Advertisement
Mayo Clinic Proceedings Home

Serum 25-Hydroxyvitamin D Values and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort Study

      Abstract

      Objective

      To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and all-cause and cause-specific mortality.

      Patients and Methods

      We identified all serum 25(OH)D measurements in adults residing in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, through the Rochester Epidemiology Project. All-cause mortality was the primary outcome. Patients were followed up until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Multivariate analyses were adjusted for age, sex, race/ethnicity, month of measurement, and Charlson comorbidity index score.

      Results

      A total of 11,022 individuals had a 25(OH)D measurement between January 1, 2005, and December 31, 2011, with a mean ± SD value of 30.0±12.9 ng/mL. Mean age was 54.3±17.2 years, and most were female (77.1%) and white (87.6%). There were 723 deaths after a median follow-up of 4.8 years (interquartile range, 3.4-6.2 years). Unadjusted all-cause mortality hazard ratios (HRs) and 95% CIs for 25(OH)D values of less than 12, 12 to 19, and more than 50 ng/mL were 2.6 (95% CI, 2.0-3.2), 1.3 (95% CI, 1.0-1.6), and 1.0 (95% CI, 0.72-1.5), respectively, compared with the reference value of 20 to 50 ng/mL. In a multivariate model, the interaction between the effect of 25(OH)D and race/ethnicity on mortality was significant (P<.001). In white patients, adjusted HRs for 25(OH)D values of less than 12, 12 to 19, 20 to 50, and greater than 50 ng/mL were 2.5 (95% CI, 2.2-2.9), 1.4 (95% CI, 1.2-1.6), 1.0 (referent), and 1.0 (95% CI, 0.81-1.3), respectively. In patients of other race/ethnicity, adjusted HRs were 1.9 (95% CI, 1.5-2.3), 1.7 (95% CI, 1.1-2.6), 1.5 (95% CI, 1.0-2.0), and 2.1 (95% CI, 0.77-5.5).

      Conclusion

      White patients with 25(OH)D values of less than 20 ng/mL had greater all-cause mortality than those with values of 20 to 50 ng/mL, and white patients had greater mortality associated with low 25(OH)D values than patients of other race/ethnicity. Values of 25(OH)D greater than 50 ng/mL were not associated with all-cause mortality.

      Abbreviations and Acronyms:

      HR (hazard ratio), ICD-10 (International Classification of Diseases, Tenth Revision), NHANES (National Health and Nutrition Examination Survey), 25(OH)D (25-hydroxyvitamin D), REP (Rochester Epidemiology Project)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Holick M.F.
        Vitamin D deficiency.
        N Engl J Med. 2007; 357: 266-281
        • Thacher T.D.
        • Clarke B.L.
        Vitamin D insufficiency.
        Mayo Clin Proc. 2011; 86: 50-60
        • Ross A.C.
        • Manson J.E.
        • Abrams S.A.
        • et al.
        The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know.
        J Clin Endocrinol Metab. 2011; 96: 53-58
        • Durup D.
        • Jørgensen H.L.
        • Christensen J.
        • Schwarz P.
        • Heegaard A.M.
        • Lind B.
        A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study.
        J Clin Endocrinol Metab. 2012; 97: 2644-2652
        • Zittermann A.
        • Iodice S.
        • Pilz S.
        • Grant W.B.
        • Bagnardi V.
        • Gandini S.
        Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.
        Am J Clin Nutr. 2012; 95: 91-100
        • Gaksch M.
        • Jorde R.
        • Grimnes G.
        • et al.
        Vitamin D and mortality: individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium.
        PLoS One. 2017; 12: e0170791
        • Schöttker B.
        • Haug U.
        • Schomburg L.
        • et al.
        Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study.
        Am J Clin Nutr. 2013; 97: 782-793
        • Ginde A.A.
        • Scragg R.
        • Schwartz R.S.
        • Camargo Jr., C.A.
        Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults.
        J Am Geriatr Soc. 2009; 57: 1595-1603
        • Melamed M.L.
        • Michos E.D.
        • Post W.
        • Astor B.
        25-Hydroxyvitamin D levels and the risk of mortality in the general population.
        Arch Intern Med. 2008; 168: 1629-1637
        • Chowdhury R.
        • Kunutsor S.
        • Vitezova A.
        • et al.
        Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.
        BMJ. 2014; 348: g1903
        • Sempos C.T.
        • Durazo-Arvizu R.A.
        • Dawson-Hughes B.
        • et al.
        Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? results from the U.S. nationally representative NHANES.
        J Clin Endocrinol Metab. 2013; 98: 3001-3009
        • Amrein K.
        • Quraishi S.A.
        • Litonjua A.A.
        • et al.
        Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study.
        J Clin Endocrinol Metab. 2014; 99: 1461-1469
        • Dudenkov D.V.
        • Yawn B.P.
        • Oberhelman S.S.
        • et al.
        Changing incidence of serum 25-hydroxyvitamin D values above 50 ng/mL: a 10-year population-based study.
        Mayo Clin Proc. 2015; 90: 577-586
        • Institute of Medicine
        Dietary Reference Intakes for Calcium and Vitamin D.
        National Academies Press, Washington, DC2011
        • Melton III, L.J.
        History of the Rochester Epidemiology Project.
        Mayo Clin Proc. 1996; 71: 266-274
        • Rocca W.A.
        • Yawn B.P.
        • St Sauver J.L.
        • Grossardt B.R.
        • Melton III, L.J.
        History of the Rochester Epidemiology Project: half a century of medical records linkage in a US population.
        Mayo Clin Proc. 2012; 87: 1202-1213
        • St Sauver J.L.
        • Grossardt B.R.
        • Yawn B.P.
        • Melton III, L.J.
        • Rocca W.A.
        Use of a medical records linkage system to enumerate a dynamic population over time: the Rochester Epidemiology Project.
        Am J Epidemiol. 2011; 173: 1059-1068
        • Jacobsen S.J.
        • Xia Z.
        • Campion M.E.
        • et al.
        Potential effect of authorization bias on medical record research.
        Mayo Clin Proc. 1999; 74: 330-338
        • St Sauver J.L.
        • Grossardt B.R.
        • Leibson C.L.
        • Yawn B.P.
        • Melton III, L.J.
        • Rocca W.A.
        Generalizability of epidemiological findings and public health decisions: an illustration from the Rochester Epidemiology Project.
        Mayo Clin Proc. 2012; 87: 151-160
        • Grambsch P.M.
        • Therneau T.M.
        Proportional hazards tests and diagnostics based on weighted residuals.
        Biometrika. 1994; 81: 515-526
        • William B.A.
        • Mandrekar J.N.
        • Mandrekar S.J.
        • Cha S.S.
        • Furth A.F.
        Finding optimal cutpoints for continuous covariates with binary and time-to-event outcomes.
        Department of Health Sciences Research, Mayo Clinic, Rochester, MN2006 (Technical Report Series 79)
        • Contal C.
        • O'Quigley J.
        An application of changepoint methods in studying the effect of age on survival in breast cancer.
        Comput Stat Data Anal. 1999; 30: 253-270
        • Garland C.F.
        • Kim J.J.
        • Mohr S.B.
        • et al.
        Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D.
        Am J Public Health. 2014; 104: e43-e50
        • Schöttker B.
        • Saum K.U.
        • Perna L.
        • Ordóñez-Mena J.M.
        • Holleczek B.
        • Brenner H.
        Is vitamin D deficiency a cause of increased morbidity and mortality at older age or simply an indicator of poor health?.
        Eur J Epidemiol. 2014; 29: 199-210
        • Schöttker B.
        • Ball D.
        • Gellert C.
        • Brenner H.
        Serum 25-hydroxyvitamin D levels and overall mortality: a systematic review and meta-analysis of prospective cohort studies.
        Ageing Res Rev. 2013; 12: 708-718
        • Kestenbaum B.
        • Katz R.
        • de Boer I.
        • et al.
        Vitamin D, parathyroid hormone, and cardiovascular events among older adults.
        J Am Coll Cardiol. 2011; 58: 1433-1441
        • Kritchevsky S.B.
        • Tooze J.A.
        • Neiberg R.H.
        • et al.
        25-Hydroxyvitamin D, parathyroid hormone, and mortality in black and white older adults: the Health ABC Study.
        J Clin Endocrinol Metab. 2012; 97: 4156-4165
        • Bjelakovic G.
        • Gluud L.L.
        • Nikolova D.
        • et al.
        Vitamin D supplementation for prevention of mortality in adults.
        Cochrane Database Syst Rev. 2014; : CD007470
        • Durazo-Arvizu R.A.
        • Dawson-Hughes B.
        • Kramer H.
        • et al.
        The reverse J-shaped association between serum total 25-hydroxyvitamin D concentration and all-cause mortality: the impact of assay standardization.
        Am J Epidemiol. 2017; 185: 720-726
        • Kroll M.H.
        • Bi C.
        • Garber C.C.
        • et al.
        Temporal relationship between vitamin D status and parathyroid hormone in the United States.
        PLoS One. 2015; 10: e0118108
        • Saliba W.
        • Barnett O.
        • Rennert H.S.
        • Rennert G.
        The risk of all-cause mortality is inversely related to serum 25(OH)D levels.
        J Clin Endocrinol Metab. 2012; 97: 2792-2798
        • Kramer H.
        • Sempos C.
        • Cao G.
        • et al.
        Mortality rates across 25-hydroxyvitamin D (25[OH]D) levels among adults with and without estimated glomerular filtration rate <60 ml/min/1.73 m2: the Third National Health and Nutrition Examination Survey.
        PLoS One. 2012; 7: e47458
        • Eaton C.B.
        • Young A.
        • Allison M.A.
        • et al.
        Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI).
        Am J Clin Nutr. 2011; 94: 1471-1478
        • Daraghmeh A.H.
        • Bertoia M.L.
        • Al-Qadi M.O.
        • Abdulbaki A.M.
        • Roberts M.B.
        • Eaton C.B.
        Evidence for the vitamin D hypothesis: the NHANES III extended mortality follow-up.
        Atherosclerosis. 2016; 255: 96-101
        • Powe C.E.
        • Evans M.K.
        • Wenger J.
        • et al.
        Vitamin D-binding protein and vitamin D status of black Americans and white Americans.
        N Engl J Med. 2013; 369: 1991-2000
        • Lips P.
        Worldwide status of vitamin D nutrition.
        J Steroid Biochem Mol Biol. 2010; 121: 297-300
        • Durazo-Arvizu R.A.
        • Camacho P.
        • Bovet P.
        • et al.
        25-Hydroxyvitamin D in African-origin populations at varying latitudes challenges the construct of a physiologic norm.
        Am J Clin Nutr. 2014; 100: 908-914
        • Signorello L.B.
        • Han X.
        • Cai Q.
        • et al.
        A prospective study of serum 25-hydroxyvitamin D levels and mortality among African Americans and non-African Americans.
        Am J Epidemiol. 2013; 177: 171-179
        • Aloia J.F.
        African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox.
        Am J Clin Nutr. 2008; 88: 545S-550S
        • Cauley J.A.
        • Danielson M.E.
        • Boudreau R.
        • et al.
        Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women's Health Initiative (WHI).
        J Bone Miner Res. 2011; 26: 2378-2388
        • Gutiérrez O.M.
        • Farwell W.R.
        • Kermah D.
        • Taylor E.N.
        Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey.
        Osteoporos Int. 2011; 22: 1745-1753
        • Harris S.S.
        Does vitamin D deficiency contribute to increased rates of cardiovascular disease and type 2 diabetes in African Americans?.
        Am J Clin Nutr. 2011; 93: 1175S-1178S
        • Michos E.D.
        • Reis J.P.
        • Post W.S.
        • et al.
        25-Hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: the NHANES-III linked mortality files.
        Nutrition. 2012; 28: 367-371
        • Fiscella K.
        • Franks P.
        Vitamin D, race, and cardiovascular mortality: findings from a national US sample.
        Ann Fam Med. 2010; 8: 11-18
        • McKibben R.A.
        • Zhao D.
        • Lutsey P.L.
        • et al.
        Factors associated with change in 25-hydroxyvitamin D levels over longitudinal follow-up in the ARIC Study.
        J Clin Endocrinol Metab. 2016; 101: 33-43

      Linked Article

      • The Death D-fying Vitamin
        Mayo Clinic ProceedingsVol. 93Issue 6
        • Preview
          In this issue of Mayo Clinic Proceedings, Dudenkov et al1 report on a retrospective study relating vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) with the risk of all-cause and cause-specific mortality in their patients registered in the Rochester Epidemiology Project. The article reported that vitamin D deficiency was associated with increased mortality. There was a statistically significant inverse relationship with mortality in both white and nonwhite patients, as well as with their serum 25(OH)D level.
        • Full-Text
        • PDF