Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism

Background and Purpose-Al though risk factors for carotid artery stenosis c aused by atherosclerosis are known, it is unclear what triggers "activation " of the atherosclerotic plaques and the ensuing thromboembolic cerebral ev ents. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated w ith a risk of ischemic events in patients with significant carotid stenosis . Methods-Consecutive patients with greater than or equal to 50% carotid sten osis, whether symptomatic (with ipsilateral ischemic events) or asymptomati c, who were evaluated and followed in a neurovascular clinic were tested fo r plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolat e reductase, G20210A mutation of factor II, factor V Leiden, antiphospholip id antibodies, and polymorphisms of platelet membrane GP: human platelet an tigen (HPA)-1, GP la (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2). Results-Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7 +/- 6.9 versus 69.5 +/- 9.1 years, P = 0. 02). Major risk factors for stroke were similar in both groups. In symptoma tic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P = 0.002) and HPA-1a/b wa s almost 2-fold more common (38.8% versus 20.9%, respectively; P = 0.01). A ll other thrombophilic factors and platelet polymorphisms studied did not d iffer significantly between the 2 groups. Multivariate analysis revealed th at hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant r isk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively. Conclusions-Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.