Identifying the cause of mysterious heart disease in women

Researchers are investigating the genetics of spontaneous coronary artery dissection.


SCAD (spontaneous coronary artery dissection) is a relatively unknown cause of myocardial infarction. It is a dangerous disorder that primarily affects women in which a tear forms in one of the heart’s blood channels, resulting in a heart attack. It is unknown how much SCAD differs genetically from other cardiovascular disorders, such as atherosclerotic coronary artery disease (CAD).

UNSW Sydney researchers and the Victor Chang Cardiac Research Institute work together to shed insight on the leading cause of heart attacks in women under 50.

Many SCAD patients are generally fit and healthy. Unlike classic heart attacks, SCAD doesn’t come with plaque buildup and artery obstruction. Until recently, little was known about this condition.

A global effort led by Conjoint Associate Professor Eleni Giannoulatou, Professor Robert Graham, and Professor Jason Kovacic aims to identify the disease’s source and speed up preventive treatments.

They published their findings in Nature Genetics, showing that at least 16 genes are linked to SCAD, with one gene named PHACTR1 likely to be an important driver.

They showed that the genes involved in creating SCAD are primarily engaged in forming the matrix or scaffolding around the cells developing coronary arteries, as well as a gene involved in blood clotting, after analyzing data from nearly 2000 individuals.

This clotting factor shortage is thought to increase the likelihood of spontaneous bleeding into the artery wall, which reduces blood flow as it expands and leads to a SCAD heart attack.

Prof. Eleni Gionnulatou, who, together with Prof. Graham and Prof. Kovacic, led the Australian arm of the study, said, “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.”

The Australian arm of the study was led by Eleni Gionnulatou, Prof. Graham, and Prof. Kovacic, who discovered that people who develop SCAD have subtle genetic changes that affect their blood vessels, putting them at a higher risk of a catastrophic tear or a spontaneous bleed involving the wall of the heart arteries.

They now have a much better understanding of the genetic risk of SCAD and its relationship to other cardiovascular disorders. Understanding these pathways should result in novel approaches to management and treatment.

Scientists are researching the PHACTR1 gene, which has one of the strongest genetic associations with SCAD.

Prof. Kovacic said, “SCAD is still a relatively little-known disease, but it has a huge impact and is behind a quarter of all heart attacks in women under 50. We urgently need to learn more about this disease and discover what is causing it.”

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

The researchers are the first outside of the United States to join the iSCAD Registry, a global collaboration of researchers and patients studying the characteristics and pathogenesis of SCAD.

The iSCAD Registry contains the medical histories of 1271 SCAD patients, all previously from the United States. Patients in Australia will soon be able to donate their data to help throw more light on this disease.

Journal Reference:

  1. Adlam, D., Berrandou, T., Georges, A., et al. Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation. Nature Genetics. DOI: 10.1038/s41588-023-01410-1


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