Association between atherogenic index of plasma (AIP) and all-cause and cardiovascular mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): a cohort study based on NHANES 1999-2018.

Abstract

Background: Lipid metabolism plays a pivotal role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MASLD). However, the effect of the atherogenic index of plasma (AIP)-a novel biomarker for assessing lipid metabolic abnormalities and atherosclerosis risk-on MASLD-related mortality remains unclear.

Methods: This study included 6,567 patients with MASLD from the National Health and Nutrition Examination Survey (1999-2018), with mortality data linked to National Death Index records through 31 December 2019. Participants were categorised into quartiles based on AIP. The association between baseline AIP and all-cause mortality (ACM) or cardiovascular disease mortality (CVM) were investigated using multivariate Cox Models, with restricted cubic spline (RCS) curves evaluated to assess potential nonlinear associations. Subgroup and mediation analyses explored modifiers and mediator (HbA1c, neutrophils, hypertension), while sensitivity analyses tested the robustness .

Results: During a median follow-up period of 122 months, 1,323 all-cause and 447 CVD-related deaths occurred. After adjusting for confounders, higher AIP was significantly associated with an increased CVM risk (HR = 1.34, 95% CI = 1.01-1.79, P = 0.05). No significant association was observed between AIP and ACM (HR = 1.05, 95% CI = 0.89-1.24, P = 0.50). RCS analysis revealed a J-shaped relationship between AIP and ACM (threshold = 1.71), with a significant increase in ACM risk when AIP > 1.71 (HR = 1.48, 95% CI = 1.14-1.92, P = 0.003). Subgroup analyses showed a significant interaction between AIP and age (P_{for_interaction} = 0.018); among individuals < 60 years, elevated AIP significantly increased ACM (HR = 1.25; 95% CI = 1.04-1.51; P = 0.018). Mediation analysis revealed that HbA1c mediated 73.17% of the total effect of AIP on ACM and 42.98% of the effect on CVM. Neutrophils accounted for 20.10% and 12.48%, respectively, whereas hypertension mediated 9.80% and 11.96%, respectively. Sensitivity analysis confirmed their robustness.

Conclusions: In US patients with MASLD, baseline AIP exhibited a J-shaped relationship with ACM. An AIP > 1.71 may warrant early intervention. Baseline AIP may be an effective predictor of future ACM and CVM in individuals aged < 60. However, further research is required to validate these findings.