Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

• Grant number: 11/17761-9
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2011
• End date: March 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Antonio Augusto Barbosa Lopes
• Grantee: Antonio Augusto Barbosa Lopes
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Biomarkers have been identified in pulmonary arterial hypertension (PAH), but are less well defined in specific etiologies such as congenital-heart-disease associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and explored possible associations with survival. A cohort of 46 inoperable CHDPAH patients (aged 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator and its inhibitor, P-selectin, reactive C-protein, tumor necrosis factor alfa, and interleukins 6 and 10 were measured at baseline, and 30, 90 and 180 days in all subjects. Levels of six of the proteins were significantly increased in patients versus controls (13% to 106% increase, p<0.003). In patients, the predominant cytokine response appeared to be of the Th2 subtype (interleukin 10 level 2.06 times normal, p=0.0003). Increased levels of four proteins correlated with indices of severity of the disease (p<0.05). Seven patients died during the follow-up period. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was associated with a high risk of death (hazard ratio 6.56, 95% CI 1.46 to 29.4, p=0.014). The risk was not modified after adjustment for demographic, functional and treatment-related variables in multivariate analysis (hazard ratios of 5.75 to 8.45, p<0.03). Thus, in CHDPAH, microvascular dysfunction appears to involve inflammatory responses, similarly to idiopathic PAH. Of the biomarkers, plasma vWF:Ag was independently associated with survival. (AU)