Clinician Reviews

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.

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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

TOPLINE:

Most patients who receive antibiotics rather than surgical treatment for appendicitis have successful long-term outcomes, but some may require surgery up to 20 years later.

METHODOLOGY:

• Follow-up on 292 patients involved in two randomized controlled trials conducted in the 1990s by the Swedish National Patient Registry
• Both trials divided patients into two groups: those who underwent appendectomy and those who received antibiotic treatment for appendicitis.
• Researchers looked at rates of recurrent appendicitis that required surgery later in life.

TAKEAWAY:

• 29% of patients in the nonoperative group who were discharged successfully during the initial study eventually underwent surgery.
• Some patients who initially received antibiotics required surgery up to 20 years later.
• 9.5% of patients who didn’t undergo surgery went to a surgical outpatient clinic for abdominal pain, compared with 0.01% of those who had surgery.

IN PRACTICE:

“More than half of the patients treated nonoperatively did not experience recurrence and avoided surgery over approximately 2 decades. There is no evidence for long-term risks of nonoperative management other than that of recurrence of appendicitis,” the authors report.

SOURCE:

Simon Eaton, PhD, of UCL Great Ormond Street Institute of Child Health in London, was the corresponding author of the study, published online in JAMA Surgery. The study was funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Swedish Research Council.

LIMITATIONS:

The data were retrospective, so the researchers could not track how patients’ circumstances and characteristics changed over time. Most patients were male, and the researchers lacked histopathology results for patients for whom nonsurgical treatment succeeded initially but who later required appendectomy. They also relied on diagnostic standards used in the 1990s, when the initial studies were performed; these were less sophisticated and accurate than recent standards.

DISCLOSURES:

Coauthor Jan Svensson, MD, PhD, reported receiving grants from the Lovisa Foundation during the conduct of the study. No other disclosures were reported.

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

TOPLINE:

Most patients who receive antibiotics rather than surgical treatment for appendicitis have successful long-term outcomes, but some may require surgery up to 20 years later.

METHODOLOGY:

• Follow-up on 292 patients involved in two randomized controlled trials conducted in the 1990s by the Swedish National Patient Registry
• Both trials divided patients into two groups: those who underwent appendectomy and those who received antibiotic treatment for appendicitis.
• Researchers looked at rates of recurrent appendicitis that required surgery later in life.

TAKEAWAY:

• 29% of patients in the nonoperative group who were discharged successfully during the initial study eventually underwent surgery.
• Some patients who initially received antibiotics required surgery up to 20 years later.
• 9.5% of patients who didn’t undergo surgery went to a surgical outpatient clinic for abdominal pain, compared with 0.01% of those who had surgery.

IN PRACTICE:

“More than half of the patients treated nonoperatively did not experience recurrence and avoided surgery over approximately 2 decades. There is no evidence for long-term risks of nonoperative management other than that of recurrence of appendicitis,” the authors report.

SOURCE:

Simon Eaton, PhD, of UCL Great Ormond Street Institute of Child Health in London, was the corresponding author of the study, published online in JAMA Surgery. The study was funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Swedish Research Council.

LIMITATIONS:

The data were retrospective, so the researchers could not track how patients’ circumstances and characteristics changed over time. Most patients were male, and the researchers lacked histopathology results for patients for whom nonsurgical treatment succeeded initially but who later required appendectomy. They also relied on diagnostic standards used in the 1990s, when the initial studies were performed; these were less sophisticated and accurate than recent standards.

DISCLOSURES:

Coauthor Jan Svensson, MD, PhD, reported receiving grants from the Lovisa Foundation during the conduct of the study. No other disclosures were reported.

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

TOPLINE:

Most patients who receive antibiotics rather than surgical treatment for appendicitis have successful long-term outcomes, but some may require surgery up to 20 years later.

METHODOLOGY:

• Follow-up on 292 patients involved in two randomized controlled trials conducted in the 1990s by the Swedish National Patient Registry
• Both trials divided patients into two groups: those who underwent appendectomy and those who received antibiotic treatment for appendicitis.
• Researchers looked at rates of recurrent appendicitis that required surgery later in life.

TAKEAWAY:

• 29% of patients in the nonoperative group who were discharged successfully during the initial study eventually underwent surgery.
• Some patients who initially received antibiotics required surgery up to 20 years later.
• 9.5% of patients who didn’t undergo surgery went to a surgical outpatient clinic for abdominal pain, compared with 0.01% of those who had surgery.

IN PRACTICE:

“More than half of the patients treated nonoperatively did not experience recurrence and avoided surgery over approximately 2 decades. There is no evidence for long-term risks of nonoperative management other than that of recurrence of appendicitis,” the authors report.

SOURCE:

Simon Eaton, PhD, of UCL Great Ormond Street Institute of Child Health in London, was the corresponding author of the study, published online in JAMA Surgery. The study was funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Swedish Research Council.

LIMITATIONS:

The data were retrospective, so the researchers could not track how patients’ circumstances and characteristics changed over time. Most patients were male, and the researchers lacked histopathology results for patients for whom nonsurgical treatment succeeded initially but who later required appendectomy. They also relied on diagnostic standards used in the 1990s, when the initial studies were performed; these were less sophisticated and accurate than recent standards.

DISCLOSURES:

Coauthor Jan Svensson, MD, PhD, reported receiving grants from the Lovisa Foundation during the conduct of the study. No other disclosures were reported.

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

SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.

“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.

Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
 

Does growth hormone cause incident T2D at puberty?

Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.

Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.

A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver. 

“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.

The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.

The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
 

Growth hormone correlates of glycemic failure

The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.

The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.

In contrast, increasing plasma levels of growth hormone receptor significantly linked with an increased rate of glycemic failure, hyperglycemia, insulin resistance, and diminished beta-cell function. Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.

But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.

Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.

Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.

Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.

The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.

“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.

Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
 

Does growth hormone cause incident T2D at puberty?

Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.

Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.

A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver. 

“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.

The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.

The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
 

Growth hormone correlates of glycemic failure

The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.

The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.

In contrast, increasing plasma levels of growth hormone receptor significantly linked with an increased rate of glycemic failure, hyperglycemia, insulin resistance, and diminished beta-cell function. Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.

But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.

Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.

Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.

Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.

The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.

“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.

Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
 

Does growth hormone cause incident T2D at puberty?

Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.

Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.

A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver. 

“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.

The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.

The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
 

Growth hormone correlates of glycemic failure

The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.

The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.

In contrast, increasing plasma levels of growth hormone receptor significantly linked with an increased rate of glycemic failure, hyperglycemia, insulin resistance, and diminished beta-cell function. Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.

But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.

Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.

Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.

Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.

The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Young people diagnosed with a genetic heart disease (GHD) predisposing them to ventricular arrhythmia are at very low risk for a cardiac event while playing video games or other electronic games, provided their condition is properly treated, say researchers based on their large, single-center study.

Among more than 3,000 patients in the study with such a genetic vulnerability, just 6 – or less than 0.2% – experienced an electronic gaming–associated cardiac event.

A previous study had concluded that e-gaming, particularly with war games, might trigger potentially fatal arrhythmias in some vulnerable children. That study “sparked controversy in the field, with both clinicians and patients wondering whether electronic gaming is safe for patients with GHDs,” Michael J. Ackerman, MD, PhD, of Mayo Clinic in Rochester, Minn., said in an interview.

Dr. Ackerman and colleagues conducted the current study, published online in the Journal of the American College of Cardiology, to determine just how often e-gaming triggered cardiac events (CE) in these patients – and who was most at risk.
 

‘Extremely low’ risk

The investigators looked at records from all patients evaluated and treated at the Mayo Clinic’s genetic heart rhythm clinic from 2000 to 2022. They identified those with a history of playing electronic games at the time of their CE, defined here as such an event occurring before diagnosis, or breakthrough cardiac event (BCE), meaning an event occurring after diagnosis.

A total of 3,370 patients with a GHD (55% female) were included in the analysis. More than half (52%) were diagnosed with long-QT syndrome (LQTS). The remainder had various GHDs including, among others, catecholaminergic polymorphic ventricular tachycardia (CPVT) or hypertrophic cardiomyopathy (HCM).

The mean age at first evaluation was 27; 14% of the participants were age 6 or younger, 33% were age 7-20, and 53% were 21 or older. Most patients in each of the three age groups were diagnosed with either LQTS or CPVT.

Of the 3,370 GHD patients, 1,079 (32%) had a CE before diagnosis.

Six patients (0.5%) had a CE in the setting of e-gaming, including five for whom it was the sentinel CE. Five also had CEs in settings not involving e-gaming. Their average age at the time of the CE was 13.

Three of the six patients were diagnosed with CPVT (including two CPVT1 and one CPVT2). Of the others, one was diagnosed with LQT1, one with ventricular fibrillation triggered by premature ventricular contractions, and one with catecholamine-sensitive right ventricular outflow tract ventricular tachycardia (RVOT-VT).

After appropriate treatment, none of the six experienced a BCE during follow-ups ranging from 7 months to 4 years.

Among the full cohort of 3370 patients with GHD, 431 (13%) experienced one or more BCE during follow-up. Of those, one with catecholamine-sensitive RVOT-VT experienced an e-gaming–associated BCE.

“Although anecdotal e-gaming–associated cardiac events, including [sudden cardiac death], have been reported, the absolute risk is extremely low,” the authors wrote.

“Although there are no clear health benefits associated with e-gaming,” Dr. Ackerman said, “the risk of sudden death should not be used as an argument in an effort to curtail the amount of time patients spend e-gaming.”

Furthermore, he added, e-gaming is important to some patients’ quality of life. If patients are “properly diagnosed, risk stratified, and treated, it is okay to engage in e-gaming.”

However, “given that e-gaming may pose some risks, especially when compounded with additional factors such as dehydration, sleep deprivation, and use of performance-enhancing substances such as energy drinks, patients need to be counseled on the potential adverse health consequences,” Dr. Ackerman said.

“To this end,” he added, “we are proponents of incorporating e-gaming status into the clinical evaluation and electronic health record.”

“We would continue to urge common sense and individual risk assessment, with shared decision-making, for those where this may be an issue,” Claire M. Lawley, MBBS, PhD, Children’s Hospital at Westmead (Australia), said in an interview.

“Additionally, syncope during electronic gaming should prompt medical review,” said Dr. Lawley, lead author of the study that prompted Ackerman and colleagues to investigate the issue further.
 

Buddy system

Maully J. Shah, MBBS, led a study published in 2020 focusing on two case reports of syncope and potentially life-threatening ventricular arrhythmias provoked by emotional surges during play with violent video games. 

Nevertheless, “we do not restrict patients from participating in e-games,” Dr. Shah, a pediatric cardiac electrophysiologist at the Cardiac Center at Children’s Hospital of Philadelphia, said in an interview. “We inform them about the available data regarding the very rare but possible occurrence of an event from e-gaming so that they can make an informed decision.”

Dr. Shah agreed that, “even in children not known to have a cardiac condition, syncope associated with emotional responses during violent video games should prompt cardiac evaluation, similar to exercise-induced syncope.”

If a patient wishes to play e-games, clinicians should ensure medication compliance and recommend a “buddy” system. “Don’t be alone while playing,” she said.

“The present study and previous reports make one pause to think whether these CEs and catecholaminergic drives can occur with sports only. If we now consider electronic gaming as a potential risk, what other activities need to be included?” wrote the authors of an accompanying editorial, led by Shankar Baskar, MD, Cincinnati Children’s Medical Center.

“A catecholaminergic drive can occur in many settings with activities of daily living or activities not considered to be competitive,” the editorialists wrote. “Ultimately these events [are] rare, but they can have life-threatening consequences, and at the same time they might not be altogether preventable and, as in electronic gaming, might be an activity that improves quality of life, especially in those who might be restricted from other sports.”

Dr. Ackerman disclosed consulting for Abbott, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr. Ackerman and the Mayo Clinic have license agreements with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. The other coauthors reported no relevant relationships. Dr. Baskar and colleagues reported no relevant relationships. Dr. Shah disclosed she is a consultant to Medtronic.

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

Young people diagnosed with a genetic heart disease (GHD) predisposing them to ventricular arrhythmia are at very low risk for a cardiac event while playing video games or other electronic games, provided their condition is properly treated, say researchers based on their large, single-center study.

Among more than 3,000 patients in the study with such a genetic vulnerability, just 6 – or less than 0.2% – experienced an electronic gaming–associated cardiac event.

A previous study had concluded that e-gaming, particularly with war games, might trigger potentially fatal arrhythmias in some vulnerable children. That study “sparked controversy in the field, with both clinicians and patients wondering whether electronic gaming is safe for patients with GHDs,” Michael J. Ackerman, MD, PhD, of Mayo Clinic in Rochester, Minn., said in an interview.

Dr. Ackerman and colleagues conducted the current study, published online in the Journal of the American College of Cardiology, to determine just how often e-gaming triggered cardiac events (CE) in these patients – and who was most at risk.
 

‘Extremely low’ risk

The investigators looked at records from all patients evaluated and treated at the Mayo Clinic’s genetic heart rhythm clinic from 2000 to 2022. They identified those with a history of playing electronic games at the time of their CE, defined here as such an event occurring before diagnosis, or breakthrough cardiac event (BCE), meaning an event occurring after diagnosis.

A total of 3,370 patients with a GHD (55% female) were included in the analysis. More than half (52%) were diagnosed with long-QT syndrome (LQTS). The remainder had various GHDs including, among others, catecholaminergic polymorphic ventricular tachycardia (CPVT) or hypertrophic cardiomyopathy (HCM).

The mean age at first evaluation was 27; 14% of the participants were age 6 or younger, 33% were age 7-20, and 53% were 21 or older. Most patients in each of the three age groups were diagnosed with either LQTS or CPVT.

Of the 3,370 GHD patients, 1,079 (32%) had a CE before diagnosis.

Six patients (0.5%) had a CE in the setting of e-gaming, including five for whom it was the sentinel CE. Five also had CEs in settings not involving e-gaming. Their average age at the time of the CE was 13.

Three of the six patients were diagnosed with CPVT (including two CPVT1 and one CPVT2). Of the others, one was diagnosed with LQT1, one with ventricular fibrillation triggered by premature ventricular contractions, and one with catecholamine-sensitive right ventricular outflow tract ventricular tachycardia (RVOT-VT).

After appropriate treatment, none of the six experienced a BCE during follow-ups ranging from 7 months to 4 years.

Among the full cohort of 3370 patients with GHD, 431 (13%) experienced one or more BCE during follow-up. Of those, one with catecholamine-sensitive RVOT-VT experienced an e-gaming–associated BCE.

“Although anecdotal e-gaming–associated cardiac events, including [sudden cardiac death], have been reported, the absolute risk is extremely low,” the authors wrote.

“Although there are no clear health benefits associated with e-gaming,” Dr. Ackerman said, “the risk of sudden death should not be used as an argument in an effort to curtail the amount of time patients spend e-gaming.”

Furthermore, he added, e-gaming is important to some patients’ quality of life. If patients are “properly diagnosed, risk stratified, and treated, it is okay to engage in e-gaming.”

However, “given that e-gaming may pose some risks, especially when compounded with additional factors such as dehydration, sleep deprivation, and use of performance-enhancing substances such as energy drinks, patients need to be counseled on the potential adverse health consequences,” Dr. Ackerman said.

“To this end,” he added, “we are proponents of incorporating e-gaming status into the clinical evaluation and electronic health record.”

“We would continue to urge common sense and individual risk assessment, with shared decision-making, for those where this may be an issue,” Claire M. Lawley, MBBS, PhD, Children’s Hospital at Westmead (Australia), said in an interview.

“Additionally, syncope during electronic gaming should prompt medical review,” said Dr. Lawley, lead author of the study that prompted Ackerman and colleagues to investigate the issue further.
 

Buddy system

Maully J. Shah, MBBS, led a study published in 2020 focusing on two case reports of syncope and potentially life-threatening ventricular arrhythmias provoked by emotional surges during play with violent video games. 

Nevertheless, “we do not restrict patients from participating in e-games,” Dr. Shah, a pediatric cardiac electrophysiologist at the Cardiac Center at Children’s Hospital of Philadelphia, said in an interview. “We inform them about the available data regarding the very rare but possible occurrence of an event from e-gaming so that they can make an informed decision.”

Dr. Shah agreed that, “even in children not known to have a cardiac condition, syncope associated with emotional responses during violent video games should prompt cardiac evaluation, similar to exercise-induced syncope.”

If a patient wishes to play e-games, clinicians should ensure medication compliance and recommend a “buddy” system. “Don’t be alone while playing,” she said.

“The present study and previous reports make one pause to think whether these CEs and catecholaminergic drives can occur with sports only. If we now consider electronic gaming as a potential risk, what other activities need to be included?” wrote the authors of an accompanying editorial, led by Shankar Baskar, MD, Cincinnati Children’s Medical Center.

“A catecholaminergic drive can occur in many settings with activities of daily living or activities not considered to be competitive,” the editorialists wrote. “Ultimately these events [are] rare, but they can have life-threatening consequences, and at the same time they might not be altogether preventable and, as in electronic gaming, might be an activity that improves quality of life, especially in those who might be restricted from other sports.”

Dr. Ackerman disclosed consulting for Abbott, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr. Ackerman and the Mayo Clinic have license agreements with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. The other coauthors reported no relevant relationships. Dr. Baskar and colleagues reported no relevant relationships. Dr. Shah disclosed she is a consultant to Medtronic.

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

Young people diagnosed with a genetic heart disease (GHD) predisposing them to ventricular arrhythmia are at very low risk for a cardiac event while playing video games or other electronic games, provided their condition is properly treated, say researchers based on their large, single-center study.

Among more than 3,000 patients in the study with such a genetic vulnerability, just 6 – or less than 0.2% – experienced an electronic gaming–associated cardiac event.

A previous study had concluded that e-gaming, particularly with war games, might trigger potentially fatal arrhythmias in some vulnerable children. That study “sparked controversy in the field, with both clinicians and patients wondering whether electronic gaming is safe for patients with GHDs,” Michael J. Ackerman, MD, PhD, of Mayo Clinic in Rochester, Minn., said in an interview.

Dr. Ackerman and colleagues conducted the current study, published online in the Journal of the American College of Cardiology, to determine just how often e-gaming triggered cardiac events (CE) in these patients – and who was most at risk.
 

‘Extremely low’ risk

The investigators looked at records from all patients evaluated and treated at the Mayo Clinic’s genetic heart rhythm clinic from 2000 to 2022. They identified those with a history of playing electronic games at the time of their CE, defined here as such an event occurring before diagnosis, or breakthrough cardiac event (BCE), meaning an event occurring after diagnosis.

A total of 3,370 patients with a GHD (55% female) were included in the analysis. More than half (52%) were diagnosed with long-QT syndrome (LQTS). The remainder had various GHDs including, among others, catecholaminergic polymorphic ventricular tachycardia (CPVT) or hypertrophic cardiomyopathy (HCM).

The mean age at first evaluation was 27; 14% of the participants were age 6 or younger, 33% were age 7-20, and 53% were 21 or older. Most patients in each of the three age groups were diagnosed with either LQTS or CPVT.

Of the 3,370 GHD patients, 1,079 (32%) had a CE before diagnosis.

Six patients (0.5%) had a CE in the setting of e-gaming, including five for whom it was the sentinel CE. Five also had CEs in settings not involving e-gaming. Their average age at the time of the CE was 13.

Three of the six patients were diagnosed with CPVT (including two CPVT1 and one CPVT2). Of the others, one was diagnosed with LQT1, one with ventricular fibrillation triggered by premature ventricular contractions, and one with catecholamine-sensitive right ventricular outflow tract ventricular tachycardia (RVOT-VT).

After appropriate treatment, none of the six experienced a BCE during follow-ups ranging from 7 months to 4 years.

Among the full cohort of 3370 patients with GHD, 431 (13%) experienced one or more BCE during follow-up. Of those, one with catecholamine-sensitive RVOT-VT experienced an e-gaming–associated BCE.

“Although anecdotal e-gaming–associated cardiac events, including [sudden cardiac death], have been reported, the absolute risk is extremely low,” the authors wrote.

“Although there are no clear health benefits associated with e-gaming,” Dr. Ackerman said, “the risk of sudden death should not be used as an argument in an effort to curtail the amount of time patients spend e-gaming.”

Furthermore, he added, e-gaming is important to some patients’ quality of life. If patients are “properly diagnosed, risk stratified, and treated, it is okay to engage in e-gaming.”

However, “given that e-gaming may pose some risks, especially when compounded with additional factors such as dehydration, sleep deprivation, and use of performance-enhancing substances such as energy drinks, patients need to be counseled on the potential adverse health consequences,” Dr. Ackerman said.

“To this end,” he added, “we are proponents of incorporating e-gaming status into the clinical evaluation and electronic health record.”

“We would continue to urge common sense and individual risk assessment, with shared decision-making, for those where this may be an issue,” Claire M. Lawley, MBBS, PhD, Children’s Hospital at Westmead (Australia), said in an interview.

“Additionally, syncope during electronic gaming should prompt medical review,” said Dr. Lawley, lead author of the study that prompted Ackerman and colleagues to investigate the issue further.
 

Buddy system

Maully J. Shah, MBBS, led a study published in 2020 focusing on two case reports of syncope and potentially life-threatening ventricular arrhythmias provoked by emotional surges during play with violent video games. 

Nevertheless, “we do not restrict patients from participating in e-games,” Dr. Shah, a pediatric cardiac electrophysiologist at the Cardiac Center at Children’s Hospital of Philadelphia, said in an interview. “We inform them about the available data regarding the very rare but possible occurrence of an event from e-gaming so that they can make an informed decision.”

Dr. Shah agreed that, “even in children not known to have a cardiac condition, syncope associated with emotional responses during violent video games should prompt cardiac evaluation, similar to exercise-induced syncope.”

If a patient wishes to play e-games, clinicians should ensure medication compliance and recommend a “buddy” system. “Don’t be alone while playing,” she said.

“The present study and previous reports make one pause to think whether these CEs and catecholaminergic drives can occur with sports only. If we now consider electronic gaming as a potential risk, what other activities need to be included?” wrote the authors of an accompanying editorial, led by Shankar Baskar, MD, Cincinnati Children’s Medical Center.

“A catecholaminergic drive can occur in many settings with activities of daily living or activities not considered to be competitive,” the editorialists wrote. “Ultimately these events [are] rare, but they can have life-threatening consequences, and at the same time they might not be altogether preventable and, as in electronic gaming, might be an activity that improves quality of life, especially in those who might be restricted from other sports.”

Dr. Ackerman disclosed consulting for Abbott, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr. Ackerman and the Mayo Clinic have license agreements with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. The other coauthors reported no relevant relationships. Dr. Baskar and colleagues reported no relevant relationships. Dr. Shah disclosed she is a consultant to Medtronic.

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

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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