{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T23:28:43Z","timestamp":1763767723323,"version":"3.41.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Impaired cholesterol efflux capacity (CEC) is a novel lipid metabolism trait associated with atherosclerotic cardiovascular disease. Mechanisms underlying CEC variation are unknown. We evaluated associations of circulating metabolites with CEC to advance understanding of metabolic pathways involved in cholesterol efflux regulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) who underwent nuclear magnetic resonance metabolome profiling and CEC measurement (N=3543) at baseline were included. Metabolite associations with CEC were evaluated using standard linear regression analyses. Repeated ElasticNet and multilayer perceptron regression were used to assess metabolite profile predictive performance for CEC. Features important for CEC prediction were identified using Shapley Additive Explanations values.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Greater CEC was significantly associated with metabolite clusters composed of the largest-sized particle subclasses of VLDL (very-low-density lipoprotein) and HDL (high-density lipoprotein), as well as their constituent apo A\n              <jats:sub>1<\/jats:sub>\n              , apo A\n              <jats:sub>2<\/jats:sub>\n              , phospholipid, and cholesterol components (\u03b2=0.072\u20130.081;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). Metabolite profiles had poor accuracy for predicting in vitro CEC in linear and nonlinear analyses (R\n              <jats:sup>2<\/jats:sup>\n              &lt;0.02; Spearman \u03c1&lt;0.18). The most important feature for CEC prediction was race, with Black participants having significantly lower CEC compared with other races.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>We identified independent associations among CEC, the largest-sized particle subclasses of VLDL and HDL, and their constituent apolipoproteins and lipids. A large proportion of variation in CEC remained unexplained by metabolites and traditional clinical risk factors, supporting further investigation into genomic, proteomic, and phospholipidomic determinants of CEC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318222","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T09:00:34Z","timestamp":1692867634000},"page":"2030-2041","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolomic Profiling of Cholesterol Efflux Capacity in a Multiethnic Population: Insights From MESA"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-594X","authenticated-orcid":true,"given":"Wynn G.","family":"Hunter","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Smith","sequence":"additional","affiliation":[{"name":"MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health (A.G.S., R.C.P., I.T.), Imperial College London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-4873","authenticated-orcid":true,"given":"Rui C.","family":"Pinto","sequence":"additional","affiliation":[{"name":"MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health (A.G.S., R.C.P., I.T.), Imperial College London, United Kingdom."},{"name":"UK Dementia Research Institute (R.C.P), Imperial College London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Saldanha","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anamika","family":"Gangwar","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandana","family":"Pahlavani","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sneha","family":"Deodhar","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-1329","authenticated-orcid":true,"given":"John","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and Department of Preventive Medicine, Feinberg School of Medicine, Chicago, IL (J.W., P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9651-3836","authenticated-orcid":true,"given":"Ambarish","family":"Pandey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Texas Southwestern School of Medicine, Dallas (W.G.H., S.S., A.G., M.P., S.D., A.P., A.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Herrington","sequence":"additional","affiliation":[{"name":"Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC 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