Aims High-density lipoprotein (HDL) cholesterol concentrations are inversely associated with cardiovascular disease and mortality across a range of concentrations, but genetic evidence suggest that extreme high concentrations may paradoxically lead to more cardiovascular disease. We tested the hypothesis that extreme high concentrations of HDL cholesterol are associated with high all-cause mortality in men and women. Methods and results A total of 52 268 men and 64 240 women were included from the two prospective population-based studies, the Copenhagen City Heart Study and the Copenhagen General Population Study. During 745 452 person-years of follow-up, number of deaths from any cause were 5619 (mortality rate, 17.1/1000 person-years (95% confidence interval (CI): 16.7-17.6)) in men and 5059 (mortality rate, 12.1/1000 person-years (11.8-12.4)) in women. The association between HDL cholesterol concentrations and all-cause mortality was U-shaped for both men and women, with both extreme high and low concentrations being associated with high all-cause mortality risk. The concentration of HDL cholesterol associated with the lowest all-cause mortality was 1.9 mmol/L (95% CI: 1.4-2.0) (73 mg/dL (54-77)) in men and 2.4 mmol/L (1.8-2.5) (93 mg/dL (69-97)) in women. When compared with the groups with the lowest risk, the multifactorially adjusted hazard ratios for all-cause mortality were 1.36 (95% CI: 1.09-1.70) for men with HDL cholesterol of 2.5-2.99 mmol/L (97-115 mg/dL) and 2.06 (1.44-2.95) for men with HDL cholesterol ≥3.0 mmol/L (116 mg/dL). For women, corresponding hazard ratios were 1.10 (0.83-1.46) for HDL cholesterol of 3.0-3.49 mmol/L (116-134 mg/dL) and 1.68 (1.09-2.58) for HDL cholesterol ≥3.5 mmol/L (135 mg/dL). Conclusion Men and women in the general population with extreme high HDL cholesterol paradoxically have high all-cause mortality. These findings need confirmation in other studies.

中文翻译：

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极高的高密度脂蛋白胆固醇与男性和女性的高死亡率自相矛盾：两项前瞻性队列研究

目标 高密度脂蛋白 (HDL) 胆固醇浓度与一系列浓度的心血管疾病和死亡率呈负相关，但遗传证据表明，极高的浓度可能自相矛盾地导致更多的心血管疾病。我们检验了极高浓度的 HDL 胆固醇与男性和女性高全因死亡率相关的假设。方法和结果 哥本哈根市心脏研究和哥本哈根普通人群研究这两项前瞻性人群研究共纳入了 52268 名男性和 64240 名女性。在 745 452 人年的随访中，男性和 5059 人（死亡率，17.1/1000 人年（95% 置信区间 (CI)：16.7-17.6））因任何原因死亡, 12.1/1000 人年 (11.8-12. 4)) 在女性中。HDL 胆固醇浓度与全因死亡率之间的关联在男性和女性中均呈 U 型，极高和极低浓度都与高全因死亡率风险相关。与最低全因死亡率相关的 HDL 胆固醇浓度在男性中为 1.9 mmol/L (95% CI: 1.4-2.0) (73 mg/dL (54-77))，在男性中为 2.4 mmol/L (1.8-2.5) (93 mg/dL (69-97)) 在女性中。与风险最低的组相比，HDL 胆固醇为 2.5-2.99 mmol/L (97-115 mg/dL) 的男性全因死亡率的多因素调整风险比为 1.36 (95% CI: 1.09-1.70) ) 和 2.06 (1.44-2.95) 对于 HDL 胆固醇≥3.0 mmol/L (116 mg/dL) 的男性。对于女性，HDL 胆固醇 3.0-3.49 mmol/L (116-134 mg/dL) 和 1.68 (1.09-2) 的相应风险比为 1.10 (0.83-1.46)。58) HDL 胆固醇≥3.5 mmol/L (135 mg/dL)。结论 HDL 胆固醇极高的普通人群中男性和女性的全因死亡率却自相矛盾。这些发现需要在其他研究中得到证实。