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Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study
Karin Amrein1, Sadeq A Quraishi, Augusto A Litonjua
1Division of Endocrinology and Metabolism (K.A.), Department of Internal Medicine, and Division of Endocrinology and Metabolism (T.R.P.), Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria; Department of Anesthesia, Critical Care, and Pain Medicine (S.A.Q.), Division of Pulmonary and Critical Care Medicine (F.K.G.), Department of Medicine, and Department of Emergency Medicine (C.A.C.), Massachusetts General Hospital, Boston, Massachusetts 02114; Channing Division of Network Medicine and Pulmonary and Critical Care Division (A.A.L.), Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Departments of Nutrition and Epidemiology (E.G.), Harvard School of Public Health, and The Nathan E. Hellman Memorial Laboratory (K.B.C.), Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Objective:
The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission.
Design:
We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011.
Setting:
The study was conducted at two Boston teaching hospitals.
Patients:
A total of 24,094 adult inpatients participated in the study.
Intervention:
There was no intervention.
Measurements:
All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 30-49.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders.
Results:
After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68-2.40), 1.89 (1.64-2.18), 1.34 (1.16-1.56), 0.94 (0.69-1.26), 1.52 (1.03-2.25), and 1.69 (1.09-2.61), respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL].
Limitations:
A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study.
Conclusions:
Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.
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