Abstract 16095: Plasma NT-proBNP Concentrations are Two-fold Lower in Pacific versus European Population Samples: Evidence for Glycosylation Impacting Assay Detection and/or ProBNP Processing

Abstract

Introduction: Pacific Islanders in New Zealand (NZ) have high rates of cardiovascular and metabolic disorders. The Pasifika Heart Study (PHS) recorded ethnic-specific clinical and biomarker data to inform clinical management in community care. Methods: For the PHS, Pacific adults (n=200) aged 20-64 years were selected from patients of a Pacific-led health centre in Christchurch, NZ, and screened for existing cardio-metabolic disorders and risk factors. Circulating concentrations of NT-proBNP (Roche Cobas NT-proBNP II), total proBNP and proBNP not glycosylated at Threonine 71 (T71) residue (both by in-house Luminex assays) were measured. Assay data were compared with European participants in the INSPIRE study (n=103 healthy volunteers, 20-70 years). Results: PHS participants had a mean age (SD) of 41.7 (11.5) years, 48% were male, mostly of Samoan and Tongan ethnicities (44% and 32% respectively). INSPIRE European participants had a mean age of 46.8 (15.0) years, 46% were male. NTproBNP concentrations measured by Cobas were two-fold lower in the PHS (median = 18.4 ng/L, IQR = [7.3, 35.8]) compared with INSPIRE (40.0 ng/L [19.8, 70.2]) (p<0.001). Moreover, consistently lower concentrations were observedin PHS across a spectrum of either age or BMI (see Figure). In contrast, total proBNP concentrations exhibited a broad range in both cohorts, but did not differ between PHS (192.8 [35.7, 414.2] ng/L) and INSPIRE (36.1 [36.1, 225.1] ng/L, p<0=0.278). This suggests that in the PHS, either the Cobas assay underestimates NT-proBNP due to glycosylation of antibody-binding sites and / or proBNP is not processed to NTproBNP due to glycosylation at the T71 cleavage site. As evidence for the latter, only 8% of PHS had proBNP not glycosylated at T71 versus 31% of INSPIRE (p<0.001). Conclusions: Use of NT-proBNP thresholds based on European reference ranges to assess cardiovascular risk in community care may lead to under-diagnosis of evolving heart failure in Pacific Islanders.