Age Dependency of Cardiovascular Outcomes With the Amyloidogenic pV142I Transthyretin Variant Among Black Individuals in the US
Year: 2023
Type: 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.
Source: JAMA Cardiology
Institutions: Duke University, Duke Medical Center, Brigham and Women's Hospital, Alexion Pharmaceuticals (United States), The University of Texas Health Science Center at Houston, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Scripps Research Institute, Scintillon Institute, University of Mississippi Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Health and Human Services, American Heart Association, Amgen, Pfizer, AstraZeneca, Brigham and Women's Hospital, Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Institute for Translational Medicine and Therapeutics, Novo Nordisk, National Institutes of Health, National Heart, Lung, and Blood Institute
Awards: G1114307781, G1206013853, G1522370804, G1788514665, G1823732541, G2262505034, G3139593554, G3461750354, G3590818488, G3744596180, G3973572274, G4028411927, G4175219461, G4525733312, G453267231, G4597579782, G4739409156, G4790942633, Mentoring patient-oriented research in deep phenotyping of cardiac function for heart failure prevention, G5352314984, G5770678025, G6060132884, Quantifying cardiac structure and function to define the progression to hear failure in African Americans, G6739173425, G6837735701, Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life, G8930081076, Late-life trajectories of cardiac function to define pathways of cardiac resilience, Proteomic signatures to identify pathways underlying the progression to heart failure
OpenAlex ID: W4377221047