A Prospective Study of Serum 25-Hydroxyvitamin D Levels and Mortality Among African Americans and Non-African Americans

Lisa B. Signorello; Xijing Han; Qiuyin Cai; Sarah S. Cohen; Elizabeth L. Cope; Wei Zheng; William J. Blot


Am J Epidemiol. 2013;177(2):171-179. 

In This Article


Mean serum 25(OH)D levels varied significantly across strata of age, race, sex, season of blood collection, body mass index, smoking status, and household income (Table 1). The 2 major determinants of 25(OH)D levels, race and season of blood collection, showed expected patterns, with African Americans having levels an average of 5.1 ng/mL lower than whites and blood collected in winter having levels 5.6 ng/mL lower than those collected in summer (a seasonal pattern seen for both African Americans and non-African Americans).

We observed a significant trend (P trend < 0.001) of increasing risk of all-cause mortality with decreasing quartiles of serum 25(OH)D (Table 2). Those in the lowest quartile had an 80% increased mortality risk (95% CI: 1.43, 2.27) compared with those in the highest quartile. To evaluate whether preexisting disease affected these results, we repeated the analyses among participants without a reported history of heart attack/bypass surgery (odds ratio for quartile 1 (ORQ1) = 1.84, 95% CI: 1.47, 2.31), diabetes (ORQ1 = 1.55, 95% CI: 1.21, 1.99), hypertension (ORQ1 = 1.55, 95% CI: 1.08, 2.21), hypercholesterolemia (ORQ1 = 1.75, 95% CI: 1.34, 2.29), stroke/transient ischemic attack (ORQ1 = 1.68, 95% CI: 1.34, 2.10), emphysema/chronic bronchitis (ORQ1 = 1.67, 95% CI: 1.33, 2.09), or any of these 6 conditions (ORQ1 = 1.65, 95% CI: 1.05, 2.60) and found that the association persisted. Vitamin D was also a mortality risk factor for subjects who were nonsmokers at baseline (ORQ1 = 1.56, 95% CI: 1.02, 2.39) and who were of healthy weight (body mass index of 18.5–<25 kg/m2) at baseline (ORQ1 = 2.29, 95% CI: 1.55, 3.38).

Although trends of increasing risk with decreasing 25(OH)D levels were significant for both racial groups, the effect was somewhat stronger for non-African Americans than for African Americans (Pinteraction < 0.001) (Table 2). By use of classifications recently issued by the Institute of Medicine[26] (with >20 ng/mL as the referent "adequate" level), African Americans with "inadequate" (12–20 ng/mL) and "deficient" (<12 ng/mL) levels had odds ratios of 0.95 (95% CI: 0.75, 1.21) and 1.35 (95% CI: 1.05, 1.74), and non-African Americans had odds ratios of 1.30 (95% CI: 0.96, 1.78) and 2.20 (95% CI: 1.51, 3.19), respectively. Using an alternate referent value suggested by others[1,27] to represent vitamin D adequacy (>30 ng/mL), we found that African Americans with levels of 12–30 ng/mL and <12 ng/mL had odds ratios of 1.18 (95% CI: 0.79, 1.75) and 1.63 (95% CI: 1.08, 2.45), and non-African Americans had odds ratios of 1.27 (95% CI: 0.82, 1.95) and 2.37 (95% CI: 1.41, 3.96), respectively.

Figure 1 shows the estimated continuous association between serum 25(OH)D levels and mortality by using race-stratified restricted cubic spline models with knots at 5, 20, and 45 ng/mL. For African Americans, the odds of overall mortality reached its minimum at 35.4 ng/mL and, for non-African Americans, at 35.7 ng/mL. We applied 20 different variations for the placement of the 3 knots, and the odds of overall mortality reached its minimum in the 25(OH)D range of 35–40 ng/mL for the majority (34 of 40) of these models among African Americans and non-African Americans (not shown).

Figure 1.

Restricted cubic spline plots of the association between serum 25(OH)D and all-cause mortality, Southern Community Cohort Study, 2002–2010. Plots for African Americans (dashed line) and non-African Americans (solid line) depict predicted odds ratios from fully adjusted restricted cubic spline models with knots at 5, 20, and 45 ng/mL. 25(OH)D, 25-hydroxyvitamin D.

Serum 25(OH)D levels were not significantly associated with total cancer mortality, although there was a suggestion of an adverse effect for the lowest quartile (odds ratio = 1.28, 95% CI: 0.78, 2.11) (Table 3). In contrast, circulatory disease mortality was significantly elevated at below-median levels of 25(OH)D, with stronger effects seen for non-African Americans (P interaction = 0.004). Having quartile 1 levels of 25(OH)D was associated with an odds ratio of 2.53 (95% CI: 1.44, 4.46) among African Americans and 3.25 (95% CI: 1.33, 7.93) among non-African Americans. Our results also suggest an inverse association between 25(OH)D and mortality for an aggregate group of all other disease causes (P trend = 0.001), with an odds ratio for the lowest quartile of 1.72 (95% CI: 1.15, 2.58).