Amanda C Coniglio1, Matthew W Segar2, Rahul S Loungani1, Jainy J Savla3, Justin L Grodin2, Ervin R Fox4, Sonia Garg1, James A de Lemos2, Jarett D Berry2, Mark H Drazner2, Sanjiv Shah5, Michael E Hall4, Amil Shah6, Sadiya S Khan7, Robert J Mentz1, Ambarish Pandey8. 1. Department of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA. 2. Department of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 3. Division of Cardiology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, Washington, USA. 4. Department of Internal Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. 5. Division of Cardiology, Department of Internal Medicine, Northwestern University School of Medicine, Chicago, Illinois, USA. 6. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. 7. Division of Cardiovascular Medicine, Department of Internal Medicine, Northwestern University School of Medicine, Chicago, Illinois, USA. 8. Department of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: ambarish.pandey@utsouthwestern.edu.
Abstract
OBJECTIVES: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults. BACKGROUND: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis. METHODS: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations. RESULTS: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007). CONCLUSIONS: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.
OBJECTIVES: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults. BACKGROUND: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis. METHODS: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations. RESULTS: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007). CONCLUSIONS: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.