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Abstract: SA-PO187

Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by Estimated Glomerular Filtration Rate in the Vitamin D and Omega-3 Trial

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Limonte, Christine P., University of Washington Division of Nephrology, Seattle, Washington, United States
  • Zelnick, Leila R., University of Washington Division of Nephrology, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington Department of Laboratory Medicine & Pathology, Seattle, Washington, United States
  • Thadhani, Ravi I., Office of the Chief Academic Officer, Mass General Brigham, Boston, Massachusetts, United States
  • Melamed, Michal L., Albert Einstein College of Medicine, Bronx, New York, United States
  • Mora, Samia, Brigham and Women's Hospital Division of Cardiovascular Medicine, Boston, Massachusetts, United States
  • Cook, Nancy R., Brigham and Women's Hospital Division of Preventive Medicine, Boston, Massachusetts, United States
  • Luttmann-Gibson, Heike, Brigham and Women's Hospital Division of Preventive Medicine, Boston, Massachusetts, United States
  • Sesso, Howard D., Brigham and Women's Hospital Division of Preventive Medicine, Boston, Massachusetts, United States
  • Lee, I-Min, Brigham and Women's Hospital Division of Preventive Medicine, Boston, Massachusetts, United States
  • Manson, Joann E., Brigham and Women's Hospital Division of Preventive Medicine, Boston, Massachusetts, United States
  • de Boer, Ian H., University of Washington Division of Nephrology, Seattle, Washington, United States
Background

Metabolism of 25-hydroxyvitamin D (25[OH]D) is reduced and secondary hyperparathyroidism is common with lower eGFR. These abnormalities may contribute to cardiovascular disease and cancer risk, which may be mitigated via vitamin D supplementation.

Methods

We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000IU vitamin D3 and/or 1g omega-3 fatty acids daily using a placebo-controlled, two-by-two factorial design and followed a median 5 years. The primary study endpoints were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined as intermediate outcomes.

Results

Baseline eGFR was available for 15,917 participants. Vitamin D3 resulted in higher serum 25(OH)D compared to placebo (difference in change throughout the trial 12.5 [95% CI 12.0, 13.0] ng/mL), without heterogeneity by eGFR. Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR: -6.9 (95% CI -10.5, -3.4), -5.8 (-8.3, -3.4), -4.0 (-5.9, -2.2), and -3.8 (-5.6, -2.0) pg/mL for eGFR <60, 60-74, 75-89, and >90 ml/min/1.73m2, respectively. The primary cardiovascular and cancer endpoints were observed among 508 (3%) and 1051 (7%) participants. Effects of vitamin D3 supplementation on cardiovascular events (p-interaction, continuous eGFR=0.61) and cancer (p-interaction=0.89) did not differ by eGFR: HR (95% CI) 1.14 (0.73, 1.79), 1.06 (0.75, 1.50), 0.92 (0.67, 1.25), and 0.92 (0.66, 1.27), across increasing eGFR categories for cardiovascular events and 1.63 (1.03, 2.58), 0.85 (0.64, 1.11), 0.84 (0.68, 1.03), and 1.11 (0.92, 1.35) for cancer, respectively. There was no significant heterogeneity in adverse events (hypercalcemia, kidney stones).

Conclusion

We observed no significant heterogeneity by baseline eGFR on the effect of long-term supplementation with vitamin D3 versus placebo on cardiovascular or cancer outcomes in VITAL. No benefits for these outcomes were observed within any eGFR subgroup despite substantial increases in circulating 25(OH)D and decreases in PTH concentrations.

Funding

  • NIDDK Support – Pharmavite and Pronova BioPharma/BASF (donated study pills)