The prognostic significance of the V122I variant (associated with wt-ATTR) in Black women has not yet been established.
A substudy of the WHI aimed to establish the association of the V122I variant with a composite of CVD and all-cause mortality in Black Women.
The V122I variant was associated with increased composite CVD and all-cause mortality in Black women; this association was particularly significant for women age 60+.
Transthyretin amyloidosis (ATTR) is an important cause of heart failure and is associated with high morbidity and mortality. There are two primary types of ATTR: hereditary (vATTR) and wild-type (wt-ATTR); each is associated with a set of genetic variants. The V122I (pV142I) variant is one of the common variants associated with wt-ATTR and is present in the USA, Caribbean, and Africa. The prognosis of this variant and any associations with underlying sex or race is so far unclear. In a breaking presentation at the 2023 ACC Conference today, Dr. Bernhard Haring (Saarland University Hospital) and his team presented their study: “Cardiovascular Disease and Mortality in Black Women carrying the Amyloidogenic V122I (pV142I) Variant: Results from the Women‘s Health Initiative.”
This substudy of the Women’s Health Initiative (WHI) was a longitudinal population-based study of postmenopausal women enrolled at 40 US clinical centers. Generally healthy women were followed for a median of 16 years. Of these, 9,862 non-Hispanic Black/African American women with available genotyping data were identified, of whom there were 333 TTR V122I carriers (3.4%). Relevant covariates included BP, HR, BMI, and physical index.
Of the carriers, the average age was 61, and 44% had a BMI>30. Carrier status was associated with an increase in the composite endpoint, including coronary artery disease, heart failure, stroke, and CVD death, after multivariable adjustment (aHR 1.52; 95% CI 1.22-1.88, p< 0.0001). Carrier status was also associated with increased all-cause mortality (aHR 1.28; 95% CI 1.04-1.56, p=0.02) as well as all the individual components of the composite other than stroke (all p<0.001). When the association between carrier status and the composite was stratified by age, this observed risk was highest in women age 60-64 (p<0.0002) and 65+ (p<0.002).
When discussing the clinical implications of the study at ACC, Dr. Haring stated: “Black female TTR V122I carriers have a substantially higher CVD and all-cause mortality risk which will inevitably become more important with age…these results challenge the “dogma“ of women being less affected…Black women age 50 to 55 with clinical suspicion of amyloidosis (“red flags”) should be screened for TTR V122I carrier status to ensure timely treatment onset.”