Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study
| Autor: | Rhodes, C.J., Wharton, J., Ghataorhe, P., Watson, G., Girerd, B., Howard, L.S., Gibbs, J.S.R., Condliffe, R., Elliot, C.A., Kiely, D.G., Simonneau, G., Montani, D., Sitbon, O., Gall, H., Schermuly, R.T., Ghofrani, H.A., Lawrie, A., Humbert, M., Wilkins, M.R. |
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| Přispěvatelé: | Imperial College Healthcare NHS Trust, National Institute for Health Research, British Heart Foundation, Wellcome Trust, Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
EXPRESSION
Adult Male Proteomics Proteome Hypertension Pulmonary Respiratory System BIOMARKERS DIAGNOSIS Risk Assessment 1117 Public Health and Health Services Cohort Studies PREDICTING SURVIVAL Critical Care Medicine Risk Factors General & Internal Medicine Humans Arterial Pressure Familial Primary Pulmonary Hypertension Aged Science & Technology IDENTIFICATION RECEPTOR Gene Expression Profiling 1103 Clinical Sciences Blood Proteins Articles Middle Aged ST2 Hypertension Female Life Sciences & Biomedicine 1199 Other Medical and Health Sciences |
| Zdroj: | The Lancet. Respiratory Medicine |
| ISSN: | 2213-2619 2213-2600 |
| Popis: | Summary Background Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. Methods In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint. Findings 20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77–0·89; p |
| Databáze: | OpenAIRE |
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