{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:41:44Z","timestamp":1792291304001,"version":"4.4.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Albuminuria predicts adverse events in heart failure with preserved ejection fraction. No therapies to date have reduced albuminuria in heart failure with preserved ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      We analyzed 1175 participants from the Americas from the TOPCAT study (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) with urinary albumin:creatinine ratio (UACR) measurements at baseline. We examined the association of UACR with the primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) and its individual components, all-cause mortality, and several safety end points using multivariable-adjusted Cox regression. We evaluated whether spironolactone reduced albuminuria at the 1-year visit in a subpopulation (N=744). Thirty-five percent had microalbuminuria, 13% had macroalbuminuria, and 80% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Increasing UACR was associated with male sex, higher systolic blood pressure, diabetes mellitus, and renal dysfunction. Macroalbuminuria (hazard ratio, 1.67; 95% CI, 1.22\u20132.28) and microalbuminuria (hazard ratio, 1.47; 95% CI, 1.15\u20131.86) were independently associated with the TOPCAT primary end point (compared with normoalbuminuria). Adjusting for placebo response, spironolactone reduced albuminuria by 39% in all participants at the 1-year visit compared with baseline (geometric mean ratio, 0.61; 95% CI, 0.49\u20130.77) and by 76% (geometric mean ratio, 0.24; 95% CI, 0.10\u20130.56) among those with macroalbuminuria. Reducing UACR by 50% was independently associated with a reduction in heart failure hospitalization (hazard ratio, 0.90;\n                      <jats:italic>P<\/jats:italic>\n                      =0.017) and all-cause mortality (hazard ratio, 0.91;\n                      <jats:italic>P<\/jats:italic>\n                      =0.019). The change in UACR was significantly associated with change in systolic blood pressure (\n                      <jats:italic>P<\/jats:italic>\n                      =0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In TOPCAT, albuminuria was independently associated with worse cardiovascular outcomes. Spironolactone significantly reduced albuminuria compared with placebo. Reducing albuminuria was independently associated with improved outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT00094302.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.118.005288","type":"journal-article","created":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T05:00:39Z","timestamp":1544504439000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Prognostic Value of Albuminuria and Influence of Spironolactone in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"11","author":[{"given":"Senthil","family":"Selvaraj","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia (S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., A.S.D., E.F.L., M.A.P., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder","family":"Anand","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, VA Medical Center and University of Minnesota, Minneapolis (I.A)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, University of Montreal, Quebec, Canada (J.L.R., E.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"O\u2019Meara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, University of Montreal, Quebec, Canada (J.L.R., E.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., A.S.D., E.F.L., M.A.P., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldrin F.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., A.S.D., E.F.L., M.A.P., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor (B.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy K.","family":"Sweitzer","sequence":"additional","affiliation":[{"name":"Sarver Heart Center, Division of Cardiology, University of Arizona College of Medicine, Tucson (N.K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Fang","sequence":"additional","affiliation":[{"name":"Cardiology Division, University of Utah, Salt Lake City (J.C.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., A.S.D., E.F.L., M.A.P., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., A.S.D., E.F.L., M.A.P., 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