Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease.

Abstract

Several fibrinolytic variables, including plasminogen activator inhibitor activity, were studied before and after exercise in 67 normolipidaemic patients with coronary artery disease and in 25 hyperlipidaemic patients with coronary artery disease. Before exercise plasminogen activator inhibitor activity was higher in the patient groups than in a group of 10 healthy volunteers. For those who were normolipidaemic plasminogen activator inhibitor activity was greater in patients with angina pectoris who had had a myocardial infarction. The concentration of antigenic tissue-type plasminogen activator was similar in all the patients with coronary artery disease and higher than in the control group. After the exercise test fibrinolytic capacity was lower in the patients with angina pectoris and a previous history of myocardial infarction. After exercise both the released immunological tissue-type plasminogen activator and fibrinolytic capacity were lower in the hyperlipidaemic patients than in the normolipidaemic patients. The concentration of plasminogen activator inhibitor was also higher in the hyperlipidaemic patients. Patients with hyperlipidaemia IV had the highest plasminogen activator inhibitor activity. The increase in plasminogen activator inhibitor activity found in the patients was partially inhibited by antiserum against plasminogen activator inhibitor-1 in vitro. The formation of a complex of about 115,000 daltons between plasminogen activator inhibitor and purified tissue-type plasminogen activator was detected by a zymographic fibrin technique. These findings show that in patients with coronary artery disease fibrinolytic activity is impaired by an increase in plasminogen activator inhibitor. Impaired fibrinolysis may be related to the clinical evolution of coronary artery disease in these patients.

Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis

“…PAI-1 levels are elevated in patients with diabetes mellitus and coronary artery disease [2,21] and are associated with an enhanced risk of coronary events [10,12]. Besides its effects on TF and TFPI, guggulsterone downregulated PAI-1 expression both in quiescent and TNF-a stimulated cells; hence, guggulsterone may be particularly beneficial in patients with diabetes mellitus.…”

Effects of moderate weight loss on anginal symptoms and indices of coagulation and fibrinolysis in overweight patients with angina pectoris

“…Increased visceral fat is particularly associated with impaired fibrinolytic activity (raised levels of plasminogen activator inhibitor, PAI; Kockx et al, 1999). Tissue plasminogen activator antigen (t-PA) and PAI activity, factor VII activity and fibrinogen all show greater elevations in those with known coronary disease and angina (Aznar et al, 1988). Bahadori et al, (1996) have reported that close to 40% of obese angina patients do not have significant coronary artery disease, and so a clinical benefit from weight loss could be expected without necessarily modifying atheroma.…”

Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity.

“…These studies have consistently shown a decreased fibrinolytic activity in patients compared with controls, a decrease that is due mainly to elevated plasma levels of PAI-1. 7 - 11 Strong support for a cause-and-effect relation between PAI-1 elevation and risk of MI has been obtained from a longitudinal cohort study of 109 unselected men who had survived a first MI before the age of 45 years. This study indicated that a high plasma concentration of PAI-1 activity was associated with reinfarction, along with dyslipoproteinemia, poor left ventricular performance, and multiple-vessel coronary artery disease.…”