Pro- and anticoagulant mechanisms in coronary artery disease. Clinical studies on factor VII and resistance to activated protein C

The triggering mechanism in myocardial infarction (MI) and unstable angina involves coronary thrombus formation following plaque rupture. Coagulation is initiated by tissue factor that activates factor VII (FVII), and is inhibited by protein C and its co-factor protein S. Resistance to activated protein C (APC resistance) is a common risk factor for venous thrombosis caused by a mutation in the gene for factor V (FV Q506). We studied FVII, protein C and FV Q506 in patients with MI, their influence on the success of thrombolytic treatment, and the response to combined anticoagulation therapy with low-dose warfarin and aspirin.

Warfarin 1.25 mg daily in combination with aspirin, investigated in 12 patients with stable coronary heart disease, reduced FVII coagulant activity (FVII:C) as well as thrombin generation, measured as prothrombin fragment 1+2 (F1+2). Applied to 97 patients with acute MI, the same regimen reduced FVII:C but not F1+2, compared to aspirin alone. A high FVII:C one month after MI was associated with a worse clinical outcome during a 4-year follow-up.

In 45 patients treated with thrombolytics for acute MI, the pre-treatment FVII antigen level was higher, and the anticoagulant protein C lower, among those in whom reperfusion was unsuccessful, according to continuous vector ECG.

The prevalence of FV Q506 among 101 patients with MI before the age of 50 years, was no less than 18%, but still not significantly higher than among healthy controls (11%). In a prospective study on 296 patients with acute MI or unstable angina, smokers carrying the FV Q506 mutation had a 2.9 times higher risk of reinfarction or death within 30 days compared to non-smokers with an normal genotype. No risk increase was seen for non-smokers with FV Q506. The results demonstrate a pathophysiological role of protein C and FVII in acute coronary syndrome.