UAB researchers have uncovered the impact of transthyretin protein levels on heart disease risk.
From left: Dr. Naman Shetty, Dr. Pankaj AroraPhysician-scientists at the University of Alabama at Birmingham’s Marnix E. Hairsink College of Medicine have uncovered important findings regarding the impact of transthyretin (TTR) protein levels on heart disease risk. The study, recently published in Nature Communications, explores how variations in TTR levels are associated with poor clinical outcomes and provides new insights into the prevention and management of amyloid heart disease. Transthyretin is a transport protein produced in the liver, whose misfolding has been linked to the development of cardiac amyloidosis, which leads to heart failure and increased mortality.
The study, led by Pankaj Arora, MD, PhD, and Naman Shetty, MD, PhD, looked at data from 35,206 participants from UK Biobank. The researchers investigated clinical correlates of TTR levels, differences in TTR levels based on genetic variants, and the association between TTR levels and health outcomes.
Arora and his team found that low TTR levels significantly increased the risk of heart failure and all-cause mortality. Specifically, people with low TTR levels had a 17% higher risk of heart failure and an 18% higher risk of all-cause mortality compared to people with high TTR levels. These results were even more pronounced in people with the V142I TTR gene mutation, which is known to destabilize the TTR protein.
The study found that TTR levels were lower in women compared to men and were influenced by several health factors. High systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels were associated with elevated TTR levels. High C-reactive protein levels were associated with decreased TTR levels. Notably, carriers of the V142I TTR gene variant had significantly lower TTR levels compared to non-carriers, highlighting a genetic influence on this protein.
“Our study highlights the important role of TTR levels in predicting heart disease risk,” Arora said. “Understanding the factors that influence TTR levels may help us better identify individuals at risk and develop targeted interventions to prevent adverse outcomes.”
“These findings highlight the potential benefits of incorporating measurement of TTR levels into screening programs, particularly for genetically predisposed populations,” Shetty said.
Arora, senior author and cardiologist at the UAB Cardiovascular Institute, said the impact of this study is far-reaching. The study suggests that monitoring TTR levels could be a valuable tool in managing heart disease risk, especially for people with known genetic mutations like the V142I TTR variant. Low TTR levels increase the chances of a pre-test genetic test coming back positive, which is especially effective at detecting the V142I variant, which takes longer to process.
“This information can be used to counsel families as they await genetic test results,” Arora said. “This study represents a major step forward in understanding and reducing the risks associated with cardiac amyloidosis and other heart-related diseases.”
