{"doi":"10.1161/circulationaha.124.069556","title":"Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol–Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis","abstract":"BACKGROUND: 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. METHODS: 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. RESULTS: 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 >50 mg/dL (≈125 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 (3.1-77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06-1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46-2.48]). CONCLUSIONS: 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.","journal":"Circulation","year":2024,"id":416995,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":88,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.885,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1202264,"name":"Simon Wandel","orcid":null,"position":1,"is_corresponding":false},{"id":17140,"name":"Peter Willeit","orcid":"0000-0002-1866-7159","position":2,"is_corresponding":false},{"id":1202265,"name":"Anastasia Lesogor","orcid":null,"position":3,"is_corresponding":false},{"id":405187,"name":"Keith Bailey","orcid":"0000-0001-8096-6291","position":4,"is_corresponding":false},{"id":21979,"name":"Paul M. Ridker","orcid":"0000-0003-1249-4522","position":5,"is_corresponding":false},{"id":466266,"name":"Paul J. Nestel","orcid":"0000-0001-5180-2132","position":6,"is_corresponding":false},{"id":962129,"name":"R. J. Simes","orcid":"0000-0002-3740-7563","position":7,"is_corresponding":false},{"id":284811,"name":"Andrew Tonkin","orcid":"0000-0001-5291-0610","position":8,"is_corresponding":false},{"id":932872,"name":"Gregory G. Schwartz","orcid":"0000-0003-2954-0695","position":9,"is_corresponding":false},{"id":594596,"name":"Helen M. Colhoun","orcid":"0000-0002-8345-3288","position":10,"is_corresponding":false},{"id":74376,"name":"Christoph Wanner","orcid":"0000-0001-9507-5301","position":11,"is_corresponding":false},{"id":323538,"name":"Sotirios Tsimikas","orcid":"0000-0001-9834-9494","position":12,"is_corresponding":false},{"id":367211,"name":"Harpreet Bhatia","orcid":"0000-0002-3964-2989","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:56:44.873714Z","pmid":"39492722","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}