Mediating Role of OCT-Defined Vulnerable Plaque in the Association of Atherogenic Index of Plasma with Adverse Acute Coronary Syndrome Outcomes

Background : Acute coronary syndrome (ACS) remains a leading global cause of mortality. Although optical coherence tomography (OCT) provides detailed assessment of adverse-outcome-associated vulnerable plaque features, and the atherogenic index of plasma (AIP) is a novel lipid-related predictor of atherosclerotic cardiovascular disease, their interrelationship and combined prognostic value in ACS patients remain unclear. Objective: This study aims to examine the association between the atherogenic index of plasma (AIP) and OCT-defined vulnerable plaque features with clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This retrospective single-center study enrolled 1,324 ACS patients undergoing OCT-guided PCI. AIP was calculated as log₁₀(TG/HDL-C). Vulnerable plaques were defined by four OCT features: thin-cap fibroatheroma (TCFA), lipid-to-cap ratio (LCR ≥0.33), macrophage infiltration, and cholesterol crystals. Primary outcome was MACEs (composite of all-cause death, cardiovascular death, unplanned revascularization, in-stent restenosis, angina rehospitalization, and heart failure rehospitalization). Multivariable Cox regression, Kaplan-Meier analysis, ROC curves, and mediation analysis were used. Results: During a median 441-day follow-up, 15.5% (206/1330) of patients experienced MACEs. Fully adjusted analyses revealed that both elevated AIP (≥0.21; HR=1.61, 95%CI:1.18–2.19) and all OCT-defined vulnerable plaque features (LCR≥0.33: HR=1.98; TCFA: HR=1.89; macrophage: HR=1.52; cholesterol crystals: HR=1.47; all P<0.05) independently predicted MACEs. Patients with high AIP plus ≥2 vulnerable plaque features had the highest MACEs risk (P<0.001). Adding AIP to a baseline model (C=0.59) improved prediction (ΔC=0.04; NRI=0.182, P=0.016), with further enhancement after incorporating plaque features (C=0.72; NRI=0.471, P<0.001). Vulnerable plaque features mediated 5.7–15.5% of AIP-associated cardiovascular risk (P<0.05). Conclusion: AIP and OCT-defined vulnerable plaque features serve as independent predictors of MACEs in ACS patients. Their combined assessment significantly enhances risk stratification. Furthermore, plaque features partially mediate AIP-associated cardiovascular risk.