Oksala Niku K J, Heikkinen Maarit, Mikkelsson Jussi, Pohjasvaara Tarja, Kaste Markku, Erkinjuntti Timo, Karhunen Pekka J
Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
Stroke. 2007 Jan;38(1):50-5. doi: 10.1161/01.STR.0000251719.59141.36. Epub 2006 Nov 30.
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.
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.
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).
Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.
吸烟、纤维蛋白原水平升高以及血小板活化均与缺血性卒中风险相关。血小板纤维蛋白原受体糖蛋白（Gp）IIb/IIIa Pl(A1/A2)多态性影响血小板与纤维蛋白原的结合，并提示与吸烟存在相互作用。
我们在卒中、衰老与记忆队列中探讨了吸烟及Pl(A1/A2)多态性与缺血性卒中和生存情况的关联，该队列包括486例连续患者（年龄55至85岁），在缺血性卒中后3个月进行分析，并随访15个月。272例患者可获得由磁共振成像确定的卒中亚型及GpIIb/IIIa Pl(A1/A2)基因型数据。
在多变量分析中，吸烟是与腔隙性梗死风险相关的唯一因素（优势比[OR]=1.87，95%置信区间[CI]=1.05至3.31；P=0.033），并且它也是15个月时死亡（n=24，8.8%）的一个预测因素（OR=5.13，95%CI=1.61至16.36；P=0.006），同时还有年龄（OR=1.10，95%CI=1.01至1.19；P=0.008）。单独的GpIIb/IIIa Pl(A1/A2)多态性与卒中亚型或生存情况无关联。然而，存在吸烟与基因型的联合作用与腔隙性梗死风险（OR=2.10，95%CI=0.90至4.89；P=0.087）以及与生存情况（OR=2.78，95%CI=0.89至8.61；P=0.077）的关联。在较年轻（55至69岁）的卒中患者中，携带Pl(A2)等位基因的吸烟者发生腔隙性梗死的风险（OR=5.81，95%CI=1.26至26.80；P=0.024）高于非携带者吸烟者（OR=3.12，95%CI=1.06至9.24；P=0.039）。Pl(A2)与吸烟联合对生存的影响（OR=8.86，95%CI=1.68至46.55；P=0.010）也强于单独吸烟的影响（OR=5.06，95%CI=1.20至21.35；P=0.027）。
我们的结果表明，促血栓形成的遗传因素可能通过改变卒中表型并影响中期生存而与吸烟相互作用。
