[Technologic evaluation of anticoagulant therapy].
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Biomedical subjects
Publications and source records attributed to J Jespersen.
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We served a low-fat (28% of energy) high-fibre (3.3 g/MJ) diet according to Nordic Nutrition Recommendations (REC diet), and a high-fat diet (39% of energy) corresponding to the average Danish diet (DANE diet) to 21 healthy middle-aged individuals in a two times two weeks cross-over study. The REC diet resulted in lower serum concentrations of low density lipoprotein (LDL) cholesterol (medians: 2.77 vs 3.04 mmol/l, p < 0.001), and high-density lipoprotein (HDL) cholesterol (1.08 vs 1.24 mmol/l, p < 0.001), and higher fasting triglycerides (1.11 vs 0.86 mmol/l, p = 0.04) than the DANE diet. Furthermore, the REC diet lowered plasma factor VII coagulant activity (FVIIc) (88 vs 96%, p = 0.002) and raised plasma fibrinolytic activity. Our observations indicate that a low-fat high-fibre diet may not only reduce the atherogenic, but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet.
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We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU unfractionated heparin, or 2000 anti-Xa IU low-molecular-weight heparin. Unfractionated and low-molecular-weight heparin induced a significant reduction in urinary albumin excretion (p = 0.04 and p = 0.004). The mechanism and clinical relevance is unknown but deserve further attention.
The biological activity of thrombin and coagulation factor Xa was assessed in 62 insulin-dependent diabetic patients. A group of non-diabetic subjects of comparable age and urinary albumin excretion rate (< 30 mg/24 h) served as control subjects (group 1, n = 14). The patients were divided into three groups according to urinary albumin excretion rate. In group 2, albumin excretion rate was less than 30 mg/24 h (n = 17), in group 3 albumin excretion rate was in the range 30-300 mg/24 h (n = 20) and in group 4 albumin excretion rate was greater than 300 mg/24 h (n = 25). Compared to non-diabetic control subjects an increase in the biological activity of factor Xa was observed in all groups of diabetic patients (prothrombin fragment 1 + 2 levels were 1.14 +/- 0.38 nmol/l in group 2, p < 0.005; 1.06 +/- 0.45 nmol/l in group 3, p < 0.05 and 1.03 +/- 0.31 nmol/l in group 4, p < 0.05 vs 0.75 +/- 0.34 nmol/l in group 1). No difference in the level of antithrombin III was seen between the groups. We reconfirmed the presence of intimal dysfunction in diabetic nephropathy demonstrated by elevated transcapillary escape rate of albumin in group 4 compared with group 2 (8.9 +/- 2.0% vs 7.0 +/- 1.9%, p < 0.05). An overall positive correlation between transcapillary escape rate and prothrombin fragment 1 + 2 was found (r = 0.36, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Elevated plasma fibrinogen levels represent an increased risk for cardiovascular disease, but the mechanism explaining this association is still not clear. Genetic differences may play a role, because it has been shown that individuals who carry the rare alleles of polymorphisms in the genes for the B beta-chain (Bcl I and G/A-455) and the A alpha-chain (Taq I) of fibrinogen have higher plasma fibrinogen levels and that patients with peripheral arterial disease have a higher frequency of the rare allele of the Bcl I polymorphism than do healthy control subjects. We studied the Greenland Inuit, a population with a low incidence of ischemic heart disease; polymorphisms of the fibrinogen gene; and their association with plasma fibrinogen level. The group studied had a small age range (30 to 34 years), 97% were smokers, 62 were men, and 71 were women. We observed that in the Inuit, frequencies of the rare alleles of the beta gene and of the common alleles of the alpha gene polymorphisms were lower than those published for other populations (all Caucasian). Accordingly, in the Inuit, these distribution patterns give a higher frequency of alleles that are associated with lower plasma fibrinogen levels. We further observed comparable linkage disequilibrium between alpha and beta gene polymorphisms in Caucasian populations. In Inuit men the rare allele of the Bcl I and G/A-455 fibrinogen polymorphisms was associated with plasma fibrinogen level comparable with the association described in Caucasian populations.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To evaluate the endothelial cell state and the possible relation to placental function in the third trimester of normal pregnancy by an indirect assessment of endothelial cell function. STUDY-DESIGN. Twenty-six pregnant women entered the study in the 30th week of pregnancy. Von Willebrand Factor, urate and key hemostatic variables were quantified at entry, and during the 33rd and 37th weeks of pregnancy. RESULTS: Levels of von Willebrand Factor, PAI-1 antigen, t-PA antigen; variables produced by the endothelial cell, increased during the third trimester of pregnancy. Serum urate, which is correlated with clinical outcome of pregnancy, increased during the study period and correlated directly with von Willebrand Factor and PAI-1 antigen, respectively. There was an inverse correlation between the concentrations of placenta-derived PAI-2 antigen and urate. CONCLUSIONS: In healthy human pregnancy the markers of endothelial related processes of coagulation and fibrinolysis pointed towards a procoagulatory state of the endothelial cell. However, the balance between fibrin formation and resolution seemed to be maintained in uncomplicated pregnancy. Our study indicated an association between this change of endothelial cell function and placental function.
In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation of the antigen assay. Today, most analyses are performed in plasma samples, as it is unknown whether FVII, to some extent, is consumed during coagulation. In the present study, we have investigated, whether FVII:Ag can be measured equally well in plasma and serum. FVII:Ag was measured in 88 plasma and serum samples. Results were compared by means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic variation existed between FVII:Ag in plasma and serum. The mean difference in FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared with a mean difference of 0.18 (SD 8.31) arbitrary units between duplicate measurements of the same plasma dilution. Our findings indicate that there is a good agreement between FVII:Ag in plasma and serum.
The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)
We introduce a new fibrin plate assay performed in microtiter plates. By means of spectroscopic studies we optimized the structure of the fibrin gel and then used the optimized fibrin gel to determine plasminogen activator activity. Plasminogen activator solutions were applied on top of the fibrin gel, and the absorbance of the gel was recorded at 405 nm. After incubation for 17 h at 25 degrees C, the absorbance was measured again. The difference in absorbance was proportional to the concentration of plasminogen activator, such that the dose-response curves were linear when the difference in absorbance was plotted as a function of the logarithmic concentration of plasminogen activator. We assayed both tissue-type and urokinase-type plasminogen activator activity. The intraassay CV was < 4.7% (n = 20); the interassay CV was < 3.1% (n = 15). Using the optimized procedure, we modified the assay for determination of plasma-coagulum lysis time in human plasma. We established a reference interval for lysis time in apparently healthy subjects of 75 to 201 ks. Patients with deep vein thrombosis showed significantly (P = 0.013) higher values.
AIM: Our objective was to examine the association between the fasting serum insulin level and coronary heart disease (CHD) and cardiovascular disease in 40-year-old men and women. METHODS: In 1976, all of the men and women born in 1936 living in four municipalities in the County of Copenhagen were invited for a health examination. The participation rate was 87% (504 men and 548 women). All of the participants were followed through the Danish register of deaths and the register of hospital admissions until 1993. RESULTS: After controlling for relevant risk factors (sex, fasting glucose, total cholesterol, high density lipoprotein cholesterol, systolic blood pressure, smoking, triglycerides, body mass index, physical activity and alcohol consumption) the P value for the association between the insulin level and CHD or cardiovascular disease was found to be 0.002; the above risk factors did not appear to be intermediate variables in a causal chain from insulin level to the development of CHD or cardiovascular disease. The significant association between body mass index and CHD disappeared when the fasting insulin level was controlled for, and insulin seemed to be an intermediate factor between body mass index and CHD. CONCLUSION: The fasting serum insulin level in both men and women is a very good predictor of the development of CHD and cardiovascular disease even after controlling for relevant confounding factors.
The mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII:C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1 + 2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied by a decrease in FVII protein, F1 + 2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII:Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part of a general change in concentrations of vitamin K-dependent proteins.
BACKGROUND: Hyperinsulinaemia is linked to cardiovascular disease. This follow-up study examines factors influencing the fasting insulin level in men. METHODS: All men born in 1936 living in a certain area within the county of Copenhagen were invited for a health examination in 1976 and 1987; 425 men (73%) participated in both examinations. The following variables were analysed: fasting insulin levels, body mass index (BMI), fasting blood glucose, physical activity during leisure time, alcohol consumption and smoking. RESULTS: In both multivariate analyses at age 40 years and age 51 years, the BMI, the fasting glucose level and lack of physical activity showed a positive independent association with the insulin level. In follow-up analyses over 11 years, only BMI changes and fasting glucose changes were associated with changes in insulin level. CONCLUSIONS: Our analyses suggest that BMI and changes in BMI over a period of time are major risk factors for an elevation of the serum insulin level, but that physical activity may have beneficial effects on the insulin level.
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In healthy nondiabetic women, oral contraceptives (OCs) affect hemostatic function. In diabetic women, there is concern that they may also increase the risk of diabetic vascular complications. This study was designed to examine the balance between coagulation activity and fibrinolytic activity--an indirect measure of endothelial cell function--in women with insulin-dependent diabetes mellitus (IDDM) during long-term use of OCs. The study group included 11 young women with uncomplicated IDDM who were prescribed ethinyl estradiol 30 micrograms and gestodene 75 micrograms. Twelve other diabetic women not taking OCs constituted the control group. Hemostatic function was evaluated at entry and after 1,3,6, and 12 months. In women taking OCs, plasma levels of factor VII(c) increased, while fibrinogen levels did not change. Inhibition of coagulation was affected by increased levels of protein C, although plasma levels of antithrombin III and protein S remained stable. The antigen concentrations of tissue-type plasminogen activator and plasminogen activator levels themselves were unchanged. There was a proportionate increase in the concentrations of thrombin-antithrombin III complexes and D-dimer. None of the hemostatic variables changed significantly in the control group. We conclude that the balance between coagulation activity and fibrnolysis does not change during use of this OC. Our findings suggest that low-dose OCs induce a procoagulatory state that is compensated for by enhanced fibrinolytic activity.
Many reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.), while the patients had significantly lower fibrinolytic activity (p < 0.02), and significantly higher protein concentrations of t-PA (p < 0.0001) and PAI-1 (p < 0.0006). We used probit scale plots to identify the consequence of different cut-off points to separate patients from controls. Reasonable separation could be obtained for t-PA with a cut-off point of 5.2 ng/ml and for PAI-1 18 ng/ml. The sensitivity and specificity for these cut-off points were for t-PA 73% (95% confidence interval 63%-84%) and for PAI-1 67% (confidence interval 55%-77%). The negative predictive value with a cut-off point t-PA concentration of 5.2 ng/ml was 85% (95% confidence interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p < 0.005) and also between PAI-1 and fibrinolytic activity (rs = -0.78; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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