Relationship between 25-hydroxyvitamin D and all-cause and cardiovascular disease mortality

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.