those yet. Right now, I think it’s a therapy for chronic, stable angina. That’s many of our patients.
I would say that if you compare the relative benefit in these trials of adding ezetimibe to a statin, that’s a 5% or 6% benefit. For PCSK9 inhibitors – we all use them – it’s about a 15% benefit. These are 25%-30% risk reductions. If we’re going to think about what’s the next drug to give on top of the statin, serious consideration should be given to low-dose colchicine.
Let me also emphasize that this is not an either/or situation. This is about the fact that we now understand atherosclerosis to be a disorder both of lipid accumulation and a proinflammatory systemic response. We can give these drugs together. I suspect that the best patient care is going to be very aggressive lipid-lowering combined with pretty aggressive inflammation inhibition. I suspect that, down the road, that’s where all of us are going to be.
Dr. O’Donoghue: Thank you so much, Paul, for walking us through that today. I think it was a very nice, succinct review of the evidence, and then also just getting our minds more accustomed to the concept that we can now start to target more orthogonal axes that really get at the pathobiology of what’s going on in the atherosclerotic plaque. I think it’s an important topic.
Dr. O’Donoghue is an associate professor of medicine at Harvard Medical School and an associate physician at Brigham and Women’s Hospital, both in Boston. Dr. Ridker is director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. Both Dr. O’Donoghue and Dr. Ridker reported numerous conflicts of interest.
AHA/ACC issue updated chronic coronary disease guidelines
The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.
Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.
It was published online in Circulation and the Journal of the American College of Cardiology .
Among the key recommendations were the following.
- Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
- Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
- Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
- Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
- The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
- Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
- Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
- Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
- Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
- Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.
Living document
The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.
“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.
“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.
“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.
The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.
Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.
It was published online in Circulation and the Journal of the American College of Cardiology .
Among the key recommendations were the following.
- Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
- Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
- Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
- Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
- The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
- Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
- Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
- Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
- Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
- Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.
Living document
The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.
“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.
“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.
“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.
The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.
Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.
It was published online in Circulation and the Journal of the American College of Cardiology .
Among the key recommendations were the following.
- Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
- Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
- Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
- Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
- The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
- Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
- Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
- Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
- Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
- Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.
Living document
The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.
“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.
“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.
“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.
The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
Stiff arteries may cause metabolic syndrome
New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence.
Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.
“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.
Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.
“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”
The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.
“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.
To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.
Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.
The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential.
Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.”
Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.
“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.
Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.
Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.
Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.
“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.
Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.
“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said.
For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.
The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
A version of this article appeared on Medscape.com.
New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence.
Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.
“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.
Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.
“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”
The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.
“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.
To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.
Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.
The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential.
Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.”
Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.
“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.
Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.
Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.
Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.
“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.
Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.
“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said.
For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.
The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
A version of this article appeared on Medscape.com.
New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence.
Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.
“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.
Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.
“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”
The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.
“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.
To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.
Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.
The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential.
Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.”
Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.
“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.
Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.
Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.
Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.
“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.
Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.
“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said.
For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.
The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
A version of this article appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PHYSIOLOGY
Vegetarian diets can improve high-risk cardiovascular disease
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Gut and oral flora linked to subclinical CAD, inflammation
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Aspirin not the best antiplatelet for CAD secondary prevention in meta-analysis
such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.
The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.
About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.
Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.
Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.
The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.
“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”
Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.
Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”
Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.
Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.
About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.
In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.
The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.
The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.
Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).
Still, the P2Y12 inhibitor group showed significant risk reductions for the following:
- GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
- Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
- Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)
The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.
It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.
“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”
In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”
But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”
Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.
A version of this article first appeared on Medscape.com.
such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.
The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.
About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.
Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.
Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.
The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.
“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”
Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.
Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”
Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.
Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.
About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.
In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.
The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.
The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.
Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).
Still, the P2Y12 inhibitor group showed significant risk reductions for the following:
- GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
- Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
- Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)
The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.
It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.
“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”
In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”
But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”
Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.
A version of this article first appeared on Medscape.com.
such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.
The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.
About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.
Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.
Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.
The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.
“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”
Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.
Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”
Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.
Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.
About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.
In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.
The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.
The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.
Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).
Still, the P2Y12 inhibitor group showed significant risk reductions for the following:
- GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
- Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
- Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)
The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.
It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.
“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”
In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”
But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”
Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.
A version of this article first appeared on Medscape.com.
FROM JACC
Heart-protective diet in PURE study allows whole-fat dairy
Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.
The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.
A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.
Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.
The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.
Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.
“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.
“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”
The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
Healthy diet score
PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.
The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.
There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:
- Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
- Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
- MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
- Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).
The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.
In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:
- Mortality: HR, 0.73 (95% CI, 0.66-0.81).
- Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
- MI: HR, 0.85 (95% CI, 0.71-0.99).
In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:
- MI: OR, 0.72 (95% CI, 0.65-0.80).
- Stroke: OR, 0.57 (95% CI, 0.50-0.65).
In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.
The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:
- Mortality: HR, 0.92 (95% CI, 0.90-0.93).
- Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
- MI: HR, 0.94 (95% CI, 0.92-0.96).
- Stroke: HR, 0.94 (95% CI, 0.89-0.99).
- Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).
“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”
Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”
Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”
Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
Common human biology
The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”
Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”
Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
Not automatically superior
“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.
“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”
The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”
Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.
The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.
The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.
A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.
Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.
The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.
Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.
“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.
“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”
The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
Healthy diet score
PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.
The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.
There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:
- Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
- Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
- MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
- Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).
The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.
In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:
- Mortality: HR, 0.73 (95% CI, 0.66-0.81).
- Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
- MI: HR, 0.85 (95% CI, 0.71-0.99).
In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:
- MI: OR, 0.72 (95% CI, 0.65-0.80).
- Stroke: OR, 0.57 (95% CI, 0.50-0.65).
In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.
The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:
- Mortality: HR, 0.92 (95% CI, 0.90-0.93).
- Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
- MI: HR, 0.94 (95% CI, 0.92-0.96).
- Stroke: HR, 0.94 (95% CI, 0.89-0.99).
- Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).
“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”
Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”
Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”
Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
Common human biology
The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”
Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”
Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
Not automatically superior
“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.
“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”
The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”
Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.
The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.
The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.
A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.
Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.
The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.
Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.
“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.
“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”
The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
Healthy diet score
PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.
The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.
There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:
- Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
- Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
- MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
- Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).
The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.
In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:
- Mortality: HR, 0.73 (95% CI, 0.66-0.81).
- Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
- MI: HR, 0.85 (95% CI, 0.71-0.99).
In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:
- MI: OR, 0.72 (95% CI, 0.65-0.80).
- Stroke: OR, 0.57 (95% CI, 0.50-0.65).
In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.
The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:
- Mortality: HR, 0.92 (95% CI, 0.90-0.93).
- Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
- MI: HR, 0.94 (95% CI, 0.92-0.96).
- Stroke: HR, 0.94 (95% CI, 0.89-0.99).
- Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).
“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”
Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”
Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”
Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
Common human biology
The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”
Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”
Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
Not automatically superior
“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.
“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”
The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”
Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.
The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EUROPEAN HEART CENTER
TAVI turmoil: Did an ANP perform transcatheter aortic valve replacement in the U.K.?
In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”
The now-deleted tweet from @GHCardiology is still visible in the Twitter thread of Mamas A. Mamas, a professor of interventional cardiology at Keele University, England. “This is so inappropriate on so many levels,” Dr. Mamas tweeted. “This is not safe for patients particularly given that there are numerous TAVI trained medically qualified operators in UK. You have also taken away training opportunities for medical / surgical trainees.”
Other followers also responded, largely negatively.
“This is crazy. Is this @TheOnion???” tweeted Martha Gulati, MD, director of preventive cardiology in the Smidt Heart Institute at Cedars-Sinai, Los Angeles, Calif., in response to Dr. Mamas, referring to the popular satirical news outlet. “Seriously I can’t see this as an actuality given the potential for so many other issues they wouldn’t know how to deal with.”
Could it happen in the U.S.?
Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.
“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
What it takes to do TAVR
Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.
Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.
“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”
The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.
In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”
Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”
In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...
“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”
The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
Why it matters: Scope creep
Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”
More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”
Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.
The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.
In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.
In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.
Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
Time for a rethink?
Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.
In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”
Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.
A version of this article originally appeared on Medscape.com.
In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”
The now-deleted tweet from @GHCardiology is still visible in the Twitter thread of Mamas A. Mamas, a professor of interventional cardiology at Keele University, England. “This is so inappropriate on so many levels,” Dr. Mamas tweeted. “This is not safe for patients particularly given that there are numerous TAVI trained medically qualified operators in UK. You have also taken away training opportunities for medical / surgical trainees.”
Other followers also responded, largely negatively.
“This is crazy. Is this @TheOnion???” tweeted Martha Gulati, MD, director of preventive cardiology in the Smidt Heart Institute at Cedars-Sinai, Los Angeles, Calif., in response to Dr. Mamas, referring to the popular satirical news outlet. “Seriously I can’t see this as an actuality given the potential for so many other issues they wouldn’t know how to deal with.”
Could it happen in the U.S.?
Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.
“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
What it takes to do TAVR
Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.
Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.
“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”
The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.
In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”
Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”
In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...
“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”
The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
Why it matters: Scope creep
Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”
More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”
Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.
The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.
In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.
In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.
Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
Time for a rethink?
Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.
In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”
Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.
A version of this article originally appeared on Medscape.com.
In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”
The now-deleted tweet from @GHCardiology is still visible in the Twitter thread of Mamas A. Mamas, a professor of interventional cardiology at Keele University, England. “This is so inappropriate on so many levels,” Dr. Mamas tweeted. “This is not safe for patients particularly given that there are numerous TAVI trained medically qualified operators in UK. You have also taken away training opportunities for medical / surgical trainees.”
Other followers also responded, largely negatively.
“This is crazy. Is this @TheOnion???” tweeted Martha Gulati, MD, director of preventive cardiology in the Smidt Heart Institute at Cedars-Sinai, Los Angeles, Calif., in response to Dr. Mamas, referring to the popular satirical news outlet. “Seriously I can’t see this as an actuality given the potential for so many other issues they wouldn’t know how to deal with.”
Could it happen in the U.S.?
Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.
“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
What it takes to do TAVR
Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.
Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.
“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”
The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.
In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”
Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”
In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...
“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”
The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
Why it matters: Scope creep
Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”
More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”
Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.
The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.
In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.
In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.
Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
Time for a rethink?
Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.
In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”
Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.
A version of this article originally appeared on Medscape.com.