|DURAZO-ARVIZU, RAMON - Loyola University|
|DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|KRAMER, HOLLY - Loyola University|
|CAO, GUICHAN - Loyola University|
|MERKEL, JOYCE - National Institutes Of Health (NIH)|
|COATES, PAUL - National Institutes Of Health (NIH)|
|SEMPOS, CHRISTOPHER - National Institutes Of Health (NIH)|
Submitted to: American Journal of Epidemiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2016
Publication Date: 3/15/2017
Citation: Durazo-Arvizu, R.A., Dawson-Hughes, B., Kramer, H., Cao, G., Merkel, J., Coates, P.M., Sempos, C.T. 2017. The reverse J shaped association between serum total 25- hydroxyvitamin D and all-cause mortality: The impact of assay standardization. American Journal of Epidemiology. doi: 10.1093/aje/kww244.
Interpretive Summary: In an earlier analysis, the authors examined the association of circulating levels of 25-hydroxyvitamin D with mortality in the National Health and Nutrition Examination Survey participants. We found that both low and high vitamin D levels were associated with increased mortality. In the current study, we reexamined the association after standardizing the vitamin D measurements to the international gold standard assay. When using standardized 25-hydroxyvitamn D levels, we found that low but not high 25-hydroxyvitamn D levels were associated with increased mortality. This study highlights the fact that assay standardization alone can provide the ability to form conclusions based on the true values of serum 25-hydroxyvitamin D.
Technical Abstract: The impact of standardizing the originally measured serum total 25-hydroxyvitamin D [25(OH)D] values from Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) on the association between 25(OH)D and rate of all-cause mortality was evaluated. Values were standardized to gold standard laboratory method. Follow-up from 1990-2006 consisted of 15,099 participants ages 20+ years at baseline with 3,784 deaths. Relative risk (RR) of death was adjusted for age, sex, race-ethnicity and season using Poisson regression. Results were given for eight 25(OH)D (nmol/L) categories: <20, 20-29, 30-39, 40-49, 50-59, 60-74, 75-99 (reference), 100+. Assay standardization dramatically shifted original 25(OH)D values towards zero. Accordingly, risk >/=120 nmol/L could not be evaluated, i.e. N=7 and Ndeaths=2. RR (+/- 95% CI) <40 nmol/l remained significant: 30-39: 1.4 (1.1-1.6); 20-29: 1.6 (1.3-1.9) and <20: 2.1 (1.6-2.7). However, adjusted RR estimates for 25(OH)D levels >/=40 nmol/L were no longer significant: 40-49: 1.2 (0.99-1.4); 50-59: 1.2 (1.04-1.4); 60-74: 1.1 (0.94-1.2); 75-99: 1.0 and 100+: 1.1 (0.6-2.1). In summary, after standardization risk of death from all-causes increased with decreasing 25(OH)D <40 nmol/L while there was no association at values above >/=40 nmol/L through the category >/=100 nmol/L.