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

BackgroundThe ratio of 24,25-dihydroxyvitamin D-3/25-hydroxyvitamin D-3 (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](2)D) with cardiovascular disease (CVD) in patients with chronic kidney disease. Methods and ResultsThis study included longitudinal and cross-sectional analyses of 1786 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. Serum 24,25-dihydroxyvitamin D-3, 25(OH)D, and 1,25(OH)(2)D 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)(2)D 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)(2)D 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/m(2.7) per 10 ng/mL lower [95% CI, 0.0-1.3]). ConclusionsDespite modest associations of 25(OH)D with left ventricular mass index, 25(OH)D, the VDMR, and 1,25(OH)(2)D were not associated with incident CVD in chronic kidney disease.

Automated summary

The study investigated the associations of the vitamin D metabolite ratio (VDMR), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH](2)D) with cardiovascular disease (CVD) in chronic kidney disease patients. The results showed that lower VDMR and 1,25(OH)(2)D were associated with incident CVD, while only 25(OH)D was associated with left ventricular mass index. However, none of these metabolites were found to be associated with incident CVD in chronic kidney disease after adjustment for relevant factors.