The effect of oral simvastatin on fibrinolytic activity after colorectal surgery-a pilot study. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. Plasminogen Activator Italian Multicenter Study (PAIMS): comparison of intravenous recombinant single-chain human tissue-type plasminogen activator (rt-PA) with intravenous streptokinase in acute myocardial infarction. Improved fibrinolysis after one year of treatment with enalapril in men and women with uncomplicated myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome A double blind placebo controlled study of early and late administration of recombinant tissue plasminogen activator in acute myocardial infarction. Improved fibrinolysis by intense lifestyle intervention. A randomized trial in subjects with impaired glucose tolerance. Fibrinolytic proteins and progression of coronary artery disease in relation to gemfibrozil therapy. Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients. Intense nonpharmacological intervention in subjects with multiple cardiovascular risk factors: decreased fasting insulin levels but only a minor effect on plasma plasminogen activator inhibitor activity. A low-glycemic-index diet reduces plasma plasminogen activator inhibitor-1 activity, but not tissue inhibitor of proteinases-1 or plasminogen activator inhibitor-1 protein, in overweight women. Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipemic heart transplant patients. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke. A comparative study of the effects of the hemostatic system of two monophasic gestodene oral contraceptives containing 20 micrograms and 30 micrograms ethinylestradiol. A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecular-weight heparins--enoxaparin, nadroparin and dalteparin. The ESCAPe-END study.
BACKGROUND Studies conducted in animal models have shown that statins ( 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ) reduce adhesion formation by upregulating fibrinolysis . The aim of this study was to determine the effect of orally administered statins on the promoters and inhibitors of the fibrinolytic pathway . METHODS In a previously described double-blinded clinical trial , 144 patients undergoing elective colorectal resection , or reversal of Hartmann 's procedure were r and omized to receive 40 mg once daily oral simvastatin 3 - 7 d before surgery or placebo . For the purpose s of the present study , peritoneal drain fluid was collected postoperatively from patients to measure active tissue plasminogen activator ( tPA ) , tissue plasminogen activator total antigen , active plasminogen activator inhibitor-1 ( PAI-1 ) , plasminogen activator inhibitor total antigen ( PAI-1TA ) , plasminogen activator inhibitor-1 and tissue plasminogen activator complex ( PAI-1/tPA ) . These were analyzed using ELISA . The number of hospitalizations and complications related to small bowel obstruction ( SBO ) were recorded at 2 y after surgery . RESULTS A total of 95 patients ( 72 % ) had sufficient peritoneal drain fluid suitable for ELISA analysis . Of them , 46 patients ( 48 % ) were from the oral simvastatin group . Mean tPA and tPA total antigen concentrations in peritoneal fluid were similar between the two groups . Mean PAI-1 and PAI-1 TA concentrations in the statin and placebo group were also similar . Mean PAI-1/tPA complex concentration was similar between the two groups . The number of hospitalizations from SBOs were 5 and 4 in the statin and placebo groups respectively ( P = 0.46 ) . The overall mortality at 2-year post-surgery was similar between the two groups ( P = 0.59 ) . CONCLUSIONS In this pilot study involving humans , oral simvastatin had no measured effect on the peritoneal fibrinolytic pathway in the first 24 h after colorectal surgery . Analysis of clinical outcomes also showed that oral simvastatin did not reduce hospitalizations for SBO in the 2 y after surgery . Further studies may be useful to evaluate whether fibrinolytic pathways beyond 24 h are altered after systemic administration of statins and to evaluate the use of higher doses of statins , perhaps used intraperitoneally rather than systemically Based on previous cross-sectional findings , we hypothesized that weight loss could improve several hemostatic factors associated with cardiovascular disease . In a r and omized controlled trial , moderately overweight men and women were assigned to one of four weight loss treatment groups or to a control group . Measurements of plasminogen activator inhibitor-1 ( PAI-1 ) antigen , tissue-type plasminogen activator ( t-PA ) antigen , D-dimer antigen , factor VII activity , fibrinogen , and protein C antigens were made at baseline and after 6 months in 90 men and 88 women . Net treatment weight loss was 9.4 kg in men and 7.4 kg in women . There was no net change ( p > 0.05 ) in D-dimer , fibrinogen , or protein C with weight loss . Significant ( p < 0.05 ) decreases were observed in the combined treatment groups compared with the control group for mean PAI-1 ( 31 % decline ) , t-PA antigen ( 24 % decline ) , and factor VII ( 11 % decline ) . Decreases in these hemostatic variables were correlated with the amount of weight lost and the degree that plasma triglycerides declined ; these correlations were stronger in men than women . These findings suggest that weight loss can improve abnormalities in hemostatic factors associated with obesity A single chain preparation of recombinant tissue-type plasminogen activator ( rt-PA ) was compared with intravenous streptokinase to determine coronary thrombolytic efficacy in patients with acute myocardial infa rct ion less than 3 h old . Eighty-six patients were r and omly selected to receive the intravenous cumulative dose of 100 mg rt-PA and 85 patients to receive 1.5 million units streptokinase . At 240 min after initiation of the thrombolytic therapy noninvasive signs of sustained reperfusion occurred in 79 % of patients in both groups ( p = NS ) . Patency of the infa rct -related vessel at follow-up angiography was observed in 81 % of patients in the rt-PA group and 74 % of patients in the streptokinase group ( p = NS ) . At hospital discharge , compared with admission , echocardiographically determined left ventricular ejection fraction increased from 52 + /- 11 % to 56 + /- 10 % ( p less than 0.01 ) in the rt-PA group ; changes in the streptokinase group ( 50 + /- 9 % to 51 + /- 11 % ) were not significant . A nadir value of less than 1 g/liter fibrinogen plasma level occurred in 6 patients ( 7 % ) receiving rt-PA versus 74 patients ( 87 % ) receiving streptokinase ( p less than 0.0001 ) . Plasma levels of fibrin(ogen ) degradation products were more than doubled in the streptokinase group ( p less than 0.01 ) . One patient in the streptokinase group developed a fatal intracranial hemorrhage ; five others showed a decline in hemoglobin greater than or equal to 5 g/dl . Other clinical events in the streptokinase-treated group included allergic reactions ( four patients ) and intrahospital reinfa rct ion ( two patients ) . None of these events occurred in the rt-PA group . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS To study long-term effects of enalapril on mass concentrations of tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor ( PAI-1 ) , tPA/PAI-1-complex and von Willebr and factor ( vWF ) in both genders with uncomplicated myocardial infa rct ion . METHODS AND RESULTS More than three months after an uncomplicated myocardial infa rct ion 82 survivors ( 46 males , 36 females ) were r and omised to enalapril/placebo .  PAI-1 , tPA , tPA/PAI-1-complex and vWF were measured after two weeks , six and 12 months following r and omisation . PAI-1 decreased significantly in both genders in the enalapril-treated group after two weeks , with a maximum decrease at six months ( mean reduction : 31 % equal to 9.8 microg x L(-1 ) , CI : 5.2 to 14.5 microg x L(-1 ) , p = 0.0001 ) and remained significantly lower at 12 months . Mass concentration of tPA decreased significantly ( mean reduction : 1.81 microg x L(-1 ) , CI : 0.903 to 2.708 microg x L(-1 ) , p < 0.001 ) after two weeks treatment in both genders but returned to baseline values at 12 months . The tPA/PAI-1-complex decreased and was significantly lower ( mean reduction 0.96 microg x L(-1 ) , CI : 0.36 to 1.56 microg x L(-1 ) , p = 0.003 ) in the enalapril group after two weeks and six months ( p = 0.037 ) . No decrease of vWF was seen in the enalapril group . CONCLUSIONS Enalapril treatment up to one year depressed mass concentrations of PAI-1 and transiently tPA and tPA/PAI-1 complex indicating an improvement of the fibrinolytic balance in both genders with uncomplicated myocardial infa rct ion The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established . Elevated circulating levels of plasminogen activator inhibitor-1 , the principle inactivator of the fibrinolytic system , have been related to the development of myocardial infa rct ion . There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels . We studied a common single nucleotide insertion/deletion ( 4G/5 G ) polymorphism by PCR in 558 patients with stroke , the pathological type of which was established by cranial computed tomography , and in 172 controls . 4G/5 G genotype and PAI-1 activity were investigated in relation to 1 ) stroke type and 2 ) mortality occurring within four weeks , three months and six months of the stroke . No difference in genotype frequency was observed when all cases of stroke were compared with controls nor between the clinical ly determined subtypes of cerebral infa rct ion . PAI-1 activity was significantly higher in patients with stroke ( n = 245 ) both at presentation ( 11.6 U/ml ) and after three months ( 11.8 U/ml ) , in paired sample s , than in control subjects ( 8.8 U/ml , p < 0.0001 ) . Thirty-seven ( 6.2 % ) , 86 ( 14.5 % ) and 122 ( 20.5 % ) patients had died within one , three and six months of admission , respectively . PAI-1 activity was independently associated with all-cause mortality at one and three months after stroke ( p = 0.02 and p = 0.03 respectively ) , but not after six months . In this population the 4G/5 G promoter polymorphism is not associated with an increased risk of stroke . PAI-1 levels were elevated at the time of acute stroke which persisted after three months . PAI-1 level but not genotype was associated with early mortality following stroke OBJECTIVE : Polycystic ovary syndrome ( PCOS ) is characterized by obesity and insulin resistance ( IR ) , which result in elevated plasminogen activator inhibitor-1 ( PAI-1 ) levels . We aim ed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss . DESIGN : Twenty-three normal weight women with PCOS were given metformin 850 mg bid for 6 months . Fifty overweight/obese women with PCOS were prescribed an energy-restricted diet , were instructed to exercise and were r and omized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months . RESULTS : In normal weight women , treatment with metformin reduced the body mass index ( BMI ) and circulating and rogens , improved markers of IR and lowered PAI-1 levels . In overweight/obese women , sibutramine and orlistat yielded comparable reductions in BMI and markers of IR . In contrast , the effects on the free and rogen index ( FAI ) differed ( p=0.027 ) : sibutramine reduced the FAI ( p=0.005 ) , whereas orlistat had no effect . The effects of sibutramine and orlistat on PAI-1 levels also differed ( p=0.042 ) : sibutramine  reduced PAI-1 levels ( p<0.001 ) , whereas orlistat had no effect . CONCLUSIONS : Metformin and sibutramine , but not orlistat , reduce PAI-1 levels in PCOS . The reduction in circulating and rogens during metformin and sibutramine treatment might be implicated in this decline Within four hours of the onset of acute myocardial infa rct ion 57 consecutive patients were r and omised blindly to infusion of 150 mg recombinant tissue plasminogen activator ( rt-PA ) ( group 1 ) over five hours or placebo ( group 2 ) when they were first seen outside hospital or in the accident and emergency department . When they were admitted to the coronary care unit patients in group 1 also had placebo infused and those in group 2 were treated with rt-PA as well as placebo . Treatment with rt-PA started at a mean of 119 minutes ( range 38 - 235 ) after the onset of pain in group 1 and 187 minutes ( range 80 - 285 ) after the onset of pain in group . In 19 ( 79 % ) of 24 in group 1 and 16 of 25 ( 64 % ) in group 2 cardiac catheterisation 10 - 14 days after infa rct ion showed thrombolysis in myocardial infa rct ion grade s 2 or 3 . There was mean percentage shortening of the infa rct related segments ( Leighton method ) of 16 % in group 1 and 10.3 % in group 2 . For patients with anterior infa rct ion mean percentage shortening was 20.5 % in group 1 and 12.2 % in group 2 . Although there was no significant difference in global ejection fraction as assessed by contrast ventriculography or radionuclide ventriculography the infa rct related regional third ejection fraction ( a measure of the function of the territory of the affected coronary artery ) was significantly improved by early treatment ( 41 % group 1 and 28 % group 2 ) . Assessment of infa rct size by the QRS scoring method of Palmeri showed QRS score less than or equal to 15/25 patients in group 1 and 8/27 in group 2 . Nine patients developed 11 episodes of ventricular fibrillation ; all patients in whom ventricular fibrillation developed during treatment with rt-PA were successfully resuscitated . There was no clinical ly significant bleeding . In seven ( 12 % ) patients clinical and electrocardiographic criteria suggested reocclusion . Five patients died from cardiac causes . Prehospital administration of rt-PA was feasible and significantly reduced the delay before thrombolysis was started . Earlier treatment improved myocardial function in the the infa rct area and reduced the infa rct size OBJECTIVE To assess the effects of lifestyle intervention on  cardiovascular  risk factors in general and especially on fibrinolysis . DESIGN R and omized clinical study . SUBJECTS A total of 186 subjects with impaired glucose tolerance and obesity . INTERVENTIONS The intervention programme included a low-fat , high-fibre diet and regular physical exercise . Half of the participants ( n = 93 ) took part in a one-month learning and training session using different behavioural modification techniques and conducted in a full-board wellness centre ( intense intervention group ) . The other half ( n = 93 ) was r and omized a one-hour counselling session with a specially trained nurse ( usual care group ) . Follow-up was carried out after 12 months . MAIN OUTCOME MEASURES Body weight , oxygen consumption , plasminogen activator inhibitor type 1 ( PAI-1 ) activity , tissue plasminogen activator ( tPA ) antigen , fibrinogen and fasting plasma insulin measured at the start of the programme and at follow-up after 1 year . RESULTS The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group . Oxygen consumption in the intense group increased 10 % vs. a 1 % decline in the usual care group . In the intense group , PAI-1 activity decreased 31 % ( -10.1 U mL(-1 ) ) , which was significantly more than in the usual care group ( 12 % ; -3.0 U mL(-1 ) ) . The corresponding reductions in tPA antigen were 14 % ( -1.65 microg L(-1 ) ) and 6 % ( -0.69 microg L(-1 ) ) . CONCLUSIONS The present r and omized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis Impaired fibrinolytic function , mainly due to increased plasma plasminogen activator inhibitor-1 ( PAI-1 ) activity , is common in patients with manifest coronary artery disease ( CAD ) and a predictor of recurrent cardiovascular events . We investigated the relationships of plasma tissue-type plasminogen activator ( tPA ) and PAI-1 antigen levels , plasma PAI-1 activity and PAI 4/5-guanosine ( 4G/5 G ) genotype to CAD progression in 203 middle-aged men participating in the Lopid Coronary Angiography Trial ( LOCAT ) . A higher tPA antigen concentration , whether baseline or on-trial , was associated with a more severe global angiographic response ( p < 0.05 ) , an association mainly accounted for by progression of diffuse lesions in graft-affected segments ( change in per-patient means of average diameters of segments haemodynamically related to bypass grafts ) . Plasma PAI-1 activity and mass concentration and 4G/5 G PAI-1 genotype were unrelated to angiographic outcome measurements . tPA and PAI-1 antigen increased significantly in the gemfibrozil group ( + 11.3 % and + 16.4 % , respectively , p < 0.001 ) , whereas there was no treatment effect on PAI-1 activity ( median change 0.0 % ) . It is concluded that fibrinolytic function does not substantially influence progression of CAD as assessed by angiography in middle-aged men . Furthermore , pronounced long-term lowering of serum triglycerides by gemfibrozil treatment does not significantly affect the plasma PAI-1 activity level but increases the plasma tPA and PAI-1 antigen concentrations Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects . A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent . We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator ( t-PA ) , plasminogen activator inhibitor-1 ( PAI-1 ) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen . Although both fibrates effectively lowered triglyceride and cholesterol levels , no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment . However , both fibrates influenced plasma fibrinogen levels , albeit in a different way . Fibrinogen antigen levels were elevated by 17.6 % ( p < 0.05 ) and 24.3 % ( p < 0.001 ) with gemfibrozil after six and twelve weeks , respectively , whereas with ciprofibrate there was no effect . Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point , no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment . However , after twelve weeks , gemfibrozil enhanced functional fibrinogen levels by 7.2 % ( p < 0.05 ) as assessed by the Clauss mechanical assay , but decreased functional fibrinogen levels by 12.5 % ( p < 0.0001 ) when a Clauss assay based on turbidity was used . After six or twelve weeks of ciprofibrate treatment , functional fibrinogen levels were decreased by 10.1 % ( p < 0.001 ) and 10.5 % ( p < 0.0001 ) , respectively on the basis of Clauss mechanical and by 14.2 % ( p < 0.001 ) and 28.2 % ( p < 0.0001 ) , respectively with the Clauss turbidimetric assay . A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen ( determined by either of the two Clauss assays ) to fibrinogen antigen . Taken together , our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates , by differences in treatment period and /or by the different outcomes of various assay systems . Interestingly , the two fibrates tested both reduced the functionality of fibrinogen Increased plasma levels of insulin and the fibrinolytic inhibitor , plasminogen activator inhibitor type 1 ( PAI-1 ) , are two new cardiovascular risk factors . The extent to which these two risk factors can be affected by nonpharmacological intervention modalities has not been convincingly proven in subjects at high risk for cardiovascular disease . This study assesses the effects on fasting plasma insulin and plasma PAI-1 activity of an intervention program including a low-fat , high-fiber diet and regular daily physical exercise . The intervention was implemented by a 1-month learning and training session in a full-boarding wellness center and included a follow-up evaluation after 12 months . The study was conducted on 108 subjects ( 31 men and 77 women ) referred for multiple risk factor treatment . After 1 month of intense intervention , the physical condition improved significantly , and this effect was maintained during the year . The body mass index ( BMI ) , fasting plasma insulin , and plasma lipids were significantly decreased . In women , PAI-1 activity was significantly reduced . At follow-up study in both sexes , the BMI and fasting insulin were still significantly decreased . In women , PAI-1 activity reverted to the preintervention level . In subjects with multiple risk factors , ie , the insulin resistance syndrome , the plasma insulin level can be reduced by an intense nonpharmacological program . Also , at least in women , plasma PAI-1 activity can be modestly modified . However , the magnitude of the decrease in PAI-1 activity was probably too small to reverse the hypofibrinolytic state characteristic of these subjects BACKGROUND The development of obesity has been suggested to involve plasminogen activator inhibitor-1 ( PAI-1 ) and tissue inhibitor of proteinases-1 ( TIMP-1 ) . Plasma PAI-1 is elevated in obesity . A low-glycemic-index ( LGI ) diet may have a beneficial effect on obesity through a decrease in plasma PAI-1 , but whether it affects plasma TIMP-1 in healthy humans has not been studied . OBJECTIVE We investigated whether a 10-wk intake of an LGI or a high-glycemic-index ( HGI ) , high-carbohydrate , low-fat , ad libitum diet is associated with decreases in plasma PAI-1 and TIMP-1 concentrations in overweight women . DESIGN Forty-four overweight women [ body mass index ( BMI ; in kg/m2 ) : 27.5+/-0.23 ] were r and omly assigned to consume an HGI or an LGI diet for 10 wk . A subgroup of 29 women was assigned to participate in an additional 4-h meal test on the last day of the 10-wk intervention . RESULTS PAI-1 activity decreased after 10 wk of the LGI diet and was significantly different between groups . Changes in PAI-1 antigen followed the same trend , but no significant difference was observed between groups . No difference in plasma TIMP-1 concentrations was observed between groups . PAI-1 and TIMP-1 concentrations after the 4-h meal test were not significantly different between groups . CONCLUSION An LGI diet reduces fasting plasma PAI-1 activity and therefore may be useful for diminishing the adverse cardiovascular effects of obesity . This trial was registered at clinical trials.gov as NCT00324090 Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients . Hyperlipemia , hyperinsulinism , and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease . Both lovastatin and bezafibrate are safe , effective , and well tolerated therapies for hyperlipidemia . Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome . Patients were given the same diet for 3 months , then r and omized to lovastatin or bezafibrate for a period of 8 weeks , and crossed over to an additional 8 weeks of either bezafibrate or lovastatin . Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment . Transplant patients had higher insulin ( 35 + /- 3 vs 24 + /- 3 microIU/L ) , fibrinogen ( 298 + /- 15 vs 261 + /- 14 mg/dl ) , and plasminogen activator inhibitor-1 ( PAI-1 ) ( 17 + /- 2 vs 11.7 + /- 2 arbitrary units/ml ) plasma levels than controls . Significant decreases in insulin ( -37 + /- 3 % ) , fibrinogen ( -12 + /- 4 % ) , and PAI-1 plasma levels ( -18 + /- 12 % ) were only observed after bezafibrate treatment . In conclusion , bezafibrate decreases plasma insulin , fibrinogen , and PAI-1 in hyperlipidemic heart transplant recipients Intravenous administration of 80 mg of recombinant tissue plasminogen activator ( rt-PA , 40 , 20 , and 20 mg in successive hours ) and streptokinase ( SK , 1.5 million units over 1 hr ) was compared in a double-blind , r and omized trial in 290 patients with evolving acute myocardial infa rct ion . These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted . Ninety minutes after the start of thrombolytic therapy , occluded infa rct -related arteries had opened in 62 % of 113 patients in the rt-PA and 31 % of 119 patients in the SK group ( p less than .001 ) . Twice as many occluded infa rct -related arteries opened after rt-PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy . Regardless of the time from onset of symptoms to treatment , more arteries were opened after rt-PA than SK . The reduction in circulating fibrinogen and plasminogen and the increase in circulating fibrin split products at 3 and 24 hr were significantly less in patients treated with rt-PA than in those treated with SK ( p less than .001 ) . The occurrence of bleeding events , administration of blood transfusions , and reocclusion of the infa rct -related artery was comparable in the two groups . Thus , in patients with acute myocardial infa rct ion , rt-PA elicited reperfusion in twice as many occluded infa rct -related arteries as compared with SK at each of seven serial observations during the first 90 min after onset of treatment BACKGROUND The 4 G allele in the promoter region of the plasminogen activator inhibitor type 1 ( PAI-1 ) gene is associated with higher plasma PAI-1 levels and activity , but its association with cardiovascular diseases is unclear . We investigated the association of polymorphisms and common haplotypes of the PAI-1 gene with plasma PAI-1 levels , as well as the risk of myocardial infa rct ion and stroke . METHODS AND RESULTS This study is a prospect i ve analysis of 2995 community-based participants ( 41 % blacks and 51 % women ) aged 70 to 79 years old in the Health , Aging , and Body Composition Study . From 1997/1998 to 2001 , 177 myocardial infa rct ion events and 101 stroke events were identified . In addition to the 4G/5 G polymorphism , 2 potential functional variants and other 4 haplotype-tagging variants were genotyped . In general linear models , the 4 G allele was associated with higher PAI-1 levels after adjusting for age , sex , race , and site ( 26 , 29 , and 32 ng/mL for 5G/5 G , 4G/5 G , and 4G/4 G , respectively ; P for trend < .0001 ) , but none of the other 6 polymorphisms was associated with PAI-1 levels . Haplotype analysis produced similar results . However , in Cox proportional hazard models , neither the polymorphisms nor the common haplotypes of the PAI-1 gene was associated with the risk of either myocardial infa rct ion or stroke . CONCLUSIONS The 4 G allele is associated with higher PAI-1 levels , but this study does not support an association of the PAI gene polymorphisms with the risk of either myocardial infa rct ion or stroke The effects of two oral contraceptives , containing gestodene and either 20 micrograms or 30 micrograms ethinylestradiol , on hemostatic parameters was investigated in a six-month r and omized study involving a total of 40 healthy women between the ages of 18 and 30 years . A large number of hemostatic parameters were measured , which were categorized as either pro-coagulatory , anti-coagulatory , profibrinolytic , anti-fibrinolytic or indicative of fibrin turnover . Additionally , tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor ( PAI-1 ) were measured before and after venous occlusion and delta and ratio values calculated . Pro-coagulatory factors as well as reaction products reflecting in vivo coagulatory activity ( thrombin-antithrombin III complex , prothrombin fragment 1 + 2 ) were found to increase . Among the anti-coagulatory parameters , only protein S concentration and protein S activity decreased , most notably in the 30 micrograms EE group . There was a corresponding increase in fibrinolytic activity reflected by reaction products of in vivo fibrinolysis ( plasmin-antiplasmin 2-complex , fibrin-degradation products ) . Measurement of t-PA and PAI-1 , before and after venous occlusion , revealed that the fibrinolytic response was more pronounced in the 20 micrograms EE group . There was also an increase in the threshold of fibrinolytic inhibition ( ratio PAI-1 ) in both groups , which was less pronounced in the 20 micrograms EE group . Apart from isolated measurements , all parameters remained within their normal ranges and values returned to baseline in the follow-up cycle . It is concluded that both preparations had a balanced effect on the hemostatic system stimulating both pro-coagulant and fibrinolytic activity . No statistically significant differences were observed between the two groups ; however , there was a trend towards greater fibrinolytic capacity in the 20 micrograms EE group BACKGROUND Comparative data for efficacy and safety between various low-molecular-weight heparins ( LMWHs ) in patients with unstable angina is not available . The present study was conducted to compare the efficacy , safety , cost-effectiveness and effects on plasminogen activator inhibitor-1 ( PAI-1 ) levels of three LMWHs -- enoxaparin , nadroparin and dalteparin . METHODS The study was a prospect i ve , r and omized , comparative , open with blinded endpoints ( PROBE design ) assessment with a 30-day follow-up . The primary endpoint of efficacy was a composite of cardiovascular death , myocardial infa rct ion , recurrent angina and need for intervention . Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio . Plasma PAI-1 levels were estimated by ELISA . RESULTS A total of 150 patients were available for intention-to-treat analysis . There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups . The secondary endpoint of silent ischemia was also not significantly different . Adverse events were similar in the three groups . The PAI-1 levels were not significantly different in the three groups . The total cost of treatment in the three groups was similar . CONCLUSION Any of the three LMWHs evaluated in this study were similar with respect to efficacy , safety , PAI-1 levels and cost-effectiveness
The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis .
This meta- analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1
OBJECTIVE The aim of this systematic review was to perform a meta- analysis of r and omized controlled trials ( RCTs ) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 ( PAI-1 ) .