Serum 25-Hydroxyvitamin D Concentration and Risk for Major Clinical Disease Events in a Community-Based Population of Older Adults, A Cohort Study
Annals of Internal Medicine May 1, 2012, vol. 156 no. 9 627-634
Ian H. de Boer, MD, MS; Gregory Levin, MS; Cassianne Robinson-Cohen, MS; Mary L. Biggs, PhD; Andy N. Hoofnagle, MD, PhD; David S. Siscovick, MD, MPH; and Bryan Kestenbaum, MD, MS
From the University of Washington, Seattle, Washington.
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
- 137 hip fractures,
- 186 myocardial infarctions,
- 335 incidences of cancer, and 3
- 60 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.
Primary Funding Source: National Institutes of Health.