Background-Several studies suggest a role for an increased circulating pool of tissue factor (TF) in atherothrombotic diseases. Furthermore, certain cardiovascular risk factors, such as diabetes, hyperlipemia, and smoking, are associated with a higher incidence of thrombotic complications. We hypothesized that the observed increased blood thrombogenicity (BT) observed in patients with type 2 diabetes mellitus may be mediated via an increased circulating tissue factor activity. We have extended our study to smokers and hyperlipidemic subjects. Methods and Results-Poorly controlled patients with type 2 diabetes mellitus (nϭ36), smokers (nϭ10), and untreated hyperlipidemic subjects (nϭ10) were studied. Circulating TF was immunocaptured from plasma, relipidated, and quantified by factor Xa (FXa) generation in the presence of factor VIIa. BT was assessed as thrombus formation on the Badimon perfusion chamber.

Long-term treatment with potent antithrombotic drugs, such as tissue factor or factor Xa inhibitors, that effectively block thrombosis without causing bleeding complications could help reduce death from cardiovascular disease.

In T2DM, there is an association between improved glycemic control and blood thrombogenicity reduction. The effect of glycemic control on the thrombotic complications of T2DM patients deserves further investigation.

Magnetic resonance imaging is a promising tool to noninvasively detect arterial thrombosis. Measurement of SI and the characteristic visual appearance of the thrombus have the potential to define thrombus age.

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In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.

Our data indicate that normalization of plasma lipid levels abolishes progression of atherosclerosis. Simvastatin elicits regression of atherosclerotic lesions, and the combination simvastatin plus PPAR-gamma agonist has additive regression effects on plaque. This is paralleled by structural alterations in plaque composition, which may increase plaque stability. These observations support the beneficial effects of statins on atherosclerosis and show additional anti-atherogenic benefits of combining a PPAR-gamma agonist with simvastatin.

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