Background and Purpose-We wanted to investigate whether common prothrombotic mutations are more prevalent in patients with atrial fibrillation who have had a stroke than in healthy controls. We also wanted to assess whether early recurrent ischemic cerebrovascular events were more frequent among carriers of the factor V Leiden or the prothrombin gene mutations than among others. Methods-We used a case-control design with 367 patients with acute ischemic stroke and atrial fibrillation (cases) and 482 healthy blood donors (controls). All mutations were detected with conventional polymerase-chain reaction protocols. Results-The odds ratios for carriers of the factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT, or platelet glycoprotein IIIa 1565TC (Pl A2 ) mutation were 0.91, (95% CI, 0.51 to 1.59), 2.25 (95% CI, 0.61 to 8.90), 0.83 (0.61 to 1.13), and 0.79 (0.57 to 1.10), respectively. Early recurrent ischemic stroke and total recurrent ischemic cerebrovascular events were slightly more frequent among carriers of the factor V Leiden mutation than among noncarriers: odds ratio 1.45 (95% CI, 0.41 to 5.1), and 1.59 (0.61 to 4.1), respectively. None of the patients with recurrent ischemic cerebrovascular events had the prothrombin gene mutation. Conclusion-These mutations are not important risk factors for thromboembolic stroke associated with atrial fibrillation.Carriers of the factor V Leiden mutation had a small, nonsignificantly higher risk of early recurrent ischemic cerebrovascular events. Key Words: atrial fibrillation Ⅲ ischemic stroke Ⅲ prothrombotic gene mutations P atients with atrial fibrillation have a 5-fold increased risk of thromboembolic stroke, probably attributable to activation of blood coagulation. We wanted to investigate whether common prothrombotic mutations are more prevalent in patients with atrial fibrillation who have had a thromboembolic stroke than in healthy controls. We also wanted to investigate whether, among patients with acute ischemic stroke and atrial fibrillation, early recurrent ischemic cerebrovascular events were more frequent in carriers of the most important of these gene mutations than in noncarriers.We chose to screen for the factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase (MTHFR) 677CT, and platelet glycoprotein (GP) IIIa 1565TC mutations. The factor V Leiden and the prothrombin gene mutations are associated with increased risk of venous thromboembolism 1,2 and possibly myocardial infarction and stroke. 3 The MTHFR mutation increases plasma homocysteine, which has emerged as a potential risk factor for cardiovascular diseases, including stroke. 4 The mutant Pl A2 allele in the platelet GPIIIa gene is associated with increased risk of coronary thrombosis 5 and stroke in young patients. 6
Materials and MethodsCases were 367 patients with acute ischemic stroke and atrial fibrillation, of which 355 had been included in the Heparin in Acute Embolic Stroke Trial (HAEST). 7 Controls were unselected healthy subjects ...