Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina

doi:10.1016/0002-8703(92)90964-W

American Heart Journal

Volume 124, Issue 4, October 1992, Pages 854-860

https://doi.org/10.1016/0002-8703(92)90964-W Get rights and content

Abstract

To elucidate the circadian variation of fibrinolytic components in vasospastic angina, plasma levels of tissue plasminogen activator antigen (t-PA), free plasminogen activator inhibitor antigen (free PAI-1), $t-PA PAI-1$ complex, and total PAI-1 were measured in venous plasma samples. Samples were taken every 6 hours (6:00 am, noon, 6:00 pm, and midnight) for 24 hours in 14 patients with vasospastic angina, in 9 patients with exertional angina, and in 19 normal subjects. Twenty-four-hour Holter monitoring (Holter monitor, Del Mar Avionics, Irvine, Calif.) was also carried out in all subjects. All of the fibrinolytic components showed circadian variation, with a peak level at 6:00 am in every study group except for the $t-PA PAI-1$ complex in the group of patients with exertional angina. The values for all of the fibrinolytic components at each sampling time were higher in patients with coronary artery disease than in normal subjects. In particular, the mean value of free PAI-1 at 6:00 am in patients with vasospastic angina was significantly higher than that in normal subjects and that in patients with exertional angina. This value of free PAI-1 in patients with vasospastic angina was closely associated with the duration of ischemic attacks. These results suggested that the circadian fluctuation of fibrinolytic components may be an important factor that leads to coronary thrombosis at the time of coronary spasm, especially in the early morning.

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Cited by (35)

Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism
2022, Journal of Thrombosis and Haemostasis
Plasminogen activator inhibitor‐1 (PAI‐1), the main inhibitor of fibrinolysis, is frequently elevated in obesity and could potentially mediate the risk of venous thromboembolism (VTE) in obese subjects. However, whether PAI‐1 is associated with VTE remains uncertain.
To investigate the association between plasma PAI‐1 levels and risk of future incident VTE and whether PAI‐1 could mediate the VTE risk in obesity.
A population‐based nested case‐control study, comprising 383 VTE cases and 782 age‐ and sex‐matched controls, was derived from the Tromsø Study cohort. PAI‐1 antigen levels were measured in samples collected at cohort inclusion. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE across PAI‐1 tertiles.
The VTE risk increased dose‐dependently across PAI‐1 tertiles (P for trend <.001) in the age‐ and sex‐adjusted model. The OR of VTE for the highest versus lowest tertile was 1.73 (95% CI 1.27–2.35), and risk estimates were only slightly attenuated with additional stepwise adjustment for body mass index (BMI; OR 1.59, 95% CI 1.16–2.17) and C‐reactive protein (CRP; OR 1.54, 95% CI 1.13–2.11). Similar results were obtained for provoked/unprovoked events, deep vein thrombosis, and pulmonary embolism. In obese subjects (BMI of ≥30 kg/m² vs. <25 kg/m²), PAI‐1 mediated 14.9% (95% CI 4.1%‐49.4%) of the VTE risk in analysis adjusted for age, sex, and CRP.
Our findings indicate that plasma PAI‐1 is associated with increased risk of future incident VTE and has the potential to partially mediate the VTE risk in obesity.
Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions
2022, Progress in Lipid Research
Citation Excerpt :
Lipid mediator profiling of plasma lipid mediator concentrations in healthy volunteers uncovered a diurnal regulation in the production of DPAn-3-derived D-series resolvins (RvDn-3 DPA) [164]. The peak in the production of these mediators is coincident with an increase in plasma plasminogen activator inhibitor-1, a serine protease inhibitor that functions as the principal inhibitor of tissue plasminogen activator and urokinase, and the activation of circulating platelets and phagocytes thereby increasing the risk of thrombosis [165]. Intriguingly we observed that RvDn-3 DPA, when added to blood from healthy volunteer's ex vivo, downregulated the expression of adhesion molecules on circulating phagocytes and the formation of phagocyte-platelet heterotypic aggregates.
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.
Ratio of oleic to palmitic acid is a dietary determinant of thrombogenic and fibrinolytic factors during the postprandial state in men
2006, American Journal of Clinical Nutrition
Background: The nature of dietary fats affects the postprandial activation of the hemostatic system.
Objective: We investigated whether the ratio of oleic to palmitic acid [and that of monounsaturated to saturated fatty acids (MUFA:SFA)] in the diet affects postprandial concentrations of triacylglycerols, tissue factor (TF), fibrinogen, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1).
Design: We studied the effects of diets enriched in olive oil (ROO), high-palmitic sunflower oil (HPSO), butter, or a mixture of vegetable and fish oils (VEFO) on circulating concentrations of the aforementioned factors in 14 healthy men. The fats had ratios of oleic to palmitic acid (MUFA:SFA) of 6.83 (5.43), 2.36 (2.42), 0.82 (0.48), and 13.81 (7.08).
Results: The largest and longest-lasting postprandial changes in plasma triacylglycerol concentrations were found with the butter-based diet (all P < 0.05). No correlation was observed between the net incremental area under the curve (netAUC) for triacylglycerol and the ratio of oleic to palmitic acid (or MUFA:SFA) in the dietary fats. The netAUCs for TF and PAI-1, however, were inversely related to the ratio of oleic to palmitic acid (and MUFA:SFA) in ROO, HPSO, butter, and VEFO. Similar results were found for the fibrinogen netAUC when VEFO was omitted from the analysis. The netAUC for t-PA was inversely correlated with postprandial concentrations of triacylglycerol.
Conclusions: Postprandial concentrations of TF, fibrinogen, and PAI-1 are associated with the ratio of oleic to palmitic acid (MUFA:SFA) in dietary fats. The postprandial t-PA response is related to postprandial concentrations of triacylglycerol.
Acute myocardial infarction after over-the-counter use of pseudoephedrine
2005, Annals of Emergency Medicine
Citation Excerpt :
Case reports of drug-induced coronary vasospasm have verified the utility of nitrates in this setting.6-9,15 Aspirin and heparin should be administered in the acute setting on the basis of the association of vasospasm with increased thrombus formation.15,17 Initially, patients with vasospasm may receive β-blockers as standard therapy for acute coronary syndrome.18
Pseudoephedrine is a commonly used over-the-counter decongestant with sympathomimetic activity. We present the case of a previously healthy young man who had an acute myocardial infarction 45 minutes after ingesting the recommended dose of an over-the-counter cold remedy containing pseudoephedrine. Elevations of cardiac-specific creatinine kinase and cardiac troponin I confirmed the diagnosis. Cardiac catheterization 8 hours later revealed normal coronary arteries, suggesting a mechanism of vasospasm. Cardiac magnetic resonance imaging confirmed findings of regional myocardial infarction. This case highlights a potential danger of pseudoephedrine even when used by otherwise healthy individuals.
Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation
1999, Journal of the American College of Cardiology
OBJECTIVES
The purpose of this study was to examine the circadian variation of ventricular arrhythmias detected by an implantable cardioverter defibrillator in patients with and without ischemic heart disease.
BACKGROUND
Previous studies have shown a circadian variation of ventricular arrhythmias, sudden death and myocardial infarction with a peak occurrence in the morning hours. The circadian pattern, which is similar for both arrhythmic and ischemic events, suggests that ischemia may play a critical role in the genesis of ventricular arrhythmias and sudden death. We hypothesized that, if ischemia plays an important role in the triggering of ventricular arrhythmias, the circadian pattern should be different in patients with ischemic heart disease compared with patients with nonischemic heart disease.
METHODS
The circadian variation of ventricular arrhythmias recorded by an implantable cardioverter defibrillator was studied in 310 patients during a mean follow-up of 181 ± 163 days. Two hundred four patients had a history of ischemic heart disease and 106 patients had nonischemic heart disease. The times of the episodes of ventricular arrhythmias were retrieved from the data log of each device during follow-up, and the circadian pattern was compared between the two groups.
RESULTS
During follow-up, 1,061 episodes of ventricular arrhythmias were recorded by the device in the 310 patients. Six hundred eighty-two episodes occurred in the group of patients with ischemic heart disease and 379 occurred in the nonischemic heart disease group. The circadian variation of the episodes showed a typical pattern with a morning and afternoon peak in both groups of patients with ischemic and nonischemic heart disease, but there was no significant difference between the two groups.
CONCLUSIONS
The circadian rhythm of ventricular arrhythmias in patients with ischemic heart disease is similar to patients with nonischemic heart disease, suggesting that the trigger mechanisms of the initiation of ventricular tachyarrhythmias may be similar, irrespective of the underlying heart disease.
Circadian variation in the onset of acute critical limb ischemia
1998, Thrombosis Research
Research has identified a circadian rhythm for several acute thrombotic cardiovascular and cerebrovascular diseases. We investigated the possible existence of a circadian variation in the onset of acute critical limb ischemia. Out of a consecutive series of 198 cases, precise determination (within 30 minutes) of the time of symptom onset was possible in 156 (78.8%). Partial Fourier series were applied to hourly data and the best-fitting curves for circadian rhythmicity were calculated. Both in the total population and in subgroups by gender and location of ischemia, a highly significant circadian pattern of occurrence was demonstrated with peak in the morning (approximately 0800) and nocturnal minimum around midnight. This study is the first demonstration of the circadian pattern of acute arterial occlusion of the limbs, in agreement with several studies showing a circadian pattern to the time of onset of acute myocardial infarction and other unfavorable acute events related to thrombosis. This opens up the potential for therapeutic implications, suggesting the need to adjust the dose of drugs based on the time of day. Further studies dealing with circadian variation in the efficacy of thrombolytic agents are so needed.

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Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina

Abstract

Thromb Res

Am Heart J

Thromb Res

J Mol Cell Cardiol

Blood

Am Heart J

Circadian variation of plasma fibrinopeptide A level in patients with variant angina

Circulation

Circadian variation in the frequency of onset of acute myocardial infarction

N Engl J Med

Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris

Circulation

Coronary angioplasty in patients with unstable angina pectoris

N Engl J Med

Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death: autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion

Circulation

Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor-1 (PAI-1)

Thromb Haemost

Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction

Thromb Haemost

Impairment of the diurnal fibrinolytic response in man. Effects of aging, type IV hyperlipoproteinemia, and coronary artery disease

Circ Res

Diurnal variation of the fibrinolytic system

Thromb Haemost

Diural variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1)

Circulation