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C Kluft

Publications and source records attributed to C Kluft.

At least 19 recordsLinked to original sources
PubMed2003

Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus.

OBJECTIVE: Statins are known to reduce CRP concentrations, but whether high doses are more effective is not known. METHODS: In a prospective double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia, the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured. RESULTS: Median CRP levels increased with 6.6% in the placebo group and were reduced by 15 and 47%, respectively, with atorvastatin 10 and 80 mg (P<0.001; significantly different from 10 mg atorvastatin and from placebo (P<0.001). Variation in IL-6 and plasma lipids associated for 21 and 8%, respectively, with variation in CRP levels (P<0.001 and P=0.01). Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l, 56% in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l, versus 23% randomized to 10 mg atorvastatin (P<0.01) and 17% in the placebo group (P<0.005). CONCLUSIONS: In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels. The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels. The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients.

Aged↗
PubMed2003

Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other.

BACKGROUND: Flow mediated dilatation (FMD) of the brachial artery and soluble intercellular adhesion molecule 1 (sICAM-1) are measures of distinct functions of the endothelium, reflecting nitric oxide (NO)-mediated and pro-inflammatory status, respectively. The comparative value of the two measures in relation to cardiovascular risk is unknown. OBJECTIVE: To study and quantify the relation between these two measures, and their relative value in relation to the risk of coronary heart disease as estimated by the Framingham risk function. METHODS: We performed a single centre population-based study of 85 men and 81 women, aged 18-73 years. Endothelial function was assessed biochemically by sICAM-1 and functionally by FMD. In addition traditional cardiovascular risk factors, CRP, leukocyte count, homocysteine and fibrinogen were determined. Analyses were performed with multivariate linear regression, adjusted for age, gender, and CRP. RESULTS: Median sICAM-1 levels were 217.0 microg/l (interquartile range: 174.0-348.5). Mean FMD was 4.5% (S.D.: 3.9). The regression coefficient for the association between sICAM-1 and FMD was -3.3 microg/l (95% CI: -6.0;-0.6) per percentage rise in FMD, after adjustment for age, gender, smoking, oral contraceptives (OC) use, classical risk factors and CRP. After adjustment for CRP and sICAM-1, the estimated risk of coronary heart disease in the next 10 years varied from 1.55% (95%CI: 0.89; 2.70) in the highest quintile of FMD to 3.92% (95% CI: 2.23; 6.92) in the lowest quintile. For sICAM-1, estimated risk, adjusted for FMD and CRP varied from 1.50% (95%CI: 0.85; 2.64) in the lowest quintile of sICAM-1 to 4.15% (95%CI: 2.35; 7.34) in the highest quintile. P-values for trends were 0.02 and 0.01 for quintiles of FMD and quintiles of sICAM-1, respectively. CONCLUSION: These findings indicate that sICAM-1 and FMD are related in healthy individuals, independently of cardiovascular risk factors and CRP, and that they are both related to the estimated risk of coronary heart disease, independently of each other.

Adolescent↗
PubMed2003

The association between birth weight and plasma fibrinogen is abolished after the elimination of genetic influences.

Low birth weight is associated with an increased risk of atherothrombosis, which may be related in part to the association between low birth weight and high plasma fibrinogen. The association between birth weight and fibrinogen may be explained by intrauterine, socio-economic or genetic factors. We examined birth weight and fibrinogen in 52 dizygotic and 56 adolescent monozygotic (genetically identical) twin pairs. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a fibrinogen level that was higher compared with their co-twins with the highest birth weight [dizygotic twins: 2.62 +/- 0.46 g L(-1) vs. 2.50 +/- 0.41 g L(-1) (P = 0.04); monozygotic twins: 2.42 +/- 0.45 g L(-1) vs. 2.49 +/- 0.39 g L(-1) (P = 0.2)]. These findings suggest that the association between birth weight and plasma fibrinogen is abolished after the elimination of genetic influences and therefore that this association has genetic causes. Improvement of intrauterine nutrition may not lower fibrinogen levels in later life.

Adolescent↗
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↗
PubMed2003

Logistics and quality control for DNA sampling in large multicenter studies.

To study associations between genetic variation and disease, large bio-banks need to be created in multicenter studies. Therefore, we studied the effects of storage time and temperature on DNA quality and quantity in a simulation experiment with storage up to 28 days frozen, at 4 degrees C and at room temperature. In the simulation experiment, the conditions did not influence the amount or quality of DNA to an unsatisfactory level. However, the amount of extracted DNA was decreased in frozen samples and in samples that were stored for > 7 days at room temperature. In a sample of patients from 24 countries of the EUROPA trial obtained by mail with transport times up to 1 month DNA yield and quality were adequate. From these results we conclude that transport of non-frozen blood by ordinary mail is usable and practical for DNA isolation for polymerase chain reaction in clinical and epidemiological studies.

Blood Banks↗
PubMed2003

Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive vs. standard dose atorvastatin on hemostatic cardiovascular risk factors in patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: The effect of 30 weeks of treatment with atorvastatin 10 and 80 mg on hemostatic cardiovascular risk factors was assessed in a randomized double-blind placebo-controlled trial on 217 patients with Type 2 diabetes mellitus and dyslipidemia. RESULTS AND CONCLUSIONS: Atorvastatin 10 and 80 mg dose-dependently reduced d-dimer (7.4% and 8.5%, respectively, P for trend = 0.004) and PAI-1 antigen levels (9.0% and 18%, respectively, P for trend = 0.021). Levels of fibrinogen, VWF, tissue-type plasminogen activator and FVIIa were not influenced by atorvastatin. In conclusion, in patients with Type 2 diabetes mellitus, atorvastatin dose-dependently improved the levels of the hemostatic risk variables d-dimer and PAI-1.

Aged↗
PubMed2002

The association between extrinsic activated protein C resistance and venous thromboembolism in women.

Recently, discussions have focused on the question of whether acquired APC resistance (APCsr) is a clue to the observed association between risk of venous thromboembolism (VTE) and OC use especially with the so-called third-generation OCs. It seems plausible that abnormalities in an extrinsic-based APCsr reflect an increased risk of VTE in women, but this has not yet been properly studied. The objective of our study was to determine whether there was an association of extrinsic APC resistance with VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis were consecutively recruited in primary health care settings, interviewed and blood samples were taken at least 6 months after VTE. Cases were age-matched to 290 population controls. Extrinsic APC resistance was measured as normalized APC ratio (APCsr). The effect of APC on tissue factor-initiated thrombin generation was measured in plasma using alpha2-macroglobulin attached thrombin activity as an endpoint. The extrinsic APCsr was significantly associated with factor V Leiden (FVL) mutation, both in the cases and in the controls. Also, in the women using OC, significantly higher values of APCsr were observed, which confirms the results of other studies. We did not identify a significant association between the extrinsic APCsr and VTE in women not using OC who are non-carriers of factor V Leiden using different approaches: comparison of medians, analyses with unconditional logistic regression using various cut-points of the APCsr distribution, and the comparison between the highest and the lowest quartile of APCsr. With all attempts, the risk estimates were close to unity. In conclusion, we were not able to find evidence for any association of extrinsic APCsr with VTE in women who were not using OCs and non-carriers of FVL.

Adolescent↗
PubMed2002

Sensitive markers of inflammation make it possible to study the chronic process: the rise of interest in low levels of C-reactive protein.

Increases in baseline levels of C-reactive protein (CRP) have been consistently identified as an independent risk indicator of cardiovascular events. The measurement of the low level is robust and well established. Increases in low levels of CRP can mark low-grade continuous inflammation and hyperresponse in acute situations. In addition, CRP can exert various actions on vascular cells and activates complement thus participating in infarction pathogenesis. Various cardiovascular drugs, notably statins, can induce a marked decrease in low levels of CRP, which is indicative of their beneficial effect on inflammation. Future studies need to demonstrate whether increases in baseline levels of CRP can become a useful practical addition to risk recognition strategies and possibly may also serve as an additional surrogate endpoint in cardiovascular disease treatments.

Animals↗
PubMed2002

Blood sample stability at room temperature for counting red and white blood cells and platelets.

Blood handling required for different cellular variables is different. In a practical setting of blood sampling approximately 4 h separated from the first analysis, we compared the analysis of blood cell variables at this 4-h point with analysis of blood stored for approximately 48 h (over the weekend) at room temperature. Blood was collected from 304 apparently healthy individuals aged between 17 and 70 years, with a female/male ratio of 1.8, in K3EDTA. Measurement was performed with a Beckman Coulter Counter Maxm. In addition to the comparison of the data and their correlation on the two time points, we investigated agreement between the data using analysis according to Bland and Altman. Counts of white and red blood cells and platelets were found stable over time and agreement of data was excellent. Platelet mean volume increased as expected between the two time points from 8.8 to 10.3 fl. The white blood cell subpopulations, however, changed over time with a decrease in neutrophils and monocytes and increases in lymphocytes and eosinophils. Apparently, ageing of the sample resulted in the alteration of certain cell characteristics leading to a change in automated cell classification without changing the total number of cells. Among the preanalytical variables recorded, only the time of the year and gender were found to be minor determinants (r < .25) of some of the differences between approximately 4 and approximately 48 h analysis delay. It is concluded that after storage at room temperature over approximately 48 h counts of red, total white cells, platelets and analysis of platelet volume can be combined in one assay session.

Adolescent↗
PubMed2002

Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment.

The effects of two third-generation monophasic combined oral contraceptives (COC) and a postmenopausal hormone replacement therapy (HRT) consisting of 2 mg 17 beta-oestradiol on the plasma level of the acute-phase indicator C-reactive protein (CRP) and other acute-phase reactants were analysed. Two studies were conducted: (1) a randomised, open-label study with two different oral contraceptive preparations with an equal dose of ethinylestradiol (30 micrograms) and a different progestogen, either 75 micrograms gestodene (GSD-EE) or 150 micrograms desogestrel (DSG-EE); blood samples of 39 young women were analysed before and after 3, 6, 12 treatment cycles; (2) a randomised, blinded placebo-controlled study with 2 mg 17 beta-oestradiol in postmenopausal women with non-insulin-dependent diabetes mellitus without signs of cardiac involvement; blood samples of 38 women were analysed before and after 6 weeks of treatment. The plasma concentration of CRP increased strongly during oral contraceptive use for both preparations; the increase persisted over 12 cycles. The already elevated CRP in postmenopausal diabetic women showed a moderate increase after 6 weeks of treatment with 17 beta-oestradiol. CRP increases during oral contraceptive use were associated with changes in some other acute-phase proteins (fibrinogen, ceruloplasmin, von Willebrand factor [vWF]) originating from the liver and vessel wall, but not in others (interleukin-6 [IL-6], serum amyloid A [SAA]). The results demonstrate an increase in a specific set of acute-phase reactants caused by oestrogen-containing preparations. It is proposed that the pro-inflammatory effect of oestrogens should be checked for a relationship with the increased risk of thromboembolism for both oral contraceptive and HRT.

Adult↗
PubMed2002

Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study.

OBJECTIVE: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. DESIGN: Randomized, diet-controlled, cross-over study. SETTING: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. SUBJECTS: Ten middle-aged men and 10 postmenopausal women, all apparently healthy, non-smoking and moderate alcohol drinkers, were included. One women dropped out because of a treatment-unrelated cause. The remaining 19 subjects finished the experiment successfully. INTERVENTIONS: Men consumed four glasses and women consumed three glasses of beer or no-alcohol beer (control) with evening dinner during two successive periods of 3 weeks. The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks. Before each treatment there was a 1 week washout period to compensate for possible carry-over effects. RESULTS: Plasma C-reactive protein and fibrinogen levels were decreased by 35% (P=0.02) and 12.4% (P< or =0.001), respectively, after 3 weeks' consumption of beer, as compared to no-alcohol beer consumption. CONCLUSIONS: Moderate alcohol consumption significantly decreased plasma C-reactive protein and fibrinogen levels. An anti-inflammatory action of alcohol may help explain the link between moderate alcohol consumption and lower cardiovascular disease risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

Alcohol Drinking↗
PubMed2002

Association of the tumour necrosis factor alpha -308G/A polymorphism with the risk of diabetes in an elderly population-based cohort.

Ample evidence supports a role for tumour necrosis factor alpha (TNFalpha) in the development of type 2 diabetes and cardiovascular disease. TNFalpha expression was found to be influenced by a -308G/A polymorphism in the promoter of the gene encoding TNFalpha (TNF). We investigated the contribution of this polymorphism to diabetes and cardiovascular mortality in a population-based cohort of 664 subjects aged 85 years and over (Leiden 85-plus Study). The -308G/A TNF promoter polymorphism was associated with the prevalence of diabetes in old age (P = 0.006). The risk of diabetes among subjects homozygous for the A-allele was estimated to be 4.6-fold (95% CI, 1.6-13.3) higher than among subjects homozygous for the common G-allele. The promoter polymorphism did not, however, predict mortality from all causes, cardiovascular diseases, cancer or infectious diseases during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa and TNFc microsatellite genotypes were determined but these polymorphisms were not associated with morbidity or mortality. In conclusion, the -308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.

Aged↗
PubMed2001

Coronary artero-venous gradient of endogenous urokinase.

Experimental data indicate that urokinase-type plasminogen activator (u-PA) contributes significantly to endogenous fibrinolysis and vascular remodeling in proportion to its local concentrations. In humans, however, it is not known whether u-PA levels vary at different sites and across specific vascular beds. We investigated possible regional and artero-venous differences in plasma u-PA concentrations in 15 patients undergoing cardiac catheterization. Three pairs of simultaneous samples were taken from: (1) the ascending aorta and coronary sinus; (2) left ventricle and right atrium; (3) femoral artery and femoral vein. Single-chain urokinase-type plasminogen activator (scu-PA) was measured by bioimmunoassay, and total u-PA antigen (including scu-Pa and two-chain urokinase-type plasminogen activator complexed with inhibitors (tcu-PA)) by enzyme-linked immunosorbent assay. Scu-PA represented, on average, 51+/-15% of total u-PA concentrations. Scu-PA and total u-PA levels were correlated (r=.72, P<.0001) and did not differ significantly among the arterial or venous locations. There was a small but consistent increase in mean (+/-standard deviation (S.D.)) scu-PA concentrations from all arterial to all venous samples (1.5+/-0.6 vs. 1.6+/-0.5 ng/ml, P=.038) and from ascending aorta to coronary sinus (1.6+/-0.5 vs. 1.7+/-0.6 ng/ml, P=.046). Similarly, total u-PA levels increased from femoral artery to femoral vein (2.9+/-0.7 vs. 3.0+/-0.8 ng/ml, P<.001). In contrast, across the lungs, no significant concentration-gradient was seen in either scu-PA or total u-PA. The changes in total u-PA roughly followed those of scu-PA. These data identify an artero-venous gradient in human plasma u-PA across the coronary and peripheral beds, but not across the lungs, suggesting differences in u-PA kinetics according to vascular location.

Aged↗
PubMed2001

Fruit and vegetables and cardiovascular risk profile: a diet controlled intervention study.

OBJECTIVE: To evaluate the effect of fruit and vegetables consumption on markers of risk for cardiovascular disease. DESIGN: Randomised, diet controlled, parallel study. SUBJECTS: Forty-eight apparently healthy (40--60 y) volunteers with a low usual consumption of fruit and vegetables. Forty-seven of them completed the study. INTERVENTIONS: During 4 weeks 24 volunteers consumed a standardised meal, consisting of 500 g/day fruit and vegetables and 200 ml/day fruit juice ('high' group) and 23 volunteers consumed 100 g/day fruit and vegetables ('low' group) with an energy and fat controlled diet. RESULTS: Final total cholesterol was 0.2 (95% CI -0.5--0.03) mmol/l lower in the high group than in the low group (P>0.05). Final fibrinogen and systolic blood pressure were 0.1 (-0.1--0.4) g/l and 2.8 (-2.6--8.1) mmHg higher in the high group than in the low group (P>0.05), respectively. Also, other final serum lipid concentrations, diastolic blood pressure and other haemostatic factors did not differ between both groups. CONCLUSIONS: This was a small randomised well-controlled dietary intervention trial of short duration with a considerable contrast in fruit and vegetable consumption. No effects on serum lipids, blood pressure and haemostatic variables were observed.

Adult↗
PubMed2001

Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy.

OBJECTIVE: We studied the effect of a diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy in order to evaluate whether abnormal transcapillary escape rate of albumin and procoagulant activity in these patients could be modified. METHODS: A double-blind, randomized, controlled study was carried out at a tertiary referral centre. The subjects were 29 insulin-dependent diabetic patients with nephropathy. One year of fish oil supplementation (4.6 g n-3 fatty acids/day) was compared with placebo (olive oil). The main outcome measures were N-3 fatty acid proportions of platelet lipids, transcapillary escape rate of albumin, prothrombin fragment 1 + 2, thrombin-antithrombin complexes, markers of fibrinolysis, fibrinogen, factor VII antigen and activity, thrombomodulin, von Willebrand factor, platelet factor 4 and beta-thromboglobulin. These were measured every 6 months. RESULTS: Neither transcapillary escape rate of albumin (7.4 (median) (5.0-9.8) (range) % vs. 7.0 (4.6-10.6) %) nor prothrombin fragment 1 + 2 (0.97 (0.72-2.40) nmol/L vs. 1.01 (0.59-3.11) nmol/L) changed after 12 months of fish oil supplementation. CONCLUSION: Increased transcapillary escape rate of albumin and activity could not be modified during diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy.

Antithrombin III↗
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↗