Deng Liang, Zhong Haicheng, Zhou Sheng, Wang Ziming, Sun Jingjing, Liu Chang, Li Xinghui, Cheng Quankai, Deng Jie
College of Traditional Chinese Medicine and Health Services, Shanxi Datong University, Datong, China.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Nutr. 2025 May 20;12:1586558. doi: 10.3389/fnut.2025.1586558. eCollection 2025.
The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has emerged as a promising biomarker for lipid metabolism, with established links to mortality in various chronic diseases. However, its prognostic value in individuals with non-hyperhomocysteinemia (NHHcy), a population often overlooked in cardiovascular risk assessment, remains unexplored. This study aimed to determine the association between NHHR and all-cause and cardiovascular disease (CVD) mortality and its predictive value among adults with NHHcy.
This study used the National Health and Nutrition Examination Survey database (1999-2006) and employed the National Death Index to determine mortality outcomes. The relationship between NHHR and mortality was evaluated using restricted cubic splines (RCS) and a multivariable Cox proportional hazards model. The threshold effects were assessed using a piecewise Cox proportional hazards model. Analysis of subgroups, interactions, and survival was done. Lastly, the NHHR's predictive value for mortality as well as its potential mediating effects were evaluated.
A total of 13,847 participants were included in our study. Over the course of the follow-up, there were a total of 2,886 mortality, of which 739 were due to CVD. A "U-shaped" correlation between NHHR and mortality was shown by the RCS. A one-unit rise in NHHR was linked to a 19 and 17.4% decrease in the odds of all-cause and CVD mortality, respectively, when NHHR was below the inflection point; the hazards rose by 6.4 and 11.9%, respectively, when NHHR was over the inflection point. There were interaction effects between several subgroups in the relationship between NHHR and mortality from all-cause and CVD. Additionally, NHHR's area under the curve for predicting death from all-cause and CVD was 0.897 (0.890-0.904) and 0.921 (0.910-0.932), respectively. According to mediation analysis, the association between NHHR and all-cause mortality was mediated by aspartate aminotransferase.
NHHR was shown to have a "U-shaped" relationship with both all-cause and CVD mortality in the NHHcy population, as well as an excellent mortality predictive value. In the future, NHHR could be used for predicting mortality risk and prognosis in the NHHcy population.
非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值（NHHR）已成为一种有前景的脂质代谢生物标志物，与多种慢性疾病的死亡率存在既定关联。然而，其在非高同型半胱氨酸血症（NHHcy）个体中的预后价值尚未得到探索，而这一人群在心血管风险评估中常被忽视。本研究旨在确定NHHR与全因死亡率和心血管疾病（CVD）死亡率之间的关联及其在患有NHHcy的成年人中的预测价值。
本研究使用了国家健康与营养检查调查数据库（1999 - 2006年），并采用国家死亡指数来确定死亡结局。使用受限立方样条（RCS）和多变量Cox比例风险模型评估NHHR与死亡率之间的关系。使用分段Cox比例风险模型评估阈值效应。进行了亚组分析、交互作用分析和生存分析。最后，评估了NHHR对死亡率的预测价值及其潜在的中介作用。
我们的研究共纳入了13,847名参与者。在随访过程中，共有2,886人死亡，其中739人死于CVD。RCS显示NHHR与死亡率之间呈“U形”相关性。当NHHR低于拐点时，NHHR每升高一个单位，全因死亡率和CVD死亡率的几率分别降低19%和17.4%；当NHHR高于拐点时，风险分别升高6.4%和11.9%。在NHHR与全因和CVD死亡率之间的关系中，几个亚组之间存在交互作用。此外，NHHR预测全因和CVD死亡的曲线下面积分别为0.897（0.890 - 0.904）和0.921（0.910 - 0.932）。根据中介分析，NHHR与全因死亡率之间的关联由天冬氨酸转氨酶介导。
在NHHcy人群中，NHHR与全因死亡率和CVD死亡率均呈“U形”关系，且具有出色的死亡率预测价值。未来，NHHR可用于预测NHHcy人群的死亡风险和预后。
