Medical scientists at the Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham have discovered significant findings about the impact of transthyretin protein levels, or TTR, on heart disease risk. The study, recently published in Nature Communicationsexplores how variations in TTR levels are associated with adverse clinical outcomes, providing new insights into the prevention and treatment of amyloid heart disease. Transthyretin is a transport protein produced in the liver, and its misfolding is linked to the development of cardiac amyloidosis, a condition that leads to heart failure and increased mortality.
The study, led by Dr. Pankaj Arora and Dr. Naman Shetty, examined data from 35,206 participants from the UK Biobank. The researchers investigated the clinical correlates of TTR levels, differences in TTR levels based on genetic variations, and the association of TTR levels with health outcomes.
Arora and his team found that low TTR levels were significantly associated with an increased risk of heart failure and all-cause mortality. Specifically, people with low TTR levels had a 17 percent higher risk of heart failure and an 18 percent higher risk of death from any cause compared to people with higher TTR levels. These findings were even more pronounced in people carrying the TTR V142I gene variant, which is known to destabilize the TTR protein.
The study revealed that TTR levels were lower in women compared to men and were influenced by several health factors. Higher systolic and diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels were associated with higher TTR levels. Higher C-reactive protein levels were associated with lower TTR levels. Notably, carriers of the TTR V142I gene variant had significantly lower TTR levels compared to non-carriers, highlighting a genetic influence on this protein.
“Our research highlights the critical role of TTR levels in predicting heart disease risk,” Arora said. “By understanding the factors that influence TTR levels, we can better identify people at high risk and develop targeted interventions to prevent adverse outcomes.”
“These findings underscore the potential benefits of incorporating TTR level measurements into screening programs, especially for individuals with genetic predispositions,” Shetty said.
Arora, senior author and a cardiologist at the UAB Cardiovascular Institute, says the implications of this study are far-reaching. It suggests that monitoring TTR levels could be a valuable tool for managing heart disease risk, particularly for those with known genetic variations such as the TTR V142I variant. Low TTR levels increase the pre-test likelihood of a positive genetic result, specifically for detecting the V142I variant, which typically takes a while to process.
“This information can be used to counsel family members as they await genetic test results,” Arora said. “This research represents a significant step forward in the quest to understand and mitigate the risks associated with cardiac amyloidosis and other heart-related diseases.”