The Role of Circulating Biomarkers in Peripheral Arterial Disease

Abstract

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease

“…These results provide the grounds to postulate that NPT can be a novel biomarker and/or biological effector in PAD pathophysiology. Whether this candidate will improve the risk estimation associated with traditional PAD risk factors is still unclear and will need further evaluation, especially by inclusion of the biomarkers and clinical parameters described by Saenz-Pipaon et al [1].…”

“…Approximately 10-25% of people over 55 years of age and 40% of people aged over 70 years suffer from this disease. With a growing aging population, the prevalence of PAD is likely to increase even further [1]. Female gender is a risk factor for PAD with apparently higher rates in low-and middle-income countries, whereas in high-income countries, the male gender tends to be an independent risk factor for PAD [2].…”

“…There have been many attempts to investigate endothelial function including nitrooxidative stress and lipoprotein oxidation, apoptotic and inflammatory mediators, etc. [1,3,4]. Endothelial inflammation stimulates the production of pro-inflammatory cytokines and adhesion molecules such as interleukin 6, adhesion molecules (MCP-1, ICAM-1, VCAM-1), and E-selectin.…”

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation

“…The activation of fibrinolysis is inhibited by plasminogen activator inhibitor type 1 (PAI-1) released from endothelium and platelets [26,29]. If the balance of fibrinolytic activators to their inhibitors is disturbed, this may result from the depletion of PAI-1 [45] and in patients with PAD, previous studies have demonstrated and increased fibrinolysis and fibrinolysis inhibition [46][47][48].…”

“…Finally, it should be noted that inflammation is a key mediator of the atherosclerotic process and likely contributes to the limb manifestations of PAD. Thus, inflammation markers such as C-reactive protein, interleukin-6 or thromboxane are also increased in PAD patients [47,49,50].…”