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 mug/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.