The V142I variant of the transthyretin gene increases the risk of heart failure in Black Americans by age 63 and mortality by age 72, according to a recent study.

The findings shed light on the significant cardiovascular risks faced by carriers of the V142I variant, a genetic variation in the transthyretin (TTR) gene present in 3% to 4% of Black Americans. This variant causes the TTR protein to misfold and accumulate in the heart, leading to transthyretin cardiac amyloidosis (ATTR-CA).

Data from 4 large cohort studies, comprising 23,338 self-reported Black participants initially free from heart failure (HF), were analyzed in the study published in JAMA. The mean age at baseline was 62 years, and 76.7% were women.

The researchers found that carriers of the V142I variant faced a significantly higher risk of HF hospitalization by age 63 years and all-cause mortality by age 72 years. Carriers also had an increased 10-year risk for HF hospitalization and mortality, with age being the only significant modifier. The estimated reduction in longevity ranged from 1.9 years at age 50 to 2.8 years at age 81. Researchers estimated that this variant contributes to approximately 1 million years of life lost among Black Americans aged 50 years and older.

"Given established and emerging treatment strategies, which may be more effective earlier in disease course, early identification and treatment of V142I carriers with ATTRv-CA may have significant public health impact," noted researchers. "Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation."

Several authors reported receiving grants and personal fees from various organizations, including pharmaceutical companies, the NIH, and the British Heart Foundation.