Physician-scientists from the University of Alabama at Birmingham Marnix E. Heersink School of Medicine have conducted a study that sheds light on the impact of transthyretin (TTR) protein levels on heart disease risk. Published in Nature Communications, the research explores how variations in TTR levels are associated with adverse clinical outcomes, offering new insights into the prevention and management 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.
Led by Pankaj Arora, M.D., and Naman Shetty, M.D., the study analyzed data from 35,206 participants in the UK Biobank. The researchers delved into the clinical correlates of TTR levels, differences in TTR levels based on genetic variations, and the association of TTR levels with health outcomes. Their findings revealed that lower TTR levels are significantly associated with an increased risk of heart failure and all-cause mortality. Individuals 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 those with higher TTR levels, with particularly pronounced effects in individuals carrying the V142I TTR gene variant known to destabilize the TTR protein.
The study also unveiled that TTR levels were lower in females compared to males and were influenced by various health factors. Higher blood pressure, cholesterol levels, albumin levels, triglyceride levels, and creatinine levels were associated with increased TTR levels. Conversely, higher C-reactive protein levels were linked to lower TTR levels. Notably, carriers of the V142I TTR gene variant had significantly lower TTR levels compared to non-carriers, indicating a genetic influence on TTR levels. This underlines the importance of understanding the factors that impact TTR levels to better identify individuals at high risk and develop targeted interventions to prevent adverse outcomes.
Senior author Pankaj Arora, a cardiologist at the UAB Cardiovascular Institute, emphasizes the far-reaching implications of the research. The study suggests that monitoring TTR levels could be a valuable tool in managing heart disease risk, especially for individuals with known genetic variations like the V142I TTR variant. Low TTR levels can raise the pre-test probability of a positive genetic test, specifically for detecting the V142I variant that may take time to process. This information can be used to counsel family members while waiting for the results of genetic testing, marking a significant step forward in understanding and mitigating the risks associated with cardiac amyloidosis and other heart-related conditions.
In light of these findings, the researchers suggest that incorporating TTR level measurements into screening programs could offer potential benefits, particularly for individuals with genetic predispositions. By understanding the critical role of TTR levels in predicting heart disease risk and the factors that influence them, targeted interventions can be developed to improve outcomes. The study underscores the importance of personalized medicine in identifying high-risk individuals and implementing preventative strategies to mitigate the impact of heart disease. Ultimately, this research represents a significant advancement in the quest to enhance our understanding of cardiac amyloidosis and related conditions, paving the way for improved risk assessment and management in the field of cardiovascular health.