{"doi":"10.1210/clinem/dgad406","title":"Does Elevated High-Density Lipoprotein Cholesterol Protect Against Cardiovascular Disease?","abstract":"High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2023,"id":322783,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":42293,"name":"Vardhmaan Jain","orcid":"0000-0001-7265-380X","position":1,"is_corresponding":false},{"id":426709,"name":"Gowtham R. Grandhi","orcid":"0000-0002-2800-2150","position":2,"is_corresponding":false},{"id":718983,"name":"Parth Patel","orcid":"0000-0002-3113-2546","position":3,"is_corresponding":false},{"id":1036952,"name":"Angelos Karagiannis","orcid":"0000-0003-3557-5077","position":4,"is_corresponding":false},{"id":430682,"name":"Nidhi Patel","orcid":"0000-0002-4446-0901","position":5,"is_corresponding":false},{"id":445437,"name":"Devinder S. Dhindsa","orcid":"0000-0003-0497-0349","position":6,"is_corresponding":false},{"id":236695,"name":"Chang Liu","orcid":"0000-0002-8918-7224","position":7,"is_corresponding":false},{"id":879498,"name":"Shivang Desai","orcid":"0000-0002-5577-8480","position":8,"is_corresponding":false},{"id":311866,"name":"Zakaria Almuwaqqat","orcid":"0000-0001-6606-1031","position":9,"is_corresponding":false},{"id":22017,"name":"Yan V. Sun","orcid":"0000-0002-2838-1824","position":10,"is_corresponding":false},{"id":292487,"name":"Viola Vaccarino","orcid":"0000-0002-9054-0654","position":11,"is_corresponding":false},{"id":236696,"name":"Arshed A. Quyyumi","orcid":"0000-0002-8166-679X","position":12,"is_corresponding":false},{"id":307077,"name":"Laurence Sperling","orcid":"0000-0001-9417-6370","position":13,"is_corresponding":false},{"id":445436,"name":"Anurag Mehta","orcid":"0000-0002-6910-5551","position":14,"is_corresponding":false},{"id":339079,"name":"Alexander C. Razavi","orcid":"0000-0002-3213-0876","position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":null,"created_at":"2026-07-19T01:07:47.432636Z","pmid":"37437107","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":[]}