Inflammation and the Development of Atherosclerosis -Effects of Lipid-Lowering Therapy

Atherosclerosis is a progressive disease causally associated with multiple cardiovascular risk factors, including dyslipidemia. Without effective intervention, atherosclerosis becomes evidenced clinically as coronary artery and cerebrovascular disease, both of which remain the leading causes of death worldwide. Multiple lines of investigation indicate a central role for inflammation in atherosclerotic plaque progression, vulnerability and thrombogenicity. Randomized clinical trials have documented the benefit of lipid-lowering therapy for both primary and secondary prevention of cardiovascular events. Statins, a class of drugs that lower cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have been shown to slow the progression of the atheroma and the frequency of associated clinical events to an extent that cannot be attributed solely to LDL reduction. The non-LDL or pleiotropic effects of statins are attributed to anti-inflammatory activity, enhanced endothelial function, and inhibition of oxidative stress. In this review, we discuss the role of inflammation in atherogenesis along with the effects of statins in slowing this process through LDL-dependent and -independent mechanisms.