Epidemiology
A large multi-cohort study fails to replicate the earlier signal that aspirin cuts cardiovascular risk specifically in high-Lp(a) adults (Eur J Prev Cardiol 2025)
Original title: Aspirin Use and the Risk for Cardiovascular Disease by Lipoprotein(a) Levels: A Multi-Cohort Study
This study tested whether small observational studies suggesting aspirin cuts cardiovascular disease (CVD) incidence by roughly 50% specifically in adults with Lp(a) of 50 mg/dL or above, without benefit below that threshold, would replicate in a larger multi-cohort analysis. Using publicly available data from CVD-free adults in ARIC (n = 13,085), CHS (n = 3,956) and MESA (n = 6,621), with aspirin use of 25.1%, 29.6% and 19.3% respectively, propensity-score-matched Cox models found no CVD benefit from aspirin in either the high-Lp(a) group (HR 1.12, 95% CI 0.96-1.31) or the low-Lp(a) group (HR 1.04, 95% CI 0.96-1.13), with no significant difference between the two HRs (P = 0.38); results for coronary heart disease specifically were similarly null in both groups (P = 0.94 for the HR comparison). The authors conclude there is no evidence that aspirin's association with CVD risk differs by Lp(a) level, directly contradicting the earlier smaller-study signal and cautioning against using elevated Lp(a) alone as a rationale for primary-prevention aspirin.
Original abstract
Aims: 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.
Methods: 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.
Results: 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.
Conclusion: There was no evidence to suggest that the association between aspirin and the incidence of CVD may differ by lipoprotein(a) levels.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.