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


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)

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