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Proteomic diversity of high‐density lipoprotein explains its association with clinical outcome in patients with heart failure
Author(s) -
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 Adriaan A.,
Ng Leong L.
Publication year - 2018
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1101
Subject(s) - medicine , proteome , heart failure , confidence interval , odds ratio , lipoprotein , filamin , cardiology , cholesterol , bioinformatics , cytoskeleton , biology , biochemistry , cell
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 R 2 =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.