高密度脂蛋白胆固醇（HDL-C）水平上升的好处受到挑战，因为有研究证明HDL-C水平与全因死亡之间存在U形关系，与死因特异性死亡的关联研究较少。共有344，556名年龄在20-79岁之间的个体（52%为女性），在1985-2003年间通过人口健康检查中受邀参与研究，根据其入组时血清HDL-C水平，分为< 30，30-39，40-49，50-59，60-69，70-79，80-89，90-99和> 99毫克/分升的组别进行随访，直至2018年底，评估其总因和特定原因的死亡情况，通过调整性别、年龄、日历时间段、吸烟、总胆固醇、甘油三酯、收缩压、身体活动、教育时间、身体质量指数和健康状况等因素，计算危险比（HR）。 随访平均为22年期间，有69505人去世。HDL-C水平与全因死亡、癌症和非心血管疾病/非癌症死亡（非CVD /非癌症）呈U形关联，而对于心血管疾病，仅在较低水平时死亡风险增加。以HDL-C水平50-59毫克/分升（1.30-1.53毫摩尔/升）为参考，HR [95％置信区间（CIs）]分别为全因死亡、CVD、癌症和非CVD /非癌症死亡水平>99毫克/分升（> 2.56毫摩尔/升）分别为1.32（1.21-1.43），1.05（0.89-1.24），1.26（1.09-1.46）和1.68（1.48-1.90）。对于HDL-C水平<30毫克/分升（0.78毫摩尔/升），相应的HR（95％ CI）分别为1.30（1.24-1.36），1.55（1.44-1.67），1.14（1.05-1.23）和1.19（1.10-1.29）。酒精性肝病、口腔-食管-肝癌、慢性肝病、慢性阻塞性肺疾病、事故和糖尿病的死亡率随HDL-C升高而明显增加，低于参考水平的HDL-C水平主要与缺血性心脏病（IHD）、其他CVD、胃癌和糖尿病的死亡率增加有关。 高HDL-C水平与多种疾病的死亡风险增加有关，其中许多疾病与重度饮酒也有关，而低HDL-C水平则与IHD、其他CVD、胃癌和糖尿病的死亡率增加有关。 ©作者（2023）。由牛津大学出版社代表国际流行病学协会出版。

Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied.A total of 344 556 individuals (20-79 years, 52 % women) recruited from population-based health screening during 1985-2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >99 mg/dl (< 0.78, 0.78-1.01, 1.04-1.27, 1.30-1.53, 1.55-1.79, 1.81-2.04, 2.07-2.31, 2.33-2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health.During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50-59 mg/dl (1.30-1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21-1.43), 1.05 (0.89-1.24), 1.26 (1.09-1.46) and 1.68 (1.48-1.90) for all-cause, CVD, cancer and non-CVD/non-cancer mortality, respectively. For HDL-C levels <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes.Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.