As the population ages and rheumatic fever declines, calcific (or degenerative) aortic stenosis has become the most frequently encountered valve lesion and is now the most common cardiac disease in developed nations after hypertension and coronary artery disease. Degeneration of a tricuspid aortic valve is most frequently seen in the elderly, though similar changes may be seen in younger subjects with a bicuspid valve. Degenerative pathology affecting the mitral valve is usually restricted to the annulus and subvalve apparatus with relative leaflet sparing and functional consquences are therefore less apparent.
Echocardiographic population studies demonstrate a prevalence of moderate aortic stenosis in 5% of the population over 75 years and severe aortic stenosis in 3%, half of these individuals being asymptomatic. A further 35-50% demonstrate aortic valve thickening or calcification with no obstruction to left ventricular outflow (so-called aortic sclerosis) which may ultimately progress to valvular stenosis.
The early lesion of aortic stenosis involves an active process with some similarities to atherosclerosis. Histological studies have demonstrated displacement of the subendothelial elastica by protein, infiltration by lipid, macrophages, foam cells and T lymphocytes, deposition of LDL-cholesterol and lipoprotein (a), high plasma leptin and tPA levels with circulating immune complexes, and osteopontin expression with mature lamellar bone formation. Consistent with these observations, risk factors for degenerative aortic stenosis (such as hypertension, smoking and hyperlipidaemia) replicate those for coronary artery disease, and aortic sclerosis is independently associated with cardiovascular events, including myocardial infarction.[1]
Progression of the degree of aortic stenosis varies markedly. Overall, the average annual rate of increase in aortic jet velocity is 0.3 m/s/year with an increase in mean aortic pressure gradient of 7mmHg/year and a fall in valve area of 0.1cm2/year.[2] Factors predicting the rate of haemodynamic progression in individual patients remain unclear though the onset of symptoms heralds a rapid decline and the need for valve surgery.
To date, no medical therapy has been shown to influence this sequence of events. However, early clinical case control studies confirmed the relation between hyperlipidaemia and calcific aortic stenosis and a number of large retrospective studies have demonstrated reduced progression of aortic stenosis in patients with hyperlipidaemia receiving statin therapy. Furthermore, in an elegant rabbit model, hypercholesterolaemia induced a proliferative atherosclerotic process in the aortic valve associated with transformation to an osteoblast-like phenotype that was inhibited by atorvastatin.[3] These and other experimental data suggest that lipid lowering therapy may attenuate the pathophysiology of degenerative aortic stenosis and set the stage for currently enrolling large scale prospective clinical studies addressing this hypothesis.
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