{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T15:02:35Z","timestamp":1793977355117,"version":"4.8.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1\u2013008"],"award-info":[{"award-number":["2021-I2M-1\u2013008"]}]},{"name":"Central Universities","award":["3332024134"],"award-info":[{"award-number":["3332024134"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Extremely high-density lipoprotein cholesterol (HDL-C) may increase cardiovascular death risk, but whether such non-linear patterns extend to other major causes of death is unclear. This study examined dose\u2013response associations between HDL-C and mortality from the 10 leading global causes of death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This study included 429 759 UK Biobank participants with baseline HDL-C data. Cause-specific deaths were obtained from national registries. HDL-C was modelled using Cox proportional hazards and Fine\u2013Gray sub-distribution hazard models. Restricted cubic splines assessed non-linear associations, stratified by sex. Over a median follow-up of 13.8 years, 37 785 deaths occurred. U-shaped associations were observed between HDL-C and death risk from ischemic heart disease, lower respiratory infections, trachea, bronchus, or lung cancers, diabetes mellitus, and kidney disease. The optimal HDL-C range for the lowest death risk from above causes was 58\u201374\u2005mg\/dL in females and 50\u201360\u2005mg\/dL in males. J-shaped curves were observed for chronic obstructive pulmonary disease and liver disease, with the lowest death risk at 30\u201350\u2005mg\/dL. Stroke and Alzheimer\u2019s disease\/dementias death risk displayed sex-specific patterns: an L-shaped curve in females and U-shaped curve in males for stroke, and the reverse for Alzheimer\u2019s disease\/dementias. Extremely high HDL-C levels were associated with increased risk of death across several causes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HDL-C is non-linearly and sex-specifically associated with the top 10 global causes of death. Both low and high HDL-C confer increased risk through different mechanisms. These findings highlight the importance of evaluating HDL functionality rather than just quantity in future research and clinical care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwaf749","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:33:48Z","timestamp":1763987628000},"source":"Crossref","is-referenced-by-count":7,"title":["Association of high-density lipoprotein cholesterol with the top 10 causes of death"],"prefix":"10.1093","author":[{"given":"Shanshan","family":"Shi","sequence":"first","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Song","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiang","family":"Ye","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Song","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8372-6338","authenticated-orcid":false,"given":"Kefei","family":"Dou","sequence":"additional","affiliation":[{"name":"Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease , 167, Beilishi Road, Xicheng District, Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"2025120506110961300_zwaf749-B1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1161\/01.RES.0000146094.59640.13","article-title":"Antiinflammatory properties of HDL","volume":"95","author":"Barter","year":"2004","journal-title":"Circ Res"},{"key":"2025120506110961300_zwaf749-B2","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/aje\/kwv305","article-title":"Primary low level of high-density lipoprotein cholesterol and risks of coronary heart disease, cardiovascular disease, and death: results from the multi-ethnic study of atherosclerosis","volume":"183","author":"Ahmed","year":"2016","journal-title":"Am J Epidemiol"},{"key":"2025120506110961300_zwaf749-B3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1161\/01.CIR.79.1.8","article-title":"High-density lipoprotein cholesterol and cardiovascular disease. 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