{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:06:19Z","timestamp":1790435179787,"version":"4.1.0"},"reference-count":48,"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":[[2018,5]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)\u2010\u03b1 (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all\u2010cause mortality. Patients were followed up for 10\u00a0years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C\u2010reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05\u20131.22;<jats:italic>P<\/jats:italic>=0.001 for<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>1; hazard ratio, 1.16; 95% confidence interval, 1.08\u20131.24;<jats:italic>P<\/jats:italic>&lt;0.001 for<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>2 to established cardiovascular risk factors improved prediction only modestly (&lt;1%).<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">Increased concentrations of circulating<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">TNFR<\/jats:styled-content>2 to improve risk prediction in these patients appears limited.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Clinical Trial Registration<\/jats:title><jats:p xml:lang=\"en\">URL:<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>. Unique identifier:<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00121550.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.117.008299","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T09:20:13Z","timestamp":1524475213000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["10\u2010Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy"],"prefix":"10.1161","volume":"7","author":[{"given":"Axel C.","family":"Carlsson","sequence":"first","affiliation":[{"name":"Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden"},{"name":"Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toralph","family":"Ruge","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Kj\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Hilden","sequence":"additional","affiliation":[{"name":"Section\u00a0of Biostatistics, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J\u00f8rn","family":"Kolmos","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Sajadieh","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital of Bispebjerg and Frederiksberg, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kastrup","sequence":"additional","affiliation":[{"name":"Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorm Boje","family":"Jensen","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital Hvidovre, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Nowak","sequence":"additional","affiliation":[{"name":"Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janus Christian","family":"Jakobsen","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark"},{"name":"Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Department of Cardiology, Holb\u00e6k Hospital, Holb\u00e6k, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Winkel","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gluud","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"\u00c4rnl\u00f6v","sequence":"additional","affiliation":[{"name":"Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden"},{"name":"School of Health and Social Studies, Dalarna University, Falun, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.02.006"},{"key":"e_1_3_5_3_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1052-3359(25)00673-8","article-title":"The macrophage, TNF, and other cytokines","volume":"5","author":"Pass HI","year":"1995","unstructured":"Pass HI, Mew D, Pass HA, Temeck BK. 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