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(Stroke. 2007;38:2912.)
© 2007 American Heart Association, Inc.

Original Contributions

B Vitamin Plasma Levels and the Risk of Ischemic Stroke and Transient Ischemic Attack in a German Cohort

Cornelia Weikert, MD, MPH; Jutta Dierkes, PhD; Kurt Hoffmann, PhD; Klaus Berger, MD, MPH; Dagmar Drogan, MPH; Kerstin Klipstein-Grobusch, MSc, PhD; Joachim Spranger, MD; Matthias Möhlig, MD; Claus Luley, MD Heiner Boeing, MSPH, PhD

From the Department of Epidemiology (C.W., K.H., D.D., K.-K.G., H.B.), German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany; the Institute of Clinical Chemistry and Pathobiochemistry (J.D., C.L.), Otto-von-Guericke University, Magdeburg, Germany; the Institute of Epidemiology and Social Medicine (K.B.), University of Muenster, Muenster, Germany; the School of Public Health (K.K.-G.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; and the Department of Clinical Nutrition (J.S., M.M.), German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.

Correspondence to Cornelia Weikert, MD, MPH, Department of Epidemiology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany. E-mail Weikert{at}mail.dife.de

Background and Purpose— Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phophate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort.

Methods— Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0±1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia.

Results— Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia.

Conclusions— Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.

Key Words: cerebrovascular ischemia • folate • methylene tetrahydrofolate reductase 677 genotype • pyridoxal 5-phosphate • vitamin B12