TY - JOUR
T1 - Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality
T2 - observational and Mendelian randomisation analyses
AU - Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies Collaboration
AU - Sofianopoulou, Eleni
AU - Kaptoge, Stephen K.
AU - Afzal, Shoaib
AU - Jiang, Tao
AU - Gill, Dipender
AU - Gundersen, Thomas E.
AU - Bolton, Thomas R.
AU - Allara, Elias
AU - Arnold, Matthew G.
AU - Mason, Amy M.
AU - Chung, Ryan
AU - Pennells, Lisa A.M.
AU - Shi, Fanchao
AU - Sun, Luanluan
AU - Willeit, Peter
AU - Forouhi, Nita G.
AU - Langenberg, Claudia
AU - Sharp, Stephen J.
AU - Panico, Salvatore
AU - Engström, Gunnar
AU - Melander, Olle
AU - Tong, Tammy Y.N.
AU - Perez-Cornago, Aurora
AU - Norberg, Margareta
AU - Johansson, Ingegerd
AU - Katzke, Verena
AU - Srour, Bernard
AU - Sánchez, María José
AU - Redondo-Sánchez, Daniel
AU - Olsen, Anja
AU - Dahm, Christina C.
AU - Overvad, Kim
AU - Brustad, Magritt
AU - Skeie, Guri
AU - Moreno-Iribas, Conchi
AU - Onland-Moret, N. Charlotte
AU - van der Schouw, Yvonne T.
AU - Tsilidis, Konstantinos K.
AU - Heath, Alicia K.
AU - Agnoli, Claudia
AU - Krogh, Vittorio
AU - de Boer, Ian H.
AU - Kobylecki, Camilla Jannie
AU - Çolak, Yunus
AU - Zittermann, Armin
AU - Sundström, Johan
AU - Welsh, Paul
AU - Weiderpass, Elisabete
AU - Aglago, Elom K.
AU - Ferrari, Pietro
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85178562933&partnerID=8YFLogxK
U2 - 10.1016/S2213-8587(23)00287-5
DO - 10.1016/S2213-8587(23)00287-5
M3 - Article
C2 - 38048800
AN - SCOPUS:85178562933
SN - 2213-8587
VL - 12
SP - e2-e11
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 1
ER -