Skip to main content

The Lancet

Endocrinology

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses.

Last Revised:
PMID: 38048800
PII: S2213-8587(23)00287-5
PII: S2213-8587(23)00287-5

Summary

The study examined the connection between 25-hydroxyvitamin D (25[OH]D) concentrations and the risk of coronary heart disease, stroke, and all-cause mortality through observational and Mendelian randomisation frameworks. The observational analyses indicated inverse associations at low 25(OH)D concentrations, while the genetic analyses found no significant links between predicted 25(OH)D levels and the stated health risks. Hence, it concludes that long-term low-dose vitamin D supplementation may not significantly reduce mortality and cardiovascular morbidity, even if targeted at individuals with low vitamin D status.

Key Takeaways

  • Despite inverse associations found in observational analyses, genetic analyses suggest no significant correlation between predicted 25(OH)D levels and risks of coronary heart disease, stroke, or all-cause mortality.
  • Stratified Mendelian randomisation analyses also show a lack of causal relationship between 25(OH)D concentrations and both cardiovascular and mortality outcomes across all levels of 25(OH)D.
  • The findings imply that vitamin D supplementation, even when directed at individuals with low vitamin D status, may not result in notable reductions in mortality or cardiovascular morbidity.

Latest Articles in Endocrinology

Authors

Full Abstract

  • BACKGROUND: Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.
  • METHODS: Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality.
  • FINDINGS: Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95-1·01), stroke (1·01, [0·97-1·05]), or all-cause mortality (0·99, 0·95-1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations.
  • INTERPRETATION: Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status.
  • FUNDING: British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Tags

Please note that the article summaries provided in this content are generated by a large language model AI system and may contain errors or omissions. While we strive to provide accurate and helpful information, we cannot guarantee the correctness or completeness of the summaries. We encourage readers to refer to the original source material for complete and accurate information.