A rare gene mutation in Black patients is associated with early-onset heart failure

New research finds a strong association between a rare genetic mutation and early-onset heart failure and hospitalization among Black Americans. Researchers found Black patients who develop heart failure — and carry this genetic mutation — develop the condition four years earlier than those not carrying it.

Dr. Ambarish Pandey, co-author of the study and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, said the study raises the question: Should Black Americans be screened for this genetic mutation?

“That's a question that I can’t answer in just one study,” he said. “But I think it raises this broader question of: Is there benefit in screening for this abnormal mutation in Black patients, particularly in those who may be identified early on — and can benefit from more aggressive risk modification for things like blood pressure control and other factors that contribute to risk of heart failure?”

The genetic mutation — known as TTR V142I — allows protein to build up inside the heart, which can make it harder for the heart to contract and relax. That eventually can cause part of the organ to die — a condition known as transthyretin amyloid cardiomyopathy.

Several prior studies linked the genetic mutation to this condition, but those studies did not explore the association with adverse clinical outcomes, including heart failure and hospitalization rates, Pandey said.

Researchers followed thousands of study participants for 12 years

This new study is the first to look at an exclusively Black cohort, he said. That’s significant because the genetic mutation is much more prevalent in people of African descent.

Pandey, along with researchers at several U.S. medical schools, followed a cohort of nearly 3,000 people of African descent over a period of 12 years and identified more than 200 patients who developed heart failure. The researchers found people with the mutation who experienced heart failure were more likely to have negative health outcomes, including early-onset heart failure, heart muscle injury and hospitalization.

Heart failure occurs when the heart can’t pump enough blood to the body’s vital organs. Without close monitoring and management, the condition can be lethal. More than 6 million Americans are living with heart failure, according to the U.S. Centers for Disease Control and Prevention.

Health issues like obesity, high blood pressure and diabetes can increase a person’s risk of heart failure. African Americans have higher rates of heart failure, hospitalization and death from the disease, according to national data.

This study was done on Black Americans participating in the Jackson Heart Study — the longest and largest study looking at cardiovascular disease in Black Americans. The researchers followed the participants from 2005 to 2016. The process included heart imaging and blood tests.

Among the other significant findings: Even when heart imaging didn’t turn up evidence of injury to the organ in study participants with the genetic mutation, blood tests that look for troponin, a marker of tissue damage, did. Those with the genetic mutation had significantly higher amounts of this protein in their blood.

The study “opens a new avenue of investigations to further develop drugs and treatments, even prevention for patients [who] have this genetic predisposition to disease,” said Dr. Patrice Desvigne-Nickens, program director at the National Heart, Lung and Blood Institute, which funded the research.

Desvigne-Nickens, who was not part of the study, said there are FDA-approved treatments that prevent heart failure when the heart begins to show signs of damage. But it remains unknown whether someone who carries the genetic mutation, but does not yet have abnormal amyloid protein deposits, could reduce their risk of heart failure by receiving those treatments.

Still, Desvigne-Nickens said these findings suggest that patients who already have heart disease may benefit from genetic testing.

If a Black patient is found to have this mutation, their physician and providers need to carefully monitor for signs and symptoms of heart failure, she said. Additionally, because this is a genetic marker, family members of patients with this mutation may also benefit from getting tested.

More research and improved health care access needed

Pandey said further research is needed before genetic testing is recommended for all people of African descent. He said in order to improve health outcomes, increasing access to genetic testing isn’t the most pressing issue.

“Access to care is a big issue in Black communities,” Pandey said. “So, forget about implementing genetic testing for amyloidosis. I think if I had to pick what to improve access to, I would improve access to blood pressure control, diabetes control, and things that are more prevalent and more common, and also associated with the risk of heart failure just as much.”

Researchers don’t know why this genetic mutation exists almost exclusively in patients of African descent. The vast majority of people’s genetic composition is consistent across races. But some genetic mutations show up with greater frequency among certain populations.

“Population genetics and origins are important, because there is a selection having to do with your environment that determines the frequency of certain genes and variations,” Desvigne-Nickens said.

For instance, the sickle cell trait — a genetic trait that can cause sickle cell anemia, a blood condition that primarily affects people of African descent — seems to be related to the prevalence of malaria in Africa.

Still, Desvigne-Nickens said the role genetic variations play in people’s health is far less significant than environmental factors. Long-standing socioeconomic and disparities in health care access facing Black Americans are among the contributing factors to many health conditions, she said.

“The majority of the largest contributors to how long you live, and how healthy your life is, have to do with your behavior and the environment in which you live,” she said. “So, genetic testing doesn't absolve you of responsibility for healthy habits, healthy living and making sure that the environment is not hostile.”

Desvigne-Nickens said this study is one type of precision medicine, which considers a person’s genetics, environment and lifestyle to inform potential treatments. The approach could help address long-standing health disparities — and the participation of African American patients makes this possible.

“A real shout out to them, the participants. These are African Americans [who] participate in these studies and allow themselves to be tested because that information then can be used to help them,” she said. “Research is not something that has been welcome in communities of color, because research in the past has represented some level of exploitation and breach of trust for a variety of reasons.”

As a physician of color herself, Desvigne-Nickens said better representation in medical and research spheres would help cultivate more trust and participation of communities of color in crucial research.

This story comes from a reporting collaboration that includes the Indianapolis Recorder and Side Effects Public Media — a public health news initiative based at WFYI. Follow Farah on Twitter: @Farah_Yousrym.

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