biostudies-literatureEmerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies CollaborationCancer Research UKBritish Heart FoundationNCATS NIH HHSUKRI Medical Research CouncilNIA NIH HHSVersus ArthritisNHLBI NIH HHSEuropean Research CouncilMedical Research CouncilNIHR Cambridge Biomedical Research CentreNational Institute for Health Research (NIHR)NIAMS NIH HHSWellcome Truste2-e11https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615586biostudies-literatureUnknown12(1)<h4>Background</h4>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.<h4>Methods</h4>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 CopenhageThe lancet. Diabetes & endocrinologyEstimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses.PMC7615586U1475000001U01 AG042139N01 HC095166N01 HC095165N01 HC095168U1475000002RG/18/13/33946N01 HC095167HDR-9004N01 HC095169N01 HC095160N01 HC095162MR/R024227/1N01 HC095161U01 AR066160N01 HC095164N01 HC09516314136R01 AR035582R01 AR035583R01 AG005394R01 AR035584MC_U147585819G1000143UL1 TR000040NIHR202397R01 AG005407U01 AG042145UL1 TR000128MC_PC_21003NIHR203769U01 AG042143U01 AG042140G0800270MC_PC_21001G0400491G0601019MC_PC_21000R01 AG027576RE/18/4/34215R01 AG027574268834MC_U147585824UL1 TR001420MC_U147585827204623/Z/16/ZMC_UU_12015/1MR/L003120/175N92020D00007RG/13/13/30194MC_UU_12011/2225790/Z/22/ZMC_UU_12011/175N92020D0000175N92020D0000210011475N92020D0000575N92020D0000675N92020D000031770275N92020D00004MR/J000094/1R01 HL096875MC_UP_A620_1014HHSN268201500003CMC_UP_A620_1015FS/18/56/34177UL1 TR001079U01 AG042124U01 AG042168N01 HC095159MC_UU_12015/5MR/T033371/1U01 AG027810NF-SI-0508-10082NF-SI-0513-1008529017MC_PC_21022MC_UU_00040/1MC_UU_00006/3MC_UU_00002/710/33/04HHSN268201500003IPennells LAMZamora Ros RZittermann AGill DWilleit PMelander OProvidencia RColak YClarke Rvan der Schouw YTBurgess SSun LWeiderpass ENordestgaard BGGundersen TEButterworth ASEmerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies CollaborationAfzal SKatzke VCawthon PJoergensen CEngstrom GMacDonald CFerrari PForouhi NGSanchez MJOnland-Moret NCSchierbeck LLMason AMArnold MGWood AMAllara EHeath AKKiechl STsilidis KKPerez-Cornago ADi Angelantonio EAgnoli CBrenner HWelsh PBoutron MCVerschuren WMSofianopoulou ELinneberg ABergmann MMSacerdote CDahm CCBrustad MSeveri GKaptoge SKJiang TSkeie GSattar NHannemann ASrour BSchulze MBNorberg MDanesh JMoreno-Iribas CImaz LKrogh VGallacher Jde Boer IHWareham NJKarhus LBolton TROvervad KMasala GSharp SJChung Rvan Schoor NMHuerta JMLundqvist ASundstrom JLangenberg CRedondo-Sanchez DPanico SBoer JBen-Shlomo YShi FKobylecki CJTong TYNOlsen ACooper CAlbertorio JRAglago EKJohansson IfalseEstimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses.<h4>Background</h4>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.<h4>Methods</h4>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 Copenhage2024-01-01T00:00:00Z2024 Jan2026-05-29T12:31:17.405Z2026-04-08T04:50:04.834ZS-EPMC76155863804880010.1016/S2213-8587(23)00287-5