Prognostic Value of the NAPLES Score and Serum Uric Acid in Chronic Coronary Syndrome: Evidence from Time-Dependent ROC and Time-Varying Hazard Ratio Analyses

<b>Background and Objectives</b>: The Naples Prognostic Score (NPS), a composite index indicative of nutritional and inflammatory status, has been suggested as an important prognostic marker. Uric acid, an indicator of oxidative stress and endothelial impairment, is also associated with cardiovascular risk. This study sought to examine the synergistic value of NPS and uric acid levels in forecasting long-term major adverse cardiovascular and cerebrovascular events (MACCE) in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), using time-varying hazard ratio and time-dependent Receiver Operating Characteristic (ROC) analyses. <b>Materials and Methods</b>: A retrospective analysis was conducted on 288 patients diagnosed with CCS from January 2020 to November 2023. The NPS was determined utilizing serum albumin, total cholesterol, the neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR). Cox regression, time-varying hazard ratio models, and time-dependent ROC curve analyses were performed to assess both temporal risk patterns and predictive performance. The principal endpoint was the incidence of MACCE. <b>Results</b>: Major adverse cardiovascular and cerebrovascular events (MACCE) occurred in 69 individuals, representing 23.4% of the total cohort. Both high NPS and elevated uric acid were independently associated with an increased risk of MACCE. The integration of the NPS with uric acid showed superior discriminative and reclassification capabilities compared to the use of each marker independently (<i>p</i> < 0.05 for all). Time-varying hazard ratio analyses demonstrated that the prognostic impact of the NPS was more pronounced in the early follow-up, while the effect of uric acid became stronger in the late phase. Time-dependent ROC analyses confirmed that the combined use of the NPS and uric acid provided superior predictive accuracy compared with either parameter alone across the follow-up period. <b>Conclusions</b>: NPS and uric acid offer complementary prognostic information in CCS. Their combined assessment improves long-term risk stratification, while time-varying and time-dependent analyses reveal that their predictive effects evolve dynamically throughout follow-up. This integrated evaluation may improve clinical decision-making and risk stratification in routine practice.