Managing cardiovascular risk factors can influence health outcomes for carriers of heart failure variant microbiologystudy

Researchers from the University of Alabama at Birmingham Marnix E. Heersink School of Medicine have published a study in JACC: Heart Failure that sheds light on how managing cardiovascular risk factors can influence health outcomes in carriers of the transthyretin V142I variant.

Some 3–4% of Black individuals in the United States have the transthyretin V142I genetic variant, which significantly increases an individual’s risk of heart failure. The UAB-led research, under the leadership of Pankaj Arora, M.D., and Garima Arora, M.D., sought to determine how cardiovascular risk profiles—encompassing hypertension, diabetes, obesity and hypercholesterolemia—could modify the risk of heart failure and mortality among V142I variant carriers.

Using data from over 48,000 participants across the TOPMed program, REGARDS study and the All of Us Research Program, researchers found that carriers with a favorable cardiovascular risk profile, a 0 or 1 risk factor, experienced a significantly reduced, but not eliminated, risk of heart failure compared to those with an unfavorable profile, 3 or 4 risk factor.

“This study is a testament to the power of collaboration across institutions and national programs,” said Pankaj Arora, lead investigator and director of the UAB Cardiogenomics Clinic. “By pooling data and expertise from programs like TOPMed, REGARDS and the All of Us Research Program, we were able to address critical questions about how genetic predispositions and clinical factors intersect to shape health outcomes.”

“Our findings underscore the critical importance of maintaining a healthy cardiovascular profile, particularly for those with genetic predispositions like the V142I variant,” said Pankaj Arora. “This study reinforces that, while genetic factors significantly influence health outcomes, proactive management of modifiable risk factors can have a profound impact.”

The study highlights that, while a favorable cardiovascular risk profile reduces the risk of heart failure and all-cause mortality among V142I carriers, it does not entirely offset their increased risk compared to noncarriers. These findings emphasize the necessity of genetic screening, early identification of at-risk individuals and rigorous cardiovascular risk factor management to mitigate adverse outcomes.

“Identifying V142I variant carriers early and focusing on cardiovascular risk management can significantly reduce their burden of heart failure,” said Naman Shetty, M.D., first author of the study. “This research highlights how genetics and clinical factors interact to shape health outcomes and underscores the importance of collaborative, precision medicine approaches.”

“Our work enhances understanding of how genetic and environmental factors interact and provides actionable insights for personalized care strategies,” said Garima Arora, co-investigator and co-director of the UAB Cardiogenomics Clinic.

Pankaj Arora says this research is expected to pave the way for improved management and preventive strategies for hereditary transthyretin cardiac amyloidosis, emphasizing the need for targeted interventions in high-risk populations.