Genetics
An apo(a) gene variant doubles cardiovascular risk in women, but aspirin cuts that risk more than two-fold, the Women's Health Study of 25,131 participants (Atherosclerosis 2009)
Original title: Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy
This study examined whether the apolipoprotein(a) variant rs3798220 is associated with elevated Lp(a) and cardiovascular risk, and modifies aspirin benefit, in 25,131 initially healthy Caucasian women from the Women's Health Study, a randomised low-dose aspirin trial. Median baseline Lp(a) was 10.0, 79.5, and 153.9 mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes (P<0.0001). Over 9.9 years, minor allele carriers (3.7% of participants) on placebo had twofold higher cardiovascular event risk than non-carriers (age-adjusted hazard ratio 2.21, 95% CI 1.39-3.52); among carriers, aspirin reduced this risk more than twofold (hazard ratio 0.44, 95% CI 0.20-0.94), while non-carriers saw no significant aspirin benefit (hazard ratio 0.91, 95% CI 0.77-1.08), a significant interaction (P=0.048). The findings show carriers of this apo(a) variant have elevated Lp(a) and doubled cardiovascular risk, but appear to benefit more from aspirin than non-carriers.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.