Yang Zuyao, Huang Ying, Wang Shuting, Zheng Wenxiao, Xiao Ying, Zhang Jiayue
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China.
Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao SAR 999078, China.
Eur J Prev Cardiol. 2025 Aug 29. doi: 10.1093/eurjpc/zwaf515.
Lipid-lowering drugs are commonly prescribed for prevention of cardiovascular disease (CVD), but their efficacy in people aged ≥75 years is less understood. This population-based cohort study aimed to examine the association of lipid-lowering drug treatment with all-cause and cardiovascular mortality among people aged ≥75 years and whether the association, if existent, varied with patient characteristics.
A nationally representative sample of 6409 adults aged ≥75 years and without CVD at baseline was drawn from the Third National Health and Nutrition Examination Survey (NHANES III) conducted between 1988 and 1994 and the 10 continuous NHANES cycles between 1999-2000 and 2017-18 in the USA. Among these participants, 1227 were on lipid-lowering drug treatment at baseline. All-cause and cardiovascular deaths were ascertained by linkage to National Death Index records through 31 December 2019. The association of lipid-lowering drug treatment with mortality was investigated through multivariable Cox regression analysis and expressed as hazard ratio (HR) with 95% confidence interval (CI), adjusting for major risk factors of CVD and mortality. Complete-case analysis, competing risk analysis, and exclusion of deaths occurring within the first year of the follow-up were conducted to examine the robustness of results. Subgroup analyses were conducted to detect potential interaction between lipid-lowering drug treatment and important patient characteristics including demographics, lifestyle factors, comorbidities, baseline CVD risk, and concurrent medications. During a median follow-up of 6.5 years (78 months), 4634 (72.3%) participants died and 1834 (28.6%) of them were attributed to cardiovascular causes. Use of lipid-lowering drugs was associated with lower risks of both all-cause mortality (adjusted HR 0.74, 95% CI 0.67-0.81, P < 0.001) and cardiovascular mortality (adjusted HR 0.64, 95% CI 0.54-0.76, P < 0.001). After adjusting for covariates, the overall survival of users was 1.6 years longer than that of non-users. For all-cause mortality, the adjusted HRs for 'within 2.5 years', '2.5-7.5 years', and 'over 7.5 years' after baseline were 0.61 (95% CI 0.49-0.76), 0.72 (95% CI 0.63-0.83), and 0.82 (95% CI 0.71-0.94), respectively. For cardiovascular mortality, the corresponding results were 0.46 (95% CI 0.30-0.68), 0.59 (95% CI 0.47-0.76), and 0.78 (95% CI 0.62-0.97), respectively. Various sensitivity analyses yielded consistent results with the main analyses. The HRs for all-cause mortality were statistically significant in all subgroups defined by age (including the '≥85 years' group), sex, self-rated current health status, body mass index, hypertension, diabetes, estimated 10-year cardiovascular risk at baseline, cancer, and concurrent use of common medications, favouring lipid-lowering drug users. In those without high cholesterol, with chronic kidney disease, or with pulmonary disease, the HRs were not statistically significant, with wide CIs, partly due to the small number of users. Similar patterns were observed for cardiovascular mortality.
In this study population of people aged ≥75 years and without CVD at baseline, use of lipid-lowering drugs was associated with significantly lower risks of all-cause and cardiovascular mortality.
降脂药物常用于预防心血管疾病（CVD），但其在75岁及以上人群中的疗效尚鲜为人知。这项基于人群的队列研究旨在探讨降脂药物治疗与75岁及以上人群全因死亡率和心血管死亡率之间的关联，以及该关联（若存在）是否因患者特征而异。
从1988年至1994年进行的第三次全国健康与营养检查调查（NHANES III）以及美国1999 - 2000年至2017 - 18年的10个连续NHANES周期中抽取了6409名基线时无CVD的75岁及以上成年人的全国代表性样本。在这些参与者中，1227人在基线时接受降脂药物治疗。通过与国家死亡指数记录建立联系，确定截至2019年12月31日的全因死亡和心血管死亡情况。通过多变量Cox回归分析研究降脂药物治疗与死亡率之间的关联，并以风险比（HR）和95%置信区间（CI）表示，同时对CVD和死亡率的主要风险因素进行调整。进行了完整病例分析、竞争风险分析以及排除随访第一年内发生的死亡病例，以检验结果的稳健性。进行亚组分析以检测降脂药物治疗与重要患者特征（包括人口统计学、生活方式因素、合并症、基线CVD风险和同时使用的药物）之间的潜在相互作用。在中位随访6.5年（78个月）期间，4634名（72.3%）参与者死亡，其中1834名（28.6%）归因于心血管原因。使用降脂药物与全因死亡率（调整后HR 0.74，95% CI 0.67 - 0.81，P < 0.001）和心血管死亡率（调整后HR 0.64，95% CI 0.54 - 0.76，P < 0.001）的较低风险相关。在调整协变量后，使用者的总体生存期比未使用者长1.6年。对于全因死亡率，基线后“2.5年内”、“2.5 - 7.5年”和“7.5年以上”的调整后HR分别为0.61（95% CI 0.49 - 0.76）、0.72（95% CI 0.63 - 0.83）和0.82（95% CI 0.71 - 0.94）。对于心血管死亡率，相应结果分别为0.46（9 5% CI 0.30 - 0.68）、0.59（95% CI 0.47 - 0.76）和0.78（95% CI 0.62 - 0.97）。各种敏感性分析得出的结果与主要分析一致。在按年龄（包括“≥85岁”组）、性别、自我评估的当前健康状况、体重指数、高血压、糖尿病、基线时估计的10年心血管风险、癌症以及同时使用常见药物定义的所有亚组中，全因死亡率的HR均具有统计学意义，支持降脂药物使用者。在无高胆固醇、患有慢性肾病或肺部疾病的人群中，HR无统计学意义，CI较宽，部分原因是使用者数量较少。心血管死亡率也观察到类似模式。
在本研究中基线时无CVD的75岁及以上人群中，使用降脂药物与全因死亡率和心血管死亡率的显著降低风险相关。
