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; Bryan Kestenbaum, MD, MS
Grant Support: By the National Heart, Lung, and Blood Institute (contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133 and grant HL080295), with additional contribution from the National Institute of Neurologic Disorders and Stroke. Additional support was provided by the National Institute on Aging (AG-023629, AG-15928, AG-20098, and AG-027058); the National Heart, Lung, and Blood Institute (grants R01HL084443 and R01HL096875); and the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK088762). A full list of principal CHS investigators and institutions can be found at www.chs-nhlbi.org/pi.htm.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2074.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. de Boer (e-mail, mailto:email@example.com). Data set: Not available.
Requests for Single Reprints: Ian H. de Boer, MD, MS, Box 359606, 325 9th Avenue, Seattle, WA 98104; e-mail, mailto:firstname.lastname@example.org.
Current Author Addresses: Drs. de Boer and Kestenbaum and Ms. Robinson-Cohen: Kidney Research Institute, Box 359606, 325 9th Avenue, Seattle, WA 98104.
Mr. Levin: Department of Biostatistics, Box 357232, 1959 Northeast Pacific Street, Seattle, WA 98195.
Dr. Biggs: Collaborative Health Studies Coordinating Center, Building 29, Suite 310, 6200 Northeast 74th Street, Seattle, WA 98115.
Dr. Hoofnagle: Department of Laboratory Medicine, Box 357110, 1959 Northeast Pacific Street, Seattle, WA 98195.
Dr. Siscovick: Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101.
Author Contributions: Conception and design: I.H. de Boer, G. Levin, B. Kestenbaum.
Analysis and interpretation of the data: I.H. de Boer, G. Levin, C. Robinson-Cohen, A.N. Hoofnagle, D.S. Siscovick, B. Kestenbaum.
Drafting of the article: I.H. de Boer, G. Levin, C. Robinson-Cohen.
Critical revision of the article for important intellectual content: G. Levin, C. Robinson-Cohen, M.L. Biggs, A.N. Hoofnagle, D.S. Siscovick, B. Kestenbaum.
Final approval of the article: I.H. de Boer, C. Robinson-Cohen, M.L. Biggs, A.N. Hoofnagle, D.S. Siscovick, B. Kestenbaum.
Statistical expertise: G. Levin, C. Robinson-Cohen, A.N. Hoofnagle.
Obtaining of funding: I.H. de Boer, B. Kestenbaum.
Collection and assembly of data: G. Levin, M.L. Biggs, A.N. Hoofnagle, D.S. Siscovick.
de Boer IH, Levin G, Robinson-Cohen C, Biggs ML, Hoofnagle AN, Siscovick DS, et al. Serum 25-Hydroxyvitamin D Concentration and Risk for Major Clinical Disease Events in a Community-Based Population of Older Adults: A Cohort Study. Ann Intern Med. 2012;156:627-634. doi: 10.7326/0003-4819-156-9-201205010-00004
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Published: Ann Intern Med. 2012;156(9):627-634.
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.
To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D.
The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis.
1621 white older adults.
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.
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 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.
The observational study was restricted to white participants.
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.
National Institutes of Health.
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Geriatric Medicine, Hematology/Oncology.
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