Evaluation of CHA2DS2-VA Score and Systemic Inflammatory Indexes in Patients with Nonvalvular Atrial Fibrillation: A Case–Control Study

<b>Background/Objectives:</b> Nonvalvular atrial fibrillation (NVAF) is a prevalent arrhythmia associated with elevated risks of stroke, systemic embolism, and mortality. Emerging evidence underscores the pivotal role of inflammation in NVAF pathogenesis. The CHA₂DS₂-VA score is currently the most powerful tool used in the management of patients with atrial fibrillation, and integrating novel inflammatory biomarkers-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)-into this score may enhance prognostic accuracy and guide personalized therapy. <b>Methods:</b> In this observational case-control study, a cohort of 330 NVAF patients and 201 controls, inflammatory and biochemical parameters were measured and compared, we employed multivariate logistic regression and ROC analyses to validate the discriminative power of novel inflammatory indexes and novel CHA₂DS₂-VA score, setting a new benchmark for biomarker integration in NVAF management. <b>Results:</b> Inflammatory indexes (NLR, PLR, SII, SIRI) were significantly higher in NVAF patients compared to controls (<i>p</i> < 0.001). Multivariate analysis identified NLR (OR = 4.02), PLR (OR = 1.04), SII (OR = 1.01), and SIRI (OR = 1.87) as independent NVAF risk markers. The CHA₂DS₂-VA score showed the strongest association with NVAF (OR = 5.55), and an optimal cutoff of ≥2 yielded 88.18% sensitivity and 74.63% specificity. <b>Conclusions:</b> Inflammatory markers NLR, PLR, SII, and SIRI, when assessed alongside the CHA₂DS₂-VA score, offer significant and complementary prognostic insight for patients with NVAF. These findings support the integration of inflammatory indexes into routine clinical risk assessment models to enhance early identification of high-risk individuals and inform personalized therapeutic strategies. Moreover, our findings provide a rationale for developing composite risk scores in future studies that integrate inflammatory biomarkers with the CHA₂DS₂-VA score (e.g., a CHA₂DS₂-VA-Inflammation Score). Further large-scale, longitudinal studies are warranted to validate these results and explore the benefits of inflammation-targeted interventions.