Body clock link to sudden death

Scientists have discovered a link between natural circadian rhythms and sudden cardiac death.

Ventricular arrhythmia, or abnormal heart rhythms, are the most common cause of sudden cardiac death.

It's already known that they most frequently occur in the morning after waking, followed by a smaller peak in the evening hours.

According to an article in the journal Nature, a protein known as kr├╝ppel-like factor 15 (Klf15) links the natural circadian rhythms to the heart's electrical activity and heartbeat.

Klf15 is a known controller of the body's circadian rhythms, or body clock, whose levels fluctuate during the day, but Klf15 is often lacking in patients with heart failure. Meanwhile, an excess of the protein can cause electrocardiography (ECG) changes as seen in patients with Brugada Syndrome, a genetic heart rhythm disorder.

A team of US scientists looked at the effect of this protein on the heart rhythm of mice which had been genetically altered to produce excess amounts of Klf15, or none at all.

Both types of genetically altered mice had an increased the risk of deadly arrhythmias, compared with their normal counterparts.
"It is the first example of a molecular mechanism for the circadian change in susceptibility to cardiac arrhythmias," said study author Dr Xander Wehrens from Baylor College of Medicine in Houston, Texas.

"If there was too much Klf15 or none, the mice were at risk for developing the arrhythmias," he added.

The authors think that Klf15 affects the levels of another protein (KChIP2) which influences the electrical activity of heart muscle cells. This in turn could lead to heart rhythm disturbances, increasing the risk of sudden death.

The findings may also help in the development of new medicines to regulate Klf15 levels, particularly at certain times of the day when sudden death is more common, the authors said.

Study co-author Professor Mukesh Jain of Case Western Reserve University in Ohio said:"This is the first time a definitive link between circadian rhythms and sudden cardiac death has been established.

"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."


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