Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals with Prediabetes: A Multi-Cohort Study

Objectives: To describe the epidemiology and prognostic value of the coronary artery calcium (CAC) among individuals with prediabetes. Research Design and Methods: We pooled participants free of clinical ASCVD from 4 prospective cohorts Multi-Ethnic Study of Atherosclerosis (MESA), Heinz-Nixdorf Recall Study (HNR), Framingham Heart Study (FHS) and Jackson Heart Study (JHS). Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100-<126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7-<6.5%, if available, among participants not taking glucose-lowering medications) and restrictive (FPG ≥110-<126 mg/dL and HbA1c ≥5.7-<6.5%, if available). Results: The study included 13,376 participants (mean age 58 years, 54% women, 57% White, 27% Black). The proportion with CAC≥100 was 17%, 22%, and 37% among those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th – 75th percentile) follow up time of 14.6 (7.8-16.4) years, individuals with prediabetes and CAC≥100 had higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared to individuals with euglycemia the hazard ratio (HR) (95% confidence interval) for ASCVD was 0.79 (0.62, 1.01) for prediabetes and CAC=0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC≥100; and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC≥100. Conclusions: CAC≥100 is frequent among individuals with prediabetes, and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to people with diabetes.