Researchers discover that the body clock may influence morning peak in adverse cardiovascular events

(Press-News.org) Contact information: Jessica Maki
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Brigham and Women's Hospital
Researchers discover that the body clock may influence morning peak in adverse cardiovascular events The internal body clock may contribute to the morning peak in heart attacks and ischemic strokes Boston – Cardiovascular disease is the number one cause of death in both men and women, and most adverse cardiovascular events tend to happen in the morning. In new findings published in the November issue of Blood, researchers from Brigham and Women's Hospital (BWH) and Oregon Health & Science University have discovered that the internal body clock may contribute to the morning peak in heart attacks and ischemic strokes.

"Our findings suggest that the circadian system, or the internal body clock, contributes to the increased risk for cardiovascular events in the morning," said Frank A.J.L. Scheer, PhD, director of the Medical Chronobiology Program at BWH and corresponding author of this study.

The researchers studied 12 healthy adult volunteers in the intensive physiological monitoring laboratories at BWH. Participants were assessed throughout a two-week laboratory protocol designed to desynchronize daily behavioral and environmental rhythms from internal circadian rhythms.

Researchers specifically evaluated the role of Plasminogen activator inhibitor-1 (PAI-1), which inhibits the breakdown of blood clots and is thus a risk factor for blood clotting, one of the major contributors to heart attack and ischemic stroke. The researchers sought out to test whether this morning peak in PAI-1 is caused by the internal circadian system or by behaviors that typically occur in the morning, such as altered posture and physical activity. The researchers found a robust circadian rhythm in circulating PAI-1 with a peak corresponding to approximately 6:30 a.m. in a regular sleep/wake cycle.

"Our findings indicate that the human circadian system causes a morning peak in circulating levels of PAI-1, independent of any behavioral or environmental influences," explained Steven Shea, PhD, director of the Oregon Institute of Occupational Health Sciences and the co-author of this paper. "Indeed, the circadian system determined to a large extent the PAI-1 rhythm observed during a regular sleep/wake cycle. This morning peak in PAI-1 could help explain adverse cardiovascular events in vulnerable individuals."

The researchers added that these studies established the circadian control of PAI-1 in healthy individuals and that future research is required to test whether this rhythm is amplified, blunted or shifted in vulnerable individuals, such as with obesity, diabetes, or cardiovascular disease.

### This research was supported by NIH-R01-HL76409 to SAS and Harvard Catalyst Clinical Research Center to FAJLS; NIH-UL1-RR025758, Harvard Clinical and Translation Science Center; NIH-P30-HL101299 in support of FAJLS; and NIH-K24-HL076446 in support of SAS.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.