Prospective Study of Serum 25-hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-cause Mortality in Older U.S. Adults

Objectives: To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults.

Design: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files.

Setting: Noninstitutionalized U.S. civilian population.

Participants: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000.

Measurements: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all-cause and cardiovascular disease (CVD) mortality, respectively.

Results: During the median 7.3 years of follow-up, there were 1,493 (44%) deaths, including 767 CVD-related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all-cause mortality risk (adjusted hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92-0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI=1.14-2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI=1.09-1.97). The association appeared stronger for CVD mortality (adjusted HR=2.36, 95% CI=1.17-4.75, for subjects with 25[OH]D levels<25.0 nmol/L vs those > or =100.0 nmol/L) than for non-CVD mortality (adjusted HR=1.42, 95% CI=0.73-2.79, for subjects with 25[OH]D levels<25.0 nmol/L vs those > or =100.0 nmol/L).

Conclusion: In noninstitutionalized older adults, a group at high risk for all-cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all-cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible.