Association Between the Remnant Cholesterol Inflammation Index and Cardiac Syndrome X

Background and Objectives: Cardiac Syndrome X (CSX), a clinical entity within the Ischaemia with Non-Obstructive Coronary Arteries (INOCA) spectrum, is increasingly recognised as an inflammatory and systemic vascular disorder. Remnant cholesterol (RC) and inflammation are emerging contributors to residual cardiovascular risk; however, their combined role in microvascular angina remains unclear. This study aimed to evaluate the association between the remnant cholesterol inflammation index (RCII), integrating RC and high-sensitivity C-reactive protein (hs-CRP), and the clinical presence of CSX. Methods: This single-centre, retrospective observational study included 392 individuals who underwent coronary angiography between January 2023 and January 2025. The study population comprised 197 patients diagnosed with CSX and 195 control subjects with normal coronary anatomy and no objective evidence of myocardial ischaemia. RC was calculated as total cholesterol minus the sum of LDL-C and HDL-C, and RCII was derived as RC × hs-CRP. Importantly, invasive microvascular testing (e.g., CFR or IMR) was not performed. Logistic regression analyses were performed to identify independent predictors of CSX, and receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. Results: Patients with CSX exhibited significantly higher levels of hs-CRP, SII, and RCII compared with controls (all p < 0.001). In the multivariable logistic regression analysis, RCII demonstrated an independent association with CSX (odds ratio 1.095, 95% confidence interval 1.060-1.131; p < 0.001). ROC curve analysis showed that RCII provided moderate but significant discrimination for CSX (area under the curve [AUC] 0.765, 95% CI 0.695-0.795). Pairwise comparisons confirmed that RCII had a significantly higher AUC than RC, hs-CRP, or SII individually. Conclusions: Higher RCII levels appear to be significantly associated with the clinical diagnosis of CSX. By integrating atherogenic remnant cholesterol burden and systemic inflammation, RCII may serve as a valuable composite biomarker for identifying residual inflammatory lipid risk. Rather than acting as a definitive diagnostic tool, these findings warrant further validation in large-scale prospective cohort studies.