Black women with genetic variant for amyloidosis face substantial CVD, mortality risk
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NEW ORLEANS — Black female carriers of the V122I genetic variant for cardiac amyloidosis have substantially higher CVD and all-cause mortality risk, which grows with age, compared with noncarriers, researchers reported.
Transthyretin amyloidosis, or ATTR cardiomyopathy, is hypothesized to be more common in men than women, leading researchers to question if female sex is protective or if the condition is underdiagnosed in women, Bernhard Haring, MD, MPH, of Saarland University Hospital, Germany, and Albert Einstein College of Medicine, New York, said during a Clinical and Investigative Horizons presentation at the American College of Cardiology Scientific Session. ATTR is increasingly recognized as an important cause of disease, especially HF; the hereditary V122I variant originated in West Africa and effects the heart, soft tissue and the peripheral nervous system.
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“That was the reason why we undertook this study,” Haring said. “We wanted to investigate the prognostic implications of the TTR mutation in women.”
Haring and colleagues analyzed data from 9,862 non-Hispanic Black women with genotyping data who participated in the Women’s Health Initiative (1993-1998), a longitudinal population-based study of postmenopausal women enrolled at 40 U.S. centers. The findings were simultaneously published in JACC: Heart Failure.
The cohort was followed for a mean of 16.1 years; women were generally healthy at baseline.
Within the cohort, 333 women (3.4%) were TTR V122I carriers.
“That is not a zebra we are talking about; that is 3.4% prevalence in a large U.S. population,” Haring said during the presentation.
The primary outcome was CVD and the secondary outcome was all-cause mortality.
Compared with noncarriers, women who carried the variant had similar systolic and diastolic BP, heart rate, BMI and physical activity levels.
In multivariate-adjusted analysis that included age, women carriers were 52% more likely to develop CVD during follow-up compared with noncarriers (HR = 1.52; 95% CI, 1.22-1.88; P = .0001) and 28% more likely to die of any cause (HR = 1.28; 95% CI, 1.04-1.56; P = .02).
Assessing component CVD events, female carriers were more than twice as likely to develop acute HF during follow-up vs. noncarriers (HR = 2.21; 95% CI, 1.53-3.18; P < .0001). Compared with noncarriers, HRs were 1.8 for CHD (95% CI, 1.3-2.47; P = .0003) and 1.7 for CV death (HR = 1.7; 95% CI, 1.26-2.3; P = .001). Researchers did not observe an increased risk for stroke among carriers vs. noncarriers.
“These hazard ratios are consistent with what has been reported previously in other population-based cohort studies,” Haring said.
In analyses stratified by age, female carriers were at twice the risk for CVD at age 60 to 64 years (HR = 2.03; 95% CI, 1.39-2.95; P = .0002) compared with same-aged noncarriers. The elevated risk remained for carriers aged 65 years or older vs. noncarriers of the same age (HR = 1.66; 95% CI, 1.21-2.3; P = .002), but was not present in carriers aged 59 years or younger.
All-cause mortality risk also grew with age; female carriers aged 60 to 64 years were more likely to die during follow-up compared with same-aged noncarriers (HR = 1.37; 95% CI, 0.93-2.02; P = .11), as were women carriers aged 65 years or older (HR = 1.54; 95% CI, 1.17-2.04; P = .002), but not women carriers aged 59 years or younger.
In interaction analyses, systolic and diastolic BP, heart rate, BMI and physical activity did not significantly change between the two groups over time.
“That was a surprising finding for us,” Haring said.
Haring noted that the study lacks detailed imaging or endomyocardial biopsies, and there were insufficient data on homozygous women.
“These results challenge the dogma of women being less affected,” Haring said. “Black women aged 50 to 55 years — that is approximately 10 years before the onset of disease — if they have clinical suspicion of amyloidosis, red flags such as increased left ventricular wall thickness, family history, carpal tunnel syndrome, these women should be screened for carrier status to ensure timely treatment.”
Reference:
Perspective
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Michelle A. Albert, MD, MPH, FACC, FAHA
TTR amyloidosis-induced HF is more prevalent among Black individuals than other race and ethnic groups. This study extended information to focus on African American women, especially at earlier ages than previously studied. Study results underscore the importance of having Black women diagnosed as early as possible, especially by age 50 or younger, with this genetic cause of HF, as when someone gets to age 65, the time to severe HF and death can be faster.
Of note, 61% of these women had hypertension. That is important because when women show up with hearts that are hypertrophied or especially thick, health care professionals might tend to say that it is due to hypertension, but we should also be looking at potential genetic causes, especially if persons have accompanying neurological symptoms such as neuropathy or carpal tunnel syndrome. Hypertrophied hearts might not be exclusive to hypertension, and could be from both hypertension and genetic causes, and in that case, these women need to be treated for both things.
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Haring B, et al. Clinical and Investigative Horizons. Presented at: American College of Cardiology Scientific Session; March 4-6, 2023; New Orleans (hybrid meeting).
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