Obesity and Cardiometabolic Health: From Clinical Trials and Available Guidelines to Patient Care
Speaker: Dr. Abraham M. Lincoff
Key Highlights
Introduction:
Obesity is now recognized as an independent cardiovascular risk factor, with its direct contribution to cardiovascular disease (CVD) being acknowledged beyond its association with diabetes and hypertension. Recent advancements in weight management, particularly through GLP-1 receptor agonists such as semaglutide, have been shown to provide promising cardiovascular benefits. Landmark evidence supporting the role of semaglutide in reducing cardiovascular events among non-diabetic patients with obesity was provided by the SELECT trial.
Aim:
The primary objective of the SELECT trial was to determine whether major cardiovascular events (MACE) could be reduced by semaglutide (2.4 mg weekly) in patients with overweight or obesity but without diabetes.
Methods:
The SELECT trial was designed as a large, randomized controlled study in which over 17,000 participants with obesity and established CVD, but no history of diabetes, were enrolled. Participants were randomized to receive either semaglutide (2.4 mg weekly) or a placebo. The primary composite outcome consisted of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Secondary outcomes included renal function decline, all-cause mortality, and reductions in inflammatory markers.
Results:
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Primary Outcome: A 20% reduction in the primary composite endpoint (CV death, nonfatal MI, and nonfatal stroke) was observed with semaglutide, with benefits emerging early and remaining consistent across subgroups.
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Renal and Mortality Benefits: Renal outcomes were improved, particularly through a reduction in macroalbuminuria, and a decrease in all-cause mortality, including deaths related to COVID-19, was noted.
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Mechanism of Cardiovascular Benefit: The cardiovascular protection observed appeared independent of weight loss and HbA1c improvement. Notably, inflammatory markers such as CRP were reduced by 35%.
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Safety Profile: No increase in major adverse effects, including pancreatitis, was reported. However, gastrointestinal side effects led to higher discontinuation rates, particularly during the dose-escalation phase.
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Future Prospects: It is anticipated that dual agonists like tirzepatide (GLP-1 + GIP) may offer enhanced weight and glycemic benefits, though cardiovascular outcome trials remain pending.
Conclusion:
Compelling evidence has been provided by the SELECT trial demonstrating that cardiovascular risk is significantly reduced by semaglutide in patients with obesity, independent of diabetes status. While weight loss and glycemic improvements contribute, the primary benefits are likely derived from additional mechanisms, including anti-inflammatory effects. These findings reinforce the importance of addressing obesity as a direct cardiovascular risk factor in clinical practice.
An Update on Obesity in the CV Health Era: Management Tips from Lifestyle to Medications
Speaker: Dr. Pam Taub
Key Highlights
Evidence-Based Lifestyle Strategy Foundations:
The foundational role of lifestyle in obesity and cardiovascular disease (CVD) management was emphasized. Misinformation from the supplement industry and internet trends was highlighted as a concern. Lifestyle interventions should focus on what, when, and how much patients eat, sleep, and move. Fad diets should be discouraged, while evidence-backed regimens such as the Mediterranean diet, with a focus on minimally processed foods, increased vegetable intake, and lean proteins, should be promoted.
Caloric Control and Time-Restricted Eating (TRE):
Personalized caloric targets were advocated, and TRE was introduced as a valuable tool to optimize metabolic rhythms. Simple strategies such as avoiding late-night snacking can have a significant impact. Continuous glucose monitoring (CGM) can be utilized to individualize meal patterns.
The Role of GLP-1 Receptor Agonists:
Lifestyle changes typically result in 2–5% weight loss, though sustainability remains a challenge. Greater weight reduction and improved metabolic outcomes are achieved through the use of GLP-1 RAs. The need for bariatric surgery has decreased due to the combination of these agents with lifestyle modifications.
Skeletal Muscle and Bone Concerns:
Concerns regarding sarcopenia and bone health with long-term GLP-1 RA use were raised. Current data, primarily from DEXA scans, is insufficient to determine the clinical relevance of muscle loss. The preservation of muscle mass, particularly in aging populations, should be ensured through strength training.
Muscle Quality vs. Quantity: A Critical Insight:
The need for better muscle assessment tools was emphasized. A comparison was made between interspersed fat in marbled Wagyu beef (higher on DEXA but metabolically worse) versus lean meat. A hypothesis was presented that GLP-1 RAs may reduce intramuscular fat, which could misleadingly suggest reduced muscle mass on DEXA without actual muscle degradation. Functional and architectural imaging studies are needed.
Managing Side Effects and Ensuring Adherence:
To manage side effects such as nausea or constipation, simple interventions—including eating smaller meals, slowing eating speed, and maintaining hydration—were recommended. In a case vignette, early nausea with semaglutide was best managed by adding an antiemetic rather than switching agents or discontinuing therapy.
Combining Therapies for Optimal Impact:
It was reinforced that the combination of lifestyle interventions and pharmacology is exponentially more effective than either alone. A broader perspective beyond weight alone should be maintained, with a focus on the full cardiometabolic profile, particularly visceral adiposity and lipid/glucose levels.
Conclusion:
A transformative era in cardiometabolic care was acknowledged. Both pharmacologic and lifestyle interventions should be leveraged while remaining cautious of potential long-term risks such as sarcopenia and bone effects. The ultimate goal remains the improvement of cardiometabolic health and clinical outcomes through evidence-based, integrated strategies.
Obesity, Heart Failure, and Beyond: Time for a Revolution (and/or a Resolution)? - Amanda Vest
Speaker: Dr. Amanda Vest
Key Highlights
Epidemiological Associations:
The role of obesity as a risk factor for heart failure with preserved ejection fraction (HFpEF) was highlighted, with hypertension being the only greater contributor. Conversely, the association between obesity and heart failure with reduced ejection fraction (HFrEF) was found to be weaker.
Obesity Survival Paradox – Fact or Illusion?
The widely discussed "obesity paradox" in heart failure was questioned, with observational studies suggesting better survival outcomes in patients with elevated BMI. However, the paradox was deemed an illusion, attributed to confounding factors, selection bias, and BMI limitations. Although mortality benefits were not clearly established, higher BMI consistently correlated with increased HF hospitalizations.
Lifestyle Interventions:
Limited evidence from clinical trials regarding lifestyle modifications in HF patients was acknowledged. Despite this, functional and cardiometabolic improvements were recognized as significant benefits of lifestyle interventions, reinforcing their role as foundational therapy.
Bariatric Surgery – Risks and Benefits:
Observational data suggested reductions in HF hospitalizations and mortality following bariatric surgery. However, concerns over perioperative risks, particularly in HFrEF patients with inadequate preoperative optimization, were emphasized. The necessity of interdisciplinary assessment involving metabolic surgery teams was underscored, given the limited data available on different HF subtypes.
Pharmacologic Management – GLP-1 Receptor Agonists:
GLP-1 receptor agonists (GLP-1 RAs), including semaglutide and tirzepatide, were identified as promising options in HF management. In HFpEF, consistent benefits such as improved quality of life (KCCQ scores), weight reduction, and decreased HF events were demonstrated in trials like STEP-HFpEF and SUMMIT. In contrast, caution was advised in HFrEF patients, particularly those with advanced disease or lacking defibrillator protection, due to potential arrhythmic risks observed in the FIGHT-HF trial.
Redefining Obesity Beyond BMI:
A proposal to redefine obesity based on body composition and organ dysfunction, rather than BMI alone, was discussed. This shift was highlighted as especially relevant in racially diverse populations and in patients with HF where fluid retention can confound BMI-based assessments.
Proposed Clinical Algorithm for Obesity in HF:
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Overweight (BMI <30): Lifestyle interventions recommended; pharmacotherapy not supported by evidence.
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Obesity Class I (BMI 30–35):
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HFpEF: Pharmacotherapy shown to be beneficial.
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HFrEF: Individualized risk assessment required; caution advised due to potential arrhythmic risks.
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Obesity Class II or higher (BMI ≥35): Pharmacotherapy and/or bariatric surgery considered, particularly for stable HF patients or those seeking transplant eligibility.
Clinical Takeaways:
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In HFpEF, intentional weight loss with GLP-1 RAs was associated with functional and potential survival benefits.
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In HFrEF, safety concerns necessitate careful patient selection, particularly in advanced disease or in the absence of defibrillator protection.
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Future obesity guidelines may incorporate a diagnostic model beyond BMI, accounting for body composition and functional impairment.
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Individualized weight management strategies should be prioritized based on HF subtype, disease severity, and patient-specific risk profiles, signaling a shift towards personalized cardio-metabolic care.
Setting Up a Cardio-metabolic Clinic: Considering Obesity and Patient Factors - Martine Altieri
Speaker: Dr. Martine Altieri
Key Highlights
Rationale for Cardio-metabolic Clinics:
Cardio-metabolic diseases, including heart disease, hypertension, type 2 diabetes, and obesity, continue to be leading causes of mortality. Many patients remain undertreated due to time constraints, limited obesity medicine training, and adherence challenges. A structured, multidisciplinary clinic model has been proposed to address these care gaps.
Core Components and Team Structure:
A cardio-metabolic clinic has been defined as a specialized center aimed at optimizing metabolic and cardiovascular health. Multidisciplinary teams—including cardiologists, endocrinologists, dietitians, behavioral specialists, and pharmacists—have been recommended to ensure comprehensive care.
Clinical Workflow and Infrastructure:
Initial assessments have been structured to include weight history, lifestyle factors, comorbidities, and prior weight-loss attempts. Objective measures such as BMI, metabolic panels, and imaging are incorporated. Inclusive clinic design and telemedicine have been emphasized for accessibility.
Patient-Centered Care Approach:
Risk reduction and functional improvement, rather than weight loss alone, have been prioritized. The use of respectful, stigma-free language and practical educational resources has been encouraged to improve patient engagement.
Case Study:
A case involving an 82-year-old male with cardiovascular comorbidities and newly diagnosed diabetes was presented, demonstrating the effectiveness of a team-based, individualized approach in a cardiometabolic clinic.
Special Considerations:
Women’s cardiometabolic health, mental health impacts, and comorbid conditions have been identified as critical factors influencing patient outcomes. Tailored interventions have been recommended.
Barriers and Proposed Solutions:
Challenges such as limited specialist access, insurance restrictions, and provider inexperience have been noted. Solutions including staff education, telemedicine integration, and oncology-inspired patient navigation models have been suggested.
ACC.25, March 29 - 31, 2025, Chicago
