Publication:
Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

dc.contributor.authorGaziano, Liam
dc.contributor.authorSun, Luanluan
dc.contributor.authorArnold, Matthew
dc.contributor.authorBell, Steven
dc.contributor.authorCho, Kelly
dc.contributor.authorKaptoge, Stephen K
dc.contributor.authorSong, Rebecca J
dc.contributor.authorBurgess, Stephen
dc.contributor.authorPosner, Daniel C
dc.contributor.authorMosconi, Katja
dc.contributor.authorRobinson-Cohen, Cassianne
dc.contributor.authorMason, Amy M
dc.contributor.authorBolton, Thomas R
dc.contributor.authorTao, Ran
dc.contributor.authorAllara, Elias
dc.contributor.authorSchubert, Petra
dc.contributor.authorChen, Lingyan
dc.contributor.authorStaley, James R
dc.contributor.authorStaplin, Natalie
dc.contributor.authorAltay, Servet
dc.contributor.authorAmiano, Pilar
dc.contributor.authorArndt, Volker
dc.contributor.authorÄrnlöv, Johan
dc.contributor.authorBarr, Elizabeth L M
dc.contributor.authorBjörkelund, Cecilia
dc.contributor.authorBoer, Jolanda M A
dc.contributor.authorBrenner, Hermann
dc.contributor.authorCasiglia, Edoardo
dc.contributor.authorChiodini, Paolo
dc.contributor.authorCooper, Jackie A
dc.contributor.authorCoresh, Josef
dc.contributor.authorCushman, Mary
dc.contributor.authorDankner, Rachel
dc.contributor.authorDavidson, Karina W
dc.contributor.authorde Jongh, Renate T
dc.contributor.authorDonfrancesco, Chiara
dc.contributor.authorEngström, Gunnar
dc.contributor.authorFreisling, Heinz
dc.contributor.authorde la Cámara, Agustín Gómez
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorHankey, Graeme J
dc.contributor.authorHansson, Per-Olof
dc.contributor.authorHeath, Alicia K
dc.contributor.authorHoorn, Ewout J
dc.contributor.authorImano, Hironori
dc.contributor.authorJassal, Simerjot K
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKatzke, Verena
dc.contributor.authorKauhanen, Jussi
dc.contributor.authorKiechl, Stefan
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorKronmal, Richard A
dc.contributor.authorKyrø, Cecilie
dc.contributor.authorLawlor, Deborah A
dc.contributor.authorLjungberg, Börje
dc.contributor.authorMacDonald, Conor
dc.contributor.authorMasala, Giovanna
dc.contributor.authorMeisinger, Christa
dc.contributor.authorMelander, Olle
dc.contributor.authorMoreno Iribas, Conchi
dc.contributor.authorNinomiya, Toshiharu
dc.contributor.authorNitsch, Dorothea
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorOnland-Moret, Charlotte
dc.contributor.authorPalmieri, Luigi
dc.contributor.authorPetrova, Dafina
dc.contributor.authorGarcia, Jose Ramón Quirós
dc.contributor.authorRosengren, Annika
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorSakurai, Masaru
dc.contributor.authorSantiuste, Carmen
dc.contributor.authorSchulze, Matthias B
dc.contributor.authorSieri, Sabina
dc.contributor.authorSundström, Johan
dc.contributor.authorTikhonoff, Valérie
dc.contributor.authorTjønneland, Anne
dc.contributor.authorTong, Tammy
dc.contributor.authorTumino, Rosario
dc.contributor.authorTzoulaki, Ioanna
dc.contributor.authorvan der Schouw, Yvonne T
dc.contributor.authorMonique Verschuren, W M
dc.contributor.authorVölzke, Henry
dc.contributor.authorWallace, Robert B
dc.contributor.authorWannamethee, S Goya
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorWilleit, Peter
dc.contributor.authorWoodward, Mark
dc.contributor.authorYamagishi, Kazumasa
dc.contributor.authorZamora-Ros, Raul
dc.contributor.authorAkwo, Elvis A
dc.contributor.authorPyarajan, Saiju
dc.contributor.authorGagnon, David R
dc.contributor.authorTsao, Philip S
dc.contributor.authorMuralidhar, Sumitra
dc.contributor.authorEdwards, Todd L
dc.contributor.authorDamrauer, Scott M
dc.contributor.authorJoseph, Jacob
dc.contributor.authorPennells, Lisa
dc.contributor.authorWilson, Peter W F
dc.contributor.authorHarrison, Seamus
dc.contributor.authorGaziano, Thomas A
dc.contributor.authorInouye, Michael
dc.contributor.authorBaigent, Colin
dc.contributor.authorCasas, Juan P
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorWareham, Nick
dc.contributor.authorRiboli, Elio
dc.contributor.authorGaziano, J Michael
dc.contributor.authorDanesh, John
dc.contributor.authorHung, Adriana M
dc.contributor.authorButterworth, Adam S
dc.contributor.authorWood, Angela M
dc.contributor.authorDi Angelantonio, Emanuele
dc.contributor.funderHealth Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII)
dc.contributor.funderRegional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain);
dc.contributor.funderCambridge Biomedical Research Centre
dc.contributor.funderBritish Heart Foundation
dc.contributor.groupEmerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program
dc.date.accessioned2023-05-03T13:32:07Z
dc.date.available2023-05-03T13:32:07Z
dc.date.issued2022-08-18
dc.description.abstractEnd-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
dc.description.sponsorshipThe Emerging Risk Factors Collaboration (ERFC) coordinating center was underpinned by program grants from the British Heart Foundation (BHF; SP/09/002; RG/13/13/30194; RG/18/13/33946), BHF Centre of Research Excellence (RE/18/1/34212), the UK Medical Research Council (MR/L003120/1), and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), with project-specific support received from the UK NIHR, British United Provident Association UK Foundation, and an unrestricted educational grant from GlaxoSmithKline. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the Department of Health and Social Care (England), the Chief Scientist Office of the Scottish Government Health and Social Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the BHF, and the Wellcome Trust. A variety of funding sources have supported recruitment, follow-up, and laboratory measurements in the studies contributing data to the ERFC, which are listed on the ERFC website (www.phpc.cam.ac.uk/ceu/erfc/ list-of-studies). EPIC-CVD (European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study) was funded by the European Research Council (268834) and the European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council, United Kingdom (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). The establishment of the EPIC-InterAct subcohort (used in the EPIC-CVD study) and conduct of biochemical assays was supported by the EU Sixth Framework Programme (FP6) (grant LSHM_ CT_2006_037197 to the InterAct project) and the Medical Research Council Epidemiology Unit (grants MC_UU_12015/1 and MC_UU_12015/5). This research is based on data from the Million Veteran Program, Office of Research and Development, and Veterans Health Administration and was supported by award I01-BX004821 (principal investigators, Drs Peter W.F. Wilson and Kelly Cho) and I01-BX003360 (principal investigators, Dr Adriana M. Hung). Dr Damrauer is supported by IK2-CX001780. Dr Hung is supported by CX001897. Dr Tsao is supported by BX003362-01 from VA Office of Research and Development. Dr Robinson-Cohen is supported by R01DK122075. Dr Sun was funded by a BHF Programme Grant (RG/18/13/33946). Dr Arnold was funded by a BHF Programme Grant (RG/18/13/33946). Dr Kaptoge is funded by a BHF Chair award (CH/12/2/29428). Dr Mason is funded by the EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart grant 116074. Dr Bolton was funded by the NIHR BTRU in Donor Health and Genomics (NIHR BTRU-2014-10024). Dr Allara is funded by a BHF Programme Grant (RG/18/13/33946). Prof Inouye is supported by the Munz Chair of Cardiovascular Prediction and Prevention and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Prof Inouye was also supported by the UK Economic and Social Research 878 Council (ES/T013192/1). Prof Danesh holds a British Heart Foundation Professorship and a NIHR Senior Investigator Award. Prof Wood is part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. Prof Wood was supported by the BHF-Turing Cardiovascular Data Science Award (BCDSA\100005). Prof Di Angelantonio holds a NIHR Senior Investigator Award.
dc.description.versionSi
dc.identifier.citationGaziano L, Sun L, Arnold M, Bell S, Cho K, Kaptoge SK, et al. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses. Circulation. 2022 Nov 15;146(20):1507-1517.
dc.identifier.doi10.1161/CIRCULATIONAHA.122.060700
dc.identifier.essn1524-4539
dc.identifier.pmcPMC9662821
dc.identifier.pmid36314129
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662821/pdf
dc.identifier.unpaywallURLhttp://diposit.ub.edu/dspace/bitstream/2445/192294/1/CIRCULATIONAHA.122.060700.pdf
dc.identifier.urihttp://hdl.handle.net/10668/20199
dc.issue.number20
dc.journal.titleCirculation
dc.journal.titleabbreviationCirculation
dc.language.isoen
dc.organizationEscuela Andaluza de Salud Pública-EASP
dc.organizationInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
dc.page.number1507-1517
dc.publisherLippincott Williams & Wilkins
dc.pubmedtypeObservational Study
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, U.S. Gov't, Non-P.H.S.
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.pubmedtypeResearch Support, N.I.H., Extramural
dc.relation.projectIDSP/09/002
dc.relation.projectIDRG/13/13/30194
dc.relation.projectIDRG/18/13/33946
dc.relation.projectIDBRC-1215-20014
dc.relation.publisherversionhttps://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.060700?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectcardiovascular diseases
dc.subjectcoronary disease
dc.subjectkidney diseases
dc.subjectstroke
dc.subject.decsAccidente cerebrovascular
dc.subject.decsAnálisis de la aleatorización mendeliana
dc.subject.decsDiabetes Mellitus
dc.subject.decsEnfermedad coronaria
dc.subject.decsEnfermedades cardiovasculares
dc.subject.decsEstudios prospectivos
dc.subject.decsFactores de riesgo
dc.subject.decsHumanos
dc.subject.decsRiñón
dc.subject.meshHumans
dc.subject.meshMendelian Randomization Analysis
dc.subject.meshProspective Studies
dc.subject.meshCardiovascular Diseases
dc.subject.meshCoronary Disease
dc.subject.meshRisk Factors
dc.subject.meshDiabetes Mellitus
dc.subject.meshStroke
dc.subject.meshKidney
dc.titleMild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number146
dspace.entity.typePublication

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