Pinpointing the cause of a mysterious heart disease affecting women

Researchers are exploring the genetics behind spontaneous coronary artery dissection.

Scientists from UNSW Sydney and the Victor Chang Cardiac Research Institute are working to shed light on the number one cause of heart attacks for women under the age of 50.

Spontaneous coronary artery dissection (SCAD) is a serious condition, mainly occurring in women, when a tear forms in one of the blood vessels of the heart. This can slow or block blood flow to the heart, leading to a heart attack.

Many people who develop SCAD are otherwise fit and healthy. Unlike traditional heart attacks, SCAD is not associated with a plaque build-up and a blockage of the arteries and until recently very little was known about this disease.

Now, a global collaboration including Conjoint Associate Professor Eleni Giannoulatou, Professor Robert Graham and Professor Jason Kovacic is working to pinpoint the cause of the disease and accelerate preventative treatments. These researchers lead cardiovascular research at the Victor Chang Cardiac Research Institute and UNSW Medicine & Health.

Identifying disease genes

The researchers are part of an international team that has just published research in Nature Genetics showing there are at least 16 genes associated with SCAD, with one gene called PHACTR1 thought to be a key driver.

By examining data from nearly 2000 patients, they discovered the genes involved in causing SCAD are mainly implicated in forming the matrix or scaffolding around the cells forming coronary arteries, as well as a gene involved in blood clotting. A deficiency in this clotting factor is thought to increase the likelihood of a spontaneous bleed into the artery wall, which reduces blood flow as it expands and leads to a SCAD heart attack. 

“We have performed the largest study to date aimed at understanding the genetic basis of SCAD, discovering multiple genetic regions that confer susceptibility to SCAD,” said A/Prof. Eleni Gionnulatou, who together with Prof. Graham and Prof. Kovacic led the Australian arm of the study.

“People who develop SCAD have subtle genetic changes that affect their blood vessels, putting them at a greater risk of a catastrophic tear or a spontaneous bleed involving the wall of the heart arteries. We now have a much clearer picture of the genetic risk of SCAD and how it is related to other cardiovascular diseases. Understanding these mechanisms should lead to new approaches to its management and treatment.”

Prof. Kovacic’s team is leading research into a gene called PHACTR1 which has been identified as having one of the strongest genetic associations with SCAD.

“This disease can not only be life-threatening but in some patients, it can reoccur and without warning.”

Leveraging global patient data

In addition, the researchers are the first research team outside of the USA to join the iSCAD Registry – the International SCAD registry - a global collaboration of researchers and patients investigating the features and pathophysiology of SCAD.

The iSCAD Registry contains the medical history of 1271 SCAD patients – who until now were all from the United States. Australian patients will soon be able to contribute their data to shed more light on this disease.

“Given we have both had heart attacks, you’d assume it was in our genetics. This is why it’s so vital we get answers so our daughters and nieces can be protected from this awful disease that hits without warning. I hope by being part of this registry I can make a difference.”