Title : Lipoprotein(a) combined with high-density lipoprotein cholesterol for predicting in-stent restenosis in patients with chronic coronary syndrome undergoing percutaneous coronary intervention
Abstract:
Background The current cardiovascular risk assessment system has not fully integrated the interaction between atherosclerotic promoting factors and protective factors. Lipoprotein(a) [Lp(a)], an independent risk factor for coronary heart disease, has a pathogenic risk that may be modified by the protective effect of high-density lipoprotein cholesterol (HDL-C). To quantify this balance, the present study newly developed the Lipoprotein(a) Proatherogenic Index (LPI) and validated its prognostic utility for in-stent restenosis (ISR) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). The value of the LPI is defined as the lipoprotein(a)/HDL-C.
Methods A total of 2,238 participants were enrolled and divided into tertiles based on natural log-transformed LPI (lnLPI) values. The primary endpoint was ISR. Kaplan-Meier survival analysis, Cox proportional hazards models, restricted cubic splines (RCS) and mediation analysis were used to examine the relationship between lnLPI and the primary endpoint, adjusting for potential covariates. The predictive performance of the models was evaluated using receiver operating characteristic (ROC) curves, with the area under curve (AUC) metric quantifying the model’s discriminative ability.
Results Over a median follow-up of 60 months, 470 (21.00%) patients had experienced at least one primary endpoint event. Kaplan-Meier survival analysis showed that higher lnLPI tertiles
were significantly associated with increased risk of the primary endpoint (p=0.003). After adjusting for potential confounders, the lnLPI index was independently associated with the primary endpoint in CCS patients (HR, 1.11; 95% CI 1.02-1.20; P=0.013). Additionally, the highest tertile of the lnLPI index group was correlated with a 1.31-fold risk of the primary endpoint compared with the lowest tertile of the lnLPI index group (HR, 1.31; 95% CI 1.05-1.63; P=0.018). Furthermore, a linear and dose-response relationship was observed between the lnLPI index and the primary endpoint (non-linear P=0.367, P overall=0.027). Mediation analysis indicated that previous PCI and previous myocardial infarction partially mediated the association between lnLPI and the primary endpoint, accounting for 9.18% and 7.24% of its effect on ISR respectively. No significant interactions were observed in the subgroup analyses (all P for interaction>0.05). The ROC analysis demonstrated that lnLPI-based multivariate prediction model had moderate predictive accuracy for the primary endpoint, with area under the curve estimates of 0.69 (95% CI 0.65-0.72) at 3 years and 0.70 (95% CI 0.67-0.73) at 5 years.
Conclusions An increased LPI index was associated with elevated risk for ISR. Our study suggested that the LPI index could be a new predictor in evaluating the prognosis of CCS patients undergoing PCI.
Keywords Lipoprotein(a); high-density lipoprotein cholesterol; chronic coronary syndrome; Percutaneous coronary intervention; In-stent restenosis
