Impact of the human circadian system, exercise, and their interaction on cardiovascular function

The risk of adverse cardiovascular events peaks in the morning (approximate to 9:00 AM) with a secondary peak in the evening (approximate to 8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough approximate to 85% of mean, peaking at a circadian phase corresponding to approximate to 9:00 AM) and in circulating catecholamines (epinephrine, approximate to 70%; norepinephrine, approximate to 35%, peaking during the biological day). At approximate to 8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks:at approximate to noon and approximate to 11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at approximate to 9:00 AM and peaks in catecholamine reactivity at approximate to 9:00 AM and approximate to 9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.