Article Impact Level: HIGH Data Quality: STRONG Summary of JACC: Heart Failure, 13(1), 91–101. https://doi.org/10.1016/j.jchf.2024.08.019 Dr. Naman S. Shetty et al.
Points
- The study investigated how cardiovascular risk factors (CV RFs) influence heart failure risk in Black individuals carrying the transthyretin V142I genetic variant using data from 48,365 participants across multiple cohorts.
- While V142I carriers showed no significant variation in the prevalence of CV RFs, carriers with a favorable CV RF profile (0-1 RF) had a lower heart failure risk (HR 2.26) compared to those with an unfavorable profile (3-4 RFs, HR 4.14).
- Effective management of CV RFs significantly reduces heart failure risk in V142I carriers, though it does not entirely negate the genetic risk, emphasizing the need for proactive risk management.
- The study underscores the value of integrating genetic screening and targeted strategies for early identification and management of high-risk individuals in precision medicine.
- Researchers advocate for further studies to refine preventive and therapeutic strategies for hereditary transthyretin cardiac amyloidosis and other genetically driven heart failure risks.
Summary
This study investigates the impact of cardiovascular risk factors (CV RFs) on heart failure risk in carriers of the transthyretin V142I variant. This genetic mutation significantly increases the risk of heart failure in Black individuals. The research utilized data from six cohorts in the TOPMed program, the REGARDS study, and the All of Us Research Program, comprising 48,365 participants. 1,625 V142I carriers were identified, and the prevalence of common CV RFs, including hypertension, diabetes, obesity, and hypercholesterolemia, was assessed. The study found no significant variation in the prevalence of these risk factors based on V142I carrier status. However, when analyzing longitudinal data from 18,407 participants, including 587 V142I carriers, the study revealed that a favorable CV RF profile (with 0 or 1 RF) was associated with a significantly reduced heart failure risk compared to an unfavorable CV RF profile (with 3 or 4 RFs). The adjusted hazard ratio (HR) for heart failure risk among V142I carriers with a favorable CV RF profile was 2.26 (95% CI: 1.58-3.23), while the HR for those with an unfavorable CV RF profile was 4.14 (95% CI: 2.79-6.14).
The findings highlight the significant role of CV RF management in reducing heart failure risk in individuals with the V142I genetic variant. While a favorable CV RF profile significantly lowered the risk of heart failure, it did not fully offset the increased risk associated with the V142I variant, underscoring the need to manage CV RFs in these individuals proactively. This research emphasizes the importance of genetic screening and early intervention for V142I carriers to reduce the burden of heart failure and improve overall health outcomes.
These results suggest that managing modifiable cardiovascular risk factors can substantially reduce heart failure risk in genetically predisposed individuals. The study advocates for targeted strategies in precision medicine, which consider genetic and clinical factors in the early identification and management of high-risk individuals. The authors recommend further studies to refine preventive and therapeutic strategies, aiming for better outcomes in patients with hereditary transthyretin cardiac amyloidosis and other genetic predispositions to heart failure.
Link to the article: https://www.sciencedirect.com/science/article/abs/pii/S2213177924006255
References Shetty, N. S., Gaonkar, M., Pampana, A., Patel, N., Morrison, A. C., Reiner, A. P., Carson, A. P., Yu, B., Psaty, B. M., Kooperberg, C., Fatkin, D., Boerwinkle, E., Rotter, J. I., Taylor, K. D., Hou, L., Irvin, M. R., Hall, M. E., Maurer, M., Fornage, M., … Arora, P. (2025). Cardiovascular risk factors and genetic risk in transthyretin v142i carriers. JACC: Heart Failure, 13(1), 91–101. https://doi.org/10.1016/j.jchf.2024.08.019
