{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:36:22Z","timestamp":1787726182593,"version":"build-2784847793"},"reference-count":149,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The status of lipoprotein (a) [Lp(a)] as a cardiovascular risk factor has been resurrected by advances in genetics. Mendelian randomization studies show a causal link of Lp(a) with coronary artery disease (CAD), peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). The genetics of Lp(a) is complex and extends beyond the kringle-IV type 2, as it is also dependent on ancestry. The plasma concentration of Lp(a) is determined by the hepatic production of apolipoprotein(a) [apo(a)] component of Lp(a), supporting the use of nucleic acids that inhibit the messenger RNA (mRNA) gene transcript for apo(a). Analytical barriers to measurement of Lp(a) are being addressed using isoform independent assays and a traceable standard. The association of Lp(a) and atherosclerotic cardiovascular disease is higher for myocardial infarction than PAD and CAVS. Increased risk of type 2 diabetes mellitus associated with low Lp(a) levels is perplexing and requires further investigation. The greatest advancement in Lp(a)-lowering therapies is based on using RNA therapeutics that are now being investigated in clinical trials. Proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibition lowers Lp(a) modestly, but whether cardiovascular benefit is independent of low-density lipoprotein lowering remains unclear. Opportunistic and selective testing for Lp(a) is supported by moderate evidence, with the case for universal screening premature. Modification of behavioral and clinical risk factors may be targeted to mitigate Lp(a)-mediated risk of cardiovascular disease. Clinical practice guidelines have been developed to address gaps in care of high Lp(a), but full implementation awaits the findings of clinical outcome trials using RNA-directed therapies currently underway.<\/jats:p>","DOI":"10.1210\/clinem\/dgac541","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T17:58:36Z","timestamp":1663264716000},"page":"e4281-e4294","source":"Crossref","is-referenced-by-count":20,"title":["New Horizons: Revival of Lipoprotein (a) as a Risk Factor for Cardiovascular Disease"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-2132","authenticated-orcid":false,"given":"Paul","family":"Nestel","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute , Melbourne , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wann Jia","family":"Loh","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Western Australia , Perth , Australia"},{"name":"Department of Cardiology and Internal Medicine, Royal Perth Hospital , Perth , Australia"},{"name":"Department of Endocrinology, Changi General Hospital , Singapore"},{"name":"Duke-NUS Medical School , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie C","family":"Ward","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Western Australia , Perth , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F","family":"Watts","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Western Australia , Perth , Australia"},{"name":"Department of Cardiology and Internal Medicine, Royal Perth Hospital , Perth , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"2022112301490686500_dgac541-B1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1699-0463.1963.tb01808.x","article-title":"A new serum type system in man\u2014the Lp system","volume":"59","author":"Berg","year":"1963","journal-title":"Acta Pathol Microbiol Scand"},{"issue":"10","key":"2022112301490686500_dgac541-B2","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1161\/01.CIR.102.10.1082","article-title":"Lipoprotein(a) and coronary heart disease. 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