Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy.

ABSTRACT

OBJECTIVE: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers. METHODS AND RESULTS: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes, respectively (P<0.0001). During the 9.9 years of follow-up, minor allele carriers (3.7%) in the placebo group had twofold higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR)=2.21, 95% CI 1.39-3.52). Among carriers, risk was reduced more than twofold by aspirin for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI 0.20-0.94); risk was not significantly reduced among non-carriers (age-adjusted HR=0.91, 95% CI 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P=0.048). CONCLUSIONS: In the Women's Health Study, carriers of an apolipoprotein(a) variant had elevated Lp(a), doubled cardiovascular risk, and appeared to benefit more from aspirin than non-carriers.