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From the Departments of Psychiatry and Neuropsychology (R.v.D.), Hematology (K.H., C.v.Z.), Medical, Clinical, and Experimental Psychology (A.A.), Maastricht University, Maastricht, The Netherlands; and the Department of Medical and Clinical Psychology (W.J.K.), Uniformed Services University of the Health Sciences, Bethesda, MD.
Address reprints requests to: R. van Diest, Department of Psychiatry and Neuropsychology, Maastricht University, Box 616, 6200 MD Maastricht, The Netherlands. Email: rob.vandiest{at}pn.unimaas.nl
OBJECTIVE: Vital exhaustion (VE) predicts a first myocardial infarction (MI) and new cardiac events after a coronary angioplasty. To explore potential underlying pathophysiological mechanisms, we tested whether VE is associated with more pronounced diurnal variations in hemostasis.
METHODS: Blood was drawn from 29 VE and 30 control males, all healthy and nonsmokers, to assess hemostatic measures at 7:00 AM and 6:00 PM.
RESULTS: All measures of fibrinolysis were in their normal range and showed significant diurnal variations. These variations were more pronounced in VE as all fibrinolytic measures were significantly higher in VE at 7:00 AM and similar to those of controls at 6:00 PM, thus supporting our hypothesis with respect to fibrinolysis. Diurnal decreases in tPA and tPA-PAI ranged from 1.5 (VE) to 1.3 (controls), whereas the diurnal decrease in PAI-1 was more than fourfold in VE and 2.7-fold in controls. This suggests a decreased fibrinolytic capacity in VE during the early morning. All coagulation measures were in their normal range, and prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes, and activated factor VII showed significant diurnal variations. These variations were similar in VE and control individuals, thus not supporting our hypothesis with respect to coagulation. Finally, F1+2 and fibrinogen were both significantly higher throughout the day in VE.
CONCLUSIONS: VE is associated with decreased early morning fibrinolysis and increased fibrinogen levels throughout the day. These hemostatic changes may promote thrombus formation and provide a potential pathophysiological mechanism by which VE is related to MI and its circadian variation.
Key Words: stress, • coagulation, • fibrinolysis, • diurnal variations, • myocardial infarction.
Abbreviations: AF = alkaline phosphatase;; ALAT = alanin-aminotransferase;; ASAT = aspartic-aminotransferase;; BMI = body mass index;; CAD = coronary artery disease;; CV = intraassay coefficient of variation;; EDTA = ethylenediaminetetraacetic;; ELISA = enzyme-linked immunosorbent assay;; FNG = fibrinogen;; F1+2 = prothrombin fragment 1+2;; 
-GT = gamma-glutamyl transferase;; GSQ = Groningen sleep questionnaire;; LDH = lactate dehydrogenase;; Ldlevel = lower detection level;; MI = myocardial infarction;; MIVE = Maastricht interview vital exhaustion;; MQ = Maastricht questionnaire;; PAI-1:act = plasminogen activator inhibitor activity;; PSS = perceived stress scale;; RR = relative risk;; SCID = structured clinical interview for DSM-IV;; SEM = standard error of the mean;; TAT = thrombin-antithrombin complexes;; tPA:ag = tissue plasminogen activator antigen;; tPA-PAI:ag = tPA-PAI complexes’ antigen;; VE = vital exhaustion;; VII:a = activated factor VII;; VII:c, VIII:c = factor VII and VIII coagulant activity;; vWf:ag = von Willebrand factor antigen.
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