25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population

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Previous studies have suggested that low 25-hydroxyvitamin D (25[OH]D) levels are associated with diabetes mellitus, hypertension, and cancers. Low levels are also associated with all-cause mortality in hemodialysis patients. Although there is a reduced risk of all-cause mortality in incident dialysis patients treated with vitamin D agents, including calcitriol and activated vitamin D3, no published studies have evaluated the risk of mortality in the general population.

To test the association of low 25(OH)D levels with all-cause cancer, and cardiovascular disease (CVD) mortality, the authors analyzed the data from the Third National Health and Nutrition Examination Survey (NHANES III)-linked mortality files for 13,331 adults 20 years or older. Patient mortality rates were assessed from 1988 through 1994, with a median 8.7 years of follow-up. In multivariate logistic regression analyses, independent predictors of 25(OH)D deficiency were defined as being in the lowest quartile 25(OH)D levels ≤17.8 ng/ml.

Independent risk factors associated with higher odds of 25(OH)D deficiency (≤17.8 ng/ml) were increasing age, female sex, nonwhite race/ethnicity, diabetes, higher body mass index, and current smoking. Decreased odds of deficiency were associated with vitamin D supplementation, physical activity, and nonwinter season. During the median 8.7 years of follow-up, 1806 deaths were recorded, including 777 from CVD. The all-cause mortality rate was adjusted in multivariate models for baseline demographics, season, and traditional and novel CVD risk factors. Compared with the highest quartile, the lowest quartile (25[OH]D levels <17.8 ng/ml) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio,1.26; 95% confidence interval [CI], 1.08–1.46) and a population attributable risk of 3.1%. There was a higher, although statistically insignificant, risk of CVD and cancer mortality. No association was found for other causes of death.

These data show that low levels of 25(OH)D (≤17.8 ng/ml) are associated with a higher risk of all-cause mortality in the general US population. To the authors’ knowledge, this is the first study to evaluate this association.

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