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A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study

Darshana Durup1, Henrik Løvendahl Jørgensen1, Jane Christensen1

  • 1Department of Drug Design and Pharmacology (D.D.M., A.-M.H.), and Faculty of Health and Medical Sciences (P.S.), University of Copenhagen, 2650 Glostrup, Denmark; Department of Clinical Biochemistry (H.L.J.), Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, Denmark; Danish Cancer Society Research Center (J.C., A.T., A.O., J.H.), 2100 Copenhagen, Denmark; and The Elective Laboratory of the Capital Region (B.L.) and the Research Centre of Ageing and Osteoporosis (P.S.), Department of Medicine M, Copenhagen University Hospital Glostrup, 2600 Glostrup, Denmark.

The Journal of Clinical Endocrinology and Metabolism
|February 25, 2015
PubMed

Insights

Low and high levels of 25-hydroxyvitamin D are linked to increased cardiovascular disease mortality. The highest risk was observed at the lowest vitamin D levels, suggesting a nonlinear association.

Area of Science:

  • Cardiovascular Health
  • Endocrinology
  • Public Health

Background:

  • Cardiovascular disease (CVD) is a leading cause of death globally.
  • The relationship between 25-hydroxyvitamin D [25(OH)D] levels and CVD mortality risk is not fully understood.
  • Clarifying this association is crucial for public health strategies.

Purpose of the Study:

  • To investigate the association between serum 25(OH)D levels and mortality from cardiovascular disease.
  • To examine the relationship between 25(OH)D levels and mortality specifically from stroke and acute myocardial infarction.
  • To identify potential optimal 25(OH)D levels for cardiovascular health.

Main Methods:

  • An observational cohort study, the Copenhagen Vitamin D Study, was conducted.
  • Serum 25(OH)D levels were analyzed in 247,574 individuals from Copenhagen general practice.
  • Multivariate Cox regression analysis was used to assess mortality risk across different 25(OH)D levels.

Main Results:

  • A total of 16,645 deaths occurred during the follow-up period (0-7 years).
  • The lowest cardiovascular disease mortality risk was associated with a 25(OH)D level of approximately 70 nmol/L.
  • Both very low (∼12.5 nmol/L) and high (∼125 nmol/L) 25(OH)D levels were associated with increased CVD mortality risk, with the highest risk at the lowest levels.

Conclusions:

  • Low and high serum 25(OH)D levels are associated with increased mortality from cardiovascular disease, stroke, and acute myocardial infarction in a nonlinear, reverse J-shaped manner.
  • The highest mortality risk was observed at the lowest 25(OH)D levels.
  • Further randomized clinical trials are needed to confirm causality and investigate effects of very high 25(OH)D levels (>100 nmol/L).
Abstract

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