Lipid Lowering and Plaque Regression

T reatments designed to favorably affect the clinical impact of coronary artery disease (CAD) have two fundamental goals. The first goal is to diminish the symptomatic limitations imposed by arterial obstructive disease, in which the vessel's capacity to fully meet the varying oxygen demands of the myocardium is impaired. Vascular capacity may be abnormal because of a fixed flow-limiting coronary stenosis,12 abnormal epicardial vessel tone,3,4 intermittent arterial vasospasm,5 microvascular dysfunction,6'7 or inadequate collateral development. A variety of medical approaches are now used to palliate symptoms by favorably altering the oxygen supply-demand imbalance. Alternatively, this first goal of symptom relief may be achieved through more direct structural and/or physiological changes that favorably affect the diminished vascular flow capacity. These include relaxation of excess vasoconstrictor tone, development of collateral vessels, or reduction in the severity of flow-limiting stenosis ("regression"). The latter has been questioned as a possible mechanism for symptom relief. In this report, the data supporting the occurrence of regression and its mechanisms are reviewed, together with the role of lipid lowering in achieving it. The second fundamental goal of therapy in CAD is to prevent the anticipated worsening of symptoms or progression to a clinical event such as sudden death, myocardial infarction, or worsening angina requiring bypass surgery or angioplasty. In this report, the mechanisms of gradually progressive arterial obstruction are discussed together with the mechanisms of plaque disruption resulting in abrupt worsening of arterial obstruction. Data presented indicate a linkage between lipid lowering and stabilization of the plaque structure. This set of observations supports the hypothesis that lipid-lowering therapy prevents clinical events by selectively depleting of lipids, or "regressing," a relatively small subgroup of lipid-rich plaques that are predisposed to plaque fissuring, ulceration, and hemorrhage and that account for the great majority of clinical events.