Aspirin use, lipoprotein(a), and calcific aortic valve disease: the Multi-ethnic Study of Atherosclerosis

Abstract Background and Aims Lipoprotein(a) [Lp(a)] and LDL cholesterol (LDL-C) are causally linked to aortic valve calcium (AVC) and aortic stenosis (AS). Lipoprotein(a) has anti-fibrinolytic properties; therefore, aspirin may reduce cardiovascular disease risk among individuals with high Lp(a). This analysis sought to determine the association of aspirin with incident AVC and AS across Lp(a) and LDL-C levels. Methods This observational study included up to 6598 participants in the Multi-Ethnic Study of Atherosclerosis. Aortic valve calcium was measured on non-contrast cardiac computed tomography. Multivariable Cox hazards regression assessed the association of self-reported regular aspirin use (≥3 days/week) with incident AVC and severe AS, stratified by Lp(a) and LDL-C. Aortic valve calcium and Lp(a) values were not reported to participants. Results Mean age was 62 years, 53% were women, 23% reported regular aspirin use, 8% developed AVC (median 8.9 years), and 1% developed severe AS (median 16.7 years). Among individuals with elevated Lp(a), regular aspirin use was associated with a lower risk of incident AVC (Lp(a) ≥75 mg/dL: hazard ratio (HR) .42, 95% confidence interval (CI) .19–.93; Lp(a) ≥100 mg/dL: HR .17, 95% CI .04–.67) and severe AS (Lp(a) ≥50 mg/dL: HR .13, 95% CI: .04–.47; Lp(a) ≥75 mg/dL: HR .02, 95% CI .001–.29). For participants with elevated LDL-C, there was no association of regular aspirin use with incident AVC (LDL-C ≥130 mg/dL: HR 1.02, 95% CI .66–1.58; LDL-C ≥160 mg/dL: HR 1.51, 95% CI .53–4.28) or severe AS (LDL-C ≥100 mg/dL: HR .70, 95% CI .39–1.26; LDL-C ≥130 mg/dL: HR .46, 95% CI .14–1.47). Conclusions In this exploratory analysis of prospective observational cohort data, regular aspirin use was associated with a lower risk of AVC and severe AS in persons with high Lp(a), but not high LDL-C. Confirmatory studies are required to determine the role of aspirin in the prevention of AVC and AS for persons with high Lp(a).