Circadian rhythm can influence a heart attack

By Dr. Ananya Mandal, MDFeb 23 2012

Researchers have found that a biological clock can influence a heart attack. The risk of “sudden cardiac death” peaks in the morning and rises again in the evening as shown in lab animals.

The inner workings of the body go through a daily routine known as a circadian rhythm, which keeps the body in sync with its surroundings. Jet lag is the result of the body getting out of sync. As the chemistry of the body changes throughout the day, this can impact on health. US researchers say they have identified, in mice, how the time can affect the risk of sudden cardiac death, which kills 100,000 people a year in the UK.

A study published in the journal Nature suggests that levels of a protein which controls the heart's rhythm fluctuates through the day. The protein called kruppel-like factor 15 (Klf15), which was controlled by the body clock and whose levels in the body went up and down during the day was detected. Genetically modified mice which produced too much Klf15 and those which produced none at all both had an increased risk of developing deadly disturbances in cardiac rhythm.

“It is the first example of a molecular mechanism for the circadian change in susceptibility to cardiac arrhythmias,” said Xander Wehrens of Baylor College School of Medicine in Houston, Texas. “If there was too much Klf15 or none, the mice were at risk for developing the arrhythmia.”

Prof Darwin Jeyaraj, from the Case Western Reserve University School of Medicine, said, “Our study identifies a hitherto unknown mechanism for electrical instability in the heart. It provides insights into day and night variation in arrhythmia susceptibility that has been known for many years.”

Klf15 is only one step in a complex molecular cascade, the researchers believe. It controls another protein, KChIP2, which affects potassium-generated electrical current that flows though heart muscle cells called cardiac myocytes. When levels of KChIP2 fluctuate, this causes electrical instability in the myocytes. As a result, the heart muscle's action becomes impaired and it takes longer (or conversely, less time) to empty the ventricle - the heart's pumping chamber. The heart loses the regularity of the beat and labors to pump blood efficiently.

There are important differences in the way that human and mouse hearts work, so it is unknown whether the same mechanism exists in people. Fellow researcher Prof Mukesh Jain said, “We are just scratching the surface. It might be that, with further study, assessment of circadian disruption in patients with cardiovascular disease might lead us to innovative approaches to diagnosis, prognosis, and treatment.”

Dr Michael Hastings, from the Medical Research Council's Laboratory of Molecular Biology, told the BBC, “It's a great paper, it gives a beautiful molecular mechanism which explains a phenomenon that's been kicking around for a long time.” He said all that was needed now was to target the “most vulnerable stage” such as slow-release blood pressure drugs, which become active first thing in the morning when the risk is highest.