OBJECTIVE: Emerging evidence has highlighted the clinical significance of residual inflammation risk (RIR) in cardiovascular and cerebrovascular diseases, with studies demonstrating its association with disease recurrence and poor prognosis. This study aimed to investigate the relationship between RIR and leukoaraiosis (LA) severity in patients with ischemic stroke. METHODS: In this observational cohort study, we classified patients into four groups based on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels: RIR (LDL-C <
2.6 mmol/L and hsCRP ≥ 2 mg/L), residual cholesterol risk (RCR) (LDL-C ≥ 2.6 mmol/L and hsCRP <
2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥ 2.6 mmol/L and hsCRP ≥ 2 mg/L) and neither risk (LDL-C <
2.6 mmol/L and hsCRP <
2 mg/L). LA presence and severity were assessed using magnetic resonance imaging (MRI) and graded according to the Fazekas scale. Ordinal logistic regression analyses were performed to evaluate the association between RIR and LA severity. RESULTS: Among 643 enrolled patients, 413 (64.2%) exhibited LA. The distribution of patients across RIR, RCR, RCIR, and neither risk groups was 28.9%, 19.8%, 20.4%, and 30.9%, respectively. Comparative analysis revealed that LA patients exhibited significantly higher age (P <
0.001), elevated BMI (P <
0.001), increased hypertension prevalence (P = 0.004), greater RIR proportion (P <
0.001), and higher smoking rates (P = 0.007) compared to non-LA counterparts. Ordinal logistic regression analysis demonstrated that RIR (OR 1.447, 95% CI 1.044-1.851, P <
0.001) was independently associated with the severity of LA after adjusting for multiple confounding variables. Subgroup analysis stratified by BMI further revealed that RIR (OR 2.994, 95% CI 2.259-3.730, P <
0.001) was significantly correlated with LA severity in patients with a BMI ≥ 25.0. CONCLUSIONS: These findings suggest that RIR may serve as an independent risk factor for LA in patients with ischemic stroke, particularly among those with a BMI ≥25.0.