Serum 25-Hydroxyvitamin D Concentration and Risk for Major Clinical Disease Events in a Community-Based Population of Older Adults A Cohort Study

Background: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25(OH)D concentration. Objective: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D. Design: Cohort study. Setting: The Cardiovascular Health Study conducted in 4 U. S. communities. Data from 1992 to 2006 were included in this analysis. Participants: 1621 white older adults. Measurements: Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards)and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. Results: Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH) D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. Limitation: The observational study was restricted to white participants. Conclusion: Threshold concentrations of 25-(OH) D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH) D concentration may be more appropriate than static targets when evaluating health risk.