Abstract
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, which might progress due to inflammation. This systematic review assessed the association of specific inflammatory biomarkers with morbidity and mortality in PAD patients. MEDLINE and EMBASE databases were systematically searched for studies assessing evidence between inflammatory biomarkers and morbidity and mortality risks in PAD patients. Results were reported as Hazard Ratios (HR), Odds Ratios (OR), or mean and standard deviation. Effect estimates for high-sensitivity C-reactive protein (hs-CRP) were pooled using a random-effects model and respectively displayed in forest plots. The study reviewed a total of 7024 records, out of which 26 studies were included for qualitative synthesis and nine for quantitative synthesis. A total of 4673 patients were analyzed in the meta-analysis. Elevated baseline IL-6 levels were consistently linked to poor outcomes, including loss of patency and composite endpoints, such as major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Tumor necrosis factor-α (TNF-α) and related biomarkers were associated with adverse outcomes like mortality and patency loss. Elevated IL-1 levels predicted worse cardiovascular outcomes and IL-1 receptor antagonist levels indicated recurrence or new lesions post-surgery. Hs-CRP was statistically significantly associated with all-cause mortality and MALE in the pooled analysis. The study highlights the ability of inflammatory biomarkers to predict clinical outcomes in PAD patients. The strength of these associations varies based on the specific biomarker and clinical context.
