Medial Arterial Calcification

Peripheral arterial disease (PAD) refers to occlusion or narrowing of the upper and lower extremity arteries, causing insufficient blood flow to the limbs. Patients with PAD often present with symptoms, such as claudication, ischemic rest pain, ischemic ulcerations, and limb loss. These patients are also highly predisposed to cardiovascular morbidity and mortality. PAD is underdiagnosed, and little is known about its pathogenesis, although it has generally been considered as secondary to atherosclerotic disease, which mainly affects lower limb vascularization. Indeed, the major treatment for PAD is based around revascularization therapies to bypass/alleviate stenosis and occlusions. However, recent literature has uncovered a role for vascular calcification not only as a major factor limiting treatment but also as a potential driver of PAD. Vascular calcification is a pathology characteristic of aging but is accelerated in chronic kidney disease (CKD), diabetes mellitus, and atherosclerosis. Although localized intimal calcification is a feature of atherosclerosis, extensive, widely disseminated medial calcification, often visible on plain X-ray, is a common presenting feature of lower extremity PAD. The prevalence of medial arterial calcification (MAC) in PAD is imprecisely reported because of the methods by which diagnosis is reached, as well as asymptomatic cases that are often unreported. Currently, the gold standard by which PAD is diagnosed is by noninvasive means via the ankle brachial pressure index and toe brachial pressure index measurements and subsequently confirmed by duplex scan and angiography which can be extended to computed tomography and magnetic resonance imaging. Accurate diagnosis can be challenging because of preexisting CKD or diabetes mellitus. For example, the effectiveness of the ankle brachial pressure index ratio in diagnosis of PAD for diabetic and CKD patients on dialysis is reduced when there is presence of MAC and peripheral neuropathy. Moreover, endovascular treatment strategies are often ineffective in patients with PAD and MAC, despite advances in recanalization techniques. Thus, there is much incentive for a paradigm shift and closer examination of the pathology of MAC in PAD to develop better therapies.