THERAPEUTIC IMPLICATIONS OF THE EPIDEMIOLOGY AND TIMING OF MYOCARDIAL-INFARCTION AND OTHER CARDIOVASCULAR-DISEASES

Cardiovascular diseases (CVD) account for almost 50% of the 2 million deaths annually in the United States. Coronary heart disease (CHD) (ie , myocardial infarction, sudden death) account for the largest proport ion (32%) of this mortality. Over the last 3 decades both CVD and age- adjusted coronary death rates have fallen dramatically. However, crude CVD (and CHD) incidence is actually increasing, almost exclusively as a function of rising CVD incidence amongst older Americans. Populatio n groups at highest for premature CVD complications include African-Am ericans, diabetics, men, smokers, and those with high levels of single risk factors (ie, stage III hypertension). Individuals with multiple CVD risk factors as well as those with manifestations of blood pressur e (BP)-related target-organ damage (TOD) tie, left ventricular hypertr ophy, hypercreatinemia) are at an inordinately high risk for clinical events. CVD events do not randomly occur throughout the 24-h time peri od. The peak incidence of myocardial infarction (IV11), thrombotic str oke, sudden cardiac death, and transient myocardial ischemia is betwee n 6 am and 12 noon. During the morning hours coinciding with the peak incidence of CVD events, coronary vasomotor tone, plasma catecholamine s, and platelet aggregability are at their highest levels while corona ry blood flow and plasma fibrinolytic activity are at their lowest lev els of the day. Moreover, BP rapidly rises from its nocturnal nadir du ring the early morning hours. Prevention of pressure-related CVD event s in hypertensive patients over the long term can be best accomplished by controlling BP throughout the 24 h time period with drugs that do not adversely impact (or favorably affect) other metabolic, neurohormo nal, and hemostatic parameters. BP control (minimally to <140/90 mm Hg ) may be particularly important in the early morning hours since eleva ted BP and/or rapidly rising BP is a plausible biological trigger for the aforementioned CVD events. One effective strategy for achieving th is goal is to utilize antihypertensive drugs with long therapeutic hal f-lives. Such agents will provide smooth whole-day BP control and also will minimize the loss of BP control during time period(s) between mi ssed medication doses in the setting of therapeutic non-compliance. Pr actitioners should give due consideration to nocturnal administration of antihypertensive drugs prescribed once-daily as a means of achievin g more effective morning BP control.