A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation

OBJECTIVES First, we sought to determine whether there is diurnal variation in hemostatic factors related to thrombogenesis and hypercoagulability amo ng patients with chronic atrial fibrillation (AF). Second, we sought to det ermine whether levels of soluble thrombomodulin (sTM), a marker of endothel ial function, or soluble P-selectin (sP-sel), an index of platelet activati on, are altered in patients with AF as compared with subjects in sinus rhyt hm. BACKGROUND Atrial fibrillation is associated with an increased risk of stro ke and thromboembolism and is known to confer a hypercoagulable state, with abnormalities of thrombosis, platelet activation and endothelial cell func tion. Many cardiovascular events, such as acute myocardial infarction, have thrombosis as an underlying process, and they undergo diurnal variation. METHODS Fifty-two patients (45 men, mean [+/-SD] age 66 +/- 6 years) with c hronic AF, none of whom received antithrombotic therapy, were studied. Base line levels of fibrinogen, sP-sel, sTM and von Willebrand factor (vWF) were compared to those levels in matched healthy control subjects in sinus rhyt hm. In a subgroup of 20 patients, five venous blood samples were collected through an indwelling cannula at 6-h intervals from 12 PM to 12 PM the foll owing day and were analyzed for the same markers. RESULTS Patients with chronic AF had higher plasma sP-scl, sTM, vWF and fib rinogen levels as compared with control subjects in sinus rhythm. Significa nt correlations were found between fibrinogen and sP-sel in patients with A F (r = 0.567 [Spearman], p < 0.001) and in control subjects (r = 0.334, p = 0.016). There was no significant diurnal variation in plasma levels of sP- sel, sTM, vWF or fibrinogen over the 24-h study period (repeated measures a nalysis of variance, p = NS). CONCLUSIONS There is no circadian or diurnal variation in the hypercoagulab le state seen in AF, as assessed by plasma fibrinogen and markers of platel et (sP-scl) and endothelial function (vWF and sTM). The persistent hypercoa gulable state, together with the loss of diurnal variation in various hemos tatic markers, in chronic AF may contribute to the high risk of stroke and thromboembolic complications in these patients. (J Am Coll Cardiol 2000;35: 1926-31) (C) 2000 by the American College of Cardiology.