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Relationship between 25-Hydroxyvitamin D and All-cause and Cardiovascular Disease Mortality

  • Muhammad Amer, MD, MHS, FACP

      Affiliations

    • Requests for reprints should be addressed to Muhammad Amer, MD, Johns Hopkins University, 600 North Wolfe Street, Osler 264, Baltimore, MD 21287
    • ,
  • Rehan Qayyum, MD, MHS

Department of Medicine, Johns Hopkins University, Baltimore, Md

published online 18 April 2013.
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Abstract 

Background

Observational studies have suggested a strong relationship between 25(OH)D and all-cause and cardiovascular disease mortality. A few studies also have described a nonlinear trend for this relationship in population subgroups, but less is known about this relationship in healthy adults. We examined the presence of a nonlinear relationship between 25(OH)D and all-cause and cardiovascular disease mortality among healthy adults.

Methods

We examined 10,170 participants (≥18 years of age) using National Health and Nutrition Examination Survey data (2001-2004) combined with National Death Index for vital status information through December 2006. Cox proportional hazard models with spline (single knot at population median of 25[OH]D) were fit to estimate hazard ratios (HRs) for all-cause and cardiovascular disease mortality for each 10-unit increase in serum 25(OH)D. Models were adjusted for demographic and conventional cardiovascular disease risk factors.

Results

Mean age of study participants was 46.6 (20.5) years, while median (interquartile range) 25(OH)D was 21 (15-27) ng/mL. After a median follow-up of 3.8 years (range 2.8-4.9), 509 all-cause and 184 cardiovascular diseases-related deaths were observed. In univariate analysis, 25(OH)D decreased hazards of all-cause (HR 0.59; 95% confidence interval [CI], 0.45-0.77) and cardiovascular disease (HR 0.56; 95% CI, 0.38-0.82) mortality below but not above its population median. In adjusted models, 25(OH)D retained the inverse association for all-cause (HR 0.54; 95% CI, 0.35-0.84) and cardiovascular disease (HR 0.50; 95% CI, 0.26-0.98) mortality below but not above its population median.

Conclusions

We found an inverse association between 25(OH)D and all-cause and cardiovascular disease mortality in healthy adults with serum 25(OH)D levels of ≤21 ng/mL. Clinical trials for the primary prevention of cardiovascular disease with 25(OH)D supplementation may target healthy adults with serum 25(OH)D levels of ≤21 ng/mL to validate these findings.

 

 Funding: Rehan Qayyum was supported by National Institute of Health grant No. 1K23HL105897-01.

 Conflict of Interest: None.

 Authorship: Both authors had access to the data and a role in writing the original manuscript.

PII: S0002-9343(13)00084-3

doi:10.1016/j.amjmed.2012.11.021

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