{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:39:52Z","timestamp":1787243992640,"version":"build-2736575974"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,12,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD.<\/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                      A fibrosis\u20104 index cutoff value \u22652.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high\u2010sensitivity C\u2010reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all\u2010cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29\u20131.92];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001) and cardiovascular death: (subdistribution HR, 1.50 [95% CI, 1.14\u20131.95];\n                      <jats:italic>P<\/jats:italic>\n                      =0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%\u201381.2%];\n                      <jats:italic>P<\/jats:italic>\n                      =0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.031230","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T06:04:07Z","timestamp":1702015447000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Activation Mediates the Association of Advanced Hepatic Fibrosis With Adverse Outcomes in Patients With Coronary Artery Disease"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7265-380X","authenticated-orcid":false,"given":"Vardhmaan","family":"Jain","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-5551","authenticated-orcid":false,"given":"Anurag","family":"Mehta","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University Health Pauley Heart Center Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-9670","authenticated-orcid":false,"given":"Terence B.","family":"Lee","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University Health Pauley Heart Center Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-7224","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-0430","authenticated-orcid":false,"given":"Nicholas W. S.","family":"Chew","sequence":"additional","affiliation":[{"name":"Department of Cardiology National University Heart Centre, National University Health System Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6543-9765","authenticated-orcid":false,"given":"Yi\u2010An","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1214-9469","authenticated-orcid":false,"given":"Matthew E.","family":"Gold","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA 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Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-0284","authenticated-orcid":false,"given":"Jonathan H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-3273","authenticated-orcid":false,"given":"Alireza","family":"Rahbar","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazan","family":"Haroun","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-3606","authenticated-orcid":false,"given":"Kiran","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-349X","authenticated-orcid":false,"given":"Salim S.","family":"Hayek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad S.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University 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