“Statins may have beneficial cardiovascular effects in addition to cholesterol lowering. These findings suggest that statins may be useful in non cardiovascular conditions or in conditions where cholesterol is not elevated.”

HMG-CoA reductase inhibitors, or statins, are widely used lipid-lowering agents, which are recommended for the treatment of cardiovascular diseases. However, they appear to be effective in reducing cardiovascular events regardless of serum cholesterol levels. Our paper describes potential mechanisms, explaining some of the cholesterol-independent or "pleiotropic" effects of statins.

One important finding was that inhibition of HMG-CoA reductase by statins does not only lower serum cholesterol, but also inhibits the production of intermediates of the cholesterol biosynthetic pathway. These isoprenoid intermediates are important for the post- translational modification of signaling molecules, such as the Rho GTPases, which may contribute to cardiovascular pathophysiology. Modification of these proteins, therefore, may contribute to some of the benefits of statin therapy beyond cholesterol reduction.

Statins may have beneficial cardiovascular effects in addition to cholesterol lowering. These findings suggest that statins may be useful in non-cardiovascular conditions or in conditions where cholesterol is not elevated.

We were interested in how statins could improve endothelial function and be effective in stroke prevention. We found that statins increase the expression and activity of a key enzyme that regulates endothelial function—endothelial nitric oxide synthase—through a cholesterol-independent mechanism. Many investigators, at that time, doubted the significance of our findings because most, if not all, of the effects of statins were ascribed to cholesterol lowering.

Because statins are one of the most widely prescribed drugs and many of them are becoming generic, our research could have immense socioeconomic implications.

One of the main questions confronting many heathcare institutions and industry, is whether the use of statins should extend to lower-risk populations or to other health conditions that do not involve elevation of serum cholesterol levels, especially if these patients are expected to receive life-long therapy.