Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.
OBJECTIVE
Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD.


RESULTS
Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01.


CONCLUSIONS
Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.
Oldgren
J
J
Department of Medical Sciences, Cardiology, University Hospital, Uppsala, Sweden.
Wallentin
L
L
Grip
L
L
Linder
R
R
Nørgaard
B L
BL
Siegbahn
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D005998:Glycine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D009205:Myocarditis / Q000209:etiology* / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage*; D016019:Survival Analysis; D020107:Troponin T / Q000097:blood
D000991:Antithrombins; D010880:Piperidines; D020107:Troponin T; C099871:inogatran; D005340:Fibrinogen; D002097:C-Reactive Protein; D005998:Glycine