Current Prognostic Biomarkers for Peripheral Arterial Disease: A Comprehensive Systematic Review of the Literature

Background: Peripheral arterial disease (PAD) is a chronic atherosclerotic disease characterized by atheromatous plaque buildup within arteries of the lower limbs. It can lead to claudication, skin ulcerations, and, in severe cases, chronic limb-threatening ischemia, requiring amputation. There are several plasma protein biomarkers that have been suggested as prognostic markers for adverse events, including major adverse cardiovascular and limb events. However, the clinical benefit and ability to clinically adapt these biomarkers remains uncertain due to inconsistent findings possibly related to heterogenous study designs and differences in methodology. Objectives: This review aims to evaluate the current literature on the prognostic value of plasma protein biomarkers for PAD, their predictive ability for PAD-related adverse outcomes, and their potential roles in guiding PAD management. Methods: To address these challenges, we conducted a systematic review of MEDLINE, Embase, and Cochrane CENTRAL libraries of the current literature (2010-2024). Results: We found 55 studies that evaluated the prognostic value of 44 distinct plasma proteins across various pathophysiological processes. These included markers of immunity and inflammation, markers of metabolism, cardiac biomarkers, markers of kidney function, growth factors and hormones, markers of coagulation and platelet function, extracellular matrix and tissue remodeling proteins, and transport proteins. This review summarizes the existing evidence for prognostic protein plasma biomarkers for PAD and their association with adverse events related to PAD. Conclusions: With this review, we hope to provide a comprehensive list of the prognostic markers and their value as prognostic biomarkers to guide clinical decision making in these patients.