{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:27:31Z","timestamp":1793831251130,"version":"4.6.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T00:00:00Z","timestamp":1545609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Steering Committees of ONTARGET and TRANSCEND"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB TTR 219"],"award-info":[{"award-number":["SFB TTR 219"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Astra Zeneca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We examined 30\u2009937 patients aged 55\u2009years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56\u2009months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and \u03c72 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19\u2009450 patients without diabetes and 11\u2009487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 \u00b1 9.0 vs. 67.9 \u00b1 8.8, P\u2009&amp;lt;\u20090.0001). In the categories of &amp;lt;60 bpm, 60\u2009\u2264\u200965 bpm, 65\u2009\u2264\u200970 bpm, 70\u2009\u2264\u200975 bpm, 75\u2009\u2264\u200980 bpm and \u226580 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75\u2009\u2264\u200980 bpm (adjusted hazard ratio [HR] 1.17 (1.01\u20131.36)) compared to RHR 60\u2009\u2264\u200965 bpm. For patients with in-trial RHR \u226580 bpm the hazard ratios were highest (diabetes: 1.96 (1.64\u20132.34), no diabetes: 1.73 (1.49\u20132.00), For cardiovascular death hazards were also clearly increased at RHR \u226580 bpm (diabetes [1.99, (1.53\u20132.58)], no diabetes [1.73 (1.38\u20132.16)]. Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Mean RHR above 75\u201380 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75\u201380 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial registration<\/jats:title>\n                  <jats:p>http:\/\/clinicaltrials.gov.Unique identifier: NCT00153101.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehy808","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T12:45:36Z","timestamp":1542113136000},"page":"231-238","source":"Crossref","is-referenced-by-count":52,"title":["Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET\/TRANSCEND trials"],"prefix":"10.1093","volume":"41","author":[{"given":"Michael","family":"B\u00f6hm","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Universit\u00e4tsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Statistical Consultant , 55218 Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koon K","family":"Teo","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University , Hamilton, Ontario L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M","family":"Lonn","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University , Hamilton, Ontario L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Mahfoud","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Universit\u00e4tsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ukena","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Universit\u00e4tsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F E","family":"Mann","sequence":"additional","affiliation":[{"name":"KfH Kidney Centre , Menzinger Str. 44, 80638 M\u00fcnchen, Germany"},{"name":"Department of Nephrology and Hypertension, University Hospital, Friedrich-Alexander University , Schlossplatz 4, 91054 Erlangen\/Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mancia","sequence":"additional","affiliation":[{"name":"University of Milano-Bicocca, Istituto Clinico Universitario Policlinico di Monza , Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Redon","sequence":"additional","affiliation":[{"name":"Hypertension Unit, Hospital CI\u00ednico Universitario, University of Valencia , Av. de Blasco Ib\u00e1\u00f1ez, 13, 46010 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland E","family":"Schmieder","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Hospital, Friedrich-Alexander University , Schlossplatz 4, 91054 Erlangen\/Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sliwa","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Hatter Institute for Cardiovascular Research in Africa & IIDMM, University of Cape Tow n, Anzio Road, Observatory, Cape Town, 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital RWTH Aachen , Pauwelsstra\u00dfe 30, 52074 Aachen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Weber","sequence":"additional","affiliation":[{"name":"Downstate College of Medicine, State University of New York , 450 Clarkson Ave, Brooklyn, NY 11203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Williams","sequence":"additional","affiliation":[{"name":"University College London (UCL), Institute of Cardiovascular Science, National Institute for Health Research (NIHR), UCL Hospitals Biomedical Research Centre , 149 Tottenham Court Road, London W1T 7D, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University , Hamilton, Ontario L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,24]]},"reference":[{"key":"2022102610210955700_ehy808-B1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"American Heart Association Statistics Committee; Stroke Statistics Subcommittee. 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