Heart health: 16 genes tied to higher heart attack risk in women

• Researchers looked into the genetics behind Spontaneous Coronary Artery Dissection (SCAD), a condition that can be life threatening.
• Spontaneous Coronary Artery Dissection can lead to heart attacks, particularly in women under the age of 60.
• The condition can occur with no warning and often affects people who are otherwise healthy, making it difficult to detect early.
• The scientists conducted a genome-wide association meta-analysis and found 16 gene variants associated with an increased risk of developing the condition.

Researchers from the United Kingdom, France, Australia, Canada, and United States collaborated to study if there are genetic factors that contribute to someone developing Spontaneous Coronary Artery Dissection (SCAD). Since SCAD can be life-threatening and difficult to predict, scientists want to learn more about what causes it.

The study, published in Nature Genetics, identified 16 genes, including genes involved in artery integrity and blood clotting that are associated with an increased risk.

This research into the genetic factors of SCAD has the potential to lead to preventive strategies.

Conducting a meta-analysis

The researchers performed a meta-analysis of eight independent studies to search for genetic factors associated with SCAD.

They compared a group of 1,917 people with SCAD to a control group of 9,292 people. The researchers included patients with SCAD that had similar clinical characteristics and met diagnostic criteria.

To search for genes associated with SCAD, the researchers performed a particular type of analysis called genome wide association study. The researchers looked at genes likely involved in some of the issues that can contribute to SCAD. They analyzed genes likely “regulated in vascular smooth muscle cells,” as well as genes involved in blood coagulation.

This is significant because blood coagulation, or blood clotting, prevents an injured vessel from bleeding profusely. An injured blood vessel can lead to a heart attack in SCAD.

The research team also investigated the causal relationships between cardiovascular disease risk factors (predicted based on genetics) and SCAD and coronary artery disease (CAD).

16 genes associated with SCAD

In their combined genetic analysis of the eight studies, comparing the control group to the SCAD group, the team found 16 genes that factor into SCAD.

They found that lower expression of the tissue factor gene F3, involved in blood coagulation, is associated with a higher risk of SCAD.

The scientists found a “novel association signal with SCAD” with the gene THSD4 that is associated with fibrillin, which regulates heart functioning.

The team also found causal genes involved in maintaining arterial wall integrity and function, including genes HTRA1, TIMP3, ADAMTSL4, LRP1, COL4A1, and COL4A2.

“This research confirms that there are multiple genes involved in determining the risk of a person having a SCAD,” says lead study author Dr. David Adlam, associate professor of acute and interventional cardiology at the University of Leicester in England.

“These genes give us the first key insight into the underlying causes of this disease and provide new lines of inquiry, which we hope will guide future new treatment approaches.”
— Dr. David Adlam

The team also found that some of the genetic variants in SCAD and coronary artery disease (CAD) are connected but have an opposite impact.

“Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms,” write the authors.

What is Spontaneous Coronary Artery Dissection?

SCAD happens when a tear spontaneously occurs within the artery wall and causes blood to get trapped. According to the American Heart Association, “This narrows or blocks the artery and can cause a heart attack because blood flow can’t reach the heart muscle.”

While typical coronary artery disease often affects people with certain risk factors (such as a family history of it or people with high cholesterol levels), SCAD can occur without warning and in people who are healthy.

SCAD mostly affects young women and is the cause of 25% of acute coronary syndrome cases in women under 50. Additionally, SCAD can cause heart attacks in pregnant women.

While symptoms of SCAD can vary, they may resemble symptoms of a heart attack and may include chest pain, shortness of breath, profuse sweating, and dizziness.

Experts weigh in

Dr. Shahid Rahman, an interventional cardiologist at Memorial Hermann in Houston, spoke with Medical News Today after reviewing the study.

“This study was able to provide insight on this understudied disease process (SCAD). A genetic basis for SCAD appears to be suggested, and thus, any woman with a family history of SCAD, or who has had SCAD prior, should have regular follow-ups,” said Dr. Rahman.

Dr. Rahman also emphasized the importance of women talking with their doctors about their risks for SCAD before becoming pregnant.

“SCAD is an uncommon cause of myocardial infarction but a leading cause of myocardial infarction in young women, especially around the time of childbirth. Women should be aware of this risk and not delay seeking care if they have symptoms of a heart attack (such as chest pain).”
— Dr. Shahid Rahman

Dr. Meesha Dogan, co-founder, CEO, and board member of Cardio Diagnostics, also spoke with MNT.

“While SCAD is a less common cause of heart attacks compared to coronary artery disease, its unexpected occurrence in younger women without any prior suspicion can be alarming,” said Dr. Dogan.

Dr. Dogan believes that the study findings could help with preventive strategies in the future.

“The findings from this study on the genetic basis of SCAD could potentially help women and their providers obtain insights on risk ahead of time, lead to new prevention and treatment strategies, and drive greater advocacy for research funding, clinical attention, and public health initiatives focused on women’s heart health,” said Dr. Dogan.

Reducing heart disease risk

Sometimes people are genetically at a higher risk for heart disease. For example, they may have a family history of heart disease or conditions such as a heart arrhythmia.

In these situations, it is important for people to be proactive with their health to prevent heart disease, which can often be life threatening.

One thing people with this concern can do is lead a healthy lifestyle. That includes eating a heart-healthy diet, avoiding smoking, and participating in regular physical activity (particularly aerobic exercise).

Having annual check-ups with a doctor is important, too, so people can get their cholesterol and blood pressure checked. If these are elevated, then the doctor can offer suggestions or medications and monitor their condition regularly.

It is also important for people with a higher risk of heart disease to manage their stress levels, as chronic stress can lead to high blood pressure, which can cause heart attacks and strokes. Focusing on meditation, talk therapy, or yoga are some ways to help with this.

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