Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association

J Clin Endocrinol Metab. 2013 May;98(5):2160-7. doi: 10.1210/jc.2013-1185. Epub 2013 Mar 26.


Context: Low serum calcidiol has been associated with multiple comorbidities and mortality but no "safe" range has been found for the upper concentration.

Objective: We aim to establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality.

Design, setting, and participants: We extracted data for 1,282,822 Clalit Health Services members aged >45 between July 2007 and December 2011. Records of mortality or acute coronary syndrome were extracted during the follow-up period. Kaplan-Meier analysis calculated time to episode and Cox regression models generated adjusted hazard ratios for episode by calcidiol group (<10, 10.1-20, 20.1-36, and >36.1 ng/mL).

Outcome measures: Acute coronary syndrome subsuming all-cause mortality.

Results: During the 54-month study period, 422,822 Clalit Health Services members were tested for calcidiol, of which 12,280 died of any cause (905 with acute coronary syndrome) and 3933 were diagnosed with acute coronary syndrome. Compared to those with 20-36 ng/mL, the adjusted hazard ratios among those with levels of <10, 10-20, and >36 ng/mL were 1.88 (confidence interval [CI]: 1.80-1.96), 1.25 (CI: 1.21-1.30), and 1.13 (CI: 1.04-1.22) (P < .05), respectively.

Limitations: The study cohort comprised only 30% of the population, those tested for vitamin D. The small sample size of those with calcidiol >36 ng/mL prevented further analysis of this group.

Conclusions: Vitamin D in the 20-36 ng/mL range was associated with the lowest risk for mortality and morbidity. The hazard ratio below and above this range increases significantly.

MeSH terms

  • Acute Coronary Syndrome / epidemiology
  • Acute Coronary Syndrome / etiology
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / prevention & control*
  • Aged
  • Aged, 80 and over
  • Calcifediol / blood*
  • Cohort Studies
  • Dietary Supplements* / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Israel / epidemiology
  • Male
  • Middle Aged
  • Mortality
  • Proportional Hazards Models
  • Prospective Studies
  • Risk
  • Severity of Illness Index
  • Survival Analysis
  • Vitamin D / administration & dosage
  • Vitamin D / adverse effects
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / diet therapy
  • Vitamin D Deficiency / mortality
  • Vitamin D Deficiency / physiopathology


  • Vitamin D
  • Calcifediol