Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor?
OBJECTIVE
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.
Chung
Natali A Y
NA
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Belgore
Funmi
F
Li-Saw-Hee
Foo Leong
FL
Conway
Dwayne S G
DS
Blann
Andrew D
AD
Lip
Gregory Y H
GY
D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D001794:Blood Pressure; D016022:Case-Control Studies; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000097:blood*; D003430:Cross-Sectional Studies; D003710:Demography; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology; D013925:Thromboplastin / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D014859:Warfarin / Q000008:administration & dosage
D000925:Anticoagulants; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014859:Warfarin; D013925:Thromboplastin; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1