@article {9869, title = {Cardiovascular Risk Factors and Genetic Risk in Transthyretin V142I Carriers.}, journal = {JACC Heart Fail}, volume = {13}, year = {2025}, month = {2025 Jan}, pages = {91-101}, 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.

}, keywords = {Aged, Black or African American, Cardiovascular Diseases, Cross-Sectional Studies, Diabetes Mellitus, Female, Genotype, Heart Disease Risk Factors, Heart Failure, Heterozygote, Humans, Hypercholesterolemia, Hypertension, Male, Middle Aged, Obesity, Prealbumin, Risk Factors, United States}, issn = {2213-1787}, doi = {10.1016/j.jchf.2024.08.019}, author = {Shetty, Naman S and Gaonkar, Mokshad and Pampana, Akhil and Patel, Nirav and Morrison, Alanna C and Reiner, Alexander P and Carson, April P and Yu, Bing and Psaty, Bruce M and Kooperberg, Charles and Fatkin, Diane and Boerwinkle, Eric and Rotter, Jerome I and Taylor, Kent D and Hou, Lifang and Irvin, Marguerite R and Hall, Michael E and Maurer, Mathew and Fornage, Myriam and Armstrong, Nicole D and Bart, Nicole and Goyal, Parag and Rich, Stephen S and Vasan, Ramachandran S and Li, Peng and Arora, Garima and Arora, Pankaj} }