Positron emission tomography and the changing paradigm in coronary artery disease

While lowering cholesterol with HMG-CoA reductase inhibitors appears to affect little if at all the severity of coronary artery stenoses, at least over the time periods studied, it markedly reduces cardiac morbidity and mortality. The beneficial effects of these agents have therefore been attributed to plaque stabilization and improved coronary vasomotor function. This then has shifted the emphasis of detection and treatment of coronary artery disease from the assessment of structural to functional alterations. With PET based measurements of regional myocardial blood flow, the function of the coronary circulation in humans can now be evaluated noninvasively. Multiple studies with this approach reported diminished hyperemic flow responses in patients without hemodynamically significant coronary stenoses but with coronary risk factors. Furthermore, lipid lowering with HMG-CoA reductase inhibitors was consistently found to enhance hyperemic flow responses to pharmacologic vasodilation as an index of the integrated function of the human coronary circulation. Recent studies with PET based measurements of blood flow target specifically the endothelial dependent coronary vasomotion and revealed abnormalities in chronic smokers and in postmenopausal women, that is, after estrogen withdrawal. Conversely, L-arginine supplementation in smokers and hormone replacement therapy in postmenopausal women without coronary risk factors normalized endothelial dependent flow responses. These observations suggest that endothelial dysfunction as a pivotal event early in the development of coronary atherosclerosis can be identified noninvasively with PET which will also be useful for measuring responses to lifestyle modification and pharmacologic treatment for improving coronary circulatory function.