New Potential Diagnostic Biomarkers for Pulmonary Hypertension
Svenja L. Tiede, PhD1*; Henning Gall, MD1*; Oliver Dörr, MD2; Christian Troidl, PhD3; Christoph Liebetrau, MD3; Sandra Voss, DVM3 ; Robert Voswinckel, MD1; Ralph T. Schermuly, PhD1; Werner Seeger, MD1; Friedrich Grimminger, PhD1; Andreas M. Zeiher, MD3; Stefanie Dimmeler, PhD4; Helge Möllmann, MD4; Christian W. Hamm, MD4; Hossein Ardeschir Ghofrani, MD1;Holger M. Nef, MD2
1University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany; 2Giessen University, Department of Internal Medicine I, Cardiology/Angiology, Giessen, Germany;3Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany 4Johann Wolfgang Goethe University, Department of Cardiology and Molecular Cardiology, Frankfurt, Germany.
*Svenja L. Tiede and Henning Gall contributed equally to this work.
Take home message
Several published biomarkers show potential as disease severity and/or prognostic biomarker, but to date no biomarker is established to diagnose or exclude pulmonary hypertension. This study shows a high potential for the VEGF family members placental growth factor and soluble fms-like tyrosine kinase 1 as diagnostic biomarkers for pulmonary hypertension.
Abstract
This study aimed to determine whether the VEGF family members soluble VEGF receptor 1 (sVEGFR1/soluble fms-like tyrosine kinase 1, sFlt-1) and placental growth factor (PlGF) could be used as biomarkers for PH.
Consecutive patients undergoing right heart catheterization were enrolled (those with mPAP ≥25 mmHg were classed as having PH; those with mPAP <25 mmHg acted as non-PH controls). Plasma from the time of PH diagnosis was analyzed 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 LD-PH vs controls; PlGF levels were significantly higher in all PH groups vs controls. PlGF and sFlt-1 combined had a sensitivity of 62.4% and a specificity of 100% to detect any PH etiology. There was no association between sFlt-1 or PlGF and hemodynamic parameters, 6-minute walking distance, or survival.
In summary, PlGF and sFlt-1 are promising diagnostic biomarkers for PH.