Relationship between serum endothelin-1 level and spontaneous reperfusion in patients with acute myocardial infarction :

Coronary artery disease remains a major cause of morbidity and mortality. Experimental and clinical data have indicated an important role of endothelin-1 at various subclinical and clinical stages of the disease. Endothelin-1 causes endothelial dysfunction and inflammation and may contribute to atherosclerotic plaque formation. During acute myocardial infarction, endothelin-1 enhances myocardial necrosis and arrhythmogenesis, but seems to exert a favorable effect on subsequent infarct healing and early ventricular remodeling. In the chronic postinfarction phase, endothelin-1 increases left ventricular afterload and participates in the myocardial fibrotic process. The progressive understanding of these actions has stimulated a large number of experimental and clinical studies examining the various effects of endothelin receptor blockade in coronary artery disease and chronic heart failure. However, this research has yielded largely contradictory results that have stirred scientific debates and controversies. This review summarizes the current state-of-the-art on this exciting topic, focusing on potential clinical ramifications.

Based on pathophysiological findings Lp(a) is considered to be a cardiovascular risk factor. The Göttingen Risk Incidence and Prevalence Study (GRIPS) provides the possibility to evaluate this impact of Lp(a) on the basis of a large prospective cohort study. GRIPS included 6002 men, aged 40-59.9 years at baseline. Data of a 5 year follow-up period is now available for > 95% of the study participants. Multivariate logistic regression models for the estimation of MI risk confirm Lp(a) as an important risk factor, ranking fifth behind LDL cholesterol, family history of MI, plasma fibrinogen and HDL cholesterol (inversely related). The GRIPS data strongly support strategies for the identification and treatment of persons at increased MI risk which focus on LDL cholesterol. However, Lp(a) and fibrinogen have to be seriously considered as additional risk factors and should be included in diagnostic panels for the estimation of MI risk.

No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.