A complex chain of events leads to the development of end stage heart disease (fig 1). It starts with seemingly normal subjects with certain risk factors, such as high cholesterol, hypertension, and diabetes. Atherosclerosis is the final common pathway, affecting blood vessels in the brain, the coronary circulation, and the peripheral circulation. What determines the prognosis for these patients is not the presence of myocardial ischaemia or angina pectoris, but the development of myocardial infarction—a complex disease involving coronary thrombosis, plaque rupture and vasospasm. As cardiac remodelling occurs in heart failure, other mechanisms also come into play. Throughout these stages of heart failure development, the renin-angiotensin system plays an important role and provides a valuable target for therapeutic intervention.

Ten to 20 years ago the cardiovascular system was thought to be controlled by circulating factors such as the renin-angiotensin system and the sympathetic nervous system which were able to regulate the heart, the kidney, and the blood vessels. More recently, however, it has become evident that the blood vessel itself plays an important role that involves many factors including nitric oxide, which is a vasodilator, and endothelin, a vasoconstrictor. In fact, the endothelium is altered morphologically as a result of coronary artery disease.