Role of Inflammatory Biomarkers in Peripheral Arterial Disease: A Comprehensive Review of Prognostic and Therapeutic Implications

Background: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis characterized by chronic inflammation, endothelial dysfunction, and high residual risk of major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). This review aimed to summarize the prognostic role of inflammatory biomarkers in PAD and to discuss their therapeutic implications. Methods: A comprehensive narrative review was performed using PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library, focusing mainly on English-language studies published in recent years. Randomized trials, observational studies, systematic reviews, and meta-analyses evaluating inflammatory biomarkers and anti-inflammatory or vasculoprotective therapies in PAD were included. Results: Both classical and emerging inflammatory biomarkers were associated with PAD severity and adverse outcomes. C-reactive protein, fibrinogen, interleukins, tumor necrosis factor-α, myeloperoxidase, galectin-3, and growth differentiation factor-15 showed prognostic value for MACEs, MALEs, restenosis, amputation, and mortality. Among newer indices, the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, C-reactive protein-to-albumin ratio, and HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) score appear especially promising for risk stratification. Anti-inflammatory and pleiotropic therapies, including canakinumab, colchicine, statins, and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, may help reduce residual inflammatory risk. Conclusions: Inflammatory biomarkers may improve prognostic stratification and support more personalized management in PAD. Their integration into clinical practice could enhance limb preservation and long-term cardiovascular outcomes.