Association between plasmin activation system and intravascular ultrasound signs of plaque instability in patients with unstable angina and non-st-segment elevation myocardial infarction.
BACKGROUND
The association between intravascular ultrasound (IVUS) signs of plaque instability and plasma levels of biomarkers was determined in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI).


METHODS
Fifty-two patients underwent coronary angiography and IVUS 8 +/- 5 hours after the onset of chest pain. IVUS analysis included plaque morphology, disruption, thrombi and eccentricity, lumen, external elastic membrane, and plaque plus media areas of culprit lesion and reference segments and arterial remodeling. Plasma levels of the thrombin activation system (thrombin-antithrombin complex [TAT], tissue factor pathway inhibitor [TFPI], and prothrombin fragments 1+2 [F1+2]) and plasmin activation system (tissue and urokinase-type plasminogen activator [t-PA and u-PA], plasminogen activator inhibitor-1 [PAI-1], and D-dimer) were measured with enzyme-linked immunosorbent assay kits before angiography.


RESULTS
Elevated levels of TAT (7.2 +/- 6.0 microg/L), F1+2 (1.8 +/- 1.0 nmol/L), TFPI (179.1 +/- 131.0 ng/mL), PAI-1 (95.4 +/- 54.6 ng/mL), t-PA (10.6 +/- 8.8 ng/mL), and u-PA (2.6 +/- 0.9 ng/mL) were found in patients with UA/NSTEMI. The serum levels of D-dimer (40.0 +/- 39.5 ng/mL) remained in reference range. Expansive and constrictive remodeling were found in 18 (35%) and 12 (23%) patients, respectively. Expansive remodeling of the culprit lesion was associated with significantly higher plasma levels of PAI-1 (121.6 +/- 55.0 vs 87.7 +/- 61.5 and 77.4 +/- 42.8 ng/ml, P =.039), and u-PA (3.0 +/- 1.2 vs 2.2 +/- 0.5 and 2.5 +/- 0.7 ng/mL, P =.026) as compared with constrictive and neutral remodeling. Increased plasma levels of u-PA were associated with plaque rupture (3.0 +/- 0.7 vs 2.5 +/- 0.9 ng/mL, P =.062). Plasma levels of PAI-1 and u-PA correlated positively with plaque plus media (P =.0297 and P =.0093) and external elastic membrane areas (P =.010 and P =.0002).


CONCLUSIONS
Elevated levels of biomarkers of plasmin activation system are associated with signs of plaque instability of culprit lesion in UA/NSTEMI and might therefore serve as non-invasive determinants of the population that is at high risk for subsequent adverse events.
Gyöngyösi
Mariann
M
Department of Cardiology, University of Vienna, Vienna, Austria. mariann.gyongyosi@univie.ac.at
Glogar
Dietmar
D
Weidinger
Franz
F
Domanovits
Hans
H
Laggner
Anton
A
Wojta
Johann
J
Zorn
Gerlinde
G
Iordanova
Nelli
N
Huber
Kurt
K
D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000000981:diagnostic imaging*; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000000981:diagnostic imaging*; D015588:Observer Variation; D010447:Peptide Hydrolases / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D011516:Prothrombin / Q000032:analysis; D012044:Regression Analysis; D015203:Reproducibility of Results; D010959:Tissue Plasminogen Activator / Q000097:blood; D014463:Ultrasonography; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D020257:Ventricular Remodeling
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator