Von Willebrand factor in type 1 diabetes: its production and coronary artery calcification.
BACKGROUND
Von Willebrand factor (vWF) has generally been regarded as a good predictor of vascular risk. However, no previous studies have examined its relationship with coronary calcification. The aim of this study was to determine whether vWF activity is higher in type 1 diabetic patients than controls; its relationship with cardiovascular risk factors; and to endothelial nitric oxide production and coronary artery calcification.


METHODS
Von Willebrand factor activity was measured in 181 type 1 diabetic patients and 188 controls. Coronary artery calcification was measured by Electron Beam Computed Tomography. Forearm blood flow was measured by venous plethysmography in response to intra-brachial infusion of bradykinin, glyceryl trinitrate, noradrenaline and NG-monomethyl-L-arginine (L-NMMA) in 149 subjects.


RESULTS
Von Willebrand factor was significantly increased in diabetic patients compared to controls (median 100% vs 87%, p=0.001). Von Willebrand factor activity was significantly higher in diabetic patients with micro/macroalbuminuria than those with normoalbuminuria (109% vs 93%, p<0.001). Among diabetic subjects, being in the top quartile for vWF was associated with a lower response to L-NMMA (p=0.009). There was no association between vWF activity and coronary artery calcification in either the diabetic (p=0.9) or control group (p=0.8).


CONCLUSIONS
Cardiovascular risk factors including albuminuria do not explain the high vWF activity in type 1 diabetic patients. There is some evidence that vWF correlates with endothelial nitric oxide production. The lack of correlation with coronary artery calcification indicates that vWF is not a useful marker of atheroma burden.
Chan
Norman N
NN
EURODIAB, Department of Epidemiology and Centre for Clinical Pharmacology, University College London, UK. nnchjan@cuhk.edu.hk
Fuller
John Harry
JH
Rubens
Michael
M
Colhoun
Helen Martina
HM
D000328:Adult; D000419:Albuminuria / Q000378:metabolism; D019540:Area Under Curve; D001920:Bradykinin / Q000378:metabolism / Q000627:therapeutic use; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000378:metabolism / Q000627:therapeutic use; D012307:Risk Factors; D013223:Statistics as Topic; D014665:Vasodilator Agents / Q000378:metabolism / Q000627:therapeutic use; D019323:omega-N-Methylarginine / Q000378:metabolism / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000378:metabolism*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D014841:von Willebrand Factor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005996:Nitroglycerin; D001920:Bradykinin