HDL Cholesterol Is Remarkably Cardioprotective Against Coronary Artery Disease in Native Hawaiians and Pacific Islanders
Open accessAbstract
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.
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- [19]National Academies of Sciences, Engineering, and Medicine Using Population Descriptors in Genetics and Genomics Research: a New Framework for an Evolving Field 2023 The National Academies Press 36989389
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Zhao, J., Wei, C., Gong, F., Pang, Z., & Zhao, H. (2026) · BMC Cardiovascular Disorders · doi:10.1186/s12872-026-05799-5
“KD raised HDL-C by 3.5 mg/dL, which according to epidemiological data could translate to an estimated 7–11% decrease in CVD risk [27]; however, given questions about HDL-C's causal role from Mendelian randomization studies [28], these estimates should be interpreted cautiously.”
Influential
- Authors
- Szatrowski, A., Maggio, Z., & Khomtchouk, B.
- Affiliations
- University of Chicago (US)
- Indiana University Indianapolis (US)
- Corresponding author
- Khomtchouk, Bohdan
- Venue
- JACC: Advances
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 4
- Issue
- 6
- Pages
- 101741
- ISSN
- 2772-963X (ISSN-L)
- PMC
- PMC12124629
- OpenAlex
- W4410021931
- Cited by
- 4
- References
- 37
- Citations by year
- 2026: 4
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JACC Advances (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- NIDDK (R01DK132090)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- HDL cholesterol, coronary artery disease, Native Hawaiians and Pacific Islanders, major adverse cardiovascular events, type 2 diabetes, cardiometabolic risk, ethnic disparities, cardioprotection
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