Journal article
Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
Circulation (New York, N.Y.), Vol.146(20), pp.1507-1517
11/15/2022
DOI: 10.1161/CIRCULATIONAHA.122.060700
PMCID: PMC9662821
PMID: 36314129
Abstract
Background:
End-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.
Methods:
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.
Results:
There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >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 <60 mL·min–1·1.73 m–2, with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min–1·1.73 m–2 lower genetically predicted eGFR, but not for those 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.
Conclusions:
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.
Details
- Title: Subtitle
- Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
- Creators
- Liam Gaziano - VA Boston Healthcare SystemRobert B. Wallace - University of IowaLuanluan Sun - Harvard UniversityMatthew ArnoldSteven Bell - Harvard UniversityKelly Cho - VA Boston Healthcare SystemStephen K. Kaptoge - Harvard UniversityRebecca J. Song - VA Boston Healthcare SystemStephen Burgess - Harvard UniversityDaniel C. Posner - VA Boston Healthcare SystemKatja Mosconi - Harvard UniversityCassianne Robinson-Cohen - Vanderbilt University Medical CenterAmy M. Mason - Harvard UniversityThomas R. Bolton - Harvard UniversityRan Tao - Vanderbilt University Medical CenterElias Allara - Harvard UniversityPetra Schubert - VA Boston Healthcare SystemLingyan Chen - Harvard UniversityJames R. Staley - Harvard UniversityNatalie Staplin - University of OxfordServet Altay - Trakya UniversityPilar Amiano - Basque GovernmentVolker Arndt - German Cancer Research CenterJohan Ärnlöv - Karolinska InstitutetElizabeth L.M. Barr - Baker Heart and Diabetes InstituteCecilia Björkelund - Baker Heart and Diabetes InstituteJolanda M.A. Boer - National Institute for Public Health and the EnvironmentHermann Brenner - Karolinska InstitutetEdoardo Casiglia - University of PaduaPaolo Chiodini - Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi VanvitelliJackie A. Cooper - Queen Mary University of LondonJosef Coresh - Johns Hopkins UniversityMary Cushman - University of VermontRachel Dankner - Tel Aviv UniversityKarina W. Davidson - Feinstein Institute for Medical ResearchRenate T. de Jongh - Amsterdam University Medical CentersChiara Donfrancesco - Istituto Superiore di SanitàGunnar Engström - Lund UniversityHeinz Freisling - Centre international de recherche sur le cancerVilmundur Gudnason - Icelandic Heart AssociationAgustín Gómez de la Cámara - Research Institute Hospital 12 de OctubreGraeme J. Hankey - The University of Western AustraliaPer-Olof Hansson - University of GothenburgAlicia K. Heath - Imperial College LondonEwout J. Hoorn - Erasmus MCHironori Imano - The University of OsakaSimerjot K. Jassal - German Cancer Research CenterRudolf Kaaks - German Cancer Research CenterVerena Katzke - German Cancer Research CenterJussi Kauhanen - University of California San DiegoStefan Kiechl - Innsbruck Medical UniversityWolfgang Koenig - Universität UlmRichard A. Kronmal - University of WashingtonCecilie Kyrø - Danish Cancer SocietyDeborah A. Lawlor - At BristolBörje Ljungberg - Umeå UniversityConor MacDonald - Université Paris-SaclayGiovanna Masala - Florence (Netherlands)Christa Meisinger - Helmholtz Zentrum MünchenOlle Melander - Lund UniversityConchi Moreno Iribas - Navarre Institute of Health ResearchToshiharu Ninomiya - Kyushu UniversityDorothea Nitsch - London School of Hygiene & Tropical MedicineBørge G. Nordestgaard - Gentofte HospitalCharlotte Onland-Moret - University Medical Center UtrechtLuigi PalmieriDafina Petrova - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaJose Ramón Quirós Garcia - Gobierno del Principado de AsturiasAnnika Rosengren - University of GothenburgCarlotta Sacerdote - Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy (C. Sacerdote).Masaru Sakurai - Kanazawa Medical UniversityCarmen Santiuste - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaMatthias B. Schulze - University of PotsdamSabina Sieri - Fondazione IRCCS Istituto Nazionale dei TumoriJohan Sundström - Uppsala UniversityValérie Tikhonoff - University of PaduaAnne Tjønneland - Danish Cancer SocietyTammy Tong - University of OxfordRosario Tumino - Vanderbilt University Medical CenterIoanna Tzoulaki - Imperial College LondonYvonne T. van der Schouw - University Medical Center UtrechtW. M. Monique Verschuren - University Medical Center UtrechtHenry Völzke - Universitätsmedizin GreifswaldS. Goya Wannamethee - University College LondonElisabete Weiderpass - Centre international de recherche sur le cancerPeter Willeit - Harvard UniversityMark Woodward - The George Institute for Global HealthKazumasa Yamagishi - University of TsukubaRaul Zamora-Ros - Institut d'Investigació Biomédica de BellvitgeElvis A. Akwo - Vanderbilt University Medical CenterSaiju Pyarajan - University of CambridgeDavid R. Gagnon - Boston UniversityPhilip S. Tsao - Stanford UniversitySumitra Muralidhar - United States Department of Veterans AffairsTodd L. Edwards - Vanderbilt UniversityScott M. Damrauer - University of PennsylvaniaJacob Joseph - VA Boston Healthcare SystemLisa Pennells - Harvard UniversityPeter W.F. Wilson - Atlanta VA Health Care SystemSeamus Harrison - Harvard UniversityThomas A. Gaziano - Brigham and Women's HospitalMichael Inouye - Harvard UniversityColin Baigent - University of GothenburgJuan P. Casas - VA Boston Healthcare SystemClaudia Langenberg - Brigham and Women's HospitalNick Wareham - University of CambridgeElio Riboli - Imperial College LondonJ.Michael Gaziano - VA Boston Healthcare SystemJohn Danesh - Harvard UniversityAdriana M. Hung - Vanderbilt University Medical CenterAdam S. Butterworth - Harvard UniversityAngela M. Wood - Harvard UniversityEmanuele Di Angelantonio - Harvard UniversityAnna KoettgenJonathan ShawRobert AtkinsPaul ZimmetPeter WhincupJohann WilleitChristoph LeitnerAnne Tybjaerg-HansenPeter SchnohrShoaib AfzalDavid Lora PablosCristina Martin ArriscadoCarmen Romero FerreiroHannah StockerBen SchöttkerBernd HolleczekAngela ChetritLennart WelinKurt SvärdsuddLauren LissnerDominique HangeKirsten MehligDorothea NagelPaul E. NormanOsvaldo AlmeidaLeon FlickerJun HataTakanori HondaYoshihiko FurutaHiroyasu IsoAkihiko KitamuraIsao MurakiJukka T. SalonenTomi-Pekka TuomainenE. M. van ZutphenN. M. van SchoorCinzia Lo NoceGeorg LappasPeter M. NilssonBo HedbladJonathan ShafferJoseph SchwartzDaichi ShimboShinichi SatoMina Hayama-TeradaThor AspelundBolli ThorssonGunnar SigurdssonLayal ChakerKamran M. IkramMaryam KavousiHugh Tunstall-PedoeGünay CanHüsniye YükselUğur ÖzkanHideaki NakagawaYuko MorikawaMasao IshizakiEdith FeskensJohanna M GeleijnseDaan KromhoutEmerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.146(20), pp.1507-1517
- DOI
- 10.1161/CIRCULATIONAHA.122.060700
- PMID
- 36314129
- PMCID
- PMC9662821
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/15/2022
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364410102771
Metrics
5 Record Views