The effects of aspirin and nonselective beta blockade on the acute prothrombotic response to psychosocial stress in apparently healthy subjects.
We hypothesized that the 2 cardiovascular drugs aspirin and propranolol attenuate the prothrombotic response to acute psychosocial stress relative to placebo medication. We randomized 56 healthy subjects, double-blind, to 5-day treatment with an oral dose of either 100 mg of aspirin plus 80 mg of propranolol combined, single aspirin, single propranolol, or placebo medication. Thereafter, subjects underwent a 13-minute psychosocial stressor. Plasma levels of von Willebrand factor antigen (VWF:Ag), fibrinogen, coagulation factor VII (FVII:C) and XII (FXII:C) activity, and D-dimer were determined in blood samples collected immediately pre- and post-stress and 45 minutes post-stress. The stress-induced changes in prothrombotic measures were adjusted for gender, age, body mass index, mean arterial blood pressure, smoking status, and sleep quality. There was an increase in VWF:Ag levels from immediately pre-stress to 45 minutes post-stress in the placebo group relative to the 3 subject groups with verum medication (P's </= 0.019; relative increase in VWF:Ag between 17% and 21%); however, the VWF:Ag response to stress was not significantly different between the three groups with verum medication. The stress responses in fibrinogen, FVII:C, FXII:C, and D-dimer were similar in all 4 medication groups. The combination of aspirin with propranolol, single aspirin, and single propranolol all attenuated the acute response in plasma VWF:Ag levels to psychosocial stress. This suggests that these cardiovascular drugs might exert limited protection from the development of stress-triggered coronary thrombosis.
von Känel
Roland
R
Department of General Internal Medicine, University Hospital Berne, Switzerland. roland.vonkaenel@insel.ch
Kudielka
Brigitte M
BM
Helfricht
Susanne
S
Metzenthin
Petra
P
Preckel
Daniel
D
Haeberli
André
A
Cung
Trinh
T
Fischer
Joachim E
JE
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism; D005174:Factor XII / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D013315:Stress, Psychological / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D005338:Fibrin Fibrinogen Degradation Products; D010975:Platelet Aggregation Inhibitors; C036309:fibrin fragment D; D014841:von Willebrand Factor; D005167:Factor VII; D005174:Factor XII; D005340:Fibrinogen; D011433:Propranolol; D001241:Aspirin