{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:11:02Z","timestamp":1784549462467,"version":"3.55.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Triglycerides have traditionally occupied an uncertain role in atherosclerotic cardiovascular disease (ASCVD) prevention, often considered secondary to LDL-C. Emerging evidence indicates that triglycerides are best viewed not as a direct cause of atherosclerosis, but as a clinical marker of triglyceride-rich lipoprotein and remnant particle burden. These apolipoprotein B\u2013containing particles can enter the arterial wall, promote lipid deposition, and amplify vascular inflammation. Genetic and Mendelian randomization studies support a causal link between remnant lipoproteins and ASCVD that is independent of LDL-C levels and proportional to atherogenic particle number. Despite effective LDL-C lowering, substantial residual ASCVD risk persists, particularly in patients with diabetes mellitus, obesity, and metabolic dysfunction. However, reducing triglyceride concentrations alone does not consistently translate into fewer cardiovascular events. Clinical benefit appears to depend on whether therapy meaningfully reduces atherogenic particle burden or modifies causal pathways. Icosapent ethyl has demonstrated reductions in major adverse cardiovascular events, although the mechanism of benefit remains incompletely understood and is not explained entirely by triglyceride lowering. Fibrates have shown modest benefit in selected populations, whereas mixed omega-3 formulations have not consistently demonstrated cardiovascular risk reduction. Emerging therapies targeting key regulators of remnant metabolism, including apolipoprotein C-III and angiopoietin-like protein 3, offer more direct approaches to modifying causal pathways. In contemporary practice, triglycerides should be interpreted longitudinally within a framework of remnant lipoprotein biology and residual cardiovascular risk rather than pursued as an isolated therapeutic target.<\/jats:p>","DOI":"10.1093\/eurjpc\/zwag341","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:41:17Z","timestamp":1782992477000},"source":"Crossref","is-referenced-by-count":0,"title":["Rethinking triglycerides in the management of atherosclerotic cardiovascular disease"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-1096","authenticated-orcid":false,"given":"Shaun","family":"Khanna","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, UNSW Sydney , Sydney, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-502X","authenticated-orcid":false,"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-4808","authenticated-orcid":false,"given":"Aditya","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Westmead and Blacktown Hospital , corner of Hawkesbury and Darcy Roads, Westmead, NSW 2145 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"2026072008005782500_zwag341-B1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0140-6736(14)61177-6","article-title":"Triglycerides and cardiovascular disease","volume":"384","author":"Nordestgaard","year":"2014","journal-title":"Lancet"},{"key":"2026072008005782500_zwag341-B2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1186\/s12967-019-02156-3","article-title":"Triglyceride is an independent predictor of type 2 diabetes among middle-aged and older adults: a prospective study with 8-year follow-ups in two cohorts","volume":"17","author":"Zhao","year":"2019","journal-title":"J Transl Med"},{"key":"2026072008005782500_zwag341-B3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/VHRM.S104369","article-title":"Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease","volume":"12","author":"Toth","year":"2016","journal-title":"Vasc Health Risk Manag"},{"key":"2026072008005782500_zwag341-B4","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1001\/jamacardio.2019.3780","article-title":"Apolipoprotein B particles and cardiovascular disease: a narrative review","volume":"4","author":"Sniderman","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2026072008005782500_zwag341-B5","doi-asserted-by":"crossref","first-page":"e647","DOI":"10.1016\/j.jacl.2024.08.013","article-title":"Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: an expert clinical consensus from the national lipid association","volume":"18","author":"Soffer","year":"2024","journal-title":"J Clin Lipidol"},{"key":"2026072008005782500_zwag341-B6","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1093\/eurheartj\/ehad337","article-title":"Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study","volume":"44","author":"Bj\u00f6rnson","year":"2023","journal-title":"Eur Heart J"},{"key":"2026072008005782500_zwag341-B7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1307095","article-title":"Loss-of-function mutations in APOC3, triglycerides, and coronary disease","volume":"371","author":"Crosby","year":"2014","journal-title":"N Engl J Med"},{"key":"2026072008005782500_zwag341-B8","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. 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