IBMS BoneKEy | Perspective
Vascular calcification: A perspective on an imminent disease epidemic
Dwight A Towler
DOI:10.1138/20080298
Abstract
Westernized societies are on the verge of an epidemic of vascular calcification. Aging, metabolic syndrome and type II diabetes (T2DM), and chronic kidney disease increasingly characterize our populace – and promote valve and arterial calcium deposition. Epidemiology, histopathology, and pathobiology define at least 5 distinct and prevalent types of vascular calcification: calcific aortic stenosis (CAS), medial artery calcification, atherosclerotic intimal calcification, vascular calcification of chronic kidney disease, and calcific uremic arteriolopathy. The clinical impact of these 5 mineralization disorders is highly significant. For example, 2%-3% of individuals ≥ 65 years old have CAS, and require surgery to prevent precocious death and to improve quality of life. Valve calcium load is the best predictor of clinical progression; if unaddressed, interactions between longevity and T2DM prevalence will increase the future incidence of CAS. Reduced vascular compliance – arising in part from arterial calcification – impairs macrovascular Windkessel function and normal tissue perfusion; thus, medial artery calcification of T2DM conveys a 3-fold increased risk for lower extremity amputation, a debilitating and costly outcome. Once considered a passive process only, data from laboratories world-wide have now established that vascular calcification is an actively regulated type of biomineralization. As in bone, morphogenetic, mechanical, metabolic, endocrine, and inflammatory signals control vascular mineral deposition. Molecular and cellular mechanisms familiar to bone biologists are activated with disease initiation and progression. This Perspective briefly recounts the pathobiology of vascular calcification and conveys the urgent need to pursue the basic, translational, and outcomes-based research necessary to address an imminent epidemic of abnormal vascular calcium metabolism.
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