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Biomedical subjects

M P de Maat

Publications and source records attributed to M P de Maat.

At least 19 recordsLinked to original sources
PubMed2001

C-reactive protein in patients with familial hypercholesterolemia: no effect of simvastatin therapy.

Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the effect of one year of simvastatin treatment on serum levels of CRP and to assess the influence of risk factors for CVD on CRP concentrations in patients with FH. We measured baseline CRP levels in 337 patients with FH. A second blood sample, collected after one year of treatment with simvastatin (20--40 mg once daily) was measured in a subgroup of 129 patients. Patients with CVD present at baseline had significantly higher serum levels of CRP (2.26 mg/l versus 1.55 mg/l, P<0.001). CRP levels were associated with smoking, body mass index, age, levels of triglycerides (TG), and the use of NSAIDs or anticoagulation drugs. Simvastatin therapy significantly improved lipid profiles in the intervention group. There was a small, but non-significant decrease of CRP levels upon treatment. CRP decreased from 1.51 mg/l median (interquartile range (IQR) 0.76--3.41) at baseline to 1.24 mg/l median (IQR 0.72--2.92) after treatment, (P=0.328). In conclusion, CRP levels were associated with the presence of CVD in FH patients. Simvastatin therapy had no significant effect on CRP levels in these patients.

Adolescent↗
PubMed2001

Variations of cardiovascular disease associated genes exhibit sex-dependent influence on human longevity.

This article investigates the relationship between the polymorphic variations in genes associated with cardiovascular disease and longevity in the Danish population. A new procedure that combines both demographic and the individual genetic information in determining the relative risks of the observed genetic variations is applied. The sex-dependent influences can be found by introducing sex-specific population survival and incorporating the risk of gene-sex interaction. Three genetic polymorphisms, angiotensinogen M/T235, blood coagulation factor VII (FVII) R/Q353 and FVII-323ins10, manifest significant influences on survival in males, with reduced hazards of death for carriers of the angiotensinogen M235 allele, the F VII Q353 allele, and the FVII-323P10 allele. The results show that some of these genotypes associated with lower risk of CVD could also reduce the carrier's death rate and contribute to longevity. However, the presence of sex-dependent effects and the fact that major CVD-associated genes failed to impose detrimental influence on longevity lead us to concur that the aging process is highly complicated.

Alleles↗
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

Effects of diet, drugs, and genes on plasma fibrinogen levels.

Plasma levels of fibrinogen have been identified as independent risk predictors of cardiovascular disease. This has greatly increased interest in the regulation of plasma fibrinogen levels. Many demographic and environmental factors are known to affect fibrinogen levels, such as diet, use of several drugs, age, smoking, body mass, gender, physical exercise, race, and season. Additionally, it is also known that genetic factors determine the fibrinogen levels, and also that they determine the response of fibrinogen levels to environmental factors. Estimates, based on twin studies, suggest that 30-50% of the plasma fibrinogen level is genetically determined. The effect of dietary components on plasma fibrinogen levels is modest. Several components have been identified as factors that influence fibrinogen levels. Among those are fish oil, other lipids, and fibers. Dietary components that were expected to have an effect on fibrinogen, but for which no association was observed are black and green tea. Several drugs are known to influence fibrinogen levels, the most studied of which are platelet aggregation inhibiting drugs, such as ticlopidine, and the lipid lowering fibric acid derivatives (fibrates). Both types of drugs decreased the plasma fibrinogen level by about 10%, and bezafibrate lowers fibrinogen even more in patients with diabetes. No clear effect was observed for the HMG-CoA reductase inhibitors (statins). In the Bezalip study, fibrinogen levels decreased in patients treated with bezafibrate, but this had no clear effect on the risk of cardiovascular disease. This suggests that several mechanisms influence the fibrinogen level and that these mechanisms may contribute differently to cardiovascular disease. Several variations in the fibrinogen genes have been described and especially variations in the promoter region of the fibrinogen beta-gene are interesting, because the synthesis of the fibrinogen B beta chain is considered to be the rate limiting step in the fibrinogen biosynthesis. In many studies the fibrinogen beta-gene polymorphisms (-455G/A, -148C/T, and BclI) are found to be associated with the plasma levels of fibrinogen. However, they are not associated with the risk of cardiovascular events, although in several studies an association with the severity and progression of atherosclerosis has been reported. It has also been observed frequently that the fibrinogen beta-gene promoter polymorphisms are associated with the response of fibrinogen levels to environmental factors, such as exercise and trauma. In conclusion, plasma fibrinogen levels are regulated by an interesting and complex interplay between environmental and genetic factors.

Diet↗
PubMed2001

Determination of the habitual low blood level of C-reactive protein in individuals.

In order to use C-reactive protein (CRP) in risk prediction in individuals, it is necessary to know how to obtain the habitual level of an individual and hence its biological variations: i.e. longitudinal variability within subjects and variability between individuals. This paper provides data on biological variability that is used to propose a strategy for assessing individual low levels of CRP. The longitudinal variability in individuals (intraindividual variability) is essential to know, but only reported in a very limited way. Additional data were calculated from in-house and requested databases for periods of follow-up from 5 days to 1 year. The intraindividual coefficient of variation (CVi) was found to be rather similar for several groups and periods and on average was approximately 30%. Reported analytical coefficients of variation of commercial and in-house methods generally are below 6%, which is well below the desired limit of half the CVi. The distribution of CRP in apparently healthy individuals is wide and skewed with interquartile values ranging between 150-250% of the median and an estimate of the composite coefficient of variation (CVc) of approximately 120%. The distribution is equally broad in several other groups studied such as type II diabetics and pregnant women. It is concluded that the coefficient of variation for the determination of CRP in a single blood sample is as high as approximately 30%, but that this is acceptable for the reliable positioning of individuals within the distribution of CRP in the group with a CVc as high as -120%. CRP can show unexpected outliers (increases) which can sometimes be explained by information from a short questionnaire and definitely identified by the analysis of a second blood sample after an interval of approximately 2 weeks. Similarly, to ascertain high values in a first sample a second blood sample can be analyzed. It should be noted that, in view of the significant intraindividual variability of CRP, the difference between the first and second values may reach 71%. The large intraindividual variability of CRP approximating 30% renders it difficult to position an individual reliably in smaller categories such as tertiles, quartiles or quintiles of the total distribution. It is suggested that it would be most practical to have a goal of a single decision level or threshold only. Positioning an individual into two groups with equally wide distribution is on the borderline of reliability for one blood sample. Multiple blood samplings are required for smaller categories and higher threshold levels. The use of a decision limit should further acknowledge the limited interclass stability of around r = approximately 0.5 for a single blood sample. The above considerations are summarized in a practical working scheme. This scheme can serve as a basis for further refinement, discussions and development of sampling and decision limits to be selected from medical and economical perspectives and tested in practice.

Biomarkers↗
PubMed2001

Determinants of C-reactive protein concentration in blood.

C-reactive protein (CRP) is a very strong acute phase protein. During the acute phase of disease the CRP concentration can increase up to a thousand-fold. However, a higher CRP concentration is also observed during chronic stages of disease, for example in subjects with chronic bronchitis, periodontal disease or subjects with increased titers of Helicobacter pylori or Chlamydia pneumoniae. The concentration of CRP is also reported to be associated with age, sex, race, smoking, obesity, consumption of coffee and alcohol, stress, physical training, lipid levels, and blood pressure. Statins decrease the CRP concentration whereas estrogen increases it. With regard to most other drugs no consistent relationship has been reported.

Acute Disease↗
PubMed2000

The -323Ins10 polymorphism for factor VII is not associated with coronary atherosclerosis in symptomatic men. The REGRESS study group.

Elevated factor VII coagulant activity (FVII:C) has been associated with an increased risk of ischaemic heart disease, particularly for fatal events. Results of studies on the association between FVII:C and atherosclerosis are not consistent. FVII:C levels are influenced by several environmental factors and by genetic factors. One of the genetic factors is the -323Ins10 polymorphism in the promoter region of the factor VII gene, which is strongly related to FVII:C, and thus may be associated with ischaemic heart disease. We studied the association of this polymorphism with the severity and progression of atherosclerosis. In 511 male patients of the Regression Growth Evaluation Statin Study, the genotype for the -323Ins10 polymorphism was determined. The minimum obstruction diameter and the mean segment diameter were determined at baseline and after a 2-year follow-up period, and new lesion formation was assessed as well. Cardiovascular events were recorded. No relationship was observed between the -323Ins10 polymorphism and angiographic measures of disease progression, nor on the risk of new cardiovascular events. The results suggest that there is no association between the -323Ins10 polymorphism for factor VII and the severity or progression of coronary atherosclerosis in male patients with symptomatic coronary artery disease.

Adult↗
PubMed2000

Antibodies to Chlamydia pneumoniae and clinical course in patients with unstable angina pectoris.

Inflammation is one of the most important mechanisms that contribute to coronary artery disease (CAD). One of the micro-organisms that is mentioned as a source of the inflammation is Chlamydia pneumoniae. In this study, we investigated the relationship between titres of IgG and IgA antibodies to C. pneumoniae and the clinical course, during hospitalisation and during an 18-month follow-up, in 211 patients admitted to hospital with unstable angina pectoris. Slightly more patients who were refractory during their hospitalisation were positive for C. pneumoniae antibodies than patients who could be stabilised by drug treatment (53 vs. 43%, for IgG and 16 vs. 11% for IgA, respectively)(n.s.). In logistic regression analysis no significant predictive values were observed for the relationship between antibody titres and clinical course. The antibody titres to C. pneumoniae were lower in the unstable angina patients who had plasma levels of interleukin-10 (IL-10) above 5 pg/ml than in the patients with levels below 5 pg/ml, and higher in smokers than in non-smokers. No associations were observed between antibody titres to C. pneumoniae and C-reactive protein (CRP), interleukin-6 (IL-6), age, total cholesterol levels, fibrin degradation products (FDP), plasminogen activator inhibitor-1 (PAI-1) and erythrocyte sedimentation rate (ESR). In conclusion, there was no significant association between antibody titres to C. pneumoniae and risk of events during hospitalisation and the 18-month follow-up period in patients admitted for unstable angina pectoris.

Angina, Unstable↗
PubMed2000

Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals.

OBJECTIVE: Firstly, to study the effect of tea and tea polyphenols on cardiovascular risk indicators of the inflammatory system (IL6, IL1beta and TNF-alpha, CRP), and on haemostasis and endothelial proteins with an acute phase behaviour (fibrinogen, vWF, PAI-1, FVIIa and u-PA). Secondly, to study the relationship between plasma levels of antioxidants (alpha-tocopherol, beta-carotene and vitamin C) and these acute-phase, cardiovascular risk indicators. DESIGN: Randomized study. SUBJECTS: Sixty-four smoking healthy volunteers were recruited by newspaper advertisements; there were five dropouts. INTERVENTION: Four-week administration of black tea, green tea, green tea polyphenol isolate and mineral water ( 13-16 per group). MEASURES: Plasma levels of the inflammatory markers IL6, IL1beta, TNF-alpha, CRP, fibrinogen, vWF, PAI-1, FVIIa and u-PA and of the antioxidants alpha-tocopherol, beta-carotene and vitamin C. RESULTS: Different dosages of tea polyphenols had no effect on inflammation, haemostasis and endothelial markers. There was a significant negative correlation between the levels of the antioxidant beta-carotene and the inflammation markers IL6 and fibrinogen (r = -0.35 and r = -0.37, respectively, P<0.01) in this group of smokers. Remarkably, there was a significant positive correlation between the levels of the antioxidant alpha-tocopherol and the inflammation marker IL6 (r = 0.28, P<0.05). CONCLUSIONS: Tea drinking had no effect on the levels of the inflammation, haemostasis and endothelial cardiovascular risk factors measured. We did observe a relationship between the antioxidant variables alpha-tocopherol and beta-carotene and inflammation markers in this group of healthy smoking subjects.

Acute-Phase Reaction↗
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

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Activated Protein C Resistance↗
PubMed1999

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis.

It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in those with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore act as a predictor, not only of disease progression, but also of response to therapy and risk of restenosis.

Anticholesteremic Agents↗
PubMed1999

Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects.

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence of tcu-PA/T in human subjects with a varying degree of hypercoagulability. tcu-PA/T was assessed in the plasma of patients with disseminated intravascular coagulation (DIC), endotoxin-treated volunteers, patients with unstable angina pectoris, and patients selected for hip replacement. Relationships between tcu-PA/T and several markers reflecting thrombin generation were examined. tcu-PA/T was observed only in the plasma of patients with DIC and was associated with all thrombin markers and with scu-PA and urokinase antigen. Prothrombin fragment 1 + 2 and urokinase antigen were independent predictors of tcu-PA/T. The fact that tcu-PA/T could not be detected in the other three groups was explained by a lower extent of thrombin generation, a greater inhibition of thrombin by antithrombin, or less available urokinase antigen in these groups. The contribution of scu-PA to total urokinase antigen was decreased in the patients with DIC because of inactivation by thrombin, which may be an additional explanation for the inadequate fibrinolysis observed in these patients. These findings show that scu-PA can be inactivated in the circulation under severe pathophysiologic circumstances and that the process of inactivation depends not only on the generation of thrombin but also on the control of thrombin activity by its inhibitor antithrombin.

Angina Pectoris↗
PubMed1999

Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation and endothelial cell function.

AIMS: Inflammation, endothelial cell function and the coagulation system have been demonstrated to be involved in the onset and course of unstable angina. Whether a proinflammatory state independently determines outcome is unknown and has not been determined yet in a clinically well defined study population of consecutive patients admitted with unstable angina. METHODS AND RESULTS: Markers of inflammation, coagulation activation and endothelial cell function were determined on admission in blood of 211 consecutive patients with severe unstable angina and were related to the in-hospital course. Refractory unstable angina occurred in 76 patients (36%) during their hospital stay. In a univariate analysis, C-reactive protein (P = 0.03), fibrinogen (P < 0.001) and erythrocyte sedimentation rate (P = 0.001) levels were significantly higher in patients with refractory unstable angina, when compared with patients who had an uneventful clinical course. The odds ratios (95% CI) adjusted for age, sex, body mass index, smoking behaviour and cholesterol levels of the occurrence of refractory unstable angina for patients in the highest quartile compared with patients in the lowest quartile of inflammatory markers were 2.19 (0.94-5.11) for C-reactive protein, 2.83 (1.13-7.10) for fibrinogen and 4.72 (1.70-13.09) for the erythrocyte sedimentation rate. The findings were not affected by the presence or absence of myocardial necrosis or the interval between onset of angina and blood collection. No association was found between markers of coagulation activation or markers of endothelial cell function, and in-hospital outcome. CONCLUSION: We found that in a clinically well-defined study population of patients with severe unstable angina, a proinflammatory state is an important and independent determinant of short-term outcome. The data strengthen the importance of inflammation in this syndrome.

Adult↗
PubMed1999

Postprandial response of activated factor VII in elderly women depends on the R353Q polymorphism.

BACKGROUND: Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect. OBJECTIVE: The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism. DESIGN: Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500. RESULTS: The mean (+/-SD) fasting FVIIa concentration was 93.3 +/- 26.7 U/L in women with the RR genotype, 49.3 +/- 19.1 U/L in those with the RQ genotype and 39.5 +/- 17.2 U/L in those with the QQ genotype. The mean absolute response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16. 1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FVIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele. CONCLUSION: This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.

Aged↗
PubMed1999

DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit--is there a relation with the low risk of cardiovascular disease in the Inuit?

Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared with Caucasian populations. We have extended this study and evaluated whether or not this was also true for the genetic polymorphisms of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin-converting enzyme (ACE) and angiotensinogen in a group of 133 Greenland Inuit, aged 30-34 gamma. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians. In the Inuit, the f(insertion allele) of the t-PA intron8ins311 polymorphism was 0.37 (CI 0.32-0.43), the f(4G allele) of the PAI-1 promoter polymorphism was 0.88 (CI 0.83-0.91), the f(deletion allele) of the ACE intron16ins287 polymorphism was 0.40 (CI 0.33-0.47) and the f(M-allele) of the angiotensinogen M/T353 polymorphism was 0.30(CI 0.25-0.38). As for fibrinogen and FVII polymorphisms, these frequencies are all significantly different from what is reported for Caucasian populations. In the Inuit, plasma levels of fibrinogen and D-Dimer were higher than in the Danes, the PAI-1 levels were lower and FVII, t-PA and CRP levels were comparable. The observed allele frequencies of the polymorphisms of t-PA, fibrinogen, FVII, ACE, angiotensinogen and the plasma levels of PAI-1 and D-Dimer were in accordance with the low CVD risk in the Inuit, considering the observed associations between these measures and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA). In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared with Caucasian populations, and these differences were sometimes, but not always, in accordance with the observed low cardiovascular disease risk of the Inuit population.

Adult↗