{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:30:35Z","timestamp":1753889435466,"version":"3.41.2"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,5,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients with stable atherothrombotic disease vary in their risk of developing heart failure (HF). Circulating cardiovascular biomarkers may improve HF risk assessment and identify patients who may benefit from emerging HF preventive therapies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We measured high\u2010sensitivity cardiac troponin I and BNP (B\u2010type natriuretic peptide) in 15\u00a0833 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease from the TRA 2\u00b0P\u2010TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events\u2010Thrombolysis in Myocardial Infarction 50) trial, excluding patients with recent myocardial infarction (&lt;30\u00a0days). Biomarkers were categorized using a priori cut points. Hospitalization for HF (HHF) end points were adjudicated with blinded structured review of serious adverse events. Associations between biomarkers and HHF outcomes were adjusted for sex and independent clinical risk predictors of HHF in our cohort (age \u226575, prior HF, type 2 diabetes mellitus, polyvascular disease, body mass index, anemia, chronic kidney disease, hypertension). Baseline high\u2010sensitivity cardiac troponin I and BNP each identified a significant graded risk of HHF independent of clinical risk predictors, including in the subgroups of patients with and without type 2 diabetes mellitus and with and without prior HF. Patients with both high\u2010sensitivity cardiac troponin I \u22655\u00a0ng\/L and BNP \u2265100\u00a0pg\/mL had the highest HHF event rates. When added to a multivariable Cox regression model with clinical risk predictors (C\u2010index 0.88; 95% CI, 0.85\u20130.90), BNP (C \u2010index 0.92; 95% CI, 0.90\u20130.93), and high\u2010sensitivity cardiac troponin I (C\u2010index 0.90; 95% CI, 0.88\u20130.92) each significantly improved the prognostic performance of the model (both\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>LRT<\/jats:sub>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Biomarkers of myocardial injury and hemodynamic stress are independent predictors of HHF risk in patients with stable atherothrombotic disease, with and without prior HF and\/or type 2 diabetes mellitus.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\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: NCT00526474.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.018673","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T10:02:28Z","timestamp":1619085748000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiovascular Biomarkers and Heart Failure Risk in Stable Patients With Atherothrombotic Disease: A Nested Biomarker Study From TRA 2\u00b0P\u2010TIMI 50"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-5492","authenticated-orcid":false,"given":"David D.","family":"Berg","sequence":"first","affiliation":[{"name":"TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin L.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-3584","authenticated-orcid":false,"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"CPC Clinical Research University of Colorado School of Medicine Aurora CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-8652","authenticated-orcid":false,"given":"Petr","family":"Jarolim","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7093-7048","authenticated-orcid":false,"given":"Benjamin M.","family":"Scirica","sequence":"additional","affiliation":[{"name":"TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-264X","authenticated-orcid":false,"given":"Erica L.","family":"Goodrich","sequence":"additional","affiliation":[{"name":"TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-3359","authenticated-orcid":false,"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-5382","authenticated-orcid":false,"given":"David A.","family":"Morrow","sequence":"additional","affiliation":[{"name":"TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.01.022"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.008506"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30054-X"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025941"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000509"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.08.2160"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.12.026"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805299"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.03.038"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000039105.49749.6F"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.25.2981"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.7588"}],"container-title":["Journal 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