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Large Study Points to Aortic Valve Defects and Aortic Disease Clustering in Families

Chris Palmer for University of Utah Health


Researchers at University of Utah Health have tapped a large database with medical and genealogical records to show that first- and second-degree relatives of patients with bicuspid aortic valve (BAV) and thoracic aortic disease are at increased risk for aortic complications and related mortality. The results, published recently in Circulation, point to the need for expanding screening to a broad range of family members. Because treatments are easier and outcomes are better when diagnosis comes earlier, expanded screening could have a profound impact on patients and their families.

A bicuspid aortic valve (BAV) is a common congenital heart condition affecting 1-2% of the population. In this condition, the aortic valve, which regulates blood flow from the heart's left ventricle into the aorta, has only two cusps (leaflets) instead of the normal three. This can affect the valve’s ability to open and close properly and lead to serious complications—including aortic stenosis, aortic regurgitation, aortic aneurysm, and endocarditis—requiring surgical intervention.

Doctor examining heart

Thoracic aortic disease includes aortic aneurysms and dissections, atherosclerotic disease, infections, and traumatic injuries. Prevalence of thoracic aortic aneurysms ranges from 5 to 10 per 100,000 individuals per year.

Screening for both conditions involves a combination of medical history assessment, physical examination, and diagnostic imaging tests such as echocardiogram, CT scan, or cardiac MRI.

“I take care of a lot of patients with bicuspid aortic valve and aortic aneurysms,” said Jason Glotzbach, MD, assistant professor of surgery in the Division of Cardiothoracic Surgery at the University of Utah. “They always ask, ‘What’s the risk to my family members?’”

The risk, it turns out, is not insignificant. A handful of studies over the years indicate a heritable component to these conditions, and current American Medical Association guidelines recommend screening of first-degree relatives of people with BAV or thoracic aortic disease, the benefits of which Glotzbach has seen firsthand on numerous occasions.

“We’ve had many, many families where one relative heard a heart murmur, came in, got tested, received a bicuspid valve diagnosis, then diagnosis of an aneurysm,” said Glotzbach, who serves as the co-director of the University of Utah Aortic Disease Program. “We then test their relatives and find the same thing, and we end up performing surgery on multiple family members to prevent problems with aneurysms. That’s really satisfying when we can do that. You can tell people, ‘Look, this could have been a problem, but now it’s fixed.’ And they’re back to normal lifetime risk.”

“The observed familial risk we saw in this large population warrants routine screening of close and extended family members of affected individuals."

To more deeply explore the familial links with BAV and thoracic aortic disease beyond first-degree relatives, Glotzbach and a team of physicians and researchers at U of U Health turned to the Utah Population Database, which contains genealogy, residential history, and medical data for most people who have ever lived in Utah.

The research team identified 14,731 individuals with aortic conditions in the database and their first-degree relatives, second-degree relatives, and first cousins, yielding more than 3.8 million unique relatives for analysis, as well as age- and sex-matched controls.

They found that first-degree relatives of patients with BAV and thoracic aortic aneurysm were 6.88 and 5.09 times more likely, respectively, to also have the condition than controls. First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection also had a nearly three-fold higher risk of aortic-specific mortality compared with controls. A smaller, but still significant, effect was seen in second-degree relatives and first cousins.

Family tree

“The study provides the most robust evidence so far that there are likely many asymptomatic relatives of BAV and aortic aneurysm patients who are at increased risk for aortic complications and mortality,” Glotzbach said. “The observed familial risk we saw in this large population warrants routine screening of close and extended family members of affected individuals.”

Glotzbach added that the team’s findings have inspired U of U to work toward updating patient electronic health records to include relatives’ diagnoses. “We’re trying to code pop-up reminders into our EHR that will prompt these relatives’ primary care provider to consider an echocardiogram or other screening method,” he said. “Hopefully this knowledge will trickle out into the field, inspiring expanded screening everywhere.”

Glotzbach and his colleagues at U of U Health see thousands of BAV and thoracic aortic disease patients per year and performs hundreds of procedures to repair or replace the aortic valve.

“We have a very multidisciplinary approach,” Glotzbach said. “We have cardiac surgeons, interventional cardiologists, and a very strong team for transcatheter aortic valve replacement, which is a potential treatment for BAV. We all work together to provide treatment plans.”

Up next for Glotzbach and his colleagues are studies to identify genes related to BAV and thoracic aortic disease in the Utah Population Database cohort.

“The Utah Population Database is such a unique resource,” Glotzbach said. “We have access to all these families with these conditions, allowing us an opportunity to identify genome sequences that could yield an even more nuanced understanding of individuals’ risks even earlier in life.”