TY - JOUR
T1 - Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL
AU - Limonte, Christine P.
AU - Zelnick, Leila R.
AU - Hoofnagle, Andrew N.
AU - Thadhani, Ravi
AU - Melamed, Michal L.
AU - Mora, Samia
AU - Cook, Nancy R.
AU - Luttmann-Gibson, Heike
AU - Sesso, Howard D.
AU - Lee, I. Min
AU - Buring, Julie E.
AU - Manson, Jo Ann E.
AU - De Boer, Ian H.
N1 - Publisher Copyright:
Copyright © 2022 by the American Society of Nephrology.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods We assessed for heterogeneity by baseline eGFR of the effects of vitamin D 3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D 3 and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D 3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D 3 and placebo was larger with lower eGFR (P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m 2, respectively. Effects of vitamin D 3 supplementation on cardiovascular events (P interaction=0.61) and cancer (P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively. Conclusions We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D 3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.
AB - Background Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods We assessed for heterogeneity by baseline eGFR of the effects of vitamin D 3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D 3 and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D 3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D 3 and placebo was larger with lower eGFR (P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m 2, respectively. Effects of vitamin D 3 supplementation on cardiovascular events (P interaction=0.61) and cancer (P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively. Conclusions We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D 3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.
KW - cholecalciferol
KW - dietary supplements
KW - mineral metabolism
KW - neoplasms
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U2 - 10.34067/KID.0006472022
DO - 10.34067/KID.0006472022
M3 - Article
C2 - 36591342
AN - SCOPUS:85161860667
SN - 2641-7650
VL - 3
SP - 2095
EP - 2105
JO - Kidney360
JF - Kidney360
IS - 12
ER -
