Fibrin clot properties are altered in patients with chronic obstructive pulmonary disease. Beneficial effects of simvastatin treatment.
Increased risk of thrombotic events occurs in chronic obstructive pulmonary disease (COPD). Elevated fibrinogen and C-reactive protein (CRP), being common in COPD, are associated with formation of dense fibrin clots resistant to lysis. Statins have been found to display anti-inflammatory and antithrombotic effects. We investigated fibrin clot properties in COPD patients prior to and following statin therapy. Ex vivo plasma fibrin clot permeability, compaction, and fibrinolysis were assessed in 56 patients with stable COPD, aged 64.9 +/- 9.2 years (mean FEV(1), 54.7 +/- 15.9% predicted), versus 56 controls matched for age, sex and cardiovascular risk factors. Patients were then randomly assigned to receive simvastatin 40 mg/day (n = 28) or to remain without statins for three months (n = 28). Patients with COPD had lower clot permeability (6.1+/- 1.07 versus 9.2 +/- 0.9 10(-9) cm(2), p < 0.0001), decreased compaction (44.9 +/- 4.5 versus 63.9 +/- 6.1%, p < 0.0001), higher maximum D-dimer levels released from clots (4.23 +/- 0.55 versus 3.53 +/- 0.31 mg/l, p < 0.0001) with a decreased rate of this release (75.0 +/- 8.3 versus 80.9 +/- 8.0 microg/l/min, p = 0.03) and prolonged lysis time (9.84 +/- 1.33 versus 8.02 +/- 0.84 min, p < 0.0001) compared with controls. Scanning electron microscopy confirmed denser clot structure in COPD. Multiple linear regression analysis after adjustment for age and fibrinogen showed that in the COPD patients, CRP was the only independent predictor of permeability (R(2) = 0.47, p < 0.001) and lysis time (R(2) = 0.43, p < 0.001). Simvastatin improved clot properties (p < 0.05) despite unaltered CRP and irrespective of cholesterol reduction. Our study shows that fibrin clots in COPD patients are composed of much denser networks that are more resistant to lysis, and these properties can be improved by statin administration.
Undas
Anetta
A
Institute of Cardiology Jagiellonian University School of Medicine, Cracow, Poland. mmundas@cyf-kr.edu.pl
Kaczmarek
Przemyslaw
P
Sladek
Krzysztof
K
Stepien
Ewa
E
Skucha
Wojciech
W
Rzeszutko
Marcin
M
Gorkiewicz-Kot
Izabela
I
Tracz
Wieslawa
W
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D005337:Fibrin / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D019821:Simvastatin / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005337:Fibrin; D019821:Simvastatin