Highlights
- •The prevalence of the V122I transthyretin (TTR) variant in individuals with African ancestry is 3.2%.
- •In mid-life, carriers of the V122I TTR have subtle cardiac structural differences in comparison with noncarriers.
- •Over time, carriers of V122I have a greater increase in amino terminal pro-B-type natriuretic peptide in comparison with noncarriers.
- •In comparison with noncarriers, carriers of the V122I TTR are at a higher long-term risk of heart failure and death
Abstract
Background
The V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation
worldwide. The aim of this study is to describe the cardiac phenotype and risk for
adverse cardiovascular outcomes of young V122I TTR carriers in the general population.
Methods and Results
TTR genotypes were extracted from whole-exome sequence data in participants of the Dallas
Heart Study. Participants with African ancestry, available V122I TTR genotypes (N = 1818) and either cardiac magnetic resonance imaging (n = 1364) or long-term follow-up (n = 1532) were included. The prevalence of V122I TTR carriers (45 ± 10 years) was 3.2% (n/N = 59/1818). The V122I TTR carriers had higher baseline left ventricular wall thickness (8.52 ± 1.82 vs 8.21
± 1.62 mm, adjusted P = .038) than noncarriers, but no differences in other cardiac magnetic resonance
imaging measures (P > .05 for all). Although carrier status was not associated with amino terminal pro-B-type
natriuretic peptide (NT-proBNP) at baseline (P = .79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than noncarriers (median
28.5 pg/mL, interquartile range 11.4–104.1 pg/mL vs median 15.9 pg/mL, interquartile
range 0.0–43.0 pg/mL, adjusted P = .018). V122I TTR carriers were at a higher adjusted risk of heart failure (hazard ratio 3.82, 95%
confidence interval 1.80–8.13, P < .001), cardiovascular death (hazard ratio 2.65, 95% confidence interval 1.14–6.15,
P = .023), and all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08–3.51,
P = .026) in comparison with noncarriers.
Conclusions
V122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater
left ventricular wall thickness, and a higher risk for heart failure, cardiovascular
death, and all-cause mortality. These findings suggest the need to develop amyloidosis
screening strategies for V122I TTR carriers.
Graphical Abstract
Graphical Abstract
Key Words
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Article info
Publication history
Published online: October 08, 2021
Accepted:
September 30,
2021
Received in revised form:
September 25,
2021
Received:
July 2,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
