{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:05:47Z","timestamp":1788671147587,"version":"build-2803163510"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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\u2013Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648\u2009135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42\u2009858 and 15\u2009693 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\u2009718 participants (25\u2009917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values &lt;60 or &gt;105 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      , compared with those with eGFR between 60 and 105 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      . Mendelian randomization analyses for CHD showed an association among participants with eGFR &lt;60 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      , with a 14% (95% CI, 3%\u201327%) higher CHD risk per 5 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      lower genetically predicted eGFR, but not for those with eGFR &gt;105 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      . 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.060700","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T05:00:17Z","timestamp":1667192417000},"page":"1507-1517","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses"],"prefix":"10.1161","volume":"146","author":[{"given":"Liam","family":"Gaziano","sequence":"first","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanluan","family":"Sun","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6774-3149","authenticated-orcid":true,"given":"Steven","family":"Bell","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."},{"name":"Stroke Research Group, Department of Clinical Neurosciences (S. Bell), University of Cambridge, UK."},{"name":"NIHR Blood and Transplant Research Unit in Donor Health and Behaviour (S. Bell, T.R.B., E.A., J.D., A.S.B., A.M.W., E.D.A.), University of Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Aging (K.C., S.P., J.P.C. J.M.G.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen K.","family":"Kaptoge","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, MA (R.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke\u2019s Hospital (A.M.M., S. Burgess, J.D., A.M.W., A.S.B., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."},{"name":"Medical Research Council Biostatistics Unit (A.M.M., S. Burgess), University of Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3056-6924","authenticated-orcid":true,"given":"Daniel C.","family":"Posner","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Mosconi","sequence":"additional","affiliation":[{"name":"Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (L.G., K.C., R.J.S., D.C.P., P.S., J.J., J.P.C., J.M.G.)."},{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassianne","family":"Robinson-Cohen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine (C.R.-C., E.A.A.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-0777","authenticated-orcid":true,"given":"Amy M.","family":"Mason","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke\u2019s Hospital (A.M.M., S. Burgess, J.D., A.M.W., A.S.B., E.D.A.)"},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge UK (L.G., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., E.A., L. Pennells, M.I., J.D., A.S.B., A.M.W., E.D.A.)."},{"name":"Medical Research Council Biostatistics Unit (A.M.M., S. Burgess), University of Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Bolton","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (L.G., L.S., S. Bell, S.K.K., S. Burgess, K.M., A.M.M., T.R.B., E.A., L.C., J.R.S., P.W., L. Pennells, S.H., M.I., J.D., A.S.B., A.M.W., E.D.A.)"},{"name":"NIHR Blood and Transplant Research Unit in Donor Health and Behaviour (S. 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Melbourne, VIC, Australia (E.L.M.B., M.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bj\u00f6rkelund","sequence":"additional","affiliation":[{"name":"Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit (N.S., C.B.), Nuffield Department of Population Health, University of Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-4304","authenticated-orcid":true,"given":"Jolanda M.A.","family":"Boer","sequence":"additional","affiliation":[{"name":"National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands (J.M.A.B., W.M.M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":true,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Family Medicine and Primary Care, 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