Out of Whack

Circadian misalignment helps explain higher cardiovascular risk in shift workers

Image: Jacek Kita/iStock

Image: Jacek Kita/iStock

Shift workers frequently undergo circadian misalignment, a disruption of the body clock, caused by inverted wake and sleep cycles.

Although shift work, which requires workers to be awake when the brain’s circadian clock is expecting sleep, is known to be a risk factor for hypertension, inflammation and cardiovascular disease, little is known about the specific impact of circadian misalignment on cardiovascular disease risk in humans.

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A new study led by Harvard Medical School researchers at Brigham and Women’s Hospital may help explain why shift work increases the risk for cardiovascular disease.

The researchers found that short-term circadian misalignment, resulting from a rapid 12-hour inversion of the sleep/wake and fasting/feeding cycle that is typical in shift workers, leads to adverse cardiovascular and inflammatory consequences in healthy adults.

The findings are published Feb. 8 in PNAS.

“We were able to determine, under highly controlled laboratory conditions, the independent impact of circadian misalignment on cardiovascular disease risk factors—blood pressure and inflammatory markers,” said neuroscientist Frank Scheer, HMS associate professor of medicine at Brigham and Women’s and the senior author of the study.

“Our findings provide evidence for circadian misalignment as an underlying mechanism to explain why shift work is a risk factor for elevated blood pressure, hypertension, inflammation and cardiovascular disease,” he said.

The researchers measured blood pressure and inflammatory markers, which are strongly predictive of cardiovascular disease risk, and compared circadian misalignment with circadian alignment in 14 healthy subjects during two eight-day stays in the Brigham and Women’s sleep laboratory. One stay included circadian misalignment, and the other maintained circadian alignment.

Controlling for other contributing factors, such as work stressors, dietary habits and physical activity, as well as family, financial, genetic, health and social factors, the researchers found that circadian misalignment increased 24-hour systolic blood pressure and diastolic blood pressure; reduced blood pressure dipping, usually associated with sleep; decreased measures of autonomic nervous system activity, which controls bodily functions such as blood pressure; and increased inflammatory markers.

During one of the eight-day periods, the participants maintained normal sleep patterns. During the other test period, the subjects maintained a normal sleep period for the first three nights and were then shifted by 12 hours to an 11 a.m. to 7 p.m. sleep period.

“Our study evaluated ‘short-term’ circadian misalignment in healthy adults,” said first author Christopher Morris, associate physiologist in the Division of Sleep and Circadian Disorders at Brigham and Women’s. “The effect of circadian misalignments on cardiovascular function and inflammatory markers may be different in people with hypertension, and in shift workers.”

“Further research is needed to investigate countermeasures for the adverse cardiovascular effects of circadian misalignment, such as the timing of eating and exercise,” he said.

This study was supported by the National Institutes of Health (grants R01 HL094806, R01 HL118601, R01 DK099512, R00 HL102241, P01AG009975 and UL1RR025758) and the National Space Biomedical Research Institute (through NASA grant NCC 9-58).

Adapted from a Brigham and Women’s news release.