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P Meijer

Publications and source records attributed to P Meijer.

At least 19 recordsLinked to original sources
PubMed2005

The harmonization of quantitative test results of different D-dimer methods.

Nowadays D-dimer testing is frequently applied in the diagnosis of venous thromboembolism. However, the test results of different quantitative D-dimer tests can differ significantly. The background of this variability, which is mainly caused by the variety of fibrin degradation products in plasma, the specificity of D-dimer assays, and the calibrators used in the test, is summarized here. Because D-dimer is not a single entity in plasma but a mixture of heterogeneous fibrin degradation products, method standardization is in principle impossible. Efforts undertaken in the past to standardize D-dimer methods are summarized. All these projects failed and it was concluded that only harmonization of D-dimer test results seems to be feasible. The results of a large field study on which a new approach to the harmonization of quantitative D-dimer methods will be based is summarized in this article. This approach seems to be an adequate solution for overcoming the practical problem of variation of test outcome in different D-dimer assays.

Fibrin Fibrinogen Degradation Products↗
PubMed2004

ATP-induced vasodilation in human skeletal muscle.

1. The purine nucleotide adenosine-5'-triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium-derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. 2. Adenosine 5'-triphosphate (0.2, 0.6, 6 and 20 nmol dl(-1) forearm volume min(-1)) evoked a dose-dependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 microg dl(-1) min(-1), n=10), the blocker of Na(+)/K(+)-ATPase ouabain (0.2 microg dl(-1) min(-1), n=8), the blocker of K(Ca) channels tetraethylammonium chloride (TEA, 0.1 microg dl(-1) min(-1), n=10), nor by the K(ATP)-channel blocker glibenclamide (2 microg dl(-1) min(-1), n=10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and l-NMMA (n=6) significantly increased the baseline forearm vascular resistance. The ATP-induced relative decreases in forearm vascular resistance were 48+/-5, 67+/-3, 88+/-2, and 92+/-2% in the absence and 23+/-7, 62+/-4, 89+/-2, and 93+/-1% in the presence of the combination of TEA, indomethacin and l-NMMA (P<0.05, repeated-measures ANOVA, n=6). A similar inhibition was obtained for sodium nitroprusside (SNP, P<0.05 repeated-measures ANOVA, n=6), indicating a nonspecific interaction due to the blocker-induced vasoconstriction. 3. ATP-induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and l-NMMA. Endothelium-independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies.

Adenosine Triphosphate↗
PubMed2003

The long-term within- and between-laboratory variability for assay of antithrombin, and proteins C and S: results derived from the external quality assessment program for thrombophilia screening of the ECAT Foundation.

A stable laboratory performance is important for comparability and transferability of laboratory data both within and between laboratories. The lack of a reference system within hemostasis hampers laboratories in establishing their laboratory performance over a prolonged period of time. Therefore, based on data from an external quality assessment program, we evaluated the between laboratory variation (CVBETWEEN) and the long-term within-laboratory variation (LCVa) for antithrombin, and proteins C and S. We evaluated the CVBETWEEN for the period 1996-2001, including the results of 64-240 laboratories from 23 different surveys (protein S activity 15 surveys). We observed a quite high CVBETWEEN and a broad range for each analyte. The CVBETWEEN was significantly higher for antithrombin and protein S for samples with low levels similar to heterozygous deficiencies. We also evaluated the LCVa, including the results of 136 laboratories. The lowest LCVa[median and 95% content interval (CI)] was observed for antithrombin (7.6%; 3.6-35.5%), intermediate values for protein C activity and antigen (8.6%; 3.5-25.3% and 10.8%; 4.8-33.1%, respectively) and highest values for the protein S variables (13.4%; 6.4-50.6% for total protein S antigen, 14.1%; 6.5-79.1% for free protein S antigen and 17.2%; 7.2-84.3% for protein S activity). We concluded that the main reason for the high CVBETWEEN is the long-term within-laboratory variability. Application of linear regression on data of an external quality assessment program is a useful model to demonstrate per analyte per laboratory the long-term variability (LCVa). It is concluded that improvement of the long-term within-laboratory test performance is the first priority in hemostasis to yield important improvements in the comparability and transferability of laboratory data.

Antithrombin III↗
PubMed2002

Identification of determinants of the between-operator variation of the total protein S antigen assay: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis.

In a previous study, a between-operator variability (CVOBETWEEN) of 9.6% and 15.0%) was observed for total protein S antigen assays in 11 laboratories using a frozen or lyophilized reference plasma, respectively, and the need to standardize the use of lyophilized reference plasma was identified. The aim of the present study was to identify further determinants of this CVOBETWEEN in order to improve between-laboratory comparisons of test results for one method for protein S antigen assay. Two protocols were carried out: the first again involving local execution but using a joint standardized and detailed prescription of the technical performance in each laboratory; the second using a central session for all operators with the same prescription but with joint reagent and equipment. In the present study, improved handling of lyophilized reference plasma was included and resulted in comparable CVOBETWEEN of 10.9% and 9.6% for the use of frozen and lyophilized reference plasma for the local test performance. An improvement was found in the CVOBETWEEN in the central session compared with the standardized local performance, showing lower values for the central performance of 8.5 and 6.6% for frozen and lyophilized reference plasma, respectively. Further analysis of the difference between the local and central test performance identified the use of different curve fit options of data evaluation software as a significant source of this difference. Interestingly, the within-operator variability in the central performance was around 2% lower (5.9 and 6.0% for frozen and lyophilized plasma, respectively) than that in the local performance (8.1 and 8.0% for frozen and lyophilized plasma, respectively). Although the reduction is not statistically significant, it suggests an effect of reduction of the workload and simplification of procedures for individual operators on the within-operator variability. In this study, in which 11 operators/laboratories participated, the lowest variability between operators andwithin laboratories was obtained in the central test performance, which is suggested to be the lowest attainable variability for the measurement of total protein S antigen. The practical factors involved in local performance that require attention to reach similar levels of variability are mainly liquid handling, curve-fit procedures and simplicity of practical procedures.

Adult↗
PubMed2002

Effect of a common reference plasma on the inter-laboratory variation of the measurement of total and free protein S: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis.

The comparability of test results for protein S between laboratories is hampered by a high inter-laboratory variability. The effect of the use and type of common reference plasma on the inter-laboratory variability of the total and free protein S measurement was evaluated. The results of 10 plasma samples measured against a centrally distributed frozen plasma and a centrally distributed lyophilized plasma were compared with those of various local reference plasmas regularly used by the 11 participating laboratories. The mean intra-assay coefficient of variation for total protein S in each laboratory varied from 3.8 to 12.8% (mean intra-assay CV of all laboratories: 7.4+/-2.3%); for free protein S this range was 3.1 to 13.3% (mean intra-assay CV of all laboratories: 6.6+/-2.7%). We confirmed the high inter-laboratory coefficient of variation (mean+/-SD) with the several local reference plasmas for both total protein S (13.4+/-5.6%; n = 10) and free protein S (17.1+/-7.5%: n = 11). For total protein S, the inter-laboratory CV was reduced to 11.5+/-4.8%, (p=0.05) by using a common frozen reference plasma, while it was increased to 16.8+/-3.4%, (p=0.022) using a common lyophilized reference plasma. For free protein S, these values decreased only statistically significantly for the common lyophilized reference plasma, to 15.1+/-6.0%, (p = 0.008). For free protein S, the dilution factor used was identified as a factor influencing the inter-laboratory variability. This study shows that, for both types of protein S measurements, using one frozen reference plasma shows a slight decrease in inter-laboratory variability, while a common lyophilized plasma shows inconsistent results. It is concluded that further investigation is necessary to examine other sources of variability to increase the comparability of laboratory results for both total and free protein S.

Adult↗
PubMed2001

Urokinase-type plasminogen activator system predicts risk of cardiovascular events in patients with angina pectoris: results of the ECAPTURE study. European Concerted Action on Prevention from Thrombosis by URokinase Enhancement.

In most Westernized societies cardiovascular diseases are the leading cause of death over the age of 45 years and one-quarter of these deaths occur in men below the age of 65 years. The haemostasis system has been identified as an important system in cardiovascular disease (CVD). The European Concerted Action on Prevention from Thrombosis by URokinase Enhancement (ECAPTURE) has focused on the contribution of the urokinase system to CVD. In 2298 patients with angina pectoris the relationship between plasma levels of single-chain urokinase (scu-PA), urokinase antigen (u-PA) and u-PA-inhibitor complex and the risk of cardiovascular events (n = 84) during a 2 year follow-up period was studied. Plasma levels of total u-PA and u-PA-inhibitor complex predicted the risk of cardiovascular events, the adjusted relative risks of the highest quintile versus the lowest were 2.71 [95% confidence interval (CI), 1.34-5.48] and 2.34 (95% CI, 1.08-5.11), respectively. These results suggest that the urokinase system plays a role in cardiovascular disease.

Angina Pectoris↗
PubMed2001

Disagreement between bedside and laboratory activated partial thromboplastin time and international normalized ratio for various novel anticoagulants.

During studies on warfarin, heparin and various anticoagulants with novel mechanisms of action, the activated partial thromboplastin time (aPTT) and the (apparent) international normalized ratio (INR) from a bedside monitor (Coagucheck Plus(R)) were compared with laboratory assay results. Data were compared using the Bland and Altman method of comparison where systematic differences result in significant slopes of the regression line. During heparin treatment, the bedside monitor largely underestimated the aPTT (slope = -0.80). During treatment with the direct thrombin inhibitor napsagatran (slope = 0.99), the pentasaccharides Org31540/SR90107A (slope = 0.77) and SanOrg34006 (slope = 0.35), and warfarin (slope = 0.60), the bedside monitor underestimated the aPTT at lower aPTT levels, while at higher aPTT levels it overestimated the laboratory values. The bedside monitor slightly overestimated the INR during treatment with warfarin (slope = 0.33). Apparent INR was largely overestimated during treatment with Org31540/SR90107A (slope = 1.38), SanOrg34006 (slope = 0.97), Napsagatran (slope = 1.23), and recombinant tissue factor pathway inhibitor (slope = 1.48, P < 0.001 for all regression lines). These results indicate that a substantial disagreement in aPTT or (apparent) INR exists between the bedside monitor and laboratory assay during treatment with the studied 'classic' and novel anticoagulants. The amount of disagreement depended on the anticoagulant given.

Anticoagulants↗
PubMed2001

Activation products of the haemostatic system in coronary, cerebrovascular and peripheral arterial disease.

To determine the presence of a 'hypercoagulable state' as assessed by indices of thrombin and plasmin generation and of the amount of fibrin that is lysed, in patients with stable coronary, cerebral and peripheral arterial disease a population-based cross-sectional study was performed. From a population-based cohort comprising 7983 men and women aged 55 years and over, we randomly selected 127 subjects with a history of myocardial infarction, 124 with a history of stroke and/or transient ischemic attack, 131 patients with peripheral arterial disease and 263 control subjects in the same age group without arterial disease. Subjects using anticoagulant drugs were not selected. F1+2, TAT, and PAP were not associated with a history of cardiovascular events, nor with peripheral arterial disease. In contrast, positive associations were found for D-Dimer. Mean D-Dimer level was 40 microg/l (95% CI 35, 44) in control subjects; 53 microg/l (47, 61) in those with a history of myocardial infarction and 51 microg/l (45, 58) in those with a history of stroke and or transient ischemic attack. D-Dimer increased gradually with increasing severity of peripheral atherosclerosis; a decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an increase in D-Dimer of 3.9 microg/l (p<0.01). This was more pronounced in subjects with higher F1+2, TAT and PAP concentration. In conclusion, the markers of onset of coagulation F1+2, TAT and PAP are not associated with the presence of arterial disease, but increased levels of these markers are necessary for the positive association between D-Dimer and arterial disease.

Aged↗
PubMed2000

Performance of semiquantitative and quantitative D-dimer assays in the ECAT external quality assessment program.

D-dimer levels are used in clinical practice as markers for the presence or exclusion of venous thrombosis. Therefore, it is important that the performance of the D-dimer tests is well controlled. One of the components of a laboratory quality program is external quality assessment (EQA). The main aim of EQA is to identify the degree of agreement among laboratories. In addition to identifying the individual laboratory performance, it also identifies the characteristics of the different reagents and methods that are used in different laboratories. Recently, the D-dimer test was included in the ECAT External Quality Assessment program. Eighty-one laboratories in four rounds applied semiquantitative and quantitative D-dimer assays to three samples (concentrations normal, slightly elevated, and elevated). Although the reported values varied widely, the classification of the samples was mostly correct for the normal and the elevated samples. The slightly elevated sample was classified as normal by all laboratories using semiquantitative methods and by 60% of the laboratories using quantitative methods, and this varied between 45% and 86% for the different methods. In conclusion, D-dimer methods show a large variation, and the quality of the D-dimer assessment could be improved by standardization and by using cut-off ranges.

Antifibrinolytic Agents↗
PubMed1999

Specific determination of plasmin inhibitor activity in plasma: documentation of specificity of manual and automated procedures.

Recently, a chromogenic kit for determination of plasmin inhibitor activity, Coamatic Plasmin Inhibitor, has been developed with the aim to increase specificity and to allow application to a wide range of automates. The highly sensitive plasmin substrate S-2403 is used and, to further improve specificity, a low level of plasmin and a short incubation time is utilized as well as the incorporation of methylamine to quench alpha2-macroglobulin activity. The Coamatic Plasmin Inhibitor kit has been evaluated regarding specificity and compared with six commercially available plasmin inhibitor (also denoted alpha2-antiplasmin) kits and with the manual Immediate Plasmin Inhibition Test (IPIT) method, the reference method within the framework of the European Concerted Action against Thrombosis and Disabilities. Analysis of plasmin inhibitor deficient plasma with Coamatic Plasmin Inhibitor resulted in activities below 5% for all instrument applications, whereas all other commercial kits displayed unexpectedly higher values for this plasma (16-35%). There was a good agreement between the Coamatic Plasmin Inhibitor method and the IPIT method for all tested instrument applications; slope =0.80-1.02 and r = 0.92-0.97. No interference was detected from alpha2-macroglobulin, lysine, unfractionated and low-molecular weight heparin, and epsilon-amino caproic acid or from the non-plasminogen binding form of plasmin inhibitor.

Adult↗
PubMed1999

Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: A 2-year, placebo-controlled study.

Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54. 8+/-3.5 (mean+/-SD) years who entered this double-blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (n=15) or 150 mg/d (n=13), placebo (n=13), or CEEs 0.625 mg/d (n=15). At baseline and after 6, 12, and 24 months of treatment, we assessed serum lipids, blood pressure, glucose metabolism, C-reactive protein, and various hemostatic parameters. Compared with placebo, both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L (all P<0.04) and lowered, at 24 months, the level of fibrinogen by 0.71 to 0.86 g/L (all P<0.05). The effects of raloxifene and CEEs did not differ significantly. In contrast to raloxifene, from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL (all P<0.02 versus both placebo and raloxifene). CEEs transiently increased C-reactive protein by 1.0 mg/L at 6 months (P<0.05 versus placebo) and prothrombin-derived fragment F1+2 by 0. 79 nmol/L at 12 months (P<0.001 versus placebo). Finally, from 12 months on, CEEs increased triglycerides by 0.33 to 0.56 mmol/L (all P<0.05 versus both placebo and raloxifene). Our findings suggest that in healthy postmenopausal women, raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels. These treatments differ, however, in their effects on high density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1+2 and C-reactive protein.

Biomarkers↗
PubMed1999

Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I.

Lupus anticoagulants (LA) are immunoglobulins directed to either prothrombin or Beta-2-glycoprotein 1(beta1GPI) bound to phospholipids. Most patients with LA have both beta2GPI- and prothrombin-dependent antibodies. Several recent reports have shown that LA is more strongly associated with thrombosis than anticardiolipin antibodies (aCL). Therefore, an accurate detection of LA is of utmost importance in patients suspected of an antiphospholipid syndrome. We recently raised a series of murine monoclonal antibodies against human Beta-2-glycoprotein I (beta2GPI) with LA activity similar to affinity purified human beta2GPI-dependent LAs. A normal plasma pool, and the same pool spiked with LA positive anti-beta2GPI antibodies at two potency levels, were used as materials in an external quality assessment scheme organised by the European Concerted Action on Thrombosis (ECAT). Fifty nine laboratories participating in this trial were asked to test for the presence of a LA in the 3 samples submitted. The majority (82%) of the participants found the high potency LA sample to be positive. Only 37% of the laboratories considered the weak potency LA sample to be positive. The submission of a normal sample, a weakly positive sample and a clearly positive sample enabled us to compare the relative LA responsiveness of the different screening assays used. Clotting time ratios varied from 0.81 to 3.28 for sample B and from 0.66 to 5.32 for sample D. In general, the highest clotting time ratios were found with the dilute prothrombin time (dPT), the dilute Russell Viper Venom time (dRVVT) and the Kaolin Clotting time. The most frequently used screening tests were the aPTT and the dRVVT. With the various assay systems, LA responsiveness varied largely according to the reagents used. For the beta2GPI-dependent LA used in this study, PTT LA clearly showed the highest responsiveness among the aPTT reagents and Innovin among the dPT reagents. The present study also shows that many laboratories still rely on poorly responsive screening assays for their LA tests. Other laboratories rely on sensitive and more specific integrated test systems based on a sensitive screening assay with a low phospholipid content and a confirmatory test employing high phospholipid concentrations. The most used integrated system was dRVVT based. However, also here the LA responsiveness was largely reagent dependent. In conclusion, many laboratories still rely on poorly responsive screening assays by which weakly positive LA samples are misdiagnosed. LA positive anti-beta2GPI moabs have a potential for the unlimited production of LA control specimens, that may help hemostasis laboratories choose more LA responsive assay systems and to assess intralaboratory precision of their LA testing.

Antibodies, Monoclonal↗
PubMed1997

Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam Study.

BACKGROUND: Impaired fibrinolytic capacity, as assessed by euglobulin clot lysis time or plasma concentration of fibrinolytic parameters, has been associated with an increased risk of myocardial infarction (MI). We studied the association of a polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and activity) with the prevalence of MI. METHODS AND RESULTS: A case-control study was performed. Subjects with a history of MI (n = 121) and controls (n = 250) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects > or = 55 years old. We determined TPA antigen and activity in plasma and genotyped all subjects for the Alu repeat insertion/deletion polymorphism in intron h in the TPA gene. Homozygosity for the insertion was associated with twice as many cases of MI as was homozygosity for the deletion (odds ratio, 2.24; 95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI; compared with that in the lowest quartile, the relative risks (odds ratio) in the second, third, and upper quartiles were 1.7 (CI, 0.9-3.3), 2.3 (1.2-4.4), and 2.0 (1.0-3.8), respectively. When adjusted for body mass index, HDL and total cholesterol, systolic and diastolic blood pressures, and current smoking, the risk associated with TPA antigen concentration was attenuated. Increased concentrations of TPA activity tended to be associated with an increased risk of MI. CONCLUSIONS: This study provides evidence for an independent association of the insertion allele of the insertion/deletion polymorphism in the TPA gene with nonfatal MI. Increased TPA antigen is associated with an increased risk of MI; however, this association was not independent of cardiovascular disease risk factors.

Aged↗
PubMed1996

Reduced response to activated protein C is associated with increased risk for cerebrovascular disease.

BACKGROUND: Resistance to activated protein C (APC), which results from various factors, including a mutation in the gene for coagulant factor V, has been associated with increased risk for venous thrombosis. However, its relation to arterial disease is still not well defined. OBJECTIVE: To investigate the association of both response to APC and the factor V Leiden mutation with arterial disease. DESIGN: Population-based case-control study. SETTING: A district of Rotterdam, the Netherlands. PARTICIPANTS: 115 patients with a history of myocardial infarction; 112 patients with a history of stroke, transient ischemic attack, or both; and 222 age-matched controls without arterial disease chosen from among 7983 persons in the Rotterdam Study cohort. Patients using anticoagulant drugs were excluded. MEASUREMENTS: Response to APC was determined in double-centrifuged platelet-poor plasma. Patients were genotyped for the Arg 506 to Gln mutation in the gene for coagulant factor V. RESULTS: The prevalence of cerebrovascular disease increased gradually and corresponded to a decreasing response to APC (odds ratio per 1-unit decrease of response to APC, 1.43 [95% CI, 1.12 to 1.81], adjusted for age and sex). Adjustment for the factor V mutation did not change the findings. We found no association between response to APC and myocardial infarction or between factor V mutation and cerebrovascular disease or myocardial infarction. CONCLUSIONS: Low response to APC is associated with an increased risk for cerebrovascular disease but not with an increased risk for myocardial infarction, independent of the factor V Leiden mutation. The association between the factor V Leiden mutation and cerebrovascular disease or myocardial infarction remains to be determined.

Aged↗
PubMed1996

Interindividual and intraindividual variability in plasma fibrinogen, TPA antigen, PAI activity, and CRP in healthy, young volunteers and patients with angina pectoris.

We compared intraindividual and interindividual variability in the plasma levels of fibrinogen, tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor (PAI) activity, and C-reactive protein (CRP) in 20 healthy, young individuals and 26 patients with stable angina pectoris (AP) who were at higher risk for cardiovascular disease. For each of the four parameters, the contribution of the intraindividual variation to the total variance (13% and 9% for fibrinogen, 3% and 5% for TPA antigen, 4% and 20% for In[PAI activity], and 14% and 9% for In[CRP] for the healthy volunteers and AP patients, respectively) was smaller than the contribution from the interindividual variation. These results indicate that single sampling is sufficient to assess an individual level for TPA antigen and PAI activity, whereas duplicate sampling for fibrinogen and triplicate sampling for CRP are recommended. In an epidemiological study the sample sizes, based on the variances found in the transverse part of the study, needed to detect a 15% difference between the two groups (with alpha = 0.01 and a statistical power = .90) are 31 and 40 for fibrinogen, 568 and 146 for TPA antigen, 603 and 119 for PAI activity, and 1490 and 2263 for CRP in healthy volunteers and patients with AP, respectively. Additionally, we studied the contribution of genetic polymorphisms of the B beta-fibrinogen (Bcl I and G-->A-455) and PAI activity (HindIII and CA-repeat) genes to intraindividual and interindividual variation. Fibrinogen genotypes were associated with plasma fibrinogen levels in the volunteers but not in the AP patients. No effects of fibrinogen or PAI polymorphisms on intraindividual variation were observed in either healthy individuals or AP patients. In this study intraindividual variation in plasma levels of the cardiovascular risk indicators fibrinogen, TPA antigen, PAI activity, and CRP was small when compared with the interindividual variation in healthy, young volunteers and patients with stable AP.

Adult↗
PubMed1995

Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men.

Impaired fibrinolytic activity has been reported in the elderly and is thought to play a role in the etiology of cardiovascular disease, one of the leading causes of death in most Western countries. Since restriction of energy intake has been demonstrated to act beneficially on the aging process in a variety of species, we studied the effect of a 10-week moderately energy-restricted (ER) regimen (80% of habitual) on plasminogen activator inhibitor (PAI) activity, PAI-1 antigen, tissue plasminogen activator (tPA) activity, and tPA antigen in non-obese, middle-aged men. Moreover, the relationship between these fibrinolytic markers and glucose tolerance was investigated. Weight loss in the ER group (n = 16) was considerable (-7.4 +/- 1.7 kg, P < .001). Subjects in the control group (n = 8) also lost some weight (-2.1 +/- 1.5 kg, P < .01). Fasting glucose levels decreased in the ER group (-0.31 +/- 0.48 mmol/L, P < .05), which was correlated with the extent of weight loss (P < .01). Baseline insulin levels at 2 hours after an oral glucose load correlated with baseline PAI activity (P < .001) and PAI-1 antigen levels (P < .001). PAI activity decreased in the ER group (-2.94 +/- 2.90 IU/mL, P < .001), particularly in subjects with a high baseline PAI activity (> 9 IU/mL). Furthermore, energy restriction led to decreased PAI-1 antigen concentration (P < .05), a nonsignificant increase in tPA activity, and a decrease in tPA antigen concentration (P < .001). All these changes were more clear in subjects with a high baseline PAI activity. These results suggest that 10 weeks of moderate energy- restriction has a profibrinolytic effect in non-obese, middle-aged men, at least in subjects with higher baseline PAI activity (> 9 IU/mL). Moreover, in line with the suggestion that high PAI activity goes together with insulin resistance, a relationship between insulin concentration after a glucose load and PAI activity was found.

Adult↗