title: New potential diagnostic biomarkers for pulmonary hypertension.
abstract: This study aimed to determine whether the vascular endothelial growth factor (VEGF) family members soluble VEGF receptor 1 (also called soluble fms-like tyrosine kinase 1 (sFlt-1)) and placental growth factor (PlGF) could be used as biomarkers for pulmonary hypertension (PH). Consecutive patients undergoing right heart catheterisation were enrolled (those with mean pulmonary arterial pressure ≥25 mmHg were classed as having PH; those with mean pulmonary arterial pressure <25 mmHg acted as non-PH controls). Plasma from the time of PH diagnosis was analysed for PlGF and sFlt-1 using enzyme immunoassays. In total, 247 patients with PH were enrolled: 62 with idiopathic pulmonary arterial hypertension (IPAH), 14 with associated pulmonary arterial hypertension (APAH), 21 with collagen vascular disease (CVD), 26 with pulmonary venous hypertension, 67 with lung disease-associated PH and 57 with chronic thromboembolic PH. The non-PH control group consisted of 40 patients. sFlt-1 plasma levels were significantly higher in patients with IPAH, APAH, CVD and lung disease-associated PH versus controls; PlGF levels were significantly higher in all PH groups versus controls. The combination of sFlt-1 and PlGF resulted in a sensitivity of 83.7% with specificity of 100% for pulmonary arterial hypertension. There was no association between sFlt-1 or PlGF and haemodynamic parameters, 6-min walking distance or survival. In summary, PlGF and sFlt-1 are promising diagnostic biomarkers for PH.
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany Both authors contributed equally to this work.
authors.forename: Svenja L
authors.initials: SL
authors.lastname: Tiede
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany Dept of Pneumology, Kerckhoff Clinic, Bad Nauheim, Germany Both authors contributed equally to this work.
authors.forename: Henning
authors.initials: H
authors.lastname: Gall
authors.affiliation: Dept of Internal Medicine I, Cardiology/Angiology, Giessen University, Giessen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dörr
authors.forename: Marina
authors.initials: M
authors.lastname: dos Santos Guilherme
authors.affiliation: Dept of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Troidl
authors.affiliation: Dept of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.affiliation: Dept of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Voss
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany Dept of Pneumology, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Dept of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.affiliation: Department of Cardiology and Molecular Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: Department of Cardiology and Molecular Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
authors.affiliation: Department of Cardiology and Molecular Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany Dept of Pneumology, Kerckhoff Clinic, Bad Nauheim, Germany Dept of Medicine, Imperial College London, London, UK ardeschir.ghofrani@innere.med.uni-giessen.de.
authors.forename: Hossein Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Dept of Internal Medicine I, Cardiology/Angiology, Giessen University, Giessen, Germany.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Nef
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D016022:Case-Control Studies; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification* / Q000175:diagnosis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood*; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1