Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/40855
Title: Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure.
Authors: Emmens, Johanna Elisabeth
Jones, Donald J. L.
Cao, Thong H.
Chan, Daniel C. S.
Romaine, Simon P. R.
Quinn, Paulene A.
Anker, Stefan D.
Cleland, John G.
Dickstein, Kenneth
Filippatos, Gerasimos
Hillege, Hans L.
Lang, Chim C.
Ponikowski, Piotr
Samani, Nilesh J.
van Veldhuisen, Dirk J.
Zannad, Faiz
Zwinderman, Aeilko H.
Metra, Marco
de Boer, Rudolf A.
Voors, Adrian A.
Ng, Leong L.
First Published: 18-Dec-2017
Publisher: Wiley for European Society of Cardiology
Citation: European Journal of Heart Failure, 2017
Abstract: 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.
DOI Link: 10.1002/ejhf.1101
ISSN: 1388-9842
eISSN: 1879-0844
Links: http://onlinelibrary.wiley.com/doi/10.1002/ejhf.1101/abstract
http://hdl.handle.net/2381/40855
Embargo on file until: 18-Dec-2018
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Wiley for European Society of Cardiology. Deposited with reference to the publisher’s open access archiving policy.
Description: 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.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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