Fu Zhiqing, Zhang Wei, Li Shan
Department of Cardiology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.
Front Nutr. 2025 Jun 13;12:1591705. doi: 10.3389/fnut.2025.1591705. eCollection 2025.
Non-high-density lipoprotein cholesterol (non-HDL-C) is a well-established residual causal risk factor for the progression of atherosclerotic cardiovascular disease. However, studies of large, broadly generalizable populations are lacking, and the effect of non-HDL-C on all-cause and cause-specific mortality, particularly in different age groups, remains uncertain.
We conducted a population-based cohort study using data from the National Health and Nutrition Examination Survey from 1999 to 2018. Participants were divided into six groups according to non-HDL-C levels (≤100, 101-130, 131-160, 161-190, 191-220, >220 mg/dL). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Restricted cubic spline curves and subgroup analysis were also performed to further explore the association between non-HDL-C and mortality.
Of 51,252 individuals (mean age 48.1 ± 19.2 years), 7,605 (14.8%) died during follow-up. Both low and high non-HDL-C levels were significantly associated with increased risk of all-cause and cause-specific mortality, suggesting a U-shaped association. Thresholds of 156, 142, 162, and 152 mg/dL were identified for all-cause, cardiovascular, cancer, and other-cause mortality, respectively. We observed significant interactions between non-HDL-C and age for all-cause and cardiovascular mortality (P interaction<0.05 for each). The association of high non-HDL-C (>220 mg/dL) with all-cause and cardiovascular mortality was strongest in adults aged <50 years (HR, 1.51 [1.09-2.08] and 1.97 [1.07-3.12], respectively), intermediate in adults aged 50 to 69 years, and weakest in adults aged ≥70 years.
Non-HDL-C was U-shaped associated with all-cause and cause-specific mortality in the US general population. However, in younger adults (<50 years), the higher the non-HDL-C, the higher the risk of cardiovascular and all-cause mortality. These observations support clear public health messaging and strict adherence to primary prevention strategies for atherosclerosis in younger adults. This has important implications for the development of age-specific interventions to reduce mortality associated with non-HDL-C levels.
非高密度脂蛋白胆固醇（non-HDL-C）是动脉粥样硬化性心血管疾病进展中一个公认的残余因果风险因素。然而，缺乏对大型、广泛可推广人群的研究，并且non-HDL-C对全因死亡率和特定病因死亡率的影响，尤其是在不同年龄组中的影响，仍不确定。
我们使用1999年至2018年美国国家健康与营养检查调查的数据进行了一项基于人群的队列研究。参与者根据non-HDL-C水平（≤100、101 - 130、131 - 160、161 - 190、191 - 220、>220mg/dL）分为六组。使用多变量Cox比例风险模型计算风险比（HR）和相应的95%置信区间（CI）。还进行了受限立方样条曲线和亚组分析，以进一步探讨non-HDL-C与死亡率之间的关联。
在51252名个体（平均年龄48.1±19.2岁）中，7605人（14.8%）在随访期间死亡。低和高non-HDL-C水平均与全因死亡率和特定病因死亡率风险增加显著相关，呈U形关联。全因、心血管、癌症和其他病因死亡率的阈值分别确定为156、142、162和152mg/dL。我们观察到non-HDL-C与年龄在全因和心血管死亡率方面存在显著交互作用（每项P交互作用<0.05）。高non-HDL-C（>220mg/dL）与全因和心血管死亡率的关联在<50岁成年人中最强（HR分别为1.51[1.09 - 2.08]和1.97[1.07 - 3.12]），在50至69岁成年人中为中等强度，在≥70岁成年人中最弱。
在美国普通人群中，non-HDL-C与全因死亡率和特定病因死亡率呈U形关联。然而，在较年轻成年人（<50岁）中，non-HDL-C越高，心血管和全因死亡率风险越高。这些观察结果支持明确的公共卫生信息，并严格遵守针对较年轻成年人动脉粥样硬化的一级预防策略。这对于制定特定年龄的干预措施以降低与non-HDL-C水平相关的死亡率具有重要意义。
