Abstract

Introduction: Vitamin D deficiency has been implicated in vascular dysfunction and the risk of recurrent vascular events. Previous studies, limited by a small sample size and lack of comparisons with long-term events, have yielded discordant results. To assess the hypothesis that low vitamin D levels predict long-term vascular events in patients with ischemic stroke, we conducted a large hospital-based study to compare the association between baseline vitamin D levels and the subsequent risk of vascular events. Methods: Between January 2010 and July 2011, 590 participants (mean age, 60.7 years; 69% men) diagnosed with ischemic stroke and transient ischemic attack at the National University Hospital, Singapore, were prospectively followed for vascular events (recurrent stroke, myocardial infarction and vascular death). Serum 25-hydroxyvitamin D levels were determined using the Roche Cobas e411 analyzer. Cox proportional hazards models were used to assess the associations between quartiles of serum 25-hydroxyvitamin D and the risk of vascular events, which were adjusted for demographic, stroke severity and subtype, and vascular risk factor covariates. Results: During a mean follow-up of 3.2 years (1,190 person-year), 116 participants developed a recurrent vascular event (recurrent stroke, n=63; myocardial infarction, n=30; vascular death, n=23). Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval) for recurrent vascular events in participants with lower levels of serum 25-hydroxyvitamin D (<14.9 mmol/l, 14.9-21.4 mmol/l and 21.5-28.9 mmol/l) were 1.43 (0.81-2.55), 1.70 (0.97-2.91) and 2.09 (1.22-3.58) compared to participants with higher concentrations (>28.9 mmol/l). Kaplan-Meier plots for unadjusted rates of vascular events show clear differences in risk by quartiles of serum 25-hydroxyvitamin D after a year of follow-up. Conclusions: Our results support the association between vitamin D deficiency and increased risk of recurrent vascular events in patients with ischemic stroke. Clinical trials are needed to ascertain whether correcting for this deficiency could indeed reduce the burden of vascular events in these individuals.

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