The impact on cardiovascular events achieved by statin therapy seems to be mostly attributable to their cholesterol-
lowering effect, with a highly debated contribution of the lipid-independent pleiotropic effects. Statins have an established
role in the treatment of hypercholesterolemia with a clear and robust reduction in cardiovascular morbidity and
mortality. Nevertheless, the pathophysiologic effect of statins on inflammatory responses and local atherosclerotic plaque
morphology in humans remains a matter of debate. In particular, the question remains whether statin-induced alterations
in plaque composition can be ascribed mainly to low density lipoprotein cholesterol (LDL-C) lowering or an antiinflammatory
pleiotropic effect, or both.
This review summarizes the available evidence of the effects of statins on carotid plaque cellular composition in clinical
settings, focusing on lipid-related and lipid-independent effects of statin therapy. A systematic review of the web online
databases was performed. Studies in humans evaluating the effect of statins on composition of carotid plaque removed at
endarterectomy were eligible for inclusion.
Data support the view that plaque composition even after a short-term lipid lowering therapy is significantly modulated by
the degree of LDL-C lowering. A contribution of LDL-C independent, anti-inflammatory mechanisms of statins on plaque
stability is only suggested by some of the studies. Actually, data strongly support the current guidelines based on progressively
lower LDL-C targets depending upon the cardiovascular risk of individual patients.