title: 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.
  
  
  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.
authors.affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States. dchasman@rics.bwh.harvard.edu
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Zee
authors.forename: Judy Z
authors.initials: JZ
authors.lastname: Louie
authors.forename: May M
authors.initials: MM
authors.lastname: Luke
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001054:Apolipoproteins A; D001241:Aspirin
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