The Association Between Hyperhomocysteinemia and Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

Background and Objectives. Atrial fibrillation is complicated by a high rate of ischemic stroke. Previous studies have shown that an increased level of circulating total plasma homocysteine (tHcy) is an independent predictor of stroke, but it is unclear whether it is also predictive of stroke in patients with atrial fibrillation. The objective of this study was to evaluate whether increased tHcy is an independent predictor of cardio-embolic stroke in patients with non-valvular atrial fibrillation.Design and Methods. We studied 163 consecutive patients (77 males and 86 females; mean age 72.3 +/- 8.8 years) with permanent (n=118) or paroxysmal (n=45) atrial fibrillation of non-valvular origin hospitalized for cardiac reasons. Ischemic stroke, documented by nuclear magnetic resonance or computerized tomography imaging, had occurred at an average of 2 years before hospitalization in 40 patients (16 males and 24 females, mean age 74.8 +/- 8.8 years). Fasting tHcy levels were determined by high performance liquid chromatography.Results. Multivariate analysis adjusting for traditional cardiovascular risk factors, thromboembolic risk factors and predictors of tHcy (glomerular filtration rate, uric acid, gender) and fibrinogen levels (age, alcohol intake) showed that total homocysteine (OR:1.056; for each 1 mu mol/L increase, 95% C.I.: 1.00-1.12; p=0.042) and fibrinogen (OR:1.008 for each 1 mg/dL increase; 95% C.I.: 1.00-1.014; p=0.016) were independently associated with ischemic stroke. With respect to patients in the first quartile of the tHcy distribution (4.6-7.5 mu mol/L), patients in the fourth quartile of the tHcy distribution (18.7-67.1 mu mol/L) had a 2.73-fold increased probability of ischemic strokeInterpretations and Conclusions. In patients with non-valvular atrial fibrillation hospitalized for cardiac reasons, increased fasting tHcy levels are independently associated with a history of ischemic stroke.