Primary and secondary prevention trials with statins, as well as with antiplatelet, clearly
demonstrated that these drugs are able to reduce cardiovascular events. Even if the principal
mechanism of action of statins is to lower cholesterol, other effects, the so-called
pleiotropic effects, have been considered as adjunctive properties potentially accounting for
the anti-atherosclerotic effect of statins.
Inhibition of oxidative stress may be considered an intriguing pleiotropic effect in view of
the fact that oxidative stress is thought to be a key event in the initiation and progression
of atherosclerotic disease. Reduction of several markers of oxidative stress including
isoprostanes, 8-hydroxydeoxyguanosine (8-OHdG), and nitrotyrosine have been observed after
statin treatment. NADPH oxidase is among the most important sources of reactive oxygen
species involved in atherosclerotic disease. The investigators developed an ELISA to evaluate
serum levels of soluble-gp91phox, the catalytic core of phagocyte NADPH oxidase. Recently the
investigators showed that statins (30 days treatment) exert an antioxidant effect via
inhibition of soluble gp91phox expression.
The exact mechanism by which atorvastatin reduces NADPH oxidase, however, is unclear. Recent
study showed that statin treatment inhibits leukocyte ROCK activity, a protein kinase
implicated in the activation of NADPH oxidase, with a mechanism that seems to be independent
from lowering cholesterol. To further study the mechanism(s) implicate in gp91phox
downregulation by statin the investigators planned the present study in patients with high
risk of vascular events such as hypercholesterolemic and Type 2 Diabetes mellitus patients.
In addition the investigators want to evaluate the synergistic role of atorvastatin with