Zheng Wenxiao, Zhang Jiayue, Huang Ying, Wang Shuting, Gao Xiangyang, Yang Zhirong, Zong Yueqi, Yang Zuyao
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China.
High Blood Press Cardiovasc Prev. 2025 Jan;32(1):107-119. doi: 10.1007/s40292-024-00694-6. Epub 2024 Dec 9.
Abnormalities in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are each associated with increased cardiovascular risk, after adjusting for non-lipid risk factors. However, whether and to what extent the association for each lipid measure is confounded by other lipid measures is less understood.
This study aims to investigate the association of each lipid measure with cardiovascular and all-cause mortality while precluding the confounding caused by abnormalities in other lipid measures.
The study utilized data from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and ten cycles of continuous NHANES (1999-2018). The study cohort included 23,761 participants who were 20 years or older, not pregnant, not receiving lipid-lowering treatment, and had complete data on all four lipid measures and mortality status. Participants were categorized into seven subgroups based on their lipid profiles. Kaplan-Meier survival curves and Cox proportional hazards models were used to examine the association between lipid abnormalities and mortality.
During a median follow-up of 140 months, 5,003 participants (14.1%) died, with 1,665 deaths (4.2%) attributable to cardiovascular causes. Compared with the reference group in which the four lipid measures were all normal, the subgroups with isolated high TC, two to three lipid abnormalities, and four lipid abnormalities were associated with increased risks for both cardiovascular and all-cause mortality in univariate analysis. However, only those with isolated high TC (for cardiovascular mortality, HR 1.52, 95% CI 1.13-2.06) and four lipid abnormalities (for all-cause mortality, HR 1.34, 95% CI 1.04-1.72) remained statistically significant after adjusting for non-lipid risk factors. Of note, compared with the reference group, the profile of non-lipid risk factors was apparently less favorable in the subgroup with two to three lipid abnormalities but similar (and some factors even more favorable) in the subgroup with isolated high TC. When the lipid measures were analyzed as continuous variables, a U-shaped relationship between HDL-C and mortality risk was observed for both cardiovascular and all-cause mortality, and very low LDL-C level was associated with increased mortality risk. No statistically significant association was found between TG levels and mortality risk.
Isolated high TC, very low LDL-C, and concurrent abnormalities in all four lipid measures were associated with increased mortality risk, whereas isolated high TG was not. A U-shaped relationship may exist between HDL-C level and mortality. Overall, these findings underscore the need for integrated management of dyslipidemia that takes all four lipid measures as well as non-lipid cardiovascular risk factors into account, particularly for those with concurrent abnormalities in two or more lipid measures.
在对非脂质风险因素进行校正后，总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG）异常均与心血管疾病风险增加相关。然而，每种血脂指标之间的关联在多大程度上受到其他血脂指标的混杂影响，目前尚不清楚。
本研究旨在探讨每种血脂指标与心血管疾病及全因死亡率之间的关联，同时排除其他血脂指标异常所造成的混杂影响。
本研究使用了第三次全国健康与营养检查调查（NHANES III，1988 - 1994年）以及连续十轮的NHANES（1999 - 2018年）的数据。研究队列包括23761名年龄在20岁及以上、未怀孕、未接受降脂治疗且具备所有四项血脂指标及死亡状态完整数据的参与者。参与者根据其血脂谱被分为七个亚组。采用Kaplan-Meier生存曲线和Cox比例风险模型来检验血脂异常与死亡率之间的关联。
在中位随访140个月期间，5003名参与者（14.1%）死亡，其中1665例死亡（4.2%）归因于心血管疾病。在单因素分析中，与四项血脂指标均正常的参照组相比，单纯高TC、两到三项血脂异常以及四项血脂异常的亚组，其心血管疾病和全因死亡率风险均增加。然而，在对非脂质风险因素进行校正后，仅单纯高TC（心血管疾病死亡率，HR 1.52，95% CI 1.13 - 2.06）和四项血脂异常（全因死亡率，HR 1.34，95% CI 1.04 - 1.72）仍具有统计学意义。值得注意的是，与参照组相比，两到三项血脂异常亚组的非脂质风险因素状况明显较差，但单纯高TC亚组的非脂质风险因素状况相似（某些因素甚至更有利）。当将血脂指标作为连续变量进行分析时，观察到HDL-C与心血管疾病和全因死亡率风险之间呈U型关系，极低的LDL-C水平与死亡率风险增加相关。未发现TG水平与死亡率风险之间存在统计学意义的关联。
单纯高TC、极低的LDL-C以及四项血脂指标同时异常与死亡率风险增加相关，而单纯高TG则不然。HDL-C水平与死亡率之间可能存在U型关系。总体而言，这些发现强调了对血脂异常进行综合管理的必要性，应将所有四项血脂指标以及非脂质心血管风险因素都考虑在内，尤其是对于那些有两项或更多项血脂指标同时异常的患者。
