The associations between lower extremity peripheral arterial disease and immune-inflammatory biomarkers

BACKGROUND: Inflammation is recognized as a critical component in the pathogenesis of lower extremity peripheral arterial disease (PAD); however, the association between novel immune-inflammatory biomarkers - neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI) - and PAD risk in the general population remains unexplored. This study examines the associations between PAD and NLR, PLR, MLR, SII, SIRI, and AISI. METHODS: This study was a cross-sectional observational study based on the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. PAD was diagnosed using an Ankle-Brachial Index (ABI) ≤0.9. Finally, 6314 participants aged ≥40 years with complete information about ABI, blood cell counts, and other covariates were analyzed. Logistic regression analysis was used to examine the associations between inflammatory biomarkers and PAD. The predictive ability of inflammatory biomarkers for PAD was compared using receiver operating characteristic (ROC) curves. Subsequent mediation analysis examined the indirect effects of immune-inflammatory biomarkers on PAD via estimated glomerular filtration rate (eGFR). Finally, we performed propensity score matching (PSM) between PAD and non-PAD participants to verify the robustness of results. RESULTS: In 6314 US adults aged ≥40 years, 548 were diagnosed with PAD. Significant associations were observed between PAD and NLR (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 1.01-1.04), MLR (OR: 1.02; 95% CI: 1.00-1.04), SII (OR: 1.02; 95% CI: 1.00-1.03), SIRI (OR: 1.03; 95% CI: 1.01-1.04), and AISI (OR: 1.02; 95% CI: 1.01-1.03), according to logistic regression. PSM further validated the robustness of primary results. Mediation analysis revealed eGFR mediated portions of the relationship between PAD and NLR, MLR and SIRI (4.69%, 7.11% and 3.69% respectively). Additionally, ROC showed that SIRI exhibited a greater identification of PAD compared with other immune-inflammatory biomarkers. CONCLUSIONS: NLR, MLR, SII, SIRI, and AISI demonstrated independent associations with PAD risk, with SIRI showing a stronger association with PAD.