{"doi":"10.1016/j.jacadv.2025.101741","title":"HDL Cholesterol Is Remarkably Cardioprotective Against Coronary Artery Disease in Native Hawaiians and Pacific Islanders","abstract":"BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiometabolic risk and exhibits nonlinear effects at extreme levels. Cardiometabolic diseases are a leading cause of death and are particularly prevalent among Native Hawaiian and Pacific Islanders (NHPIs). OBJECTIVES: This study characterizes HDL-C's association with coronary artery disease (CAD), major adverse cardiovascular events (MACE), and type 2 diabetes (T2D) in NHPIs compared to the general population. METHODS: Using electronic health record data from the National Institutes of Health All of Us Research Program, we applied Cox proportional hazards models to compare HDL-C's protective effects on CAD, MACE, and T2D between 261 NHPIs and the remaining cohort (n = 188,802). Models were adjusted for key confounders, and restricted cubic splines were used to assess nonlinear risk dynamics. RESULTS: Tracking individuals across 10,534,661 person-years (mean age 55.7 ± 15.8 years, 38% male), HDL-C was more strongly associated with reduced CAD risk in NHPIs (HR: 0.32; 95% CI: 0.19-0.54) than in the general cohort (HR: 0.57; 95% CI: 0.56-0.58). A marginally stronger association was observed for MACE (NHPI HR: 0.40; 95% CI: 0.23-0.71 vs general HR: = 0.54; 95% CI: 0.53-0.56), while T2D associations were similar. Spline analysis indicated that low HDL-C increases risk for both CAD and T2D in NHPIs. CONCLUSIONS: HDL-C's protective role against cardiometabolic diseases is more pronounced in NHPIs, particularly for CAD. These findings support further investigation into tailored clinical assessments for this population.","journal":"JACC Advances","year":2025,"id":525646,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9692,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1241804,"name":"Zane A. Maggio","orcid":null,"position":1,"is_corresponding":false},{"id":571670,"name":"Bohdan B. Khomtchouk","orcid":"0000-0001-9607-7528","position":2,"is_corresponding":false},{"id":1147483,"name":"Austin Szatrowski","orcid":"0000-0003-0611-8387","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:50:21.274116Z","pmid":"40319838","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":[]}