Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: All-cause mortality; Atherogenic index of plasma; Atherosclerosis; Insulin resistance; Stroke; Triglyceride-glucose index.
© 2025. The Author(s).