CVD and Mortality in Black Women With V122I Transthyretin Gene Variant
- Older Black women carrying the TTR V122I variant have a substantially elevated risk for CVD and mortality compared to noncarriers.
- Furthermore, the time to incident CVD and mortality was considerably shorter in carriers >65 years of age compared to noncarriers.
- Black women showing possible signs of amyloidosis should be screened for TTR V122I carrier status to ensure early therapy, as newer therapeutics may improve clinical outcomes.
What is the relationship of transthyretin (TTR) V122I (pV142I) carrier status with cardiovascular disease (CVD) and mortality in a large cohort of postmenopausal women?
The investigators analyzed 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. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from adjusted Cox proportional hazards models.
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.
The authors report that Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers.
This cohort study found that older Black women carrying the TTR V122I variant have a substantially elevated risk for CVD and mortality compared to noncarriers. Furthermore, the time to incident CVD and mortality was considerably shorter in carriers >65 years of age compared to noncarriers. Overall, these data suggest that Black women showing possible signs of amyloidosis should be screened for TTR V122I carrier status to ensure early therapy, as the availability of newer therapeutics may improve clinical outcomes. These findings are particularly important because they add to data on a substantially under-represented group of patients in amyloidosis studies, namely, Black women.
Keywords: Acute Heart Failure, African Americans, Amyloidosis, Genetics, Postmenopause
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