Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry

• Published in: JAMA : the journal of the American Medical Association 2019-12, Vol.322 (22), p.2191-2202
• Main Authors: Damrauer, Scott M, Chaudhary, Kumardeep, Cho, Judy H, Liang, Lusha W, Argulian, Edgar, Chan, Lili, Dobbyn, Amanda, Guerraty, Marie A, Judy, Renae, Kay, Jenna, Kember, Rachel L, Levin, Michael G, Saha, Aparna, Van Vleck, Tielman, Verma, Shefali S, Weaver, JoEllen, Abul-Husn, Noura S, Baras, Aris, Chirinos, Julio A, Drachman, Brian, Kenny, Eimear E, Loos, Ruth J. F, Narula, Jagat, Overton, John, Reid, Jeffrey, Ritchie, Marylyn, Sirugo, Giorgio, Nadkarni, Girish, Rader, Daniel J, Do, Ron
• Format: Article
• Language: English
• Subjects: Academic Medical Centers; African Americans - genetics; Aged; Amyloid; Amyloid Neuropathies, Familial - complications; Amyloid Neuropathies, Familial - ethnology; Amyloid Neuropathies, Familial - genetics; Amyloidosis; Biological Specimen Banks; Cardiomyopathy; Case-Control Studies; Congestive heart failure; Cross-Sectional Studies; Diagnosis; Electronic health records; Electronic medical records; Female; Genetic diversity; Genetic variance; Genetic Variation; Geriatrics; Health care facilities; Health risk assessment; Heart attacks; Heart failure; Heart Failure - ethnology; Heart Failure - genetics; Heart rate; Hereditary diseases; Hispanic Americans; Hispanic Americans - genetics; Humans; Hypertension; Male; Middle Aged; Myocardial infarction; Original Investigation; Prealbumin - genetics; Transthyretin
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2019.17935

IMPORTANCE: Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown. OBJECTIVE: To assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018. EXPOSURES: TTR V122I carrier status. MAIN OUTCOMES AND MEASURES: The primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured. RESULTS: The cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clin