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Arthritis Res Ther. 2015 Aug 6;17:201. doi: 10.1186/s13075-015-0712-4.

Biomarkers of pulmonary hypertension in patients with scleroderma: a case-control study.

Author information

1
Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Suite 4000, Baltimore, MD, 21224, USA. zmcmaha1@jhmi.edu.
2
Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Suite 4000, Baltimore, MD, 21224, USA. florian.schoenhoff@gmail.com.
3
Department of Cardiovascular Surgery, University Hospital Berne, Berne, Switzerland. florian.schoenhoff@gmail.com.
4
Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Suite 4000, Baltimore, MD, 21224, USA. jennifer.vaneyk@cshs.org.
5
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. jennifer.vaneyk@cshs.org.
6
Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. jennifer.vaneyk@cshs.org.
7
Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. jennifer.vaneyk@cshs.org.
8
Present address: Advanced Clinical Biosystems Research Institute, Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedar-Sinai Medical Center, Los Angeles, CA, 90048, USA. jennifer.vaneyk@cshs.org.
9
Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Suite 4000, Baltimore, MD, 21224, USA. fwig@jhmi.edu.
10
Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Suite 4000, Baltimore, MD, 21224, USA. lhummers@jhmi.edu.

Abstract

INTRODUCTION:

Significant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma.

METHODS:

The circulating growth factors basic fibroblast growth factor, placental growth factor (PlGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor, and soluble VEGF receptor 1 (sFlt-1), as well as cytokines (interleukin [IL]-1β IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor-α, and interferon-γ), were quantified in patients with scleroderma with PH (n = 37) or without PH (n = 40). In non-parametric unadjusted analyses, we examined associations of growth factor and cytokine levels with PH. In a subset of each group, a second set of earlier samples, drawn 3.0±1.6 years earlier, were assessed to determine the changes over time.

RESULTS:

sFlt-1 (p = 0.02) and PlGF (p = 0.02) were higher in the PH than in the non-PH group. sFlt-1 (ρ = 0.3245; p = 0.01) positively correlated with right ventricular systolic pressure. Both PlGF (p = 0.03) and sFlt-1 (p = 0.04) positively correlated with the ratio of forced vital capacity to diffusing capacity for carbon monoxide (DLCO), and both inversely correlated with DLCO (p = 0.01). Both PlGF and sFlt-1 levels were stable over time in the control population.

CONCLUSIONS:

Our study demonstrated clear associations between regulators of angiogenesis (sFlt-1 and PlGF) and measures of PH in scleroderma and that these growth factors are potential biomarkers for PH in patients with scleroderma. Larger longitudinal studies are required for validation of our results.

PMID:
26245195
PMCID:
PMC4527208
DOI:
10.1186/s13075-015-0712-4
[Indexed for MEDLINE]
Free PMC Article

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