A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice: The CopD Study

http://press.endocrine.org/doi/abs/10.1210/jc.2012-1176

A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice: The CopD Study
D. Durup, H. L. Jørgensen, J. Christensen, P. Schwarz, A. M. Heegaard and B. Lind
DOI: http://dx.doi.org/10.1210/jc.2012-1176
Received: January 23, 2012
Accepted: April 18, 2012
Published Online: July 02, 2013
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Abstract
Context:
Optimal levels of vitamin D have been a topic of heavy debate, and the correlation between 25-hydroxyvitamin D [25(OH)D] levels and mortality still remains to be established.
Objective:
The aim of the study was to determine the association between all-cause mortality and serum levels of 25(OH)D, calcium, and PTH.
Design and Setting:
We conducted a retrospective, observational cohort study, the CopD Study, in a single laboratory center in Copenhagen, Denmark.
Participants:
Serum 25(OH)D was analyzed from 247,574 subjects from the Copenhagen general practice sector. In addition, serum levels of calcium, albumin-adjusted calcium, PTH, and creatinine were measured in 111,536; 20,512; 34,996; and 189,496 of the subjects, respectively.
Main Outcome Measures:
Multivariate Cox regression analysis was used to compute hazard ratios for all-cause mortality.
Results:
During follow-up (median, 3.07 yr), 15,198 (6.1%) subjects died. A reverse J-shaped association between serum level of 25(OH)D and mortality was observed. A serum 25(OH)D level of 50–60 nmol/liter was associated with the lowest mortality risk. Compared to 50 nmol/liter, the hazard ratios (95% confidence intervals) of all-cause mortality at very low (10 nmol/liter) and high (140 nmol/liter) serum levels of 25(OH)D were 2.13 (2.02–2.24) and 1.42 (1.31–1.53), respectively. Similarly, both high and low levels of albumin-adjusted serum calcium and serum PTH were associated with an increased mortality, and secondary hyperparathyroidism was associated with higher mortality (P < 0.0001).
Conclusion:
In this study from the general practice sector, a reverse J-shaped relation between the serum level of 25(OH)D and all-cause mortality was observed, indicating not only a lower limit but also an upper limit. The lowest mortality risk was at 50–60 nmol/liter. The study did not allow inference of causality, and further studies are needed to elucidate a possible causal relationship between 25(OH)D levels, especially higher levels, and mortality.
Affiliations
Department of Drug Design and Pharmacology (D.D., A.M.H.), Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark; Department of Clinical Biochemistry (H.L.J.), Bispebjerg Hospital, 2400 Copenhagen, Denmark; Department of Statistics and Epidemiology (J.C.), the Danish Cancer Society, 2100 Copenhagen Denmark; Research Center of Aging and Osteoporosis (P.S.), Department of Medicine, Glostrup University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; and Copenhagen General Practitioners Laboratory (B.L.), 1112 Copenhagen, Denmark

Caution for upper limit of vitamin d3.

Interesting, thanks for the study.