Abstract

Background: Tirzepatide demonstrated substantial weight loss in patients with obesity yet without diabetes and the clinical trial (SURMOUNT-MMO) evaluating its CVD benefits is ongoing. We tested whether the CAC score provides substantial risk predictive value in this setting. Methods: Participants (N=16,163; mean age 53.0 ± 9.7 years; 72.5% men) with BMI≥ 27 kg/m 2 but without diabetes from the CAC Consortium were categorized based on the inclusion criteria of SURMMOUNT-MMO trial pertaining to individuals without an established CVD. The predictive value of CAC was evaluated for all-cause and cause-specific mortality after mean follow-up of 10.6 ± 2.9 years using multivariable-adjusted Cox proportional hazard and competing risks regression, respectively. Results: Of the 16,163 participants, 14,004 (86.6%) would not qualify for the SURMMOUNT-MMO trial. Of those, those with CAC ≥ 300 had a higher rate (per 1,000 person-years) of all-cause (7.10 vs. 1.43), CVD (2.62 vs. 1.0), and CHD (1.61 vs. 0.75) mortality compared to ones with CAC=0. After adjusting for age, sex, and race, individuals who would not qualify and with CAC≥ 300, had significantly higher risk of all-cause, CVD, and CHD mortality (all P-values <0.001), compared to those who do not qualify and without CAC. Of note, individuals who would qualify but with CAC <100 did not have increased all-cause, and cause-specific mortality compared to individual who would not qualify and without CAC (Table). Conclusions: CAC strongly predicts all-cause, CVD, and CHD mortality among individuals with obesity but without diabetes, and may better risk stratify than SURMOUNT-MMO inclusion criteria. CAC may serve as an effective risk stratification tool to prioritize the allocation of therapies for weight management.

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