Aspirin Use and the Risk for Cardiovascular Disease by Lipoprotein(a) Levels: A Multi-Cohort Study

Small observational studies suggest that aspirin use may be associated with a 50% lower incidence of cardiovascular disease (CVD) in adults with lipoprotein(a) ≥ 50 mg/dL, without apparent benefit in those with lipoprotein(a) < 50 mg/dL. The current study aimed to replicate prior findings in a large, multicohort study. We analyzed publicly available data from adults without CVD in the ARIC (baseline 1987-1989), CHS (1989-1993), and MESA (2000-2002) studies. High lipoprotein(a) was defined by a mass concentration of ≥50 mg/dL or equivalent. Follow-up for CVD (myocardial infarction, stroke, or CVD death) and coronary heart disease (CHD; myocardial infarction, or CHD death) was available through 2018 in ARIC, 2011 in CHS, and 2015 in MESA. Mixed-effects models were used to obtain pooled results across studies. Aspirin use in ARIC (n = 13,085), CHS (n = 3,956), and MESA (n = 6,621) was 25.1%, 29.6%, and 19.3%, respectively. Using propensity score matching, the HR (95%CI) for CVD associated with aspirin use among participants with high and low lipoprotein(a) was 1.12 (0.96, 1.31) and 1.04 (0.96, 1.13), respectively (p-value comparing HRs: 0.38). The HR (95%CI) for CHD associated with aspirin use among participants with high and low lipoprotein(a) was 1.01 (0.82, 1.23) and 1.02 (0.92, 1.13), respectively (p-value comparing HRs: 0.94). No evidence of an association of aspirin use with lower CVD risk was present in participants with high or low lipoprotein(a) in subgroup analyses. There was no evidence to suggest that the association between aspirin and the incidence of CVD may differ by lipoprotein(a) levels.