Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure

Emmens, J. E. et al. (2018) Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure. European Journal of Heart Failure, 20(2), pp. 260-267. (doi: 10.1002/ejhf.1101) (PMID:29251807)

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Aims: Previously, low high-density lipoprotein (HDL) cholesterol was found to be one of the strongest predictors of mortality and/or heart failure (HF) hospitalisation in patients with HF. We therefore performed in-depth investigation of the multifunctional HDL proteome to reveal underlying pathophysiological mechanisms explaining the association between HDL and clinical outcome. Methods and results: We selected a cohort of 90 HF patients with 1:1 cardiovascular death/survivor ratio from BIOSTAT-CHF. A novel optimised protocol for selective enrichment of lipoproteins was used to prepare plasma. Enriched lipoprotein content of samples was analysed using high resolution nanoscale liquid chromatography-mass spectrometry-based proteomics, utilising a label free approach. Within the HDL proteome, 49 proteins significantly differed between deaths and survivors. An optimised model of 12 proteins predicted death with 76% accuracy (Nagelkerke R2=0.37, P < 0.001). The strongest contributors to this model were filamin-A (related to crosslinking of actin filaments) [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.15–0.61, P = 0.001] and pulmonary surfactant-associated protein B (related to alveolar capillary membrane function) (OR 2.50, 95% CI 1.57–3.98, P < 0.001). The model predicted mortality with an area under the curve of 0.82 (95% CI 0.77–0.87, P < 0.001). Internal cross validation resulted in 73.3 ± 7.2% accuracy. Conclusion: This study shows marked differences in composition of the HDL proteome between HF survivors and deaths. The strongest differences were seen in proteins reflecting crosslinking of actin filaments and alveolar capillary membrane function, posing potential pathophysiological mechanisms underlying the association between HDL and clinical outcome in HF.

Item Type:Articles
Additional Information:BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29].
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Emmens, J. E., Jones, D. J.L., Cao, T. H., Chan, D. C.S., Romaine, S. P.R., Quinn, P. A., Anker, S. D., Cleland, J. G., Dickstein, K., Filippatos, G., Hillege, H. L., Lang, C. C., Ponikowski, P., Samani, N. J., van Veldhuisen, D. J., Zannad, F., Zwinderman, A. H., Metra, M., de Boer, R. A., Voors, A. A., and Ng, L. L.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:18 December 2017
Copyright Holders:Copyright © 2017 The Authors and European Society of Cardiology
First Published:First published in European Journal of Heart Failure 20(2):260-267
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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