{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:33:53Z","timestamp":1792103633937,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,1,28]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Compared with an Lp(a) level of 5 mg\/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level &gt;50 mg\/dL (\u2248125 nmol\/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1\u201377.0 mg\/dL), those with Lp(a) level &gt;50 mg\/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06\u20131.79]) than those with Lp(a) level \u226450 mg\/dL. The greatest risk was observed with both Lp(a) level &gt;50 mg\/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46\u20132.48]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.069556","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T04:00:34Z","timestamp":1730692834000},"page":"312-321","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol\u2013Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis"],"prefix":"10.1161","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-2989","authenticated-orcid":true,"given":"Harpreet S.","family":"Bhatia","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (H.S.B., S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-597X","authenticated-orcid":true,"given":"Simon","family":"Wandel","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-7159","authenticated-orcid":true,"given":"Peter","family":"Willeit","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Informatics and Health Economics at the Medical University of Innsbruck, Austria (P.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Lesogor","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Bailey","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland (S.W., A.L., K.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-4522","authenticated-orcid":true,"given":"Paul M.","family":"Ridker","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (P.M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-2132","authenticated-orcid":true,"given":"Paul","family":"Nestel","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-7563","authenticated-orcid":true,"given":"John","family":"Simes","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney, NSW, Australia (J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-0610","authenticated-orcid":true,"given":"Andrew","family":"Tonkin","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-0695","authenticated-orcid":true,"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Rocky Mountain Regional VA Medical Center and University of Colorado School of Medicine, Aurora (G.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Colhoun","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics &amp; 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