Calcific Aortic Stenosis: Molecular and Cellular Mechanisms, Medical Treatment Alternatives

Aylin      Yildirir

Abstract

Calcific aortic stenosis (AS) is the most prevalent heart disease requiring valve replacement in the elderly. Mild to moderate stenosis is usually asymptomatic, however, when becomes severe it is associated with significant morbidity and mortality including left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction, congestive heart failure, angina, arrhythmias, and syncope. Aortic sclerosis, described as focal areas of increased echogenecity and thickening of aortic valve leaflets without restricted motility, is also associated with increased risk of death from cardiovascular causes. Regular follow-up is important to monitor hemodynamic progression of the aortic valve disease and the development of symptoms. Progression of AS shares many histological and immunochemical similarities with the process of atherosclerosis. They both are based on a chronic inflammatory process with infiltration and activation of leukocytes and a rise in systemic inflammatory markers. Epidemiological studies identified several risk factors for calcific aortic valve disease such as male sex, hypertension, smoking, and raised serum creatinin, cholesterol and calcium concentrations. Many of these are also the risk factors for atherosclerosis. Thus, AS is not just an age related degenerative process; its development is highly complex and shares a number of risk factors common for atherosclerosis. Lipids play an important role in the development and progression of AS, and there is growing evidence that cholesterol lowering may retard or prevent its progression. New research suggests that medical therapies may retard the progression of AS and reduce the need for surgery. This article will review the molecular and cellular basis of calcific AS, and mainly will focus on the potential for medical treatment alternatives.

Keywords: aortic sclerosis, calcific aortic stenosis, inflammation, treatment, statins