Vitamin D Metabolites and Risk of Cardiovascular Disease in Chronic Kidney Disease: The CRIC Study

J Am Heart Assoc. 2023 Jul 18;12(14):e028561. doi: 10.1161/JAHA.122.028561. Epub 2023 Jul 8.


Background The ratio of 24,25-dihydroxyvitamin D3/25-hydroxyvitamin D3 (vitamin D metabolite ratio [VDMR]) may reflect functional vitamin D activity. We examined associations of the VDMR, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) with cardiovascular disease (CVD) in patients with chronic kidney disease. Methods and Results This study included longitudinal and cross-sectional analyses of 1786 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. Serum 24,25-dihydroxyvitamin D3, 25(OH)D, and 1,25(OH)2D were measured by liquid chromatography-tandem mass spectrometry 1 year after enrollment. The primary outcome was composite CVD (heart failure, myocardial infarction, stroke, and peripheral arterial disease). We used Cox regression with regression-calibrated weights to test associations of the VDMR, 25(OH)D, and 1,25(OH)2D with incident CVD. We examined cross-sectional associations of these metabolites with left ventricular mass index using linear regression. Analytic models adjusted for demographics, comorbidity, medications, estimated glomerular filtration rate, and proteinuria. The cohort was 42% non-Hispanic White race and ethnicity, 42% non-Hispanic Black race and ethnicity, and 12% Hispanic ethnicity. Mean age was 59 years, and 43% were women. Among 1066 participants without prevalent CVD, there were 298 composite first CVD events over a mean follow-up of 8.6 years. Lower VDMR and 1,25(OH)2D were associated with incident CVD before, but not after, adjustment for estimated glomerular filtration rate and proteinuria (hazard ratio, 1.11 per 1 SD lower VDMR [95% CI, 0.95-1.31]). Only 25(OH)D was associated with left ventricular mass index after full covariate adjustment (0.6 g/m2.7 per 10 ng/mL lower [95% CI, 0.0-1.3]). Conclusions Despite modest associations of 25(OH)D with left ventricular mass index, 25(OH)D, the VDMR, and 1,25(OH)2D were not associated with incident CVD in chronic kidney disease.

Keywords: cardiovascular disease; chronic kidney disease; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cross-Sectional Studies
  • Ergocalciferols
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteinuria
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / epidemiology
  • Risk Factors
  • Vitamin D
  • Vitamins


  • Vitamin D
  • Ergocalciferols
  • Vitamins