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Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA
Camila V Blair1, Daniel Huck1, Stephanie A Besser1
1Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) identifies overweight individuals without diabetes at high cardiovascular risk. This suggests potential benefits from GLP-1 receptor agonist therapies, similar to those seen in the SELECT trial.
Area of Science:
- Cardiology
- Medical Imaging
- Pharmacology
Background:
- The SELECT trial showed semaglutide reduced cardiovascular events in patients with existing cardiovascular disease (CVD) and obesity, excluding those with diabetes.
- Coronary artery disease (CAD) is a major component of CVD.
- Coronary computed tomography angiography (CCTA) is a non-invasive imaging technique used to visualize CAD.
Purpose of the Study:
- To assess the association between CAD severity, identified via CCTA, and cardiovascular outcomes.
- To evaluate if individuals without prior CVD but with overweight/obesity and CAD share similar cardiovascular risk profiles as observed in the SELECT trial population.
Main Methods:
- Included 5,173 individuals aged ≥45 years with a body mass index ≥27 kg/m² who underwent CCTA.
- Excluded individuals with prior myocardial infarction, revascularization, stroke, diabetes, end-stage kidney disease, or malignancy.
- Categorized CAD severity as absent, nonobstructive (1-49%), or obstructive (≥50%), with extensive nonobstructive CAD defined as plaque in all coronary arteries. Used Cox modeling to analyze associations.
Main Results:
- Individuals with obstructive CAD showed a 71% higher risk of major adverse cardiovascular events (MACE) compared to those without CAD (adjusted HR: 1.71).
- At 4 years, event rates were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD.
- The number needed to treat with a hypothetical 20% relative risk reduction was comparable to the SELECT trial (66-67 vs. 56).
Conclusions:
- Obstructive or extensive nonobstructive CAD detected by CCTA identifies individuals without diabetes and prior CVD who are at elevated cardiovascular risk.
- These findings suggest that glucagon-like peptide-1 receptor agonist therapy may benefit this population, mirroring SELECT trial outcomes.
Background:
The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events among individuals with cardiovascular disease (CVD) and overweight/obesity without diabetes. We hypothesized that coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) identifies individuals with similar cardiovascular risk.
Objectives:
The aim of the study was to evaluate the association between CAD severity by CCTA and cardiovascular outcomes among individuals resembling The SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial population but without known CVD.
Methods:
We included individuals aged ≥45 years with body mass index ≥27 kg/m2 undergoing CCTA at 2 centers.
Exclusions:
prior myocardial infarction, revascularization, stroke, diabetes, end-stage kidney disease, or malignancy. CAD severity was categorized as absent (0%), nonobstructive (1%-49%), or obstructive (≥50%). Extensive nonobstructive CAD was defined as plaque in all coronary arteries. Cox modeling assessed the association between CAD and the composite outcome of cardiovascular death, myocardial infarction, or stroke.
Results:
Among 5,173 individuals, 53% were male, and 68% and 62% had hypertension and dyslipidemia, respectively. Individuals with obstructive CAD had a 71% higher risk of events (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002) vs those with no CAD. At 4 years, event risks were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD, comparable to SELECT's control arm (9.7%). Applying SELECT's relative rate reduction of 20%, the number needed to treat was 66 for obstructive and 67 for extensive nonobstructive CAD, comparable to SELECT's 56.
Conclusions:
Obstructive or extensive nonobstructive CAD by CCTA identifies overweight/obese individuals without diabetes and no prior CVD as being at elevated cardiovascular risk, suggesting potential benefit from glucagon-like peptide-1 receptor agonist therapy.
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