Cardiovascular Disease and Mortality in Black Women Carrying the Amyloidogenic V122I Transthyretin Gene Variant

Bernhard Haring, Department of Medicine III, Saarland University Hospital, Homburg, Saarland, Germany; Department of Medicine I, University of Würzburg, Würzburg, Bavaria, Germany; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. Electronic address: Bernhard.Haring@uks.eu.
Rebecca P. Hunt, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Aladdin H. Shadyab, Herbert Wertheim School of Public Health and Human Longevity Science, University of California-San Diego, La Jolla, California, USA.
Charles Eaton, Center for Primary Care and Prevention, Department of Family Medicine, Department of Epidemiology, Warren Alpert Medical Scholl of Brown University, Brown University School of Public Health, Providence, Rhode Island, USA.
Robert Kaplan, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Lisa Warsinger Martin, Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Gurusher Panjrath, Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Lewis H. Kuller, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Themistocles Assimes, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; VA Palo Alto Health Care System, Palo Alto, California, USA.
Charles Kooperberg, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Sylvia Wassertheil-Smoller, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.

Document Type

Journal Article

Publication Date

3-5-2023

Journal

JACC. Heart failure

DOI

10.1016/j.jchf.2023.02.003

Keywords

V122I; cardiovascular disease; mortality; pV142I; postmenopausal women; transthyretin amyloidosis

Abstract

BACKGROUND: Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown. OBJECTIVES: The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women. METHODS: The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers and 333 TTR V122I carriers, enrolled in the Women's Health Initiative at 40 centers in the United States. Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95% CIs were obtained from adjusted Cox proportional hazards models. RESULTS: Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95% CI: 1.22-1.88), acute heart failure (HR: 2.21; 95% CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95% CI: 1.30-2.47), CVD death (HR: 1.70; 95% CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95% CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity. CONCLUSIONS: Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.

Department

Medicine

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