Elsevier

JACC: Heart Failure

Volume 10, Issue 2, February 2022, Pages 129-138
JACC: Heart Failure

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

https://doi.org/10.1016/j.jchf.2021.09.006Get rights and content
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Abstract

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.

Key Words

amyloidosis
heart failure
survival
transthyretin V142I variant

Abbreviations and Acronyms

BNP
brain natriuretic peptide
CMR
cardiac magnetic resonance
CV
cardiovascular
HF
heart failure
LV
left ventricle
LVH
left ventricle hypertrophy
TTR
transthyretin

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs Coniglio and Segar contributed equally to this work.