Abstract
<title>Abstract</title> <p>Background In-stent restenosis (ISR) remains a critical hurdle in coronary artery disease (CAD) management. Current lipid-lowering strategies in optimal medical therapy (OMT) primarily target low-density lipoprotein cholesterol (LDL-C); however, ISR continues to occur, driven by statin-independent factors. This cross-sectional exploratory study aimed to evaluate the independent predictive value and potential mechanistic cross-talk of lipoprotein(a) [Lp(a)] and inflammatory cytokines in CAD patients post-stenting. Methods In this cross-sectional analysis, CAD patients with prior percutaneous coronary intervention (PCI) were stratified into three phenotypes: Adherent with ISR, adherent without ISR, and a non-adherent without ISR. Baseline characteristics and serum biomarkers were evaluated. Receiver operating characteristic (ROC) analysis was utilized to determine the predictive thresholds for ISR. Results As an exploratory study, the preliminary analysis indicated that despite strict adherence to OMT, the ISR group exhibited elevated levels of systemic inflammation and Lp(a) compared to patent stent controls. Incorporating the non-adherent group highlighted that these markers may act as independent risk factors. ROC analysis revealed that hsCRP is a robust independent predictor of ISR (AUC = 0.752), with an optimal cut-off of 8.31 mg/L. Concurrently, Lp(a) demonstrated a marginal predictive value (AUC = 0.735, P = 0.066), suggesting a potential trend in identifying high-risk individuals at a threshold of 149.94 nmol/L. Conclusion Our preliminary exploratory findings suggest that systemic micro-inflammation and genetically determined Lp(a) may act as statin-independent risk factors for ISR in CAD. Lp(a) may modulate the risk of ISR via inflammatory/oxidative stress pathways.</p>