title: Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease.
abstract: Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 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 (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.
authors: Instituto do Coração, Universidade de São Paulo, SP, Brasil. aablopes@usp.br
authors: A A
authors: AA
authors: Lopes
authors: A C
authors: AC
authors: Barreto
authors: N Y
authors: NY
authors: Maeda
authors: C
authors: C
authors: Cícero
authors: R P S
authors: RP
authors: Soares
authors: S P
authors: SP
authors: Bydlowski
authors: S
authors: S
authors: Rich
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D004812:Epidemiologic Methods; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood* / Q000150:complications / Q000401:mortality; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology*
chemical_list: D015415:Biomarkers; C029417:Von Willebrand antigen; D014841:von Willebrand Factor