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Age Dependency of Cardiovascular Outcomes With the Amyloidogenic pV142I Transthyretin Variant Among Black Individuals in the US. | LitMetric

AI Article Synopsis

  • Hereditary transthyretin cardiac amyloidosis is a significant cause of heart failure, especially in Black individuals, as the pV142I variant increases the risk of conditions like atrial fibrillation and mortality; this variant is found in about 3-4% of this population in the U.S. !* -
  • A cohort study followed 3,856 Black participants from the ARIC study over nearly 28 years, analyzing the cardiovascular risks associated with the pV142I variant across different ages, revealing that risks significantly increase as individuals age. !* -
  • The study found that the 10-year absolute risk for atrial fibrillation, heart failure hospitalization, and mortality becomes statistically significant at

Article Abstract

Importance: Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.

Objective: To estimate age-dependent risks for cardiovascular events with the variant.

Design, Settings, And Participants: This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023.

Exposure: pV142I carrier status.

Main Outcomes: The association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years.

Results: Among 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant.

Conclusions And Relevance: In this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203968PMC
http://dx.doi.org/10.1001/jamacardio.2023.1525DOI Listing

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