Pre-hospital Vitamin D Concentration, Mortality, and Bloodstream Infection in a Hospitalized Patient Population



      The study objective was to examine the association between pre-hospital serum vitamin D concentration and mortality after hospitalization.


      We performed a retrospective cohort study in 2 tertiary hospitals in Boston, Mass, on 23,603 patients aged ≥18 years in whom 25(OH)D was measured before hospitalization between 1993 and 2010. The main outcome measures were all-cause mortality by day 30 post-hospital admission, in-hospital mortality, and community-acquired bloodstream infection.


      Compared with patients with pre-hospital 25(OH)D ≥30 ng/mL, patients with pre-hospital 25(OH)D ≤15 ng/mL or 15 to 30 ng/mL have higher odds of mortality 30 days after hospital admission. After adjustment for age, gender, race, Deyo-Charlson index, season, type (surgical vs medical), creatinine, blood urea nitrogen, hematocrit, and time between 25(OH)D draw and hospital admission, the adjusted odds ratio (OR) of 30-day mortality in patients with 25(OH)D ≤15 ng/mL is 1.45 (95% confidence interval [CI], 1.21-1.74; P<.0001) and the adjusted OR of 30-day mortality in patients with 25(OH)D 15 to 30 ng/mL is 1.30 (95% CI, 1.10-1.54; P = .003) both compared with patients with pre-hospital 25(OH)D ≥30 ng/mL. In a subgroup analysis of patients who had blood cultures drawn (n = 5628), pre-hospital serum 25(OH)D ≤15 ng/mL was associated with increased odds of community-acquired bloodstream infection (adjusted OR, 1.29; 95% CI, 1.06-1.57; P = .01) relative to patients with 25(OH)D ≥30 ng/mL.


      Analysis of 23,603 hospitalized patients identified both 25(OH)D ≤15 ng/mL and 25(OH)D 15 to 30 ng/mL before hospital admission as associated with the odds of all-cause patient mortality at 30 days after hospitalization. In addition, pre-hospital serum 25(OH)D ≤15 ng/mL is significantly associated with the odds of community-acquired bloodstream infection.


      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 to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Holick M.F.
        High prevalence of vitamin D inadequacy and implications for health.
        Mayo Clin Proc. 2006; 81: 353-373
        • Holick M.F.
        Vitamin D deficiency.
        N Engl J Med. 2007; 357: 266-281
        • Raiten D.J.
        • Picciano M.F.
        Vitamin D and health in the 21st century: bone and beyond. Executive summary.
        Am J Clin Nutr. 2004; 80: 1673S-1677S
        • Holick M.F.
        Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis.
        Am J Clin Nutr. 2004; 79: 362-371
        • Teegarden D.
        • Donkin S.S.
        Vitamin D: emerging new roles in insulin sensitivity.
        Nutr Res Rev. 2009; 22: 82-92
        • Autier P.
        • Gandini S.
        Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.
        Arch Intern Med. 2007; 167: 1730-1737
        • 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
        • Zadshir A.
        • Tareen N.
        • Pan D.
        • Norris K.
        • Martins D.
        The prevalence of hypovitaminosis D among US adults: data from the NHANES III.
        Ethn Dis. 2005; 15 (-101): S5-S97
        • Chan T.Y.
        Vitamin D deficiency and susceptibility to tuberculosis.
        Calcif Tissue Int. 2000; 66: 476-478
        • Ginde A.A.
        • Mansbach J.M.
        • Camargo Jr, C.A.
        Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey.
        Arch Intern Med. 2009; 169: 384-390
        • Braun A.
        • Chang D.
        • Mahadevappa K.
        • et al.
        Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill.
        Crit Care Med. 2011; 39: 671-677
        • Avenell A.
        • Cook J.A.
        • Maclennan G.S.
        • Macpherson G.C.
        Vitamin D supplementation to prevent infections: a sub-study of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438).
        Age Ageing. 2007; 36: 574-577
        • Moe S.M.
        • Zekonis M.
        • Harezlak J.
        • et al.
        A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol.
        Am J Kidney Dis. 2001; 38: 792-802
        • Kelsey J.
        • Whittemore A.
        • Evans A.
        • Thompson W.
        Methods in Observational Epidemiology.
        2nd ed. Oxford University Press, New York1996
        • Giovannucci E.
        • Liu Y.
        • Hollis B.W.
        • Rimm E.B.
        25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study.
        Arch Intern Med. 2008; 168: 1174-1180
        • Braun A.B.
        • Gibbons F.K.
        • Litonjua A.A.
        • et al.
        Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality.
        Crit Care Med. 2012; 40: 63-72
        • Annweiler C.
        • Beauchet O.
        • Berrut G.
        • et al.
        Is there an association between serum 25-hydroxyvitamin D concentration and muscle strength among older women? Results from baseline assessment of the EPIDOS study.
        J Nutr Health Aging. 2009; 13: 90-95
        • Varsavsky M.
        • Reyes-Garcia R.
        • Cortes-Berdonces M.
        • et al.
        Serum 25 OH vitamin D concentrations and calcium intake are low in patients with prostate cancer.
        Endocrinol Nutr. 2011; 58: 487-491
        • 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
        • Bischoff-Ferrari H.A.
        • Zhang Y.
        • Kiel D.P.
        • Felson D.T.
        Positive association between serum 25-hydroxyvitamin D level and bone density in osteoarthritis.
        Arthritis Rheum. 2005; 53: 821-826
        • Thomas M.K.
        • Lloyd-Jones D.M.
        • Thadhani R.I.
        • et al.
        Hypovitaminosis D in medical inpatients.
        N Engl J Med. 1998; 338: 777-783
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Quan H.
        • Sundararajan V.
        • Halfon P.
        • et al.
        Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
        Med Care. 2005; 43: 1130-1139
        • Quan H.
        • Li B.
        • Couris C.M.
        • et al.
        Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.
        Am J Epidemiol. 2011; 173: 676-682
        • Rapoport J.
        • Gehlbach S.
        • Lemeshow S.
        • Teres D.
        Resource utilization among intensive care patients. Managed care vs traditional insurance.
        Arch Intern Med. 1992; 152: 2207-2212
        • Zager S.
        • Mendu M.L.
        • Chang D.
        • et al.
        Neighborhood poverty rate and mortality in patients receiving critical care in the academic medical center setting.
        Chest. 2011; 139: 1368-1379
        • Cowper D.C.
        • Kubal J.D.
        • Maynard C.
        • Hynes D.M.
        A primer and comparative review of major US mortality databases.
        Ann Epidemiol. 2002; 12: 462-468
        • Sohn M.W.
        • Arnold N.
        • Maynard C.
        • Hynes D.M.
        Accuracy and completeness of mortality data in the Department of Veterans Affairs.
        Popul Health Metr. 2006; 4: 2
        • Schisterman E.F.
        • Whitcomb B.W.
        Use of the Social Security Administration Death Master File for ascertainment of mortality status.
        Popul Health Metr. 2004; 2: 2
        • Newman T.B.
        • Brown A.N.
        Use of commercial record linkage software and vital statistics to identify patient deaths.
        J Am Med Inform Assoc. 1997; 4: 233-237
        • Deluca H.F.
        • Cantorna M.T.
        Vitamin D: its role and uses in immunology.
        FASEB J. 2001; 15: 2579-2585
        • Gysemans C.A.
        • Cardozo A.K.
        • Callewaert H.
        • et al.
        1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice.
        Endocrinology. 2005; 146: 1956-1964
        • Levin A.
        • Li Y.C.
        Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?.
        Kidney Int. 2005; 68: 1973-1981
        • Li Y.C.
        • Kong J.
        • Wei M.
        • Chen Z.F.
        • Liu S.Q.
        • Cao L.P.
        1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
        J Clin Invest. 2002; 110: 229-238
        • Banerjee P.
        • Chatterjee M.
        Antiproliferative role of vitamin D and its analogs—a brief overview.
        Mol Cell Biochem. 2003; 253: 247-254
        • Xiang W.
        • Kong J.
        • Chen S.
        • et al.
        Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems.
        Am J Physiol Endocrinol Metab. 2005; 288: E125-E132
        • Forman J.P.
        • Giovannucci E.
        • Holmes M.D.
        • et al.
        Plasma 25-hydroxyvitamin D levels and risk of incident hypertension.
        Hypertension. 2007; 49: 1063-1069
        • Chonchol M.
        • Scragg R.
        25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey.
        Kidney Int. 2007; 71: 134-139
        • Ford E.S.
        • Ajani U.A.
        • McGuire L.C.
        • Liu S.
        Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults.
        Diabetes Care. 2005; 28: 1228-1230
        • Wortsman J.
        • Matsuoka L.Y.
        • Chen T.C.
        • Lu Z.
        • Holick M.F.
        Decreased bioavailability of vitamin D in obesity.
        Am J Clin Nutr. 2000; 72: 690-693
        • Anderson J.L.
        • May H.T.
        • Horne B.D.
        • et al.
        Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population.
        Am J Cardiol. 2010; 106: 963-968
        • Kankova M.
        • Luini W.
        • Pedrazzoni M.
        • et al.
        Impairment of cytokine production in mice fed a vitamin D3-deficient diet.
        Immunology. 1991; 73: 466-471
        • Liu P.T.
        • Stenger S.
        • Tang D.H.
        • Modlin R.L.
        Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin.
        J Immunol. 2007; 179: 2060-2063
        • Liu P.T.
        • Stenger S.
        • Li H.
        • et al.
        Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
        Science. 2006; 311: 1770-1773
        • Bhalla A.K.
        • Amento E.P.
        • Krane S.M.
        Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production.
        Cell Immunol. 1986; 98: 311-322
        • Fabri M.
        • Stenger S.
        • Shin D.M.
        • et al.
        Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.
        Sci Transl Med. 2011; 3: 104ra102
        • Concato J.
        • Shah N.
        • Horwitz R.I.
        Randomized, controlled trials, observational studies, and the hierarchy of research designs.
        N Engl J Med. 2000; 342: 1887-1892
        • Platz E.A.
        • Leitzmann M.F.
        • Hollis B.W.
        • Willett W.C.
        • Giovannucci E.
        Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer.
        Cancer Causes Control. 2004; 15: 255-265
        • Diekema D.J.
        • Pfaller M.A.
        • Schmitz F.J.
        • et al.
        Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999.
        Clin Infect Dis. 2001; 32: S114-S132
        • Gottlieb S.S.
        Dead is dead—artificial definitions are no substitute.
        Lancet. 1997; 349: 662-663