Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study

Jiapeng Lu; Guiyuan Han; Xiaoying Liu; Bowang Chen; Ke Peng; Yu Shi; Mei Zhang; Yang Yang; Jianlan Cui; Lijuan Song; Wei Xu; Hao Yang; Wenyan He; Yan Zhang; Yuan Tian; Yichong Li; Xi Li

doi:10.1016/j.lanwpc.2023.100874

Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study

Lancet Reg Health West Pac. 2023 Aug 5:42:100874. doi: 10.1016/j.lanwpc.2023.100874. eCollection 2024 Jan.

Authors

Jiapeng Lu¹, Guiyuan Han², Xiaoying Liu², Bowang Chen¹, Ke Peng², Yu Shi², Mei Zhang³, Yang Yang¹, Jianlan Cui¹, Lijuan Song¹, Wei Xu¹, Hao Yang¹, Wenyan He¹, Yan Zhang¹, Yuan Tian¹, Yichong Li², Xi Li^{1

4}

Affiliations

¹ National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
² Shenzhen Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, People's Republic of China.
³ National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
⁴ Central China Sub-center of the National Center for Cardiovascular Diseases, Zhengzhou, People's Republic of China.

Abstract

Background: High-density lipoprotein cholesterol (HDL-C) has been inversely associated with cardiovascular disease (CVD) risk, but recent evidence suggests that extremely high levels of HDL-C are paradoxically related to increased CVD incidence and mortality. This study aimed to comprehensively examine the associations of HDL-C with all-cause and cause-specific mortality in a Chinese population.

Methods: The China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project included 3,397,547 participants aged 35-75 years with a median follow-up of 3.9 years. Baseline HDL-C levels were measured, and mortality data was ascertained from the National Mortality Surveillance System and Vital Registration of Chinese Center for Disease Control and Prevention.

Findings: This study found U-shaped associations of HDL-C with all-cause, cardiovascular and cancer mortality. When compared with the groups with the lowest risk, the adjusted hazard ratios (95% CIs) for HDL-C <30 mg/dL was 1.23 (1.17-1.29), 1.33 (1.23-1.45) and 1.18 (1.09-1.28) for all-cause, CVD and cancer mortality, respectively. For HDL-C >90 mg/dL, the corresponding HR (95% CIs) was 1.10 (1.05-1.15), 1.09 (1.01-1.18) and 1.11 (1.03-1.19). Similar U-shaped patterns were also found in associations of HDL-C with ischemic heart disease, ischemic stroke, and liver cancer. About 3.25% of all-cause mortality could be attributed to abnormal levels of HDL-C. The major contributor to mortality was ischemic heart disease (16.06 deaths per 100,000 persons, 95% UI: 10.30-22.67) for HDL-C <40 mg/dL and esophageal cancer (2.29 deaths per 100,000 persons, 95% UI: 0.57-4.77) for HDL-C >70 mg/dL.

Interpretation: Both low and high HDL-C were associated with increased mortality risk. We recommended 50-79 mg/dL as the optimal range of HDL-C among Chinese adults. Individuals with dyslipidemia might benefit from proper management of both low and high HDL-C.

Funding: The CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, and the 111 Project from the Ministry of Education of China (B16005), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2019ZT08Y481), Sanming Project of Medicine in Shenzhen (SZSM201811096), the Young Talent Program of the Academician Fund, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (YS-2022-006) and Guangdong Basic and Applied Basic Research Foundation (2023A1515010076 & 2021A1515220173).

Keywords: All-cause mortality; CVD mortality; Cancer mortality; High-density lipoprotein.