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

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

Simon Hsu  1 , Leila R Zelnick  1 , Nisha Bansal  1 , Julia Brown  2 , Michelle Denburg  3   4 , Harold I Feldman  4   5 , Charles Ginsberg  6 , Andrew N Hoofnagle  7 , Tamara Isakova  8 , Mary B Leonard  9 , Benjamin Lidgard  1 , Cassianne Robinson-Cohen  10 , Myles Wolf  11 , Dawei Xie  4   5 , Bryan R Kestenbaum  1 , Ian H de Boer  1 ; CRIC Study Investigators *
Collaborators, Affiliations

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

Simon Hsu et al. J Am Heart Assoc. .

Abstract

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.

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Figures

Figure 1
Figure 1. Cohort assembly.
CRIC indicates Chronic Renal Insufficiency Cohort; CVD, cardiovascular disease; and LVMI, left ventricular mass index.
Figure 2
Figure 2. Kaplan‐Meier curves for composite CVD events among study participants without prevalent CVD (N=1066) across categories of VDMR (A), 25[OH]D (B), and 1, 25[OH]2D (C).
1,25(OH)2D indicates 1, 25‐dihydroxyvitamin D; 25(OH)D, 25‐hydroxyvitamin D; CVD, cardiovascular disease; and VDMR, vitamin D metabolite ratio.
Figure 3
Figure 3. Generalized additive models of VDMR (A), 25[OH]D (B), and 1, 25[OH]2D (C) and left ventricular mass index (LVMI) among all study participants (N=1786).
Dotted lines represent 95% CIs. Below each model is a density curve of the distribution of the corresponding vitamin D metabolite.1, 25(OH)2D indicates 1,25‐dihydroxyvitamin D; 25(OH)D, 25‐hydroxyvitamin D; LVMI, left ventricular mass index; and VDMR, vitamin D metabolite ratio
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