Qian Jinhua, Chi Qinjie, Qian Chengqun, Fan Xian, Ding Wenbing, Wang Tianle, Zhu Li
Department of Radiology, Affiliated Hospital 2 of Nantong University, Nantong, 226600, China.
Department of Intervention, Affiliated Hospital 2 of Nantong University, Nantong, 226600, China.
Lipids Health Dis. 2025 May 10;24(1):173. doi: 10.1186/s12944-025-02586-7.
The "lipid paradox" describes the counterintuitive observation that traditionally unfavorable lipid profiles may be associated with improved outcomes in stroke patients. Non-traditional lipid markers such as the atherogenic index of plasma (AIP) and the triglyceride-glucose (TyG) index have been proposed to better reflect the complex metabolic disturbances following stroke. This study aims to investigate the mediating role of AIP and TyG index in the association between stroke and all-cause mortality and elucidate the potential mechanisms underlying the lipid paradox.
This cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS), including 10,220 participants enrolled from 2011 to 2020, with a maximum follow-up of 10 years. AIP and TyG index were calculated from baseline serum measurements. U-test, chi-square test, restricted cubic spline analysis (RCS), cox proportional hazards regression and mediation model were used to analyze the relationship between baseline AIP, TyG index, stroke and all-cause mortality.
A total of 1,421 deaths (13.90%) occurred during an average follow-up of 9.21 years. Compared to survivors, non-survivors were older, had a higher prevalence of stroke, and lower AIP levels (P < 0.05), while TyG index showed no significant group difference. RCS analysis revealed a nonlinear association between the TyG index and mortality, but no significant nonlinearity for AIP. Cox regression analysis identified age, gender, marital status, smoking history, hypertension, diabetes, lung disease, stroke, AIP, and the highest TyG quartile (Q4) as independent predictors of all-cause mortality (all P < 0.05). Notably, AIP showed a negative association with mortality (HR = 0.87, 95% CI: 0.77-0.98),demonstrating a lipid paradox phenomenon. Furthermore, in the chain mediation model, both AIP (β=-0.03, 95%CI: -0.072 to -0.002) and TyG index (β=-0.016, 95%CI: -0.036 to -0.002) independently mediated the association between stroke and all-cause mortality in a negative manner. However, the positive chain mediating effect of AIP through TyG index (β = 0.028, 95%CI: 0.003-0.066) offset this negative mediation, rendering the overall mediating effect insignificant.
AIP and the TyG index independently or jointly influence the risk of all-cause mortality after stroke. Notably, AIP demonstrates a significant lipid paradox phenomenon. Moreover, the chain mediating effect of AIP and TyG significantly increases post-stroke mortality risk. These findings highlight the complex interplay between lipid and glucose metabolism in stroke prognosis and offer a novel perspective for post-stroke metabolic management.
“脂质悖论”描述了一种与直觉相悖的现象，即传统上不利的脂质谱可能与中风患者更好的预后相关。血浆致动脉粥样硬化指数（AIP）和甘油三酯-葡萄糖（TyG）指数等非传统脂质标志物已被提出，以更好地反映中风后复杂的代谢紊乱。本研究旨在探讨AIP和TyG指数在中风与全因死亡率之间关联中的中介作用，并阐明脂质悖论背后的潜在机制。
这项队列研究使用了中国健康与养老追踪调查（CHARLS）的数据，包括2011年至2020年招募的10220名参与者，最长随访10年。AIP和TyG指数根据基线血清测量值计算得出。采用U检验、卡方检验、限制性立方样条分析（RCS）、Cox比例风险回归和中介模型来分析基线AIP、TyG指数、中风与全因死亡率之间的关系。
在平均9.21年的随访期间，共发生1421例死亡（13.90%）。与幸存者相比，非幸存者年龄更大，中风患病率更高，AIP水平更低（P<0.05），而TyG指数在两组之间无显著差异。RCS分析显示TyG指数与死亡率之间存在非线性关联，但AIP无显著非线性。Cox回归分析确定年龄性别、婚姻状况、吸烟史、高血压、糖尿病、肺部疾病、中风、AIP以及最高TyG四分位数（Q4）为全因死亡率的独立预测因素（均P<0.05）。值得注意的是，AIP与死亡率呈负相关（HR=0.87，95%CI：0.77-0.98），呈现脂质悖论现象。此外，在链式中介模型中，AIP（β=-0.03，95%CI：-0.072至-0.002）和TyG指数（β=-0.016，95%CI：-0.036至-0.002）均以负向方式独立介导中风与全因死亡率之间的关联。然而，AIP通过TyG指数的正向链式中介效应（β=0.028，95%CI：0.003-0.066）抵消了这种负向中介作用，使得总体中介效应不显著。
AIP和TyG指数独立或共同影响中风后全因死亡风险。值得注意的是，AIP表现出显著的脂质悖论现象。此外，AIP和TyG的链式中介效应显著增加中风后死亡风险。这些发现突出了脂质和葡萄糖代谢在中风预后中的复杂相互作用，并为中风后代谢管理提供了新的视角。
