Abstract
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss and mortality due to cardiovascular events. Currently CLI is mainly treated by surgical or endovascular revascularization, with few other treatments in routine clinical practice. There are a number of problems with current PAD management strategies, such as the difficulty in selecting the appropriate treatments for individual patients. Many patients undergo repeated attempts at revascularization surgery, but ultimately require an amputation. There is great interest in developing new methods to identify patients who are unlikely to benefit from revascularization and to improve management of patients unsuitable for surgery. Circulating biomarkers that predict the progression of PAD and the response to therapies could assist in the management of patients. This review provides an overview of the pathophysiology of PAD and examines the association between circulating biomarkers and PAD presence, severity and prognosis. While some currently identified circulating markers show promise, further larger studies focused on the clinical value of the biomarkers over existing risk predictors are needed.
Highlights
Narrowing or blockage of the arteries supplying blood to the lower limbs, usually termed peripheral artery disease (PAD), is principally caused by athero-thrombosis
It was reported for example that intramuscular injection of autologous bone marrow mononuclear cells resulted in a three-year amputation free rate of 60% with significant improvement in ischemic leg pain and walking distance in the therapeutic angiogenesis by cell transplantation (TACT) trial [41]
As the severity of the hypoxia increases, the microvascular adaptations are not able to compensate. All these changes lead to mitochondrial injury and free radical generation and subsequent muscle fibre damage, myofibre degeneration and fibrosis. These changes eventually result in decreased oxygen supply and increased metabolic demands leading to conditions such as rest pain, chronic non-healing wounds and gangrene, subsequently threatening the limb function and viability
Summary
Narrowing or blockage of the arteries supplying blood to the lower limbs, usually termed peripheral artery disease (PAD), is principally caused by athero-thrombosis. PAD is a leading cause of morbidity due to the associated functional decline and limb loss. Both asymptomatic and symptomatic PAD are significant predictors of cardiovascular disease (CVD) events and mortality [1]. Acute limb ischemia (ALI) occurs when there is a sudden interruption of blood flow to a limb typically due to an embolism or thrombosis [3]. ALI usually threatens limb viability more urgently than CLI possibly due to the absence of an established collateral blood supply to the limb
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