Nonrheumatic Calcific Aortic Stenosis: an Overview from Basic Science to Pharmacological Prevention §

Please cite this article in press as: Parolari A, et al. Nonrheumatic calcific aortic stenosis: an overview from basic science to pharmacological prevention. Summary Calcific aortic stenosis is a frequent degenerative disease, which represents the most common indication for adult heart valve surgery, and carries substantial morbidity and mortality. Due to ageing populations in western countries, its prevalence is expected to increase in the coming years. Basic science studies suggest that the progression of aortic valve stenosis involves an active biological process, and that the molecular mechanisms promoting this development resemble those of atherosclerosis, as stenotic aortic valves are characterized by complex histological lesions, consisting of activated inflammatory cells, lipid deposits, extracellular matrix remodeling, calcific nodules, and bone tissue. This has led to the hypothesis that drugs effective in delaying atherosclerosis progression (e.g. statins) might also be able to prevent the progression of calcific aortic valve stenosis. The potential benefit of statin therapy, however, is controversial and widely debated, as recent randomized studies done in patients with moderate to severe degrees of aortic stenosis failed to consistently show substantial benefits of this class of drugs. This review focuses on various aspects of molecular mechanisms underlying calcific aortic valve stenosis and discusses recent experimental and clinical studies that address the potential benefit of targeted drug therapies. Taken together, current evidence suggests that the progression of calcific aortic stenosis is a multi-factorial process; the multitude of the mechanisms potentially involved in aortic valve stenosis indicates that drug therapy aimed at reducing its progression is necessarily multi-factorial and should address the earliest stages of the disease, as it is now evident that pharmacological treatment administered in more advanced stages of the disease may be ineffective or, at best, much less effective.