Smoking and the platelet fibrinogen receptor glycoprotein IIb/IIIA PlA1/A2 polymorphism interact in the risk of lacunar stroke and midterm survival

Background and Purpose-Smoking, increased fibrinogen levels, and platelet activation are related to the risk of ischemic stroke. The platelet fibrinogen receptor glycoprotein (Gp) IIb/IIIa P1(A1/A2) polymorphism affects the binding of platelets to fibrinogen and is suggested to interact with smoking. Methods-We explored the association of smoking and the P1(A1/A2) polymorphism with ischemic stroke and survival in the Stroke Aging Memory cohort, comprising 486 consecutive patients (55 to 85 years old) who were analyzed 3 months after an ischemic stroke and followed up for 15 months. Stroke subtype determined by magnetic resonance imaging and GpIIb/IIIa P1(A1/A2) genotype data were available for 272 patients. Results-In multivariate analysis, smoking was the only factor related to the risk of lacunar infarcts (odds ratio [OR]=1.87, 95% CI=1.05 to 3.31; P=0.033), and it was also a predictor of death (n=24, 8.8%) at 15 months (OR=5.13, 95% CI=1.61 to 16.36; P=0.006), along with age (OR=1.10, 95% CI=1.01 to 1.19; P=0.008). The GpIlb/IIIa p1(A1/A2) polymorphism alone showed no association with stroke subtype or survival. However, there was a smoking-by-genotype association with the risk of lacunar infarcts (OR=2.10, 95% CI=0.90 to 4.89; P=0.087) and with survival (OR=2.78, 95% CI=0.89 to 8.61; P=0.077). Among younger (55 to 69 years) stroke patients, smokers carrying the p1(A2) allele were at a higher (OR=5.81, 95% CI=1.26 to 26.80; P=0.024) risk of lacunar infarcts than noncarrier smokers (OR=3.12, 95% CI= 1.06 to 9.24; P=0.039). The effect of P1(A2) and smoking combined on survival was also stronger (OR= 8.86, 95% CI= 1.68 to 46.55; P=0.010) than the effect of smoking alone (OR=5.06, 95% CI= 1.20 to 21.35; P=0.027). Conclusions-Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.