- Women are at greater risk of developing Long QT Syndrome, which causes irregular heartbeats (arrhythmia).
- New research indicates that estrogen may influence the heart’s ion channels.
- Ion channels are essential in signaling to the heart when to beat.
- More research is needed to understand how estrogen impacts ion channels and contributes to arrhythmia.
More than 60 million women in the United States are living with heart disease.
It is the leading cause of death of U.S. women, accounting for 1 in 5 female deaths in the nation every year.
Numerous factors contribute to the onset of heart disease, from genetics and other health concerns to stress and substance use disorders.
Now, scientists in Sweden say there is a way in which estrogen may influence heart disease risk — particularly concerning arrhythmia (irregular heartbeat).
The study findings, published in the journal Science Advances, revealed that estrogen impacts ion channels in the heart.
Ion channels are a protein that plays a crucial role in regulating the heartbeat.
The aim of the estrogen study
Women are more likely to be impacted — and more severely — by hereditary arrhythmic heart disease, so the researchers wanted to explore estrogen’s influence on the heart.
To do so, “we used cellular experimental systems to study the effect of estrogen on ion channels,” explained Sara Liin, PhD, an associate professor in the Department of Biomedical and Clinical Sciences at Linköping University in Sweden and the lead author of the study.
The team focused on an ion channel called Kv7.1/KCNE1. This channel is most often mutated in people with Long QT Syndrome (LQTS), a condition that can lead to arrhythmia.
However, as the study was pre-clinical, no human patients were involved. Instead, the scientists inserted human ion channels into frogs’ eggs, which do not have these proteins.
They then introduced estradiol — a highly active form of estrogen — into the eggs to see what happened to the ion channels.
The researchers reported that estrogen negatively impacted ion channel function, while other sex hormones did not have a similar effect.
The researchers also stated that some ion channel mutations in hereditary arrhythmia conditions led to high levels of estrogen sensitivity. Meanwhile, other mutations led to no sensitivity at all.
“I was surprised that inherited mutations in the ion channel showed such strikingly diverse responses to estrogen,” Liin told Healthline.
The importance of the findings
The researchers noted their results indicate that estrogen may enhance a person’s risk of developing certain arrhythmias.
The highlighted differences in estrogen sensitivity among ion channels were also significant.
“We envision that this [finding] could be of future importance for understanding whether inherited mutations in the ion channel could make carriers extra susceptible to the effect of estrogen,” said Liin.
Dr. JinKyung Kim, the director of women’s heart health at University of California Irvine Medical Center who was not affiliated with this study, agreed that further research on opposing estrogen sensitivities in ion channels is required.
“If validated by other [studies],” she told Healthline, “it only adds to the complexity of the hormone’s action on LQTS — because certain mutations in the ion channels would be highly active while others would not react to estrogen-targeted treatment.”
However, she said it’s important to consider that this research was only a pre-clinical study, meaning its findings are basic.
As such, “future work will be required to evaluate whether the findings of the study translate to a clinical situation, and, if so, which types of arrhythmias this would be of relevance for,” Liin noted.
What are ion channels?
Liin explained that “well-balanced ion channel function is critical for proper function of the heart.”
So what exactly do ion channels do? Essentially, they’re vital to the heart knowing when to beat.
“The heart is generally divided into plumbing and electricity,” Dr. Mark P. Abrams, a cardiac electrophysiologist at Optum, told Healthline.
“To function normally, both have to work together. The electricity of the heart is what tells it when and how to pump,” he said.
Electrical signals are sent to various chambers in the heart, telling them when to release blood into the ventricles, when they’re full up, and when to pump.
Ion channels allow cells to know when is the right time to send off the signals to beat, added Abrams.
“Each region of the heart has different amounts of various ion channels, so they can perform a highly specialized job of either initiating a signal or quickly passing it along to neighboring cells,” he said.
When these ion channels and signals are disrupted and unable to function correctly, it leads to arrhythmia.
The lowdown on LQTS
The recent study looked at the ion channels most often mutated in patients with the heart condition LQTS.
Affecting around 1 in every 2,500 people, LQTS is primarily inherited — although other factors can lead to its development.
For instance, revealed Dr. Rigved Tadwalkar, a cardiologist at Providence Saint John’s Health Center in California, “it can be acquired [through] electrolyte abnormalities or the use of certain medications, such as antipsychotics, antiemetics, and antibiotics.”
LQTS leads to a longer-than-normal “QT” interval on an electrocardiogram (ECG).
“The QT interval represents the amount of time it takes for the heart to re-polarize, or return to a resting state,” Tadwalkar told Healthline.
Duration is critical, he added, as with a “lengthier re-polarization phase, the heart is prone to dangerous heart rhythms from abnormal electrical impulses.”
Women generally have slightly longer QT intervals than men — and “this study points to a possible explanation as to why more women tend to have a certain LQTS,” noted Kim.
As a result, she said, this “may be a potential area of gender-specific treatment in the future for the LQTS that carries the specific mutation studied in the paper.”
The beat on arrhythmias
Various arrhythmias can affect the heart, either causing it to beat too fast, slowly, early, or erratically.
“Atrial arrhythmias, which arise in the heart’s top chambers, are by far the most common,” said Abrams.
“Atrial fibrillation, for example, is the most common arrhythmia,” he added. “It affects more than 2.5 million people in the United States.”
However, two different arrhythmias are commonly associated with LQTS: Torsades de Pointes (TdP) and ventricular fibrillation.
TdP causes the heart to beat too fast and is so-called due to the twisted ribbon-like pattern it creates on an ECG.
This arrhythmia impacts the heart’s ventricle muscles and “can cause loss of consciousness and lead to sudden cardiac arrest,” said Tadwalkar.
Ventricular fibrillation also affects the ventricle muscles and leads to “rapid and irregular electrical signals,” he added. This then causes the heart to contract in an ineffective, erratic, and random manner.
The outcomes are the same as those of TdP: loss of consciousness due to cardiac arrest.
Estrogen’s role in heart health
In addition to influencing ion channels, estrogen has other effects on heart health and function.
“Scientific evidence, cumulative from the last several decades, has shown that the most active form of the natural human estrogens, estradiol, has properties potentially beneficial to the heart and the body’s circulatory system,” said Kim.
For instance, studies indicate that estrogen aids in reducing “bad” LDL cholesterol, protects against cardiovascular cell death, and controls inflammation.
Despite such findings, Abrams said, “what’s less understood is how exactly all of this happens.”
“Women tend to have less risk of cardiovascular disease in general until they go through menopause, [after which] estrogen levels decline,” he said.
Abrams added, however, that providing supplemental estrogen after menopause has not been found to help.
“What this means is that it’s likely more than just having estrogen — but [also] rather how your body responds to [it],” he explained.
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