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

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Abstract
Several studies have suggested that 25-hydroxyvitamin (25[OH]D) deficiency is an unrecognized contributor to the development of cardiovascular disease (CVD), cancer, and mortality. 1,25-Dihydroxyvitamin D affects the renin-angiotensin system,1 is associated with cardiac myocyte hypertrophy,2 and has anti-inflammatory effects,3 all of which may influence CVD risk.4 In addition, 1,25-dihydroxyvitamin D has antiproliferative activity, which may influence cancer risk.5 Therapy with calcitriol or paricalcitol or other vitamin D agents (activated vitamin D therapy) is associated with lower mortality in those with end-stage renal disease.6-10 In addition, low 25(OH)D levels have been associated with multiple CVD risk factors in the Third National Health and Nutrition Examination Survey (NHANES III) population11 as well as with hypertension,12 congestive heart failure,13 cancer,14 and diabetes mellitus.15,16 Low 25(OH)D levels in incident hemodialysis patients have recently been shown to be associated with all-cause mortality.17 A meta-analysis of 18 randomized clinical trials of vitamin D supplementation in mostly older individuals found that randomization to vitamin D supplementation was associated with lower all-cause mortality.18 Despite these suggested associations, we found no published studies evaluating the relationship between 25(OH)D levels and mortality risk in the general population.