高密度脂蛋白胆固醇（HDL-C）浓度与健康老年人的原因和死亡率之间的关系尚不确定。本研究旨在分析初始健康老年男性和女性的HDL-C水平与死亡率之间的关联。该分析包括了来自“老年人事件重现的阿司匹林”（ASPREE）试验（n=18,668）和英国生物库（UKB）的配对队列（n=62,849，年龄≥65岁）的参与者。采用Cox回归分析HDL-C类别的危险比，分为<1.03 mmol/L、1.03-1.55 mmol/L（参考类别）、1.55-2.07 mmol/L和>2.07 mmol/L，分别与全因死亡、癌症、心血管疾病（CVD）和“非癌症非CVD”死亡率进行比较。使用HDL-C多基因得分评估了遗传贡献。ASPREE参与者（平均年龄75±5岁）中，在平均随访时间为6.3±1.8年的期间发生了1836例死亡。在男性中，HDL-C水平最高的类别与全因死亡（HR 1.60，95% CI 1.26-2.03）、癌症死亡（HR 1.37，95% CI 0.96-2.00）和“非癌症非CVD”死亡（HR 2.35，95% CI 1.41-3.42）有关，但与CVD死亡无关（HR 1.08，95% CI 0.60-1.94）。这些关联性在UKB参与者（平均年龄66.9±1.5岁）中得到验证，包括了在平均随访时间为12.7±0.8年的期间发生的8739例死亡。HDL-C水平与全因和特定原因死亡之间存在非线性关联。HDL-C水平与死亡率之间的关联与HDL-C多基因得分的变异无关。在女性中未发现HDL-C水平与死亡率之间的显著关联。健康老年男性的较高HDL-C水平与癌症和“非癌症非CVD”死亡的风险增加有关，但在女性中未观察到这种关系。© 2023. 作者。

The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03-1.55 mmol/L (referent category), 1.55-2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and "non-cancer non-CVD" mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26-2.03), cancer (HR 1.37, 95% CI 0.96-2.00), and "non-cancer non-CVD" mortality (HR 2.35, 95% CI 1.41-3.42) but not CVD mortality (HR 1.08, 95% CI 0.60-1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and "non-cancer non-CVD" mortality in healthy older men but no such relationship was observed in women.© 2023. The Author(s).