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01.12.2018 | Original investigation | Ausgabe 1/2018 Open Access

Cardiovascular Diabetology 1/2018

Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP

Zeitschrift:
Cardiovascular Diabetology > Ausgabe 1/2018
Autoren:
Annette Masuch, Maik Pietzner, Martin Bahls, Kathrin Budde, Gabi Kastenmüller, Stephanie Zylla, Anna Artati, Jerzy Adamski, Henry Völzke, Marcus Dörr, Stephan B. Felix, Matthias Nauck, Nele Friedrich
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12933-018-0765-1) contains supplementary material, which is available to authorized users.
Annette Masuch and Maik Pietzner contributed equally to this work

Abstract

Background

The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach.

Methods

Lipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine.

Results

An increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles.

Conclusions

Most of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.
Zusatzmaterial
Additional file 1. Detailed methods description and supporting results. Population characteristics for the replication population SHIP-2 and the results for the in-depth analysis of the lipoprotein profile are presented. Furthermore, the results of the sensitivity analysis on the influence of lipid lowering drugs on the lipoprotein profile is given.
Literatur
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