Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial.

Zhen Zhou, Andrew M Tonkin, Andrea J Curtis, Anne Murray, Chao Zhu, Christopher M Reid, Jeff D Williamson, Joanne Ryan, John J McNeil, Lawrence J Beilin, Michael E Ernst, Nigel Stocks, Paul Lacaze, Raj C Shah, Robyn L Woods, Rory Wolfe, Seana Gall, Sophia Zoungas, Suzanne G Orchard, Mark R Nelson
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Abstract

Background: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals.

Methods: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models.

Results: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05).

Conclusions: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.

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健康老年人的低密度脂蛋白胆固醇和死亡率结局:一项ASPREE试验的事后分析
背景:胆固醇水平对老年人预后的影响仍不确定。本研究旨在探讨老年人低密度脂蛋白-胆固醇(LDL-c)与死亡率之间的关系。方法:本事后分析研究了来自ASPREE试验(NCT01038583)的年龄≥65岁的个体队列中LDL-c水平与全因、心血管疾病、癌症和非心血管疾病/非癌症合并死亡风险的关系。在基线时,参与者没有诊断出痴呆、身体残疾或心血管疾病(CVD),也没有服用降脂药物。结果分析采用多变量Cox模型。结果:我们分析了12334名参与者(平均年龄:75.2岁)。在平均7年的随访中,1250人死亡。限制三次样条曲线发现LDL-c与全因死亡率、癌症死亡率和非癌症/非cve死亡率呈u型关系(最低点:3.3-3.4 mmol/L);LDL-c低于3.3 mmol/L时,心血管疾病死亡风险相似,高于3.3 mmol/L时,心血管疾病死亡风险增加。在对LDL-c按四分位数建模的分析中也观察到类似的趋势。当将LDL-c建模为连续变量时,LDL-c每升高1 mmol/L,全因死亡率、癌症死亡率和非癌症/非心血管疾病死亡率的风险分别降低9%、16%和18%,而LDL-c每升高1 mmol/L,心血管疾病死亡率的风险增加19%。结论:在健康老年人中,LDL-c与全因死亡率、癌症死亡率和非癌症/非心血管疾病死亡率之间存在u型关系。较高的LDL-c水平与心血管疾病死亡风险增加相关。未来的研究有必要证实我们的结果。
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