An altered plasma lipidome–phenome network characterizes heart failure with preserved ejection fraction

Author:

Jovanovic Nina1234ORCID,Foryst‐Ludwig Anna25,Klose Christian6,da Conceicao Cristina Rozados27,Alasfar Lina178,Birkner Till134,Forslund Sofia K.12349,Kintscher Ulrich25,Edelmann Frank2310

Affiliation:

1. Experimental and Clinical Research Center Charité—Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine Berlin Germany

2. German Centre for Cardiovascular Research (DZHK) Berlin Germany

3. Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

4. Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany

5. Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

6. Lipotype GmbH Dresden Germany

7. Department of Cardiology, Campus Virchow Klinikum Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

8. Department of Pediatric Hematology, Oncology and SCT, Campus Virchow Klinikum Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

9. Structural and Computational Biology Unit EMBL Heidelberg Germany

10. Department of Cardiology, Angiology and Intensive Care Medicine, Campus Virchow Klinikum Deutsches Herzzentrum der Charité Berlin Germany

Abstract

AbstractAimsHeart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF.Methods and resultsWe examined the human plasma lipidome in HFpEF patients (n = 18) with left ventricular ejection fraction ≥50% and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) >125 pg/mL and control subjects (n = 12) using mass spectrometry‐based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8 ± 8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist‐to‐hip ratio. The disease group experienced more fatigue (P < 0.001), had more often coronary artery disease (P = 0.04), and received more medications (beta‐blockers, P < 0.001). The disease group had significantly different levels of HFpEF‐relevant parameters, including NT‐proBNP (P < 0.001), left ventricular mass index (P = 0.005), left atrial volume index (P = 0.001), and left ventricular filling index (P < 0.001), and lower left ventricular end‐diastolic diameter (P = 0.014), with no difference in left ventricular ejection fraction. Significant differences in lipid profiles between HFpEF patients and controls could not be detected, including no significant differences in abundance of circulating lipids binned by carbon chain length or by double bonds, nor at the level of individual lipid species. However, there was a striking correlation between selected lipids with smoking status that was independent of disease status, as well as between specific lipids and hyperlipidaemia [with corresponding significance of either false discovery rate (FDR) <0.1 or FDR < 0.01]. In an exploratory network analysis of correlations, we observed significantly stronger correlations within the HFpEF group between individual lipids from the cholesterol ester and phosphatidylcholine (PC) classes and clinical/echocardiographic parameters such as left atrial volume index, left ventricular end‐diastolic diameters, and heart rate (FDR < 0.1). In contrast, the control group showed significantly stronger negative correlations (FDR < 0.1) between individual species from the PC and sphingomyelin classes and left ventricular mass index or systolic blood pressure.ConclusionsWe did not find significant direct associations between plasma lipidomic parameters and HFpEF and therefore could not conclude that any specific lipids are biomarkers of HFpEF. The validation in larger cohort is needed to confidently conclude the absence of first‐order associations.

Funder

Deutsches Zentrum für Herz-Kreislaufforschung

Deutsche Forschungsgemeinschaft

Bundesministerium für Bildung und Forschung

Publisher

Wiley

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