Higher levels of von Willebrand factor in patients with syncope due to orthostatic hypotension

Objectives: Orthostatic hypotension has been linked with increased mortality and cardiovascular morbidity; however, the underlying mechanisms are still unknown. The aim of the study was to assess markers of coagulability in patients with and without orthostatic hypotension who suffered transient loss of consciousness. Methods: A total of 233 consecutive patients more than 15 years old, with unexplained transient loss of consciousness, underwent head-up tilt test (HUT, Italian protocol). Blood samples were collected during supine rest before and at 3 min of 70 degrees HUT for determination of fibrinogen, von Willebrand factor antigen (vWF:Ag) and activity (vWF:GP1bA), factor VIII (FVIII:C), lupus anticoagulant, and functional activated protein C-resistance. Orthostatic hypotension was defined as persistent decrease in SBP and/or DBP of more than 20/10 mmHg or SBP lower than 90 mmHg during passive HUT. Results: One hundred and seventy-eight patients (81 men, 45.5%) not treated with vitamin-K antagonists were analyzed. Those with orthostatic hypotension (n = 49) were older [61 +/- 18 vs. 47 +/- 21 years (mean +/- SD), P < 0.001], had increased FVIII:C-supine (1.2 +/- 0.39 vs. 1.0 +/- 0.35, P = 0.001), FVIII:C-standing (1.2 +/- 0.36 vs. 1.0 +/- 0.34, P = 0.001), vWF:Ag-supine (1.5 +/- 0.66 vs. 1.1 +/- 0.44, P < 0.001), vWF:Ag-standing (1.5 +/- 0.67 vs. 1.1 +/- 0.46, P < 0.001), vWF:GP1bA-supine (1.5 +/- 0.73 vs. 1.1 +/- 0.42, P < 0.001), vWF:GP1bA-standing (1.5 +/- 0.75 vs. 1.1 +/- 0.42 P < 0.001), fibrinogen-standing (2.9 +/- 0.53 vs. 2.7 +/- 0.61, P = 0.03) but not fibrinogen-supine (2.8 +/- 0.54 vs. 2.7 +/- 0.61, P = 0.078) compared with patients without orthostatic hypotension. However, after adjustment for age, sex, and comorbidity, only vWF:Ag and vWF:GP1bA levels remained significantly increased in orthostatic hypotension patients. Conclusion: Concentration of vWF is elevated in patients with orthostatic hypotension who suffered a syncopal event. This observation may be helpful in understanding the increased risk of cardiovascular events in orthostatic hypotension.