Published Online
on July 17, 2008

A more recent version of this article appeared on September 1, 2008

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Submitted on January 3, 2008
Revised on January 28, 2008
Accepted on February 12, 2008

Low Vitamin D Levels Predict Stroke in Patients Referred to Coronary Angiography

Stefan Pilz MD; Harald Dobnig MD; Joachim E. Fischer MD; Britta Wellnitz LLD; Ursula Seelhorst MA; Bernhard O. Boehm MD; and Winfried März MD^*

From the Department of Public Health, Social and Preventive Medicine (S.P., J.E.F., W.M.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; the Department of Internal Medicine (S.P., H.D.), Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria; LURIC Database LLC (B.W., U.S.), Freiburg, Germany; the Department of Internal Medicine I (B.O.B.), Division of Endocrinology and Diabetes, Ulm University, Ulm, Germany; and the Synlab Center of Laboratory Diagnostics (W.M.), Heidelberg, Germany.

^* To whom correspondence should be addressed. E-mail: maerz{at}synlab.de.

Background and Purpose—Vitamin D deficiency is common among the elderly and may contribute to cerebrovascular diseases. We aimed to elucidate whether low vitamin D levels are predictive for fatal stroke.

Methods—The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study includes 3316 patients who were referred to coronary angiography at baseline between 1997 and 2000. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured in 3299 and 3315 study participants, respectively. To account for the seasonal variation of vitamin D metabolites, we calculated z values for the 25(OH)D and 1,25(OH)2D concentrations within each month of blood draw.

Results—During a median follow-up time of 7.75 years, 769 patients died, including 42 fatal (ischemic and hemorrhagic) strokes. When compared with survivors in binary logistic-regression analyses, the odds ratios (with 95% CIs) for fatal stroke were 0.58 (0.43 to 0.78; P<0.001) per z value of 25(OH)D and 0.62 (0.47 to 0.81; P<0.001) per z value of 1,25(OH)2D. After adjustment for several possible confounders, these odds ratios remained significant for 25(OH)D at 0.67 (0.46 to 0.97; P=0.032) and for 1,25(OH)2D at 0.72 (0.52 to 0.99; P=0.047). Z values of 25(OH)D and 1,25(OH)2D were also reduced in the 274 patients who had a history of previous cerebrovascular disease events at baseline.

Conclusions—Low levels of 25(OH)D and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that vitamin D supplementation is a promising approach in the prevention of strokes.

Key words: stroke • vitamins • epidemiology

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