Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aims: Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke. Methods: Progression (interval increase > 0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. Results: We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean +/- SD age was 62 +/- 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke. Conclusions: Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.