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(Stroke. 2007;38:50.)
© 2007 American Heart Association, Inc.

Original Contributions

Smoking and the Platelet Fibrinogen Receptor Glycoprotein IIb/IIIA Pl^A1/A2 Polymorphism Interact in the Risk of Lacunar Stroke and Midterm Survival

Niku K.J. Oksala, MD, PhD; Maarit Heikkinen, MD, PhD; Jussi Mikkelsson, MD, PhD; Tarja Pohjasvaara, MD, PhD; Markku Kaste, MD, PhD; Timo Erkinjuntti, MD, PhD Pekka J. Karhunen, MD, PhD

From the Division of Vascular Surgery, Department of Surgery (N.K.J.O., M.H.), and the Heart Centre (J.M.), Tampere University Hospital, Tampere; the Department of Neurology (T.P., M.K., T.E.), Helsinki University Central Hospital, Helsinki; and the School of Medicine, Forensic Medicine, University of Tampere, and Research Unit of the Centre Laboratory (N.K.J.O., P.J.K.), Tampere University Hospital, Tampere, Finland.

Correspondence to Pekka J. Karhunen, MD, PhD, Department of Forensic Medicine, Medical School, University of Tampere, FI-33014 Tampere, Finland. E-mail pekka.karhunen{at}uta.fi

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 Pl^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 Pl^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 Pl^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 GpIIb/IIIa Pl^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 Pl^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 Pl^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.

Key Words: polymorphisms • smoking • stroke • survival

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