Abstract Body (Do not enter title and authors here): Introduction: The population of men and women who are overweight (defined as a BMI 25-29.9 kg/m²) continues to grow at fast pace. The prevalence and prognostic implications of a high coronary artery calcium (CAC) score in this group are poorly defined.

Aims: Using a multiethnic cohort of men and women, we compared the ASCVD event-risk at follow up in normal weight, overweight, and obese individuals, overall and further stratified by CAC scores.

Methods: Individual-level pooled analysis of participants from MESA, JHS, HNR, and FHS free of ASCVD at baseline and in whom CAC and BMI data were available. Participants with BMI <18.5 kg/m² were excluded. CAC was categorized as =0, 1-99, and ≥100 Agatston Units. The primary outcome was ASCVD events during follow-up, comprising fatal and non-fatal coronary heart disease and stroke events.

Results: A total of 14,740 participants were included. The BMI was distributed as follows: BMI <25 kg/m²: 27.4%, BMI 25-29.9 kg/m²: 40.0%, BMI 30-34.9 kg/m²: 20.8%, BMI >=35 kg/m²: 11.8%. Among overweight participants, 52% had CAC>0, and 22% had CAC≥100 (17% prevalence among individuals with normal weight). The distribution of CAC by BMI categories is presented in the Figure. The incidence of ASCVD events among overweight participants was: 3.8 per 1000 person-years for those with CAC=0, 8.1 for CAC>0 - <=99, and 20.7 for CAC≥100. In regression analyses, compared to BMI 18.5-25 kg/m² individuals (reference group), the adjusted HR of ASCVD events for overweight participants with CAC≥100 was higher than that for unselected obese participants (Figure). A sub-analysis restricted to participants free of prediabetes and diabetes yielded similar trends, with the combination overweight+high CAC score being associated with a higher ASCVD risk than those with obesity.

Conclusions: The ASCVD risk of overweight people with CAC≥100 is higher than that observed among individuals with BMI≥30 kg/m². Overweight individuals with high CAC scores comprise relatively frequent and high-risk group, which may benefit from systematic detection and aggressive risk-reduction interventions.