• Ian H de Boer, Gregory Levin, Cassianne Robinson-Cohen, Mary L Biggs, Andy N Hoofnagle, David S Siscovick, and Bryan Kestenbaum.
• University of Washington, Seattle, USA. deboer@u.washington.edu
• Ann. Intern. Med. 2012 May 1; 156 (9): 627634627-34.

BackgroundCirculating 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.ObjectiveTo evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D.DesignCohort study.SettingThe Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis.Participants1621 white older adults.MeasurementsSerum 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.ResultsOver a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip 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.LimitationThe observational study was restricted to white participants.ConclusionThreshold 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.Primary Funding SourceNational Institutes of Health.

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