CIRCADIAN VARIATION OP PLASMINOGEN ACTIVATOR INHIBITOR (PAI) AND THE INCIDENCE OP SEVERE ISCHEMIC ATTACKS IN PATIENTS WITH CORONARY ARTERY DISEASE (CAD)

1987 ◽  
Author(s):  
K Huber ◽  
I Resch ◽  
D Rose ◽  
E Schuster ◽  
D H Glogar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Circadian Variation ◽  
Plasminogen Activator Inhibitor ◽  
High Plasma ◽  
Significant Difference ◽  
Artery Disease ◽  
Titration Assay ◽  
Group B ◽  
Activator Inhibitor

Recent studies have shown a high incidence for the onset of acute myocardial infarction (AMI) in the morning and a possible role of high plasma levels of plasminogen activator inhibitor for the risk of reinfarction. We therefore investigated the diurnal course of PAI and the incidence of severe ischemic attacks in patients with CAD. Blood was drawn from 64 patients at the coronary care unit with angiographically proven CAD (group A = unstable angina, n=37; age = 60.7 ± 10.1 years; group B = stable angina, n=27, age = 58.2 ± 10.9 years) at 4 different time points (6 a.m., noon, 6 p.m., midnight) for at least 3 consecutive days. PAI (functional titration assay; IU t-PA inhibited/ml) and time of onset of severe ischemic attacks including AMI were determined. 50 healthy volunteers (age = 39 ± 17 years) served as controls. We found a significant diurnal variation (paired t-test, p<0.05) of PAI levels in normals (6 am: 11.5±5.6; noon: 6.9±1.7; 6 pm: 5.7±2.5; x ± SD) as well as in patients (6 am: 15.6 ± 6.4; noon: 13-3 ± 1.2; 6 pm: 12.6 ± 5.3; midnight: 13.2 ± 2.8; x ± SD) with an acrophase at 6 am. Compared to the controls PAI values were significantly higher in patients (p<0.01) but showed no significant differences within the two patients’ groups. We could not demonstrate a significant difference in PAI values of patients with or without previous myocardial infarction. Furthermore, development of AMI had no demonstrable influence on preexisting PAI values in both patients’ groups. During the observation period 90 severe ischemic attacks were observed. Attacks occured significantly more often (70$) between midnight and noon with a peak incidence (44$) around 10 am. From these data it can be concluded that PAI levels are elevated in patients with CAD. Peak levels of PAI seem to precede the ischemic event by only a few hours and might thereby contribute to the onset of ischemic events on a basis of increased thrombotic tendency.

Circadian Fluctuations of Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma of Patients with Unstable Coronary Artery Disease and Acute Myocardial Infarction

1988 ◽  
Vol 60 (03) ◽  
pp. 372-376 ◽  
Author(s):  
Kurt Huber ◽  
Danuta Rosc ◽  
Irene Resch ◽  
Ernst Schuster ◽  
Dietmar H Glogar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Previous Myocardial Infarction ◽  
Unstable Coronary Artery Disease ◽  
Tissue Plasminogen ◽  
Artery Disease ◽  
Activator Inhibitor

SummaryA decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p < 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A. M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A. M. seem to be closely related.

LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR IN PATIENTS WITH ANGINA PECTORIS

1987 ◽  
Author(s):  
C Koringer ◽  
R Jäger ◽  
K Huber ◽  
K lechner
Keyword(s):  
Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Angina Pectoris ◽  
Plasminogen Activator ◽  
Normal Population ◽  
Plasminogen Activator Inhibitor ◽  
Titration Assay ◽  
Age Range ◽  
Activator Inhibitor

Several groups have shown that fibrinolytic capacity is impaired in survivors of myocardial infarction, due to increased levels of the fast-acting plasminogen activator inhibitor (PAI). In order to study the behaviour of PAI in patients with coronary heart disease, 180 patients with angina pectoris were investigated. They were 148 males and 32 females, ages ranging from 29 to 70 years (52.8 ± 8.2, mean ± S.D.). A sex- and age- matched normal population served as a control (n=105, age-range 30 to 69 years, 52.4 ± 7.9). PAI was determined by a functional titration assay, and its activity expressed as arbitrary units (AU). PAI levels were significantly (p <0.005) higher in patients with angina (24.3 ± 10.3 AU/ml, range 10.1 to 112.0 AU/ml) than in normals (20.4 ± 4.6 AU/ml, range 10.5 to 31.6 AU/ml). PAI levels were unrelated to sex or age, in both the patient and the control groups. As expected, plasma triglyceride levels were correlated to PAI in patients (r=0.19, p<0.01) and in normals (r=0.20, p<0.05). Patients with a history of previous myocardial infarction (n=114) had similar PAI levels as patients without infarction (24.2 ± 11.1 AU/ml as compared to 24.4 ± 9.6 AU/ml). It is concluded that PAI levels are elevated in patients with coronary heart disease, whether myocardial infarction has taken place or not.

Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Vessel Patency ◽  
Activator Inhibitor ◽  
Pai 1

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Relation between Plasminogen Activator Inhibitor-1 and Hepatic Enzyme Concentrations in Hyperlipidemic Patients

1994 ◽  
Vol 72 (03) ◽  
pp. 434-437 ◽  
Author(s):  
E Bruckert ◽  
A Ankri ◽  
P Glral ◽  
G Turpin
Keyword(s):  
Blood Pressure ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tolerance Test ◽  
High Plasma ◽  
Oral Glucose ◽  
Plasminogen Activator Inhibitor 1 ◽  
Glutamyl Transferase ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor type-1 (PAI-1) is a key determinant of the fibrinolytic capacity. Its activity correlates with most of the characteristic features of insulin resistance syndrome, i. e. obesity, high blood pressure and hyperlipidemia.We measured plasma PAI-1 antigen levels in 131 asymptomatic men (aged 44.2 ± 11 years) who had been referred for hyperlipidemia. Those taking medication and those with a secondary hyperlipidemia were excluded.We confirmed the correlation between PAI-1 levels and the following variables: body mass index, blood pressure, triglyceride concentration, and blood glucose and insulin levels before and after an oral glucose tolerance test. We also found a significant and independent correlation between PAI-1 and the concentration of the hepatic enzymes glutamyl transferase, alanine aminotransferase and aspartate aminotransferase.Mild liver abnormalities (presumably steatosis) may thus be one of the factors accounting for high plasma PAI-1 levels in hyperlipidemic patients.

Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction

1995 ◽  
Vol 73 (02) ◽  
pp. 261-267 ◽  
Author(s):  
Rosaire P Gray ◽  
Vidya Mohamed-Ali ◽  
David L H Patterson ◽  
John S Yudkin
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Plasma Insulin ◽  
Plasminogen Activator Inhibitor ◽  
Immunoreactive Insulin ◽  
Plasminogen Activator Inhibitor 1 ◽  
Serum Triglycerides ◽  
Fasting Plasma ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immuno-enzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs=0.43; p <0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p <0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p <0.0001) and des-31,32-proinsulin (rs = 0.54; p <0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

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