Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Dulaglutide for erectile dysfunction in type 2 diabetes

    Research output: Contribution to journalComment/debateResearchpeer-review

  1. Lipoprotein(a) levels at birth and in early childhood: The COMPARE Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Tre ønsker for 2022: Mere og bedre fokus på populationer, samarbejder og brug af data.

    Research output: Contribution to journalContribution to newspaper - Feature articleCommunication

  3. Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Triglyceride-rich Lipoprotein Cholesterol (Remnant Cholesterol) as a Therapeutic Target for Cardiovascular Disease Risk

    Research output: Chapter in Book/Report/Conference proceedingBook chapterCommunication

  5. The power of genetic diversity in genome-wide association studies of lipids

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59-0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70-1·02], p=0·09) and coronary heart disease (0·89 [0·76-1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L.

INTERPRETATION: Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies.

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.

Original languageEnglish
JournalThe Lancet Diabetes and Endocrinology
Volume9
Issue number12
Pages (from-to)837-846
Number of pages10
ISSN2213-8587
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

ID: 69414734