[Statins: therapeutic cascade of their effects]

Concept of sequence and time of appearance of various effects of statins is presented. Apart from hypolipidemic action due to inhibition of HMG CoA reductase activity statins exert multiple pleiotropic effects. Combination of these effects makes statins a unique instrument for solution of global tasks of prevention and treatment of atherosclerosis and its consequences (ischemic heart disease etc.). Manifestations of various pleiotropic effects of statins appear after different time intervals and in most cases are not related to suppression of cholesterol synthesis in the body. First 3-4 months (first level of the statin cascade) are characterized mainly by activity of pleiotropic properties aimed at restoration of endothelial function. These properties are responsible for enhanced eNOS expression, antiischemic, antithrombotic and antiatherogenic effects. During same period of time stabilization of unstable atheromas takes place. Manifestations of second level of the cascade of statin action appear after 2 years of treatment. They are represented by retardation of progression and even partial regression of atheromatosis of coronary and peripheral arteries. Third level is signified by achievement of strategic aims of therapy with statins (in 4-5 years) -- lowering of total and cardiac mortality, reduction of number of cardiac complications. Forth level of the cascade is represented by beneficial influences on nonatherogenic cardiological phenomena and comprise hypotensive, antiarrhythmic and cardiotonic effects. And finally some other important properties of statins constitute the fifth level of the therapeutic cascade. These properties are responsible for effects directed at noncardiac pathology (prevention of diabetes, dementia, including dementia associated with Alzheimer's disease, fractures). Immunodepression, ability to reduce saturation of bile with cholesterol belong to this group of effects.