Role of novel inflammatory indices in predicting major adverse cardiovascular events following revascularization in chronic limb-threatening ischemia

BACKGROUNDPeripheral artery disease (PAD) is a prevalent atherosclerotic condition leading to chronic limb-threatening ischemia (CLTI), which significantly increases the risks of limb loss and cardiovascular events.Despite advancements in revascularization techniques, long-term outcomes remain poor. AIMTo evaluate the association of pre-procedural inflammatory indices with major adverse cardiovascular events (MACE) following lower-limb revascularization in patients with CLTI, and to assess the predictive performance of clinical models incorporating Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Systemic Immune-Inflammation Response Index (SIIRI). METHODSA multicenter prospective observational study was conducted at two tertiary hospitals in Jordan, including 303 adults (≥ 18 years) with CLTI undergoing lower-limb revascularization between June and September 2024.Participants were followed for six months.Baseline demographic and clinical characteristics and pre-procedural inflammatory indices were obtained, and MACE was identified through follow-up and confirmed using medical records.Three multivariable logistic regression models were developed using the same clinical and laboratory covariates, with SII, SIRI, and SIIRI entered separately.The predictive performance of the SIRI-based model was assessed using receiver operating characteristic analysis and 1000 bootstrap resamples for internal validation. RESULTS / 48The mean age of participants was 63.6 ± 9.8 years, and 84.5% were male.Overall, MACE occurred in 22.4% of patients.The incidence of MACE increased across Wound, Ischemia, and foot Infection clinical stages, from 12.5% in the low-risk group to 17.7% in the moderate-risk group and 29.0% in the high-risk group (P = 0.038).Surgical revascularization was also more frequent among patients who developed MACE (30.5% vs 18.8%, P = 0.023).In multivariable analysis, SIRI was independently associated with MACE (odds ratio = 1.62, 95%CI: 1.156-2.279;P = 0.005).The SIRI-based model demonstrated strong discrimination, with an apparent area under the curve (AUC) of 0.937 (95%CI: 0.907-0.967),which remained robust after bootstrap internal validation, with an optimism-corrected AUC of 0.920.CONCLUSION SIRI was independently associated with MACE in patients with CLTI undergoing lower-limb revascularization and demonstrated strong discriminatory performance when incorporated into a multivariable clinical model.These findings suggest that SIRI may provide additional prognostic information beyond established clinical and laboratory characteristics and may have potential utility for cardiovascular risk stratification in this high-risk population.Further external validation is warranted before clinical implementation.