The effect of multi-factorial intervention on plasma von Willebrand factor, soluble E-selectin and tissue factor in diabetes mellitus: implications for atherosclerotic vascular disease.
BACKGROUND
Endothelial abnormalities and a hypercoagulable state may contribute to increased cardiovascular risk in diabetes mellitus, particularly in patients with overt cardiovascular disease (CVD). We sought to determine the effect of intensified multi-factorial cardiovascular risk intervention on indices of endothelial abnormality and hypercoagulability in diabetes, and if patients with overt CVD would derive similar benefit as those without.


METHODS
We measured plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble E-selectin (sE-sel, marking endothelial activation) and tissue factor (TF, an initiator of coagulation) by ELISA in 94 patients with diabetes mellitus (38 with CVD and 56 without overt CVD) and 34 comparable controls. Thirty-three patients with CVD and 31 without overt CVD then participated in multi-factorial cardiovascular risk intervention over 1 year.


RESULTS
Plasma levels of vWf (P = 0.009), sE-sel (P < 0.001) and TF (P < 0.001) were significantly higher in diabetic patients compared with controls, with TF highest in patients with overt CVD. Intensive multi-factorial intervention resulted in reductions in glycated haemoglobin (HbA(1c)), total and LDL-cholesterol (all P < 0.05), but no significant weight change. This was associated with reductions in vWf in patients with (by 26%P = 0.003), and without (by 47%, P < 0.001), overt CVD. TF was reduced only in patients without overt CVD (by 45%, P < 0.001). There were no significant changes in sE-sel levels in either group.


CONCLUSIONS
Endothelial abnormalities in diabetes are only partially influenced by contemporary intensified multi-factorial cardiovascular risk intervention. These data suggest the need for earlier and more aggressive risk factor intervention.
Lim
H S
HS
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Chong
A Y
AY
Freestone
B
B
Blann
A D
AD
Lip
G Y H
GY
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013925:Thromboplastin / Q000032:analysis*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002784:Cholesterol; D008078:Cholesterol, LDL; D019040:E-Selectin; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013453:Sulfonylurea Compounds; D013925:Thromboplastin; D014841:von Willebrand Factor