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.

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. 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. 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. 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.