{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:31:48Z","timestamp":1786422708290,"version":"build-2736575974"},"reference-count":154,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Lipoprotein(a) [Lp(a)] has emerged as a major, genetically determined, contributor to residual cardiovascular risk. Accumulating evidence from epidemiological studies, human genetics, and Mendelian randomization has unequivocally established elevated Lp(a) as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Lp(a) consists of a low-density lipoprotein-like particle in which apolipoprotein(a) is covalently linked to apolipoprotein B100. This unique structure confers proatherogenic, pro-inflammatory, and antifibrinolytic properties, largely mediated by oxidized phospholipids and the structural homology of apolipoprotein(a) with plasminogen. Circulating Lp(a) concentrations are genetically determined and remain relatively stable throughout life with minimal influence from lifestyle interventions. Conventional lipid-lowering therapies have little or no meaningful effect on circulating Lp(a) concentrations, leaving an important component of residual cardiovascular risk unaddressed. In contrast, RNA-based therapeutics targeting hepatic\n                    <jats:italic>LPA<\/jats:italic>\n                    expression have demonstrated reductions in circulating Lp(a) of up to 80\u201390% and are currently being evaluated in phase 3 cardiovascular outcome trials. This narrative review summarizes the molecular biology, genetics, epidemiology, pathophysiological mechanisms, and clinical relevance of Lp(a), and critically examines current and emerging therapeutic strategies aimed at reducing Lp(a)-mediated cardiovascular risk.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1886347","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:20:08Z","timestamp":1786422008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipoprotein(a) in cardiovascular disease: pathophysiology, residual risk, and emerging therapeutic strategies"],"prefix":"10.3389","volume":"13","author":[{"given":"Lucio Giuseppe","family":"Granata","sequence":"first","affiliation":[{"name":"UOC di UTIC con Cardiologia ed Emodinamica, AOE Cannizzaro","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Giubilato","sequence":"additional","affiliation":[{"name":"UOC di UTIC con Cardiologia ed Emodinamica, AOE Cannizzaro","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Campanella","sequence":"additional","affiliation":[{"name":"UOC di UTIC con Cardiologia ed Emodinamica, AOE Cannizzaro","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Amico","sequence":"additional","affiliation":[{"name":"UOC di UTIC con Cardiologia ed Emodinamica, AOE Cannizzaro","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania Angela","family":"Di Fusco","sequence":"additional","affiliation":[{"name":"Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furio","family":"Colivicchi","sequence":"additional","affiliation":[{"name":"Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1001\/jamacardio.2022.0987","article-title":"Lipoprotein(a) and its significance in cardiovascular disease: a review","volume":"7","author":"Duarte Lau","year":"2022","journal-title":"JAMA Cardiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1001\/jama.2021.3632","article-title":"Lipoprotein(a) and cardiovascular 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