Subclinical Coronary Artery Calcification is Associated with Future Inflammatory Conditions in the Multi-Ethnic Study of Atherosclerosis

Inflammation is integral to cardiovascular disease (CVD). We previously defined Chronic Inflammatory-Related Disease (ChrIRD) as a collective of various non-cardiovascular and non-cancer conditions with a common basis of inflammation. ChrIRD has a bidirectional association with CVD. As both coronary artery calcification (CAC) and ChrIRD have inflammatory associations, we hypothesize that that baseline CAC predicts future ChrIRD. We studied Multi-Ethnic Study of Atherosclerosis participants free of overt CVD at baseline. ChrIRD was determined based on ICD codes for hospitalizations and deaths. All participants underwent baseline ECG-gated non-contrast CT with Agatston scoring for CAC quantification. We performed proportional hazards regression to identify associations between baseline CAC, baseline inflammatory markers, and future ChrIRD. Participants (n=6791) had mean age 62±10 years, with 47% men, 38% White, 28% Black, 22% Hispanic, and 12% Chinese race/ethnicity. During 18-year follow-up, ChrIRD occurred in 16%. Increasing baseline Agatston score was associated with increased risk for future ChrIRD compared to baseline Agatston score 0. Agatston score (HR per SD 1.20) was as strong a predictor of ChrIRD as baseline interleukin-6 (IL-6) levels (HR per SD 1.21). Increasing baseline CAC among individuals free of overt CVD or other significant illness is associated with progressive risk of future ChrIRD. Agatston score was as predictive as IL-6. These findings support CAC as a subclinical marker of systemic inflammation, not limited to the coronary vasculature alone.