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


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.
Chasman
Daniel I
DI
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States. dchasman@rics.bwh.harvard.edu
Shiffman
Dov
D
Zee
Robert Y L
RY
Louie
Judy Z
JZ
Luke
May M
MM
Rowland
Charles M
CM
Catanese
Joseph J
JJ
Buring
Julie E
JE
Devlin
James J
JJ
Ridker
Paul M
PM
D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics*; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012306:Risk
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001054:Apolipoproteins A; D001241:Aspirin
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