The beta-receptor, atheroma and cardiovascular damage

In man a close interrelationship exists between hyperadrenergic states, myocardial ischemia, necrosis, infarction and sudden cardiac death. Persistent high catecholamine levels may also be associated with increased vascular endothelial turnover and permeability to calcium and lipoproteins, increased blood velocity, abnormal blood flow patterns and atheroma formation. There are thus good reasons to predict a cardiovascular protective effect of beta-blockers. Animal data indicate that in spite of apparently adverse plasma lipoprotein changes beta-blockers retard atheromatous plaque formation under conditions of high cholesterol diet with or without stress. A slow heart rate, as well as a reduction in calcium influx and inhibition of both esterification of arterial wall cholesterol (by ACAT) and endothelial permeability to lipoproteins, may be central to this process. Beta-blockers benefit a spectrum of conditions related to the atheromatous process and myocardial necrosis. These are silent ischemia; stable (including mixed), unstable and preinfarction angina; periinfarction events (including myocardial rupture and dissection of the ascending aorta); and myocardial necrosis associated with stress conditions such as head injuries and subarachnoid hemorrhage. In one study coronary deaths in hypertensive men, particularly in smokers, were significantly reduced by metoprolol (a beta 1-selective blocker) compared to a diuretic. In contrast in the MRC study of mild hypertension only nonsmoking men with mild to moderate hypertension who received a nonselective beta-blocker appeared to experience fewer myocardial infarctions. Recent clinical data showed that moderate-severe hypertensives who were optimally controlled by atenolol-based treatment over a 10-year period were less likely to die from myocardial infarction than those suboptimally controlled, irrespective of a rise in serum triglyceride levels. Thus the net effect of acute beta-blockade in hyperadrenergic states, including myocardial infarction, is to limit cardiovascular damage. Chronic beta-blockade inhibits atheroma formation (in animals) and beneficially modifies the incidence of stroke and myocardial infarction, which in man are the long-term consequences of hypertension.