Vascular Rhythms and Adaptation

The notion that the clinical manifestations of cardiovascular disease do not occur randomly throughout the course of the day has been accepted for >4 decades. Cohort studies documenting the time of chest pain onset demonstrated a morning predilection for the presentation of myocardial infarction.1 At the time, however, it was difficult to discern a morning rise in the incidence of myocardial infarction from the simple realization of longstanding nocturnal symptoms on awakening. With the advent of studies to limit myocardial infarct size, it became possible to accurately identify the myocardial infarction onset by the time-dependent increase in circulating creatine kinase levels, and these data confirmed a distribution roughly peaking in the hours between 6 am and noon.2 It soon became clear that other manifestations of cardiovascular disease, such as sudden cardiac death, stroke, and myocardial ischemia all exhibited similar time-of-day dependence, as reviewed by Muller.3 If one corrects for individual variations in the time of sleep cessation, the preponderance of events occur within the first 3 hours after awakening.4Article p 1510 The clustering of cardiovascular events to a specific time of day prompted considerable investigation into potential causes, with particular attention to phenomena that exhibit a preference for the morning hours. Arterial pressure was noted to have a rhythmic pattern characterized by a nadir at 3 am followed by a rise to peak pressures before noon. Because heart rate exhibits a similar pattern, one could suppose increased adrenergic tone might contribute to the morning clustering of cardiovascular disease events. Indeed, platelets are more susceptible to stimulation soon after awakening when circulating catecholamine levels are greatest.5 Several circulating factors such as cortisol and tissue-type plasminogen activator6 exhibit rhythmic variation that could, in principle, contribute to the onset of cardiovascular disease.In fact, most aspects …