{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:47:13Z","timestamp":1792270033668,"version":"4.4.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T00:00:00Z","timestamp":1532304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Stockholm County Council ALF","award":["20130053"],"award-info":[{"award-number":["20130053"]}]},{"name":"Strategic Research in Epidemiology at Karolinska Institutet"},{"name":"Danderyd Hospital and Stiftelsen Apotekare Hedbergs Fond"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The pro-inflammatory response to interleukin 6 (IL6) trans-signalling in atherosclerosis is driven by the IL6 and soluble IL6 receptor (sIL6R) binary complex. The binary IL6:sIL6R complex is inactivated by sgp130 through the formation of the ternary IL6:sIL6R:sgp130 complex. The aim of this study was to investigate if IL6 trans-signalling, estimated by a ratio between the binary and ternary complexes, associates with the risk of future cardiovascular events (CVE) in a Swedish cohort of 60-year-old men and women (n\u2009=\u20094232).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Binary and ternary complex levels expressed in nanomol\/Litre were derived from serum concentrations of IL6, sIL6R, and sgp130. Cox regression models were used to assess the risk of CVE (myocardial infarction, angina pectoris, and ischaemic stroke, n\u2009=\u2009525), expressed as hazard ratio (HR) with 95% confidence interval (CI), associated with increasing circulating levels of the three molecules and with the binary\/ternary complex ratio. Estimates were adjusted for the common cardiovascular (CV) risk factors. To assess the level of IL6-trans-signalling, we estimated the binary\/ternary complex ratio and then analysed the association with CVE risk. A ratio higher than the median, representing a relative excess of the active binary complex was associated with increased CVE risk (adjusted HR 1.44, 95% CI 1.21\u20131.72).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ratio between the functional moieties of IL6 trans-signalling, IL6:sIL6R, and IL6:sIL6R:sgp130, was associated with CVE risk indicating that it could be a promising marker of CV risk and possibly be used in selecting patients for anti-inflammatory therapy.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cvr\/cvy191","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T13:58:17Z","timestamp":1532095097000},"page":"213-221","source":"Crossref","is-referenced-by-count":58,"title":["Interleukin 6 trans-signalling and risk of future cardiovascular events"],"prefix":"10.1093","volume":"115","author":[{"given":"Louise","family":"Ziegler","sequence":"first","affiliation":[{"name":"Department of Clinical Science, Danderyd Hospital, S-182 88 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwini","family":"Gajulapuri","sequence":"additional","affiliation":[{"name":"Swetox, Academic Research Center for Chemicals, Health and Environment, S\u00f6dert\u00e4lje, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Frumento","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Centro Cardiologico Monzino, IRCCS, Milan, Italy"},{"name":"Unit of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Wall\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Clinical 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