Because the relationship between von Willebrand factor (vWF) and cardiovascular disease (CVD) is not consistent, this study examined whether this fact could be explained by the associations of vWF with type 2 diabetes and insulin resistance. The issue was investigated in 3,799 participants of the Framingham Offspring Study followed for 11 years, in whom 351 subjects developed CVD. Using the first quartile of the vWF as the referent, hazard ratios (HRs) for CVD adjusted for age, sex, blood pressure, smoking, body mass index, cholesterol, HDL cholesterol, treatment with aspirin, insulin, antihypertensives, and lipid-lowering medications were 0.94, 0.98, and 1.32 for quartiles 2, 3, and 4, respectively (p=0.04). Further adjustments for type 2 diabetes and/or insulin resistance (homeostasis model, HOMA-IR) attenuated the association, which became nonsignificant. When individuals were classified on the basis of presence/absence of type 2 diabetes, the relationship between vWF and CVD was only observed in type 2 diabetic patients (p=0.04). Moreover, when stratified on the basis of insulin resistance (HOMA-IR), vWF was associated with CVD only in insulin-resistant participants (p=0.01). Results of this study might explain the discrepancy in previous studies in regard to the relationship between vWF and CVD, which is observed particularly in type 2 diabetic patients and insulin-resistant individuals.
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