Matching pathophysiology and evidence-based medicine for optimal management of ischemic heart disease.

In recent years, our understanding of the pathophysiology of ischemic heart disease has evolved greatly. Atherosclerosis, traditionally considered a focal cholesterol storage disease, is now viewed as a widespread inflammatory process, responsible for the development, evolution and complications of arterial lesions. It is now recognized that most atherosclerotic lesions grow outward; thus, a substantial burden of atherosclerosis can exist in the absence of stenosis. Moreover, intravascular ultrasound and autopsy studies have indicated that vulnerable plaques are usually represented by mildly obstructive lesions. In the pathophysiology of ischemic heart disease, particular attention has been focused on endothelial and microvascular function. Structural or functional alterations of coronary microcirculation have been documented in several clinical conditions, such as stable and unstable angina. In this clinical setting, microvascular dysfunction acts not only as an independent risk marker, but can also contribute to the precipitation or maintenance of myocardial ischemia, even in the absence of coronary atherosclerosis. These observations challenge the traditional hemodynamic approach to the treatment of ischemic heart disease based on the degree of arterial stenosis. Isolated revascularization of a coronary artery can relieve angina and ischemia caused by a flow-limiting stenosis, but is often unable to protect against future atherothrombotic events or to modify the natural history of disease. Recent randomized trials have confirmed these pathophysiological findings, revealing no advantage of a routine over a selective invasive strategy in the treatment of stable angina. Global management of ischemic heart disease should aim to combine primary and secondary prevention measures directed at long-term risk reduction, with optimal revascularization therapies.