ORIGINAL RESEARCH article
Front. Med.
Sec. Family Medicine and Primary Care
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1534524
Extremely high HDL cholesterol paradoxically increases the risk of all-cause mortality in non-diabetic males from the Korean population: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohorts
Provisionally accepted
- College of Medicine, Yonsei University, Seoul, Seoul, Republic of Korea
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Background: High-density lipoprotein cholesterol (HDL-C) is associated with lower risk of mortality and cardiovascular disease. However, the relationship between extremely high HDL cholesterol level and all-cause mortality has not been thoroughly investigated. In this study, we examined the longitudinal effects of very high HDL cholesterol on all-cause mortality in a large cohort of Korean adults without type 2 diabetes mellitus.: Data from 173,195 Korean participants over 40 years of age enrolled in the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort, linked with the death certificate database of the National Statistical Office, were assessed. Participants were grouped into four according to HDL-C levels. We used multivariate Cox proportional-hazard regression models to prospectively assess hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) over an 11-year baseline period.Results: During a mean follow-up of 11.7 years, there were a total of 3,906 deaths from all causes, including 2,258 in men and 1,648 in women. The relationship between HDL-C and allcause mortality showed a U-shaped pattern, especially in men. Compared to the reference group, the HR (95% CI) for mortality in males in the highest HDL cholesterol group was 1.31 (95% CI, 1.01-1.71) after adjusting for potential confounding variables. Moreover, low HDL cholesterol showed a statistically significant association with increased mortality in both men and women.Conclusions: Extremely high HDL-C levels could paradoxically increase the risk of all-cause mortality, particularly among males, in the general population without type 2 diabetes mellitus.Non-protective effects of very high HDL-C level should be noted when predicting incident metabolic syndrome, particularly in men, in clinical settings.
Keywords: HDL cholesterol, All-cause mortality, cardiovascular risk factor, general population, HEXA cohort
Received: 26 Nov 2024; Accepted: 01 May 2025.
Copyright: © 2025 Ryu, Jung, Heo, Park and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yong Jae Lee, College of Medicine, Yonsei University, Seoul, 03722, Seoul, Republic of Korea
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