Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice. Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein. Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only "global" measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.
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PMID:Sex differences in the determinants of fibrinolytic activity. 953 Oct 46

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.
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PMID:Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. 953 45

This study examines the association between time to treatment with thrombolytic therapy and hospital outcomes in patients with acute myocardial infarction (AMI) enrolled in a national registry. A total of 71,253 patients hospitalized with AMI from June 1994 to July 1996 who received tissue plasminogen activator (t-PA) therapy in 1,474 United States hospitals were studied. In this study sample, approximately 39% of patients presented to participating hospitals within 2 hours of acute symptom onset and received t-PA; 36% were treated within 2.1 to 4 hours, 12% between 4.1 to 6 hours, and the remaining 13% thereafter. After controlling for potentially confounding factors, in-hospital death rates increased progressively with increasing delays in time of administration of t-PA. The lowest risk for dying during acute hospitalization was seen for those treated with t-PA within 2 hours of acute symptoms. No significant association was seen between time of administration of t-PA and in-hospital risk of recurrent AMI, myocardial ischemia, cardiogenic shock, major bleeding episodes, or stroke and/or intracranial bleeding. The incidence of sustained ventricular arrhythmias declined with progressively longer time to administration of t-PA. The results of this multihospital observational study suggest that patients with AMI treated earlier with t-PA are significantly more likely to survive the acute hospitalization than patients treated later. These data reinforce the benefits to be gained by treatment with t-PA as soon as possible following the onset of acute ischemic symptoms, and for community-wide efforts to reduce the duration of prehospital delay in patients with acute coronary disease.
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PMID:Impact of time to treatment with tissue plasminogen activator on morbidity and mortality following acute myocardial infarction (The second National Registry of Myocardial Infarction). 970 50

Among cardiovascular diseases, hypertension, angina pectoris, acute myocardial infarction and ischemic stroke present a circadian pattern with a greater incidence of unfavourable events between awakening and noon. Chronotherapy aims to use drugs that release their active principles at different times during the day, according to biological needs. In chronotherapy of cardiovascular diseases, a particular attention has been paid to slow-release drugs that assure a 24 hours therapeutic effect with once a day administration. In primary hypertension well controlled by monotherapy (dipper hypertensives), the morning administration of long-acting beta-blockers and calcium antagonists has shown to control blood pressure over 24 hours, whereas ACE-inhibitors have proved more effective when administered at evening. In secondary hypertension (non dipper hypertensives) the administration of calcium antagonists is more effective at evening. Patients with severe hypertension need polytherapy. In that case, at least one of the antihypertensive drugs should be given at evening to lower night blood pressure values, which are particularly elevated also during sleep, and so to prevent an excessive blood pressure rise on awakening. In chronic monotherapy of ischemic heart disease, long-acting beta-blockers and calcium antagonists have shown to be equally effective when they are administered at morning, whereas slow-release nitrates, which need a nitrate-free interval, are to be administered either at morning or at evening, according to the expected time of onset of anginal pain. ASA seems to reduce the morning incidence of acute myocardial infarction, while tissue-type plasminogen activator presents a circadian variation of its thrombolytic activity with a higher efficacy between noon and midnight.
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PMID:[Application of chronotherapy to cardiovascular diseases]. 979 79

Changes in hemostasis inducing hypercoagulability are pathogenic factors for the development of ischemic heart disease and myocardial infarction. Nevertheless, their role is unknown in the emergence of new coronary events in patients with infarction. A group of 58 patients who had survived to a first infarction episode were studied; the cardiovascular risk factors were determined and blood concentrations of fibrinogen, t-PA, PAI and FRW measured. These patients were followed for two years to observe the development of new ischemic problems. In the study only the t-PA concentration was found to be a factor for poor prognosis.
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PMID:[Tissue plasminogen activator as a prognostic factor in myocardial infarct patients]. 1036 93

This case report describes a 48-year-old woman patient with variant angina who died because of severe myocardial ischemia and cardiogenic shock, in spite of chronic therapy with nitrates and calcium-antagonists and acute intravenous administration of nitrates, calcium-antagonists and tissue-type plasminogen activator. Her Holter monitoring showed a reduction of time domain measures of heart rate variability. The hemodynamic study exhibited a normal ventriculography and angiographically normal epicardial coronary arteries. The provocative testing, performed (during intravenous therapy with nitrates and diltiazem) by intracoronary injection of progressively increasing doses of ergonovine, induced only a mild vasoconstriction of proximal left anterior descending artery, without symptoms or ST-T segment changes. This case reminds us that variant angina can be a lethal disease, confirms that a negative result of intracoronary ergonovine testing performed during intravenous therapy with nitrates and calcium-antagonists does not assure the prevention of new episodes during chronic oral therapy with the same drugs, suggests a possible prognostic value of the reduction of heart rate variability indexes and shows an unusual response to nitrate administration.
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PMID:An uncommon case of variant angina. 1054 36

Tumor necrosis factor-alpha (TNF-alpha) level, tissue-typed plasminogen activator(t-PA) activity and PA inhibitor (PAI) activity were determined in three groups: (1) 25 NIDDM patients with silent myocardial ischemia (SMI) or silent cerebral ischemia (SCI); (2) 18NIDDM patients without SMI or SCI; (3) 20 age-matched normal controls. Diagnosis of SMI or SCI was based on the finding of ischemic evidence by SPECT of myocardiotomograph or cerebrotomograph. All patients ECG and blood pressure were normal, and they had no history of clinical symptoms and signs of MI or CI. The result showed that the TNF-alpha level and PAI activity in the ischemia group were the highest and the t-PA activity in the ischemia group was the lowest, as compared with those in the other two groups respectively. It suggests that in NIDDM patients who have high TNF-alpha, high PAI activity, low t-PA, and even no symptoms and signs of MI or CI, anticoagulant therapy might be useful to prevent the progression of diabetic macroangiopathies.
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PMID:[Changes of serum TNF-alpha level, t-PA activivty and PAI activity in patients with silent myocardial ischemia or silent cerebral ischemia]. 1068 70

The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.
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PMID:Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study. 1069 Oct 98

Long-term moderate or strenuous physical activity is associated with a considerable reduction in cardiovascular morbidity and mortality. This article reviews the evidence to suggest that part of the effect is mediated through the effects on thrombogenic factors. Fibrinogen has been convincingly shown to be an independent cardiovascular risk factor. Other hemostatic and fibrinolytic parameters that are predictive of coronary events include factor VII, platelet hyperreactivity, plasminogen activator inhibitor-1, and tissue-plasminogen activator. The effects of exercise on fibrinogen have been studied intensively. One randomized, controlled trial, two other intervention studies and a large number of population-based cross-sectional studies have consistently found an inverse relationship between various measures of sport activity or leisure activity and plasma levels of fibrinogen. The magnitude of the effect might be associated with a sizeable reduction in major coronary events. Relatively few data are available on endurance exercise and markers of the fibrinolytic system. Acute exercise leads to a transient activation of the coagulation system, which is accompanied by an increase in the fibrinolytic capacity in healthy subjects. However, patients with ischemic heart disease, who cannot increase their fibrinolytic potential, may be at considerable risk for acute ischemic events if they are exposed to unaccustomed strenuous physical exertion. It is concluded that physical activity has profound effects on thrombogenic factors and that these mechanisms could contribute to its beneficial cardiovascular effects.
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PMID:Exercise and thrombosis. 1075 13

Several studies have demonstrated an increased level of plasma plasminogen activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD). However, the concentration of PAI-1 in platelets, which accounts for more than 90% of the blood PAI-1, is unknown in these patients. The present study evaluated the concentrations of PAI-1 and several fibrinolytic factors in the plasma and platelets of patients with CAD and the serial changes in patients with acute myocardial infarction (AMI). All 72 subjects had coronary angiography and were divided into 3 groups: CAD(-) group without coronary artery stenosis or myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the AMI group admitted within 24h of symptom onset who underwent successful percutaneous transluminal coronary angioplasty (n=22). The concentrations of plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA x PAI-1 complex were similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI group compared with the 2 CAD groups. There were no significant differences between the 3 groups in the plasma concentrations of thrombin antithrombin III complex (TAT), alpha2-plasmin inhibitor-plasmin complex (PIC), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF-4). The platelet PAI-1 concentrations did not differ between the CAD(-) and CAD(+) groups, but was greater on day 1 in the AMI group compared to the CAD groups. The platelet beta-TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1 rapidly decreased by day 5 and remained low on day 28 compared with day 1. The platelet PAI-1 concentration gradually decreased by day 5 and was further decreased by day 28. The serial changes of the plasma t-PA and t-PA PAI-1 complex during the course of AMI were similar to those of the plasma PAI-1. A positive correlation was found between the plasma and platelet PAI-1 in all 72 patients, but not in the AMI group alone. These results suggest that the PAI-1 that has accumulated in platelets at the onset of AMI might be released in large amounts into the plasma, resulting in an increase in thrombus formation.
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PMID:Plasma and platelet plasminogen activator inhibitor-1 in patients with acute myocardial infarction. 1095 48


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