Uncovering the genetics behind heart attacks that surprise young,
healthy women

Date:
September 4, 2020
Source:
Michigan Medicine - University of Michigan
Summary:
New genetic research finds spontaneous coronary artery dissection,
or SCAD, heart attacks may be more similar to different diseases
than to other heart attacks.



FULL STORY ========================================================================== Rather than a slow build-up of plaque over time, a heart attack caused
by spontaneous coronary artery dissection strikes suddenly, often in
younger women who didn't seem to be at risk for a cardiac event.


==========================================================================
SCAD is poorly understood, and it's so far impossible to predict which combination of genes and environmental triggers will lead coronary
arteries to spontaneously tear, or dissect, leading to a heart attack
that requires emergency, life-saving medical care.

Researchers have now uncovered additional genetic clues to better
understand SCAD, which are desperately needed, says senior author
Santhi Ganesh, M.D., from the Michigan Medicine Frankel Cardiovascular
Center. The genes Ganesh and colleagues have identified further illustrate
the difference between SCAD and the more common heart attack, when plaque builds up in the artery and limits blood flow, called atherosclerosis.

"The SCAD risk alleles were inversely associated with coronary disease
and myocardial infarction due to atherosclerotic disease, suggesting
very different underlying biology in the artery causing each type of
heart attack," Ganesh says.

"It is especially intriguing that many of the same genetic markers are involved, but in different ways, in both SCAD-induced heart attack and atherosclerotic heart attack." The researchers performed a genome-wide association study, analyzing millions of genetic markers in patients with
SCAD and healthy controls. They found a significant association of several specific genetic regions associated with SCAD, which further implicated specific genes influenced by the identified genetic variants, Ganesh says.



==========================================================================
In addition, researchers report that the genetic risk factors for SCAD
also predict SCAD among individuals with fibromuscular dysplasia, or FMD,
a vascular disease that may affect any artery in the body and is found in
some patients with SCAD. Many people with FMD also lack traditional risk factors underlying atherosclerosis, like high blood pressure and diabetes, researchers say, but still may be at risk for vascular complications
such as arterial aneurysms and dissections.

"As a physician caring for patients with both FMD and SCAD, it is
gratifying to see results from our research that are beginning to uncover
the genetic architecture and risk for these diseases about which so
little is known," Ganesh says.

"This unbiased and large-scale analysis has provided us with new
clues for where to focus our next steps of research, which is urgently
needed. We are grateful for the participation of our patients, without
whom these studies and new insights would not be possible." Finally,
the SCAD risk alleles were positively associated with migraine headache,
which highlights a shared genetic basis for migraine headache and
SCAD. Ganesh says more research is needed to precisely define the
biological relationship of SCAD to vascular diseases such as FMD and
migraine headache, as well as its implications for clinical care.

"Identifying these genetic risk alleles helps further advance our
understanding of risks of SCAD," says co-lead author Jacqueline Saw, M.D.,
from Vancouver General Hospital/University of British Columbia. "Whether
these findings have implications for SCAD in high-risk populations,
such as those with peripartum SCAD, is an important next step of this research." The team's work relied upon international large-scale collaborations including the Canadian SCAD Study, the University of
Michigan Genetic Study of Arterial Dysplasia, the UK Biobank, the
Million Veteran's Program and the Michigan Genomics Initiative, from
which thousands of healthy controls boosted the team's ability to detect genetic associations.

The next step is to conduct studies on larger groups of patients with
SCAD, and to conduct further in-depth studies of the genetic and biologic relationship between SCAD and FMD, and related dysplasia-associated
arterial diseases, Ganesh says. The group is launching a clinical and
genetic study of peripartum, or postpartum, SCAD.


========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Jacqueline Saw, Min-Lee Yang, Mark Trinder, Catherine Tcheandjieu,
Chang
Xu, Andrew Starovoytov, Isabelle Birt, Michael R. Mathis,
Kristina L.

Hunker, Ellen M. Schmidt, Linda Jackson, Natalia Fendrikova-Mahlay,
Matthew Zawistowski, Chad M. Brummett, Sebastian Zoellner, Alexander
Katz, Dawn M. Coleman, Kirby Swan, Christopher J. O'Donnell, Xiang
Zhou, Jun Z. Li, Heather L. Gornik, Themistocles L. Assimes, James
C. Stanley, Liam R. Brunham, Santhi K. Ganesh. Chromosome 1q21.2
and additional loci influence risk of spontaneous coronary artery
dissection and myocardial infarction. Nature Communications, 2020;
11 (1) DOI: 10.1038/s41467-020- 17558-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200904090318.htm

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