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

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Genetics and Genomics

Background:

• Elevated lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD).
• Previous small studies suggested aspirin may reduce CVD risk in individuals with high Lp(a) (≥50 mg/dL).
• The benefit of aspirin in relation to Lp(a) levels requires validation in larger, diverse populations.

Purpose of the Study:

• To investigate the association between aspirin use and the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD).
• To determine if lipoprotein(a) [Lp(a)] levels modify the effect of aspirin on CVD and CHD risk.
• To replicate and extend previous findings in a large, multicohort study.

Main Methods:

• Analysis of pooled data from three large observational studies: ARIC, CHS, and MESA.
• Participants without prevalent CVD were included, with follow-up for incident CVD and CHD.
• Propensity score matching and mixed-effects models were used to assess aspirin's association with CVD/CHD, stratified by high (≥50 mg/dL) vs. low Lp(a) levels.

Main Results:

• Aspirin use was not associated with a reduced risk of CVD (HR: 1.12 [0.96, 1.31] for high Lp(a); HR: 1.04 [0.96, 1.13] for low Lp(a)).
• Aspirin use was also not associated with a reduced risk of coronary heart disease (CHD) in either high or low Lp(a) groups.
• Subgroup analyses showed no evidence that aspirin use modifies CVD risk based on lipoprotein(a) concentration.

Conclusions:

• This large-scale study found no evidence that aspirin use affects cardiovascular disease (CVD) incidence differently across varying lipoprotein(a) [Lp(a)] levels.
• The findings do not support a role for aspirin in modifying CVD risk in individuals with high Lp(a).
• Further research may be needed to explore other therapeutic strategies for individuals at high CVD risk due to elevated Lp(a).