The Synergistic Risk of Insulin Resistance and Renal Dysfunction in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention

<b>Background:</b> Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked to post-PCI outcomes remain incompletely elucidated. <b>Methods:</b> A retrospective cohort study was conducted involving patients with ACS who underwent PCI at the Third People's Hospital of Chengdu from July 2018 to December 2020. Insulin resistance (IR) was quantified using the triglyceride-glucose (TyG) index, and renal function was evaluated via the estimated glomerular filtration rate (eGFR). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Multivariable Cox proportional hazards regression and mediation analyses were applied to explore the associations of TyG index and eGFR with patient prognosis, and to quantify the mediating effect of eGFR on the relationship between TyG index and prognosis. <b>Results:</b> A total of 1340 patients with ACS were included in the final analysis. Over a median follow-up duration of 31.02 (interquartile range [IQR]: 27.34-35.03) months, 124 patients (9.25%) experienced MACEs. After adjusting for potential confounders, both the TyG index and eGFR were identified as significant independent predictors of MACEs in the overall population and across predefined subgroups. Specifically, each one-unit increase in the TyG index was associated with a 73.8% higher risk of MACEs (HR 1.738; 95% CI 1.273-2.372), whereas each ten-unit decrease in eGFR was linked to a 12.7% increased MACEs risk (HR 1.127; 95% CI 1.032-1.232). Importantly, after further adjustment for confounders, eGFR significantly mediated 9.63% of the total effect of the TyG index on MACEs risk. <b>Conclusions:</b> Renal impairment partially mediates the association between IR and adverse cardiovascular outcomes in ACS patients undergoing PCI. This finding underscores the clinical importance of the metabolic-cardiorenal axis in this population, suggesting that a comprehensive assessment targeting both IR and renal function-related pathways may enhance risk-stratification accuracy and optimize therapeutic strategies for ACS patients.