Abstract
Introduction: A non-cardiac blood based biomarker could enhance treatment monitoring and prognostication for pulmonary hypertension (PH). We investigated the diagnostic and prognostic value of hepatoma derived growth factor (HDGF), a pulmonary angiogenic factor in PH. Methods: Using a cohort of Johns Hopkins Pulmonary Hypertension Clinic patients (JHPH, n=73; 49% idiopathic PAH, 51% PAH associated with scleroderma), a healthy control group (n=30) and Johns Hopkins Emergency Department (ED) patients with left sided heart failure (N=55) or chronic illnesses (DM, hypertension, hypercholesterolemia, or smoking, N=66), we investigated the association of HDGF and NT-proBNP and the diagnosis of PH, PH survival, left sided heart failure and chronic disease. Results: HDGF concentrations were significantly elevated in PH versus healthy controls (p=0.013), left sided heart failure (p=0.0026) or chronic disease (p=0.0002), but were not significantly different between healthy controls versus left sided heart failure (P=0.70) or chronic disease (P=0.29). Among PH subjects, the area under the receiver operator curve (AUC) for discriminating survival was 0.71 (p=0.001) for HDGF, with no significant difference between the survival AUC for HDGF and NT-proBNP (p=0.66). The hazard ratio of survival for a HDGF concentration of >0.426 ng/mL was 3.7 (95% CI: 1.5-8.7, P=0.02) and when adjusted for NT-proBNP increased to 4.5 (95% CI: 1.0-20.1, P <0.05) (figure 1). HDGF concentrations were significantly associated with decreased six minute walk distance (6MWD; p=0.04) but not mean PA pressure (p=0.8) or PVR (p=0.4). Conclusion: HDGF is a novel non-cardiac PH biomarker equivalent to NT-proBNP, not confounded by left sided heart failure and significantly associated with 6MWD, the single most important clinical functional measure in PH. Thus, HDGF may add additional value in PH risk stratification for clinical trials as well as future PH drug development.
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