Cardiac arrhythmia in women: estrogen to blame?

The Importance of Ion Channels in Heart Rhythm

During life, the heart beats nearly 2.5 billion times. Each beat is triggered by an electrical impulse which will cause the heart muscle to contract, all in a very coordinated movement. The electrical activity of the heart is regulated by small pores, ion channels, which cross cell membranes and regulate the flow of electrically charged ions into and out of the cell. Some ion channels act as an accelerator and others as a brake.

It is their role to regulate, coordinate the release of blood into the ventricles, when they are full, and the pumping. When these ion channels and signals are disrupted and unable to function properly, it results in arrhythmia.

Atrial fibrillation: why are women more affected?

Atrial fibrillation is an anomaly of the heart rhythm, linked to a dysfunction of the cardiac electrical system sitting at the level of the atria. It is characterized by an irregularly beating heart. While this arrhythmia can affect anyone, women are still more likely to be affected – and more severely.

Many studies are therefore underway to understand this phenomenon. It is in this context that Swedish scientists assert today in the journal Science Advances that estrogen may influence the risk of heart disease, particularly with regard to arrhythmia.

A study conducted on frog eggs at the moment

The researchers therefore wanted to explore the influence of estrogen on the heart. To do this, they used cellular experimental systems to study the effect of estrogen on ion channels. The team focused on an ion channel called Kv7.1/KCNE1. This channel is most commonly mutated in people with long QT syndrome (or LQTS), a condition that can lead to arrhythmia.

However, as the study was preclinical, no human patients were involved. Instead, the scientists inserted human ion channels into frog eggs, which do not contain these proteins. They then introduced estradiol – a highly active form of estrogen – into the eggs to see what was happening to the ion channels. The researchers reported that estrogen had a negative impact on ion channel function, while other sex hormones had no such effect.

A deleterious effect in women with long QT syndrome

The researchers also discovered exactly which parts of the ion channel were affected by estrogen. They studied ion channel mutations found in families with inherited arrhythmia syndromes. Some mutations resulted in elevated estrogen sensitivity, while others resulted in complete loss of estrogen sensitivity through the ion channel.

“We show that certain inherited mutations that reduce ion channel function appear to contribute to elevated estrogen sensitivity, so there could be two risk factors that interact, particularly in women with these mutations. We believe our study provides good reason to examine this more closely in patients.”says Sara Liin.

While estrogen has many positive effects on female heart function, in women with an increased hereditary risk of LQTS, estrogen could potentially be a risk factor. LQTS is relatively rare, affecting around 1 in 2,500 people.

However, it is important to mention that this is only a preclinical study, which means that the conclusions are yet to be confirmed. As such, “future work will be needed to assess whether the study results translate to a clinical situation and, if so, for what types of arrhythmias this would be relevant”noted Liin.

Estrogens also have beneficial effects in heart health

Estrogens are already known to have other beneficial effects on heart health and function. “Scientific evidence, accumulated over the past decades, has shown that the most active form of natural human estrogen, estradiol, has properties potentially beneficial to the heart and circulatory system of the body.”said Dr. Jinkyung Kim, professor of cardiology at the University of California in the journal Healthline.

For example, studies indicate that estrogen helps lower “bad” LDL cholesterol, protects against cardiovascular cell death, and controls inflammation. However, understanding how and why this happens remains a mystery to this day. “Women tend to be at lower risk for cardiovascular disease in general until they go through menopause, [après quoi] estrogen levels decrease”, did he declare. However the expert also clarifies that providing additional estrogen after menopause has not proven helpful.

For the scientist, this means that it is not so much the production of estrogens that counts, as the way the body reacts to them.