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 proportion (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. Population groups at highest for premature CVD complications include African-Americans, 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 pressure (BP)-related target-organ damage (TOD) tie, left ventricular hypertrophy, hypercreatinemia) are at an inordinately high risk for clinical events. CVD events do not randomly occur throughout the 24-h time period. The peak incidence of myocardial infarction (IV11), thrombotic stroke, sudden cardiac death, and transient myocardial ischemia is between 6 am and 12 noon. During the morning hours coinciding with the peak incidence of CVD events, coronary vasomotor tone, plasma catecholamines, and platelet aggregability are at their highest levels while coronary blood flow and plasma fibrinolytic activity are at their lowest levels of the day. Moreover, BP rapidly rises from its nocturnal nadir during the early morning hours. Prevention of pressure-related CVD events 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, neurohormonal, and hemostatic parameters. BP control (minimally to <140/90 mm Hg) may be particularly important in the early morning hours since elevated BP and/or rapidly rising BP is a plausible biological trigger for the aforementioned CVD events. One effective strategy for achieving this goal is to utilize antihypertensive drugs with long therapeutic half-lives. Such agents will provide smooth whole-day BP control and also will minimize the loss of BP control during time period(s) between missed medication doses in the setting of therapeutic non-compliance. Practitioners should give due consideration to nocturnal administration of antihypertensive drugs prescribed once-daily as a means of achieving more effective morning BP control.