CAC-BASED CARDIOVASCULAR RISK STRATIFICATION AMONG INDIVIDUALS WITH OBESITY BUT WITHOUT DIABETES

Abstract

Therapeutic Area: ASCVD/CVD Risk Assessment Background: New therapies for obesity have demonstrated substantial total body weight loss. The SELECT trial is underway testing the cardiovascular benefit of weight loss therapies in patients with obesity yet without diabetes. The main barrier to widespread utilization of weight loss medications is their high cost, which points to the need for further cardiovascular (CVD) risk stratification among individuals with obesity. We tested whether the coronary artery calcium (CAC) score provides substantial risk predictive value in this setting. Methods: We used data from 8,353 participants (mean age 52.7 ± 9.5 years; 68.1% men) with body mass index ≥30 kg/m2 who do not have diabetes from the CAC Consortium, a retrospectively assembled cohort of individuals with no prior CVD history. We categorized CAC as absent/present and 0, 1-99, 100-299, ≥300 Agatston Units. We then evaluated the predictive value of CAC for all-cause and cause-specific mortality (CVD and CHD) using multivariable-adjusted Cox proportional hazard and competing risks regression, respectively. Results: Of the 8,353 participants, 4,711 (47.6%) had CAC. Compared to persons without CAC, those with CAC >0 had a higher rate (per 1,000 person-years) of all-cause (5.02 vs. 1.80), cardiovascular (1.57 vs. 0.32), and CHD mortality (0.87 vs. 0.17), after a mean follow-up of 10.6 ± 2.9 years. After adjusting for age, sex, and cardiovascular risk factors, individuals with CAC >0 had a significantly higher risk of all-cause (HR:1.43; 95%CI:1.08–1.90), cardiovascular (SHR:2.51 95%CI:1.30–4.85), and CHD mortality (SHR:2.78; 95%CI:1.10–6.99), compared to those without CAC. Of note, CAC ≥300 was associated with a markedly higher risk of all-cause, cardiovascular, and CHD mortality, particularly when restricting our analysis to persons with Class II obesity or higher. Conclusions: CAC strongly predicts all-cause, cardiovascular, and CHD mortality among individuals with obesity and no diabetes. As we await the results of the SELECT trial, it appears that CAC may serve as an effective risk stratification tool to prioritize the allocation of therapies for weight management in this population.