{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T13:39:15Z","timestamp":1780753155504,"version":"3.54.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,6,6]]},"abstract":"<jats:sec id=\"jah38390-sec-0001\" sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The interplay between branched\u2010chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged the PROMISE clinical trial with centrally adjudicated coronary computed tomography angiography imaging to determine relationships between adipose depots, BCAA dysregulation, and coronary artery disease (CAD).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah38390-sec-0002\" xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10\u2009003 outpatients with stable chest pain to computed tomography angiography versus standard\u2010of\u2010care diagnostics. For this study, we included 1798 participants with available computed tomography angiography data and biospecimens. Linear and logistic regression were used to determine associations between a molar sum of BCAAs measured by nuclear magnetic resonance spectroscopy with body mass index, adipose traits, and obstructive CAD. Mendelian randomization was then used to determine if BCAAs are in the causal pathway for adipose depots or CAD. The study sample had a mean age of 60\u2009years (SD, 8.0), body mass index of 30.6 (SD, 5.9), and epicardial adipose tissue volume of 57.3 (SD, 21.3) cm\n              <jats:sup>3<\/jats:sup>\n              \/m\n              <jats:sup>2<\/jats:sup>\n              ; 27% had HS, and 14% had obstructive CAD. BCAAs were associated with body mass index (multivariable beta 0.12 per SD increase in BCAA [95% CI, 0.08\u20130.17];\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =4\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ). BCAAs were also associated with HS (multivariable odds ratio [OR], 1.46 per SD increase in BCAAs [95% CI, 1.28\u20131.67];\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =2\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ), but BCAAs were associated only with epicardial adipose tissue volume (odds ratio, 1.18 [95% CI, 1.07\u20131.32];\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.002) and obstructive CAD (OR, 1.18 [95% CI, 1.04\u20131.34];\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.009) in univariable models. Two\u2010sample Mendelian randomization did not support the role of BCAAs as within the causal pathways for HS or CAD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah38390-sec-0003\" xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">BCAAs have been implicated in the pathogenesis of cardiometabolic diseases, and adipose depots have been associated with the risk of CAD. Leveraging a large clinical trial, we further establish the role of dysregulated BCAA catabolism in HS and CAD, although BCAAs did not appear to be in the causal pathway of either disease. This suggests that BCAAs may serve as an independent circulating biomarker of HS and CAD but that their association with these cardiometabolic diseases is mediated through other pathways.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028410","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T09:52:46Z","timestamp":1684835566000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Branched\u2010Chain Amino Acids in Computed Tomography\u2013Defined Adipose Depots and Coronary Artery Disease: A PROMISE Trial Biomarker Substudy"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-2043","authenticated-orcid":false,"given":"Elizabeth","family":"Zhao","sequence":"first","affiliation":[{"name":"Duke University School of 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