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

A. A. Lopes, A. C. Barreto, N. Y. Maeda, C. Cícero, R. P S Soares, S. P. Bydlowski, S. Rich

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Biomarkers have been identified for pulmonary arterial hypertension, but are less well defend for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight micro-vascular 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-selecting, 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.

Original languageEnglish (US)
Pages (from-to)1269-1275
Number of pages7
JournalBrazilian Journal of Medical and Biological Research
Issue number12
StatePublished - Dec 2011


  • Congenital heart disease
  • Eisenmenger syndrome
  • Endothelial dysfunction
  • Pulmonary hypertension
  • Th2 cytokine response
  • Von Willebrand factor

ASJC Scopus subject areas

  • Biophysics
  • Neuroscience(all)
  • Biochemistry
  • Physiology
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Cell Biology

Fingerprint Dive into the research topics of 'Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease'. Together they form a unique fingerprint.

Cite this