Retinol Binding Protein 4 (RBP4) May Help Identify Asymptomatic hATTR in V142I Carriers

Kontorovich and colleagues at Mount Sinai Hospital, in New York City, presented information underscoring the need for plasma biomarkers to assist with early detection of preclinical hereditary transthyretin amyloidosis (hATTR). Early identification of patients who are at high genetic risk would enable initiation of treatment when it is likely to be most effective.

In the United States, up to 4% of African Americans have the hATTR variant V142I, which is associated with cardiac amyloidosis and heart failure. Clinical signs and signals may include “red flag diagnoses,” such as carpal tunnel syndrome, spinal stenosis, and polyneuropathy, that often precede a diagnosis of cardiac amyloidosis. V142I carriers with cardiac amyloidosis have increased levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and decreased levels of transthyretin transporter retinol binding protein 4 (RBP4). It is unknown whether either of these biomarkers signal preclinical hATTR.

The investigators identified V142I carriers without a diagnosis of hATTR among approximately 30,000 BioMe Biobank participants with available genotype data, clinical data, and banked plasma.

In total, plasmas from 40 V142I carriers who were heart-healthy and ranged in age between 40 and 60 years were included in the analysis. All patients self-reported as African American, 60% were female, and 50% had preexisting “red flag diagnoses.” Eighty age-, race-, and sex-matched heart-healthy noncarriers were also analyzed for target protein concentrations of RBP4 and NT-proBNP.

In young, heart-healthy V142I carriers compared with noncarriers, RBP4 levels were considerably lower (19.27 compared with 28.43 μg/mL), for both males (21.41 vs 28.42 μg/mL; P = .01) and females (17.85 vs 28.43 μg/mL; P = .01). No association was detected between the presence or absence of “red flag diagnoses” and RBP4 levels. Among V142I carriers and noncarriers, for both females and males, NT-proBNP levels were similar (1.75 vs 1.79; P = .4).

The researchers concluded that RBP4 may be useful in identifying asymptomatic hATTR in V142I carriers. This is especially important in African American populations, who are at increased genetic risk of heart failure. Improved outcomes are associated with earlier diagnosis and treatment. Identifying biomarkers such as RBP4 that may signal preclinical hATTR will enable early detection and improve care delivery and treatment.

Source: Kontorovich A, Abul-Husn N. Plasma biomarkers differentiate young preclinical TTR V142I carriers from non-carriers. Presented at: ACC.21, American College of Cardiology 70th Annual Scientific Session & Expo, May 15-17, 2021. Poster 1032-17.

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