Laurie W Geenen1, Vivan J M Baggen1, Thomas Koudstaal2, Karin A Boomars2, Jannet A Eindhoven1, Eric Boersma3, Jolien W Roos-Hesselink1, Annemien E van den Bosch4. 1. Department of Cardiology, Erasmus Medical Centre, Rotterdam, the Netherlands. 2. Department of Pulmonary Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands. 3. Department of Cardiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Clinical Epidemiology, Erasmus Medial Centre, Rotterdam, the Netherlands. 4. Department of Cardiology, Erasmus Medical Centre, Rotterdam, the Netherlands. Electronic address: a.e.vandenbosch@erasmusmc.nl.
Abstract
BACKGROUND: This study aimed to investigate the prognostic value of six different biomarkers in patients with pulmonary hypertension (PH) and to explore whether a multi-biomarker approach can contribute to a better risk stratification. METHODS: In this prospective study, patients with PH were included at the day of the diagnostic right heart catheterization between May 2012 and October 2016. Venous blood sampling included; NT-proBNP, high sensitive troponin-T, high sensitive CRP, galectin-3, red blood cell distribution width and eGFR. Associations between biomarker levels and the primary endpoint (death or lung transplantation) and secondary endpoint (death, lung transplantation or heart failure) were assessed with Cox regression, adjusted for age and sex. Additionally, adjustment for the REVEAL risk score was performed. RESULTS: In total, 106 patients were included (median age 58.7 [IQR 47.0-69.2] years, 64% women, 51% pulmonary arterial hypertension). After a median follow-up duration of 23.9 [IQR 15.1-40.0] months, respectively 29 and 37 patients reached the primary and secondary endpoint. All six biomarkers, except eGFR, were significantly associated with the endpoints. A multi-biomarker approach including the number of elevated biomarkers per patient, demonstrated that patients were at higher risk of adverse events as more biomarker levels were elevated (HR for each extra elevated biomarker; 1.33, 95% CI 1.07-1.64, P = .01). However, a single as well as a combination of multiple biomarkers, did not yield prognostic value independent of the REVEAL risk score. CONCLUSIONS: Various biomarkers are associated with the event-free survival in adults with PH. However, risk stratification exclusively based on single or a combination of biomarkers seems not superior to existing risk scores.
BACKGROUND: This study aimed to investigate the prognostic value of six different biomarkers in patients with pulmonary hypertension (PH) and to explore whether a multi-biomarker approach can contribute to a better risk stratification. METHODS: In this prospective study, patients with PH were included at the day of the diagnostic right heart catheterization between May 2012 and October 2016. Venous blood sampling included; NT-proBNP, high sensitive troponin-T, high sensitive CRP, galectin-3, red blood cell distribution width and eGFR. Associations between biomarker levels and the primary endpoint (death or lung transplantation) and secondary endpoint (death, lung transplantation or heart failure) were assessed with Cox regression, adjusted for age and sex. Additionally, adjustment for the REVEAL risk score was performed. RESULTS: In total, 106 patients were included (median age 58.7 [IQR 47.0-69.2] years, 64% women, 51% pulmonary arterial hypertension). After a median follow-up duration of 23.9 [IQR 15.1-40.0] months, respectively 29 and 37 patients reached the primary and secondary endpoint. All six biomarkers, except eGFR, were significantly associated with the endpoints. A multi-biomarker approach including the number of elevated biomarkers per patient, demonstrated that patients were at higher risk of adverse events as more biomarker levels were elevated (HR for each extra elevated biomarker; 1.33, 95% CI 1.07-1.64, P = .01). However, a single as well as a combination of multiple biomarkers, did not yield prognostic value independent of the REVEAL risk score. CONCLUSIONS: Various biomarkers are associated with the event-free survival in adults with PH. However, risk stratification exclusively based on single or a combination of biomarkers seems not superior to existing risk scores.
Authors: Zongye Cai; Siyu Tian; Theo Klein; Ly Tu; Laurie W Geenen; Thomas Koudstaal; Annemien E van den Bosch; Yolanda B de Rijke; Irwin K M Reiss; Eric Boersma; Claude van der Ley; Martijn Van Faassen; Ido Kema; Dirk J Duncker; Karin A Boomars; Karin Tran-Lundmark; Christophe Guignabert; Daphne Merkus Journal: Sci Rep Date: 2022-07-19 Impact factor: 4.996
Authors: Denise van Uden; Thomas Koudstaal; Jennifer A C van Hulst; Madelief Vink; Menno van Nimwegen; Leon M van den Toorn; Prewesh P Chandoesing; Annemien E van den Bosch; Mirjam Kool; Rudi W Hendriks; Karin A Boomars Journal: Int J Mol Sci Date: 2022-06-10 Impact factor: 6.208
Authors: Andriy O Samokhin; Steven Hsu; Paul B Yu; Aaron B Waxman; George A Alba; Bradley M Wertheim; C Danielle Hopkins; Frederick Bowman; Richard N Channick; Ivana Nikolic; Mariana Faria-Urbina; Paul M Hassoun; Jane A Leopold; Ryan J Tedford; Corey E Ventetuolo; Peter J Leary; Bradley A Maron Journal: J Heart Lung Transplant Date: 2019-12-31 Impact factor: 10.247
Authors: Laurie W Geenen; Lucas Uchoa de Assis; Vivan J M Baggen; Jannet A Eindhoven; Judith A A E Cuypers; Eric Boersma; Jolien W Roos-Hesselink; Annemien E van den Bosch Journal: Int J Cardiol Heart Vasc Date: 2020-07-21
Authors: Zongye Cai; Theo Klein; Laurie W Geenen; Ly Tu; Siyu Tian; Annemien E van den Bosch; Yolanda B de Rijke; Irwin K M Reiss; Eric Boersma; Dirk J Duncker; Karin A Boomars; Christophe Guignabert; Daphne Merkus Journal: J Clin Med Date: 2020-04-25 Impact factor: 4.241
Authors: T Koudstaal; D van Uden; J A C van Hulst; P Heukels; I M Bergen; L W Geenen; V J M Baggen; A E van den Bosch; L M van den Toorn; P P Chandoesing; M Kool; E Boersma; R W Hendriks; K A Boomars Journal: Respir Res Date: 2021-05-04
Authors: Laurie W Geenen; Vivan J M Baggen; Robert M Kauling; Thomas Koudstaal; Karin A Boomars; Eric Boersma; Jolien W Roos-Hesselink; Annemien E van den Bosch Journal: J Clin Med Date: 2019-09-20 Impact factor: 4.241
Authors: Samara M A Jansen; Anna E Huis In 't Veld; Wouter Jacobs; Hans P Grotjohan; Marc Waskowsky; Jan van der Maten; Arno van der Weerdt; Romke Hoekstra; Maria J Overbeek; Sjoerd A Mollema; Peter Hans C G Tolen; Lahssan H Hassan El Bouazzaoui; Joris W J Vriend; J Milena M Roorda; Ramon de Nooijer; Ivo van der Lee; Bart A J Voogel; Kathinka Peels; Thomas Macken; Jacqueline M Aerts; Anton Vonk Noordegraaf; M Louis Handoko; Frances S de Man; Harm Jan Bogaard Journal: J Am Heart Assoc Date: 2020-07-31 Impact factor: 5.501
Authors: Tadeu L Montagnoli; Jaqueline S da Silva; Susumu Z Sudo; Aimeé D Santos; Gabriel F Gomide; Mauro P L de Sá; Gisele Zapata-Sudo Journal: Cells Date: 2021-06-30 Impact factor: 7.666