Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor?

Stroke. 2002 Sep;33(9):2187-91. doi: 10.1161/01.str.0000023889.84649.3d.

Abstract

Background and purpose: Tissue factor (TF; an initiator of coagulation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis) are involved in the hypercoagulable state associated with malignancy. We investigated their roles in chronic atrial fibrillation (AF), a condition also associated with increased risk of stroke and thromboembolism, as well as a prothrombotic or hypercoagulable state.

Methods: We studied 25 patients with AF (20 men; mean+/-SD age, 62+/-13 years) who were compared with 2 control groups in sinus rhythm: 30 healthy control subjects (17 men; mean age, 60+/-9 years) and 35 patient control subjects with coronary artery disease (CAD; 27 men; mean age, 60+/-12 years). Plasma levels of TF, VEGF, and the VEGF receptor sFlt-1 were measured by enzyme-linked immunosorbent assay.

Results: VEGF, sFlt-1, and TF were significantly different between the 3 groups, with abnormal levels in AF and CAD patients compared with control subjects (P<0.001, P=0.022, and P=0.008, respectively). Among the AF patients, TF levels were significantly correlated with VEGF (Spearman's r=0.65, P<0.001) and sFlt (r=0.54, P=0.006) levels. Only TF and VEGF levels were significantly correlated in CAD patients (r=0.39, P=0.02). There were no significant correlations among the healthy control subjects.

Conclusions: Patients with chronic AF have high TF levels, in keeping with the prothrombotic state associated with this arrhythmia. The relationships between TF and VEGF and its receptor sFlt-1 in AF suggest a possible role for VEGF in the hypercoagulable state found in AF, as seen in malignancy and atherosclerosis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy
  • Blood Pressure
  • Case-Control Studies
  • Chronic Disease
  • Coronary Artery Disease / blood*
  • Cross-Sectional Studies
  • Demography
  • Endothelial Growth Factors / blood*
  • Female
  • Humans
  • Lymphokines / blood*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / blood
  • Receptor Protein-Tyrosine Kinases / blood
  • Thrombophilia / blood*
  • Thrombophilia / etiology
  • Thromboplastin / analysis*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors
  • Warfarin / administration & dosage

Substances

  • Anticoagulants
  • Endothelial Growth Factors
  • Lymphokines
  • Proto-Oncogene Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Warfarin
  • Thromboplastin
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-1