In their interesting study, Suessenbacher et al reported reduced peripheral arterial tone in shift workers compared to nonshift workers, and this endothelial dysfunction could explain, at least in part, the increased cardiovascular risk in shift workers.

We would like to emphasize the possible pivotal role played by circadian rhythm disturbances. Previous studies have reported the existence of a circadian variation in basal vascular tone, due at least partly to increased α-sympathetic vasoconstrictor activity, and a morning increase of ischemia-induced coronary vascular resistance, which could contribute to the higher incidence of acute cardiac ischemic events at this time. Morning hours, in fact, represent the highest risk period for the onset of various cardiovascular events, such as myocardial infarction, sudden cardiac death, stroke, aortic aneurysm rupture, or dissection.

Classically, this pattern has been explained by fluctuations in extracardiac factors (i.e., sympathetic activity, vascular tone, sheer stress, and prothrombotic factors), but a recent intriguing line of research is examining the possibility that a molecular mechanism intrinsic to cardiomyocytes, such as the circadian clock, may contribute to cardiovascular disease. Circadian clocks can be defined as a transcriptionally based molecular mechanism, composed of positive and negative feedback loops, with a free-running period of approximately 24 hours. The principal circadian clock, or master clock, located in the suprachiasmatic nucleus, is entrained by light and is supposed to entrain peripheral clocks via neurohumoral modulation. Circadian clocks have been identified within almost all mammalian cell types, including cardiomyocytes, vascular smooth muscle cells, and endothelial cells, and circadian clock genes are essential for cardiovascular health. In fact, bmal1-knockout mice or clock mutant mice exhibited impairment of normal protective endothelial responses to vascular injury with intensified pathologic remodeling and predisposition to vascular thrombosis. Anticipation is the principal role of cellular biologic clocks, because the capacity to know the time of day represents critical information and a selective advantage. In fact, such a capacity enables organisms to anticipate daily environmental changes and temporally modify behavioral and physiologic functions appropriately, and the disruption of such rhythms may lead also to negative consequences. It is possible that a dyssynchrony between different cell types (e.g., cardiomyocytes, endothelial cells) could contribute to the pathogenesis of cardiovascular diseases, exacerbating preexisting or underlying cardiovascular conditions. Mice exposed to a disrupting 20-hour instead of 24-hour circadian rhythm showed a complete disruption of their sleep and waking behaviors and a marked progression of their cardiovascular disease (e.g., myocyte hypertrophy and fibrosis). Because the suprachiasmatic nucleus central clock is entrained by light, it is possible that alterations in light and dark cycle conditions may have consequences on biologic clocks, both central and peripheral. The changes in human daily patterns, secondary to the availability of artificial light, and the related possible disruption of circadian rhythms (and sleep and waking patterns), may be responsible of cardiovascular disease onset or progression in shift workers.

In conclusion, the results of this study by Suessenbacher et al deserve high consideration. It is possible that shift or nonshift activity should be considered when designing or interpreting studies of cardiovascular risk. At present, we have no conclusive data on whether or what amount of circadian rhythm disruption or sleep deprivation may be harmful for the cardiovascular system. However, we can agree with the statement that harmony between our biology and our environment is vital to good health.