{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T19:00:36Z","timestamp":1784746836567,"version":"3.55.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Lipidomics, the comprehensive profiling of circulating lipid species, has emerged as a powerful tool to investigate metabolic alterations underlying coronary atherosclerosis. Understanding the mechanisms driving high-risk vulnerable plaque formation and progression to myocardial infarction remains a key therapeutic priority. This study investigates associations between circulating lipid metabolites and imaging-defined features of vulnerable coronary plaque.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Following revascularization, patients with myocardial infarction underwent 3-vessel coronary artery imaging with near-infrared spectroscopy and intravascular ultrasound to assess nonflow-limiting plaques for lipid core burden index and plaque burden. Multivariable models evaluated associations between 424 lipid metabolites in plasma, quantified by mass spectrometry, pan-coronary lipid, pan-coronary plaque burden, and high-risk vulnerable plaque measures (maximum lipid core burden index within any 4-mm segment across the entire lesion \u2265324.7 and\/or plaque burden \u226570%) in 877 patients. Findings were validated in the SCAPIS study (Swedish Cardiopulmonary Bioimage Study) using coronary computed tomography angiography\u2013based measures of coronary artery calcium score and segment involvement score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We identified 156 significant associations (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05) between lipid metabolites and coronary plaque characteristics across 39 metabolic pathways. Sphingomyelins were inversely associated with all plaque metrics, and 1-palmitoyl-2-oleoyl-GPE (glycero-3-phosphoethanolamine; 16:0\/18:1), a phosphatidylethanolamine, was positively associated with all plaque metrics. After correcting for multiple testing, 27 lipid species across 7 pathways remained significant (q&lt;0.05). The majority were linked to pan-coronary lipid burden, with the strongest inverse association observed for sphingomyelin d18:1\/22:1, d18:2\/22:0, and d16:1\/24:1. Similar inverse patterns were seen for select dihydrosphingomyelins and fatty acid dicarboxylates. In contrast, 1-palmitoyl-2-oleoyl-GPE (16:0\/18:1) remained positively associated with pan-coronary lipid. In the SCAPIS validation cohort, 19 of the 27 significant lipid associations were successfully replicated (q&lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study is the first to demonstrate that sphingomyelins are negatively and 1-palmitoyl-2-oleoyl-GPE (16:0\/18:1) positively associated with vulnerable coronary plaque features based on multimodality intracoronary imaging in patients with myocardial infarction. Moreover, these associations were validated in a large cohort using coronary computed tomography angiography\u2013derived measures of plaque burden. These novel results may enable the development of new diagnostic and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.324430","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:00:38Z","timestamp":1782378038000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Linking Lipidomics to Vulnerable Coronary Plaques: A PROSPECT II Substudy"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8034-609X","authenticated-orcid":true,"given":"Tania","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Cardiology, Clinical Sciences (T.S., J.G.S., S.K., R.R., D.E.), Lund University, Lund, Sweden."},{"name":"National Heart and Lung Institute, Imperial College London, United Kingdom (T.S., R.Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-5866","authenticated-orcid":true,"given":"Tove","family":"Fall","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology, Department of Medical Sciences (T.F., S.S.-B.), Uppsala University, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Sayols-Baixeras","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology, Department of Medical Sciences (T.F., S.S.-B.), Uppsala University, Sweden."},{"name":"Medical Epidemiology, Department of Surgical Sciences (S.S.-B.), Uppsala University, Sweden."},{"name":"CIBER Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain (S.S.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1910-8447","authenticated-orcid":true,"given":"Akiko","family":"Maehara","sequence":"additional","affiliation":[{"name":"New York-Presbyterian Hospital and Columbia University Irving Medical Center (A.M.)."},{"name":"Cardiovascular Research Foundation, New York, NY (A.M., M. Matsumura)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4310-6433","authenticated-orcid":true,"given":"Michael","family":"Maeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Department of Clinical Medicine, Aarhus University Hospital (M. Maeng), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-5792","authenticated-orcid":true,"given":"Lars","family":"Kj\u00f8ller-Hansen","sequence":"additional","affiliation":[{"name":"Zealand University Hospital, Roskilde, Denmark (L.K.-H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-9194","authenticated-orcid":true,"given":"Thomas","family":"Engstr\u00f8m","sequence":"additional","affiliation":[{"name":"Rigshospitalet, University of Copenhagen, Denmark (T.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9199-1660","authenticated-orcid":true,"given":"Ori","family":"Ben-Yehuda","sequence":"additional","affiliation":[{"name":"University of California, San Diego (O.B.-Y., D.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2082-0247","authenticated-orcid":true,"given":"Mitsuaki","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Foundation, New York, NY (A.M., M. 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