Aortic Stenosis: Epidemiology and Pathogenesis

Aortic (valve) stenosis (AS) is an obstruction to blood ejection from the left ventricle (LV) due to a fixed or dynamic stenosis located in the aortic valve, either over (supravalvular) or below it (subvalvular) [1]. AS is the most frequent form and accounts for the majority of congenital forms and for all of the acquired forms. AS is also the most frequent valvular heart disease in Western countries. In the Cardiovascular Health Study (5201 men and women over the age of 65), 26% of study participants had a thickening of the valve or calcification without significant obstruction, with a slight predominance of the disorder noted in men; 2% of all patients had frank AS [2]. Prevalence of aortic sclerosis increases with age: 20% in patients aged 65–75, 35% in those aged 75–85, and 48% in patients older than 85, while frank AS for the same age groups was 1–3%, 2–4%, and 4%, respectively. The most common cause is degenerative calcific valvular disease, with an incidence of 2–7% in the population over the age of 65 [3]. The mechanism by which a tricuspid aortic valve becomes stenotic is judged to be similar to that of atherosclerosis, as the initial plaque of AS is like that in coronary artery disease [4]. Risk factors commonly associated with coronary artery disease—including age, male gender, hyperlipidemia, evidence of active inflammation—seem to play a role in the development of AS, and both diseases are often present in the same individual [5–7]. Though debated, the use of statins is thought to slow the early progression of AS, while it is ineffective in the late course of the disease [8–11]. The initial and further evolution of AS usually occurs in the sixth, seventh, and eighth decades of life. The characteristic morphological appearance of the calcific AS consists in the presence of fibrous and calcific tissue on thickened cusps, preventing valve opening during outflow (Fig. 14.1). Calcific AS is determined mainly by solid calcium deposits in the valve cusps rather than fusion of the commissures, and calcification starts in the fibrous part of the valve. The stratified microscopic structure is usually preserved. The process of calcific aortic valve degeneration is secondary to inflammatory and proliferative changes, with accumulation of lipids, hyperactivity of angiotensin-converting enzymes, and infiltration of macrophages and T lymphocytes [12, 13]. These lesions involve the typical early chronic inflammatory cell infiltrates (macrophages and T lymphocytes) as the first ultrastructural changes, and lipid deposits and fibrotic thickening with collagen and elastin [14, 15].