University of Leicester
Browse
HDL+BIOSTAT+paper+25-10-2017+Accepted+version.pdf (705.81 kB)

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

Download (705.81 kB)
journal contribution
posted on 2018-01-11, 16:13 authored by Johanna Elisabeth Emmens, Donald J. L. Jones, Thong H. Cao, Daniel C. S. Chan, Simon P. R. Romaine, Paulene A. Quinn, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos Filippatos, Hans L. Hillege, Chim C. Lang, Piotr Ponikowski, Nilesh J. Samani, Dirk J. van Veldhuisen, Faiz Zannad, Aeilko H. Zwinderman, Marco Metra, Rudolf A. de Boer, Adrian A. Voors, Leong L. Ng
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.

Funding

BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29].

History

Citation

European Journal of Heart Failure, 2017

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • AM (Accepted Manuscript)

Published in

European Journal of Heart Failure

Publisher

Wiley for European Society of Cardiology

issn

1388-9842

eissn

1879-0844

Acceptance date

2017-11-09

Copyright date

2017

Available date

2018-12-18

Publisher version

http://onlinelibrary.wiley.com/doi/10.1002/ejhf.1101/abstract

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC