Abstract 9969: Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Individuals with Absent Coronary Artery Calcium: Results from the Multi-Ethnic Study of Atherosclerosis

Introduction: We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) among individuals with absent coronary artery calcium (CAC=0) over long-term follow-up. Methods: We included participants with CAC=0 at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of individuals free of clinical ASCVD at baseline. After calculating crude event rates, we used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors [cigarette smoking, diabetes mellitus, hypertension, preventive medication use (aspirin and statin), family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers] and adjudicated incident ASCVD events. Results: The study population consisted of 3,416 individuals with CAC=0 (mean (SD) age 58 (9) years; 63% were female, 33% White, 31% Black, 12% Chinese-American, and 24% Hispanic. At a median follow-up of 16 years, there were 189 ASCVD events (101 CHD, 98 stroke). The unadjusted 16-year incidence rates of ASCVD were ≤5 per 1000-person-years among individuals with CAC=0 with the exception of current cigarette smoking (7.30), diabetes mellitus (8.92), hypertension (5.44), and chronic kidney disease (6.75). ASCVD event rates were 6.19 per 1000 person-years among those with estimated baseline ASCVD risk 7.5%–<15% and 5.87 per 1000 person-years among those with estimated ASCVD risk 15%–<20%. After multivariable-adjustment, risk factors that were significantly associated with ASCVD: hazard ratio (HR) 95% confidence interval (CI) included current cigarette smoking: 2.12 (1.32,3.42), diabetes mellitus: 1.68 (1.01,2.80), and hypertension: 1.57 (1.06,2.33). Conclusion: In a middle-age population free of ASCVD at baseline, current cigarette smoking, diabetes mellitus, and hypertension are independently associated with incident ASCVD over 16-year follow-up among those with CAC=0. If considering a long treatment horizon, it may be reasonable to continue to recommend statin therapy in the presence of these risk factors despite the absence of CAC.