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
BackgroundHigh-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 longitudin...
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Frontiers Media S.A.
2025-05-01
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| author | Ha-Eun Ryu Ha-Eun Ryu Dong Hyuk Jung Dong Hyuk Jung Seok-Jae Heo Byoungjin Park Byoungjin Park Yong Jae Lee Yong Jae Lee |
| author_facet | Ha-Eun Ryu Ha-Eun Ryu Dong Hyuk Jung Dong Hyuk Jung Seok-Jae Heo Byoungjin Park Byoungjin Park Yong Jae Lee Yong Jae Lee |
| author_sort | Ha-Eun Ryu |
| collection | DOAJ |
| description | BackgroundHigh-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.MethodsData 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.ResultsDuring 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 all-cause 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.ConclusionExtremely 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. |
| format | Article |
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| institution | DOAJ |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-05-01 |
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| series | Frontiers in Medicine |
| spelling | doaj-art-a0f31f8a7d9e4beda8f6be45dc951af22025-08-20T03:10:05ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15345241534524Extremely 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) cohortsHa-Eun Ryu0Ha-Eun Ryu1Dong Hyuk Jung2Dong Hyuk Jung3Seok-Jae Heo4Byoungjin Park5Byoungjin Park6Yong Jae Lee7Yong Jae Lee8Department of Family Medicine, Yongin Severance Hospital, Yongin, Gyeonggi-do, Republic of KoreaDepartment of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Family Medicine, Yongin Severance Hospital, Yongin, Gyeonggi-do, Republic of KoreaDepartment of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaBiostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Family Medicine, Yongin Severance Hospital, Yongin, Gyeonggi-do, Republic of KoreaDepartment of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Family Medicine, Gangnam Severance Hospital, Seoul, Republic of KoreaBackgroundHigh-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.MethodsData 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.ResultsDuring 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 all-cause 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.ConclusionExtremely 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1534524/fullHDL cholesterolall-cause mortalitycardiovascular risk factorgeneral populationHEXA cohort |
| spellingShingle | Ha-Eun Ryu Ha-Eun Ryu Dong Hyuk Jung Dong Hyuk Jung Seok-Jae Heo Byoungjin Park Byoungjin Park Yong Jae Lee Yong Jae Lee 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 Frontiers in Medicine HDL cholesterol all-cause mortality cardiovascular risk factor general population HEXA cohort |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | HDL cholesterol all-cause mortality cardiovascular risk factor general population HEXA cohort |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1534524/full |
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