Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults.

Objectives: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults.
Background: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis.
Methods: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations.
Results: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007).
Conclusions: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.
Competing Interests: Funding Support and Author Disclosures The Jackson Heart Study was supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute and the National Institute for Minority Health and Health Disparities. Dr Hall has received support from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant 1K08DK099415- 01A1, NIH/National Institute of General Medical Sciences grant P20GM104357, and NIH/National Institute of General Medical Sciences grant 5U54GM115428. This study was supported by research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, National Institute of Aging GEMSSTAR grant (1R03AG067960-01), and Applied Therapeutics to Dr Pandey. Disclosures: Dr Grodin is a consultant for Pfizer, Eidos Therapeutics, and Alynlam Pharmaceuticals; and has received research funding from the Texas Health Resources Clinical Scholars fund. Dr De Lemos has received financial support from Roche Diagnostics and Abbott Diagnostics; and is a consultant for Ortho Clinical Diagnostics, Quidel, and Regeneron. Dr Berry has received financial support from Roche Diagnostics, Abbott Diagnostics, and the National Institutes of Health; is a consultant for Abbott and the Cooper Institute. Dr Butler is a consultant for Abbott, Adrenomed, Arena Pharma, Array, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sequana Medical, V-Wave Limited, and Vifor. Dr Mentz has received financial support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Medtronic, Merck, Novartis, Roche, Sanofi, and Vifor. Dr Sanjiv Shah has received financial support from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and is a consultant for Abbott, Actelion, AstraZeneca, Amgen, Aria, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cyclerion, Cytokinetics, Eisai, GlaxoSmithKline, Imara, Ionis, Ironwood, Keyto, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Amil Shah has received financial support from Novartis through Brigham and Women’s Hospital, and Philips Ultrasound through Brigham and Women’s Hospital, and personal fees from Philips Ultrasound Advisory Board outside the submitted work. Dr Pandey has served on the advisory board of Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)