ProBNP That Is Not Glycosylated at Threonine 71 Is Decreased with Obesity in Patients with Heart Failure.

Abstract

BACKGROUND:

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients.

METHODS:

Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were <15%; limits of detection were <21 ng/L; and samples diluted in parallel.

RESULT:

Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44-664), 114 (18-254), and 179 (880-3459) ng/L vs 36 (18-229), 36 (18-175), and 40 (17-68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI <30 kg/m2.

CONCLUSIONS:

Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

• Authors: Lynley K Lewis, Sara D Raudsepp, Timothy C R Prickett, Timothy G Yandle, Robert N Doughty, Christopher M Frampton, Christopher J Pemberton, A Mark Richards
• Journal: Clinical chemistry (Clin Chem) Vol. 65 Issue 9 Pg. 1115-1124 (09 2019) ISSN: 1530-8561 [Electronic] England
• PMID: 31092393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Association for Clinical Chemistry.

Chemical References

• Peptide Fragments
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Threonine

Topics

• Adult
• Body Mass Index
• Female
• Glycosylation
• Heart Failure (blood, diagnosis, metabolism)
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood, chemistry, metabolism)
• Obesity (blood, metabolism)
• Peptide Fragments (blood, chemistry, metabolism)
• Prognosis
• ROC Curve
• Threonine (chemistry)