Ischemic heart disease is one of the most common cardiovascular diseases in developed countries, and angina pectoris is the most common condition involving tissue ischemia in which vasodilator drugs are used. The name angina pectoris denotes chest pain caused by accumulation of metabolites resulting from myocardial ischemia. The organic nitrates, eg, nitroglycerin, are the mainstay of therapy for the immediate relief of angina. Another group of vasodilators, the calcium channel blockers, is also important, especially for prophylaxis, and β blockers, which are not vasodilators, are also useful in prophylaxis. Several newer drugs are available, including drugs that alter myocardial ion currents and selective cardiac rate inhibitors.
By far, the most common cause of angina is atheromatous obstruction of the large coronary vessels (coronary artery disease, CAD). Inadequate blood flow in the presence of CAD results in effort angina, also known as classic angina. Diagnosis is usually made on the basis of the history and stress testing. However, * The author thanks Dr. Kanu Chatterjee, MB, FRCP, coauthor of this chapter in prior editions.
transient spasm of localized portions of these vessels, usually associated with underlying atheromas, can also cause significant myocardial ischemia and pain (vasospastic or variant angina). Vasospastic angina is also called Prinzmetal angina. Diagnosis is made on the basis of history.
The primary cause of angina pectoris is an imbalance between the oxygen requirement of the heart and the oxygen supplied to it via the coronary vessels. In effort angina, the imbalance occurs when the myocardial oxygen requirement increases, especially during exercise, and coronary blood flow does not increase proportionately. The resulting ischemia with accumulation of acidic metabolites usually leads to pain. In fact, coronary flow reserve is frequently impaired in such patients because of endothelial dysfunction, which results in impaired vasodilation. As a result, ischemia may even occur at a lower level of myocardial oxygen demand. In some individuals, the ischemia is not always accompanied by pain, resulting in “silent” or “ambulatory” ischemia. In variant angina, oxygen delivery decreases as a result of reversible coronary vasospasm, which also causes ischemia and pain.
Unstable angina, an acute coronary syndrome, is said to be present when episodes of angina occur at rest and there is an increase in the severity, frequency, and duration of chest pain in patients with previously stable angina. Unstable angina is caused by episodes of increased epicardial coronary artery resistance or small platelet clots occurring in the vicinity of an atherosclerotic plaque. In most cases, formation of labile partially occlusive thrombi at the site of a fissured or ulcerated plaque is the mechanism for reduction in flow. Inflammation may be a risk factor, because patients taking tumor necrosis factor inhibitors appear to have a lower risk of myocardial infarction. The course and the prognosis of unstable angina are variable, but this subset of acute coronary syndrome is associated with a high risk of myocardial infarction and death and is considered a medical emergency.
In theory, the imbalance between oxygen delivery and myocardial oxygen demand can be corrected by decreasing oxygen demand or by increasing delivery (by increasing coronary flow). In effort angina, oxygen demand can be reduced by decreasing cardiac work or, according to some studies, by shifting myocardial metabolism to substrates that require less oxygen per unit of adenosine triphosphate (ATP) produced. In variant angina, on the other hand, spasm of coronary vessels can be reversed by nitrate or calcium channel-blocking vasodilators. In unstable angina, vigorous measures are taken to achieve both—increase oxygen delivery (by medical or physical interventions) and decrease oxygen demand. Lipid-lowering drugs have become extremely important in the long-term treatment of atherosclerotic disease (see Chapter 35).
Determinants of Myocardial Oxygen Demand