Naman S. Shetty MD , Mokshad Gaonkar MS , Akhil Pampana MS , Nirav Patel MD, MSPH , Alanna C. Morrison PhD , Alexander P. Reiner MD, MSc , April P. Carson PhD , Bing Yu PhD , Bruce M. Psaty MD, PhD , Charles Kooperberg PhD , Diane Fatkin MD , Eric Boerwinkle PhD , Jerome I. Rotter MD , Kent D. Taylor PhD , Lifang Hou MD, PhD , Marguerite R. Irvin PhD , Michael E. Hall MD , Mathew Maurer MD , Myriam Fornage PhD , Nicole D. Armstrong PhD , Pankaj Arora MD
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引用次数: 0
Abstract
Background
Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown.
Objectives
This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers.
Methods
This study included self-identified Black individuals without prevalent heart failure from 6 TOPMed (Trans-Omics for Precision Medicine) cohorts, the REGARDS (Reasons for Geographic And Racial Differences in Stroke) study, and the All of Us Research Program. The cohort was stratified based on the V142I genotype and the number of CV RFs (hypertension, diabetes, obesity, and hypercholesterolemia). Adjusted Cox models were used to assess the association of heart failure with the V142I genotype and CV RF profile, taking noncarriers with a favorable CV RF profile as reference.
Results
The cross-sectional analysis, including 1,625 V142I carriers among 48,365 Black individuals, found that the prevalence of CV RFs did not vary by V142I carrier status. In the longitudinal analysis, there were 587 (3.2%) V142I carriers among 18,407 Black individuals (median age: 60 years [Q1-Q3: 52-68 years], 63.0% female). Among carriers, the heart failure risk was attenuated with a favorable (0 or 1 RF) CV RF profile (adjusted HR: 2.26; 95% CI: 1.58-3.23) compared with an unfavorable (3 or 4 RFs) CV RF profile (adjusted HR: 4.14; 95% CI: 2.79-6.14).
Conclusions
A favorable CV RF profile lowers but does not abrogate V142I variant-associated heart failure risk. This study highlights the importance of having a favorable CV RF profile among V142I carriers for risk reduction of heart failure.
期刊介绍：
JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.
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