Proteomic diversity of high‐density lipoprotein explains its association with clinical outcome in patients with heart failure |
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| Authors: | Johanna Elisabeth Emmens Donald JL Jones Thong H Cao Daniel CS Chan Simon PR 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 Adriaan A Voors Leong L Ng |
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| Institution: | 1. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;2. Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary, Leicester, UK;3. Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK;4. Department of General Internal Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam;5. Division of Cardiology and Metabolism 6. – 7. Heart Failure, Cachexia and Sarcopenia, Department of Cardiology (CVK);8. and Berlin‐Brandenburg Center for Regenerative Therapies (BCRT), Deutsches Zentrum für Herz‐Kreislauf‐Forschung (DZHK) Berlin, Charité Universit?tsmedizin Berlin, Germany;9. Department of Cardiology and Pneumology, University Medical Center G?ttingen (UMG), G?ttingen, Germany;10. National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK;11. University of Bergen, Bergen, Norway;12. Stavanger University Hospital, Stavanger, Norway;13. National and Kapodistrian University of Athens, School of Medicine, Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, Athens, Greece;14. School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK;15. Department of Heart Diseases, Wroclaw Medical University, and Cardiology Department, Military Hospital, Wroclaw, Poland;16. Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France;17. Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands;18. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy |
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| 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. |
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| Keywords: | Heart failure High‐density lipoprotein Proteome |
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