Advances in Lipid-Lowering Therapy in Atherosclerosis

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Abstract
The treatment of atherosclerosis using lipid-lowering drugs has evolved markedly over the past decade. It has been driven by the results and implications of major clinical trials. There has been a paradigm shift in the last decade from stable coronary lesions of high-grade stenosis to unstable plaques of low-grade stenosis. These vulnerable culprit lesions are characterized by a large lipid core, rich in foam cells with a thin fibrous cap, rich in activated macrophages and inflammatory cells, and poor in smooth muscle cells1,2. The majority of myocardial infarctions arise from these plaques. Whereas stable, high-grade lesions allow for collateral circulation networks to form, culprit lesions are prone to rupture, hemorrhage and cause thrombus formation. There has also been renewed interest in the important contribution of endothelial dysfunction to impair myocardial perfusion in coronary artery disease (CAD)3. An acetylcholine infusion in normal arteries induces an endothelial-derived, nitric oxide-mediated vasodilation. In the presence of cardiovascular risk factors (i.e., hypercholesterolemia, smoking, hypertension, diabetes)4 or CAD, intraarterial acetylcholine induces a vasoconstriction which is inhibited by L-arginine analogues such as L-NMMA (N ω-Nitroso-Mono-Methyl-Arginine). More attention is being given to the inflammatory component of atherosclerosis5, which is assessed by plasma measurement of inflammatory markers such as C-reactive protein (CRP)6, IL-67,8, or serum amyloid-A protein (SAA)9. Methods have been developed to measure local changes in heat produced by the inflammatory reaction over atherosclerotic plaques. Using a highly sensitive special thermography catheter, Stefanadis et al.10have shown a significant increase in thermal heterogeneity of human atherosclerotic plaques studied by intravascular ultrasound (IVUS) in arteries from patients with unstable angina or myocardial infarction, as compared to those of controls or of subjects with stable plaques. They observed a correlation between plasma levels of CRP and increase in heat differences between plaque areas and normal adjacent areas.

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