Systemic Inflammation and Malnutrition Define a High-Risk Phenotype in Chronic Limb-Threatening Ischemia.

<b>Objective:</b> This study aimed to evaluate the prognostic value of inflammatory biomarkers and their interaction with nutritional status for risk stratification in patients with chronic limb-threatening ischemia (CTLI). <b>Material and Methods:</b> This was a prospective, single-center observational cohort study including adult patients admitted with CTLI. Clinical outcomes included major amputation, major vascular events (MACE), and all-cause mortality. Multivariate logistic regression analyses were performed using two separate models, one including IL-6 and another including hsCRP, to avoid potential collinearity between biomarkers. Model discrimination was assessed using ROC curves, and Kaplan-Meier survival analyses were performed. <b>Results:</b> A total of 170 patients were included (mean age 72 ± 12 years; 74% male), with high cardiovascular risk and frequent malnutrition and sarcopenia. At 6 months, major amputations occurred in 35.3% of patients, MACE in 35%, and all-cause mortality in 32%. In multivariable analyses, malnutrition was the strongest independent predictor of the composite endpoint. IL-6 (OR 2.90, 95% CI 1.45-5.81; <i>p</i> = 0.003) and hsCRP values above the median (OR 4.22, 95% CI 2.04-8.72; <i>p</i> < 0.001) remained independently associated with adverse outcomes, together with age > 72 years. The hsCRP-based model showed slightly higher discriminative performance than the IL-6 model (AUC = 0.77 VS AUC = 0.75). Kaplan-Meier analyses demonstrated significantly reduced event-free survival in patients with elevated inflammatory biomarkers. <b>Conclusions</b>: In CTLI, systemic inflammation and nutritional status jointly identify patients at extremely high risk of adverse outcomes. hsCRP, given its availability, may be a practical tool for clinical risk stratification.