**4. Atherosclerosis and cholesterol hypothesis**

The hypothesis of cholesterol suggests that lipids play a major role in the development of atherosclerosis. The 4S trial (Scandinavian Simvastanin Survival Study) showed that while there was significant reduction in total cholesterol level, LDL cholesterol level, and decrease in major coronary events, HDL cholesterol level was elevated in simvastatin receiving group [4]. After 4S study, REVERSAL, ASTEROID, and SATURN studies revealed that parallel plaque regression was observed with aggressive lipid-lowering therapy and reduction in major cardiovascular events was achieved. These similar studies have proven the relationship between hyperlipidemia and atherosclerosis [2, 5, 6].

Statins reduce macrophages and extracellular lipid accumulation in atherosclerotic plaque region and increase the content of collagen in the extracellular matrix which result in intimal calcification. Statins also stabilize inflammation and coagulation cascade after plaque rupture.
