{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:18:50Z","timestamp":1792019930096,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,4,2]]},"abstract":"\n Background<\/jats:title>\n Elevated lipoprotein(a) (Lp(a)), a low\u2010density lipoprotein\u2010like particle bound to the polymorphic apolipoprotein(a) (apo(a)), may be causal for cardiovascular disease. However, the metabolism of Lp(a) in humans is poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We investigated the kinetics of Lp(a)\u2010apo(a) and low\u2010density lipoprotein\u2010apoB\u2010100 in 63 normolipidemic men. The fractional catabolic rate (\n FCR<\/jats:styled-content>\n ) and production rate\n PR<\/jats:styled-content>\n ) were studied. Plasma apo(a) concentration was significantly and inversely associated with apo(a) isoform size (\n r<\/jats:italic>\n =\u22120.536,\n P<\/jats:italic>\n <0.001) and apo(a)\n FCR<\/jats:styled-content>\n (\n r<\/jats:italic>\n =\u22120.363,\n P<\/jats:italic>\n <0.01), and positively with apo(a)\n PR<\/jats:styled-content>\n (\n r<\/jats:italic>\n =0.877,\n P<\/jats:italic>\n <0.001). There were no significant associations between the\n FCR<\/jats:styled-content>\n s of apo(a) and low\u2010density lipoprotein\u2010apoB\u2010100. Subjects with smaller apo(a) isoform sizes (\u226422 kringle\n IV<\/jats:styled-content>\n repeats) had significantly higher apo(a)\n PR<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.05) and lower apo(a)\n FCR<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.01) than those with larger sizes. Plasma apo(a) concentration was significantly associated with apo(a)\n PR<\/jats:styled-content>\n (\n r<\/jats:italic>\n =0.930,\n P<\/jats:italic>\n <0.001), but not with\n FCR<\/jats:styled-content>\n (\n r<\/jats:italic>\n =\u22120.012,\n P<\/jats:italic>\n >0.05) in subjects with smaller apo(a) isoform size. In contrast, both apo(a)\n PR<\/jats:styled-content>\n and\n FCR<\/jats:styled-content>\n were significantly associated with plasma apo(a) concentrations (\n r<\/jats:italic>\n =0.744 and \u22120.389, respectively,\n P<\/jats:italic>\n <0.05) in subjects with larger isoforms. In multiple regression analysis, apo(a)\n PR<\/jats:styled-content>\n and apo(a) isoform size were significant predictors of plasma apo(a) concentration independent of low\u2010density lipoprotein\u2010apoB\u2010100\n FCR<\/jats:styled-content>\n and background therapy with atorvastatin and evolocumab.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In normolipidemic men, the plasma Lp(a) concentration is predominantly determined by the rate of production of Lp(a) particles, irrespective of apo(a) isoform size and background therapy with a statin and a proprotein convertase subtilisin\u2010kexin type 9 inhibitor. Our findings underscore the importance of therapeutic targeting of the hepatic synthesis and secretion of Lp(a) particles. Lp(a) particle catabolism may only play a modest role in determining Lp(a) concentration in subjects with larger apo(a) isoform size.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 02189837.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.011781","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T09:00:34Z","timestamp":1553245234000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Lipoprotein(a) Particle Production as a Determinant of Plasma Lipoprotein(a) Concentration Across Varying Apolipoprotein(a) Isoform Sizes and Background Cholesterol\u2010Lowering Therapy"],"prefix":"10.1161","volume":"8","author":[{"given":"Dick C.","family":"Chan","sequence":"first","affiliation":[{"name":"School of Medicine University of Western Australia Perth Australia"},{"name":"School of Biomedical Science 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":"The Lipid Disorders Clinic Department of Cardiology Royal Perth Hospital Perth Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blai","family":"Coll","sequence":"additional","affiliation":[{"name":"Amgen Inc. Thousand Oaks CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Amgen Inc. Thousand Oaks CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santica M.","family":"Marcovina","sequence":"additional","affiliation":[{"name":"Northwest Lipid Metabolism and Diabetes Research Laboratories Division of Metabolism, Endocrinology, and Nutrition Department of Medicine University of Washington Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Hugh R.","family":"Barrett","sequence":"additional","affiliation":[{"name":"School of Biomedical Science University of Western Australia Perth Australia"},{"name":"Faculty of Medicine and Health University of New England Armidale New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.10.1082"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R071233"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.12.023"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30088-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R067314"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy122"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117292"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.11.1151"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116221"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2004.10.001"},{"key":"e_1_3_2_12_2","first-page":"3267","article-title":"Metabolism of apo(a) and apoB100 of lipoprotein(a) in women: effect of postmenopausal estrogen replacement","volume":"83","author":"Su W","year":"1998","unstructured":"Su W, Campos H, Judge H, Walsh BW, Sacks FM. 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