Skip to main content
Journal cover image

Cardiovascular Burden of the V142I Transthyretin Variant.

Publication ,  Journal Article
Selvaraj, S; Claggett, B; Shah, SH; Mentz, RJ; Khouri, MG; Manichaikul, AW; Khan, SS; Rich, SS; Mosley, TH; Levitan, EB; Arora, P; Goyal, P ...
Published in: JAMA
June 4, 2024

IMPORTANCE: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. OBJECTIVES: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. DESIGN, SETTING, AND PARTICIPANTS: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. EXPOSURE: V142I carrier status (n = 754, 3.2%). MAIN OUTCOMES AND MEASURES: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. RESULTS: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. CONCLUSIONS AND RELEVANCE: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

June 4, 2024

Volume

331

Issue

21

Start / End Page

1824 / 1833

Location

United States

Related Subject Headings

  • United States
  • Stroke Volume
  • Prealbumin
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heterozygote
  • Heart Failure
  • General & Internal Medicine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Selvaraj, S., Claggett, B., Shah, S. H., Mentz, R. J., Khouri, M. G., Manichaikul, A. W., … Solomon, S. D. (2024). Cardiovascular Burden of the V142I Transthyretin Variant. JAMA, 331(21), 1824–1833. https://doi.org/10.1001/jama.2024.4467
Selvaraj, Senthil, Brian Claggett, Svati H. Shah, Robert J. Mentz, Michel G. Khouri, Ani W. Manichaikul, Sadiya S. Khan, et al. “Cardiovascular Burden of the V142I Transthyretin Variant.JAMA 331, no. 21 (June 4, 2024): 1824–33. https://doi.org/10.1001/jama.2024.4467.
Selvaraj S, Claggett B, Shah SH, Mentz RJ, Khouri MG, Manichaikul AW, et al. Cardiovascular Burden of the V142I Transthyretin Variant. JAMA. 2024 Jun 4;331(21):1824–33.
Selvaraj, Senthil, et al. “Cardiovascular Burden of the V142I Transthyretin Variant.JAMA, vol. 331, no. 21, June 2024, pp. 1824–33. Pubmed, doi:10.1001/jama.2024.4467.
Selvaraj S, Claggett B, Shah SH, Mentz RJ, Khouri MG, Manichaikul AW, Khan SS, Rich SS, Mosley TH, Levitan EB, Arora P, Goyal P, Haring B, Eaton CB, Cheng RK, Wells GL, Manson JE, Fontana M, Solomon SD. Cardiovascular Burden of the V142I Transthyretin Variant. JAMA. 2024 Jun 4;331(21):1824–1833.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

June 4, 2024

Volume

331

Issue

21

Start / End Page

1824 / 1833

Location

United States

Related Subject Headings

  • United States
  • Stroke Volume
  • Prealbumin
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heterozygote
  • Heart Failure
  • General & Internal Medicine