Calcific Aortic Stenosis

Abstract

Abstract-Calcific aortic stenosis is the most common indication for surgical valve replacement in the United States. For years this disease has been described as a passive degenerative process during which serum calcium attaches to the valve surface and binds to the leaflet to form nodules. Therefore, surgical treatment of this disease has been the approach toward relieving outflow obstruction in these patients. Recent studies demonstrate an association between atherosclerosis and its risk factors for aortic valve disease. In 2008, there are increasing number of epidemiology and experimental studies to provide evidence that this disease process is not a passive phenomena. There is an active cellular process that develops within the valve leaflet and causes a regulated bone formation to develop. If the atherosclerotic hypothesis is important in the initiation of aortic stenosis, then treatments used in slowing the progression of atherosclerosis may be effective in patients with aortic valve disease. This review will discuss the pathogenesis and the potential for medical therapy in the management of patients with calcific aortic stenosis by examining the lessons provided from the experimental research. Key Words: valvular heart disease Ⅲ lipids Ⅲ pathophysiology atherosclerosis Ⅲ experimental models C alcific aortic stenosis is the most common indication for surgical valve replacement in the United States. 1 With the decline of acute rheumatic fever, calcific aortic stenosis has become the most common indication for valvular disease in the United States. Landmark epidemiological studies identified risk factors for the aortic valve which are similar to those of vascular atherosclerosis, such as smoking, male gender, hypertension, elevated cholesterol levels, and renal failure. [2][3][4] For years this disease process was thought to be attributable to the build-up of nodules along the valve surface to induce a mechanical stenosis in the valve. 5 Furthermore, surgical therapy for severe symptomatic aortic stenosis is currently the only treatment option in 2008 as defined in a landmark study from 1968. 5 This study also defined the classic triad of symptoms which include chest pain, shortness of breath, and lightheadedness. This research also demonstrated that the life expectancy of this patient population is reduced significantly, if patients do not have surgical valve replacement at the onset of symptoms. 5 Currently, it is a Class I indication for surgical valve replacement according to the American Heart Association and American College of Cardiology guidelines for valvular heart disease. 6 Over the past decade, there are a growing number of studies evaluating human disease tissues to define the cellular pathways important in this calcific aortic stenosis. This review will bring together the basic science and clinical science to develop a unified approach toward treating this disease. Aortic Valve CalcificationThe presence of calcification in the aortic valve is responsible for valve stenosis. Recent descriptive ...

Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease

“…Soft tissue calcification has been thought to be an entirely passive physicochemical process that is driven by serum levels of calcium and phosphate (O'Neill, 2007). Recent evidence increasingly suggests that this process involves cellular events, extracellular matrix composition, and other regulators of mineral metabolism, supporting a notion that CAVD is also an active course (Rajamannan, 2009;Yetkin and Waltenberger, 2009). Parathyroid hormone and 25-OHD are the most important regulators of calcium and phosphate metabolism, particularly for both bone formation and osteoblast activity.…”

“…Thus, surgical valve replacement and transcatheter aortic valve implantation are considered to be the only established therapy for patients with severe symptomatic AVS. Recently, growing evidence demonstrates that CAVD also develops through an inflammatory process similar to atherosclerosis that can be possibly targeted with medical treatment (Rajamannan, 2009;Yetkin and Waltenberger, 2009). Unfortunately, several randomized, placebo-control trials have failed to show that use of statins retards the progression of AVS (Parolari et al, 2011;Teo et al, 2011), suggesting that despite similar risk factors and downstream mediators, atherogenesis is not pivotal to the pathogenesis of CAVD.…”

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis

“…Early in the development of AS, active microscopic areas of calcification are seen colocalizing in areas of lipoprotein accumulation and infiltration of inflammatory cells [1,[3][4][5]. As the disease progresses, there is active bone formation involving cells with chondrocytic and ⁄ or osteoblastic characteristics capable of phenotypic differentiation and spontaneous calcification [3,6].…”

Pathophysiologic Mechanisms of Age – Related Aortic Valve Calcification

“…As incidence of acute rheumatic fever has declined, calcific aortic stenosis (CAS) has become the most common indication for surgical valve replacement in the United States (Fig. 2) [3]. Regarding population aged>65 years, its incidence is 2-7% [2].…”

“…Interestingly, aortic sclerosis (aortic valve calcification without hemodynamic compromise) is present in more than 25% of patients older than age 65 years [5]. Recent studies provide evidence that atherosclerosis and CAS share common features in relation to risk factors and histopathologic lesions [3]. Moreover, histopathologic evidence suggests that early lesions in CAS are not just a result secondary to aging, but an active cellular process.…”