Calcific aortic stenosis: From bench to the bedside - Emerging clinical and cellular concepts

Calcific aortic stenosis is the third most common cause of aortic valve disease in developed countries. This condition increases in prevalence with advancing age, afflicting 2-3% of the population by the age of 65 years. The aging US population has led to a burgeoning number of valve replacements per year, which in turn costs the USA approximately $1 billion. The natural history, as described by Ross and Braunwald, shows that severe symptomatic aortic stenosis is associated with a life expectancy less than five years. Despite the high prevalence of this condition and the increasing morbidity and mortality, very little is known regarding the cellular basis of calcific aortic stenosis. Pathologically, progressive aortic stenosis may produce left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction, congestive heart failure, angina, arrhythmias, and syncope. Recent studies demonstrate an association between atherosclerosis and its risk factors and aortic valve disease. Although a unifying hypothesis for the role of atherosclerotic risk factors in the mechanism of vascular and aortic valve disease is emerging, progress in studying the cell biology of this disease has been limited by the paucity of experimental models available. A crucial question to ask is whether the same risk factors for vascular disease that initiate an atherosclerotic type injury in the coronary arteries initiate a similar injury in the aortic valve. If this is the case, it raises the possibility that the treatments used in slowing the progression of vascular atherosclerosis may be effective in patients with aortic sclerosis. Current management of calcific aortic valve disease focuses on defining patients with valvar disease and the development of symptoms to determine the timing of surgical valve replacement. This article will review the pathogenesis, natural history, evaluation, and management of patients with calcific aortic stenosis, taking into account emerging studies important in the understanding of the cellular mechanisms of calcific aortic stenosis. It will also address diagnostic studies for the detection and diagnosis of aortic valve calcium and summarise the current standard of treatment for calcific aortic stenosis and the potential for cholesterol lowering treatment to prevent progression or aortic valve calcification.