Women's heart attacks differ from men's, this gene may be why - study

Heart disease kills more people worldwide than any other disease, but it often goes undiagnosed in women, who are more likely to die of it than men. This gene may be why.

 Heart attack (Illustrative). (photo credit: PIXABAY)
Heart attack (Illustrative).
(photo credit: PIXABAY)

Heart attacks and heart disease in women are often overlooked by medical workers, and while the reasons behind this have often been debated, a newly identified gene may have the answer, according to a new study.

The findings, published in the peer-reviewed academic journal American Heart Journal Plus: Cardiology Research and Practice, sheds light on a possible genetic cause behind why women's heart disease and heart attacks are often undetected. 

This important study could hopefully improve standard medical practices in a way that will allow a significant gender equality gap in health care to be bridged.

Background

Heart disease –  specifically ischemic coronary heart disease (IHD), which is a collective designation for coronary artery disease (CAD) and related conditions of acute coronary syndrome (ACS) and myocardial infraction (MI) – remains one of the biggest global health dangers. Compared to every other disease on Earth, it is heart disease that kills the most people worldwide.

 3D medical animation still showing reduced blood flow in preventing the heart muscle from receiving enough oxygen. (credit: Wikimedia Commons) 3D medical animation still showing reduced blood flow in preventing the heart muscle from receiving enough oxygen. (credit: Wikimedia Commons)

The disease is present among both sex, males and females. However, there are some notable differences.

Overall, men suffer from heart attacks and IHD-induced deaths at earlier ages than women. But IHD mortality rates among women sharply spike ahead of men after age 65. After contracting MI, over a third (35%) of women have another heart attack within just six years – which is double what occurs in men.

Further, in the US, women are 2-3 times more likely to die of heart disease than men, even when taking into account the same levels of care and overall risk factors

But despite this, women are 50% more likely to be misdiagnosed or undiagnosed by doctors as having a heart attack. 

This is just the start, however, as further differences in the data also exist among different races and ethnicities, with many women of color being at an even greater risk.

So why does this happen?

On a technical level, we already know.

Firstly, diagnostic tests for hearts did not originally account for differences between bodies, especially between sexes. 

Secondly, males and females tend to experience different symptoms when it comes to heart disease. With this in mind, many current tests and symptom profiles for IHD don't often reflect these differences. 

 Heart attack (Illustrative) (credit: FLICKR) Heart attack (Illustrative) (credit: FLICKR)

It is this, according to study author Jennifer Dungan, an associate professor at the University of Florida College of Nursing, that has led to women being more likely to report out-of-the-ordinary heart disease symptoms, more likely to have treatment delayed and even have heart attacks completely undiagnosed.

The reason these differences happen is thought to be a genetic variation, but how genes vary between sexes in relation to IHD symptoms isn't fully understood.

But while this sort of intrinsic genetic variation that differs between sexes, known as sexual dimorphism, is the likely culprit and has been supported in principle by prior studies, the exact genetic factor that causes differences in the outcomes of IHD-related events such as heart attacks has stalled.

But a breakthrough may have been made.

The study

Dugan and her team worked to find genes associated with the survivorship of CAD. This was done thanks to data gathered from the Duke Catheterization Genetics (CATHGEN) biorepository.

And through this complex study of analyzing data from both sexes and the varying genes, the researchers highlighted a number of possible candidate genes. But overall, Dungan and her team think they found the likely culprit: RAP1GAP2.

This gene is known to have encoded a certain protein that in turn activates another protein in platelets, which are colorless cells that help with blood clots

Essentially, this gene helps manage platelet activity, which in turn means it influences blood clots. 

Now, blood clotting is important and serves a vital role in the function of our bodies. However, that doesn't mean it doesn't pose certain risks. If for whatever reason, too many platelets activate in response to a clot, this could cause the flow of blood and oxygen to the heart to be blocked. 

This, in turn, is what can cause a heart attack.

And an overactive gene – specifically one that can influence platelets like RAP1GAP2 – would be able to cause this.

Now, this isn't the first time Dugan's team has looked at RAP1GAP2. However, with men, this gene wasn't linked to poor heart disease outcomes in males. But she thinks it may work differently with women.

Of course, there are limits to this study. For instance, it didn't adequately cover differences between ethnicities, Dungan very much believes that genetics may play a role in the ethnic and racial disparities in heart disease outcomes among women. Overall, more research will be needed to better study RAP1GAP2 and other genes.

Luckily, that research seems very much to be on the way, with Dungan having received a two-year grant from the National Institutes of Health's National Institute on Aging to find which RAP1GAP2 gene markers correlate with heart disease, symptoms and deaths in women of different racial and ethnic groups.

“At the end of the study, if RAP1GAP2 gene markers accurately reflect women’s heart symptoms and predict their likelihood of a future heart attack, stroke or death, then those gene markers could help us be more confident in their diagnosis and future prognosis.”

Jennifer Dungan

“At the end of the study, if RAP1GAP2 gene markers accurately reflect women’s heart symptoms and predict their likelihood of a future heart attack, stroke or death, then those gene markers could help us be more confident in their diagnosis and future prognosis,” she said in a statement. 

“Having more accurate biomarkers for women would save lives and improve health equity for all women.”