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Biomedical subjects

J Jespersen

Publications and source records attributed to J Jespersen.

At least 127 records · Page 7Linked to original sources
PubMed1993

Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group.

Hyperinsulinemia, a major indicator of insulin resistance, may exert its influence on the risk of coronary artery disease partially through disturbances of the hemostatic system. The relations of fasting insulin concentrations with the degree of coronary atherosclerosis, other coronary risk factors (including some markers of the insulin resistance syndrome such as body mass index and triglyceride), markers of inflammation, and hemostatic factors were investigated in 1484 patients with angina pectoris. Mean insulin levels were higher in patients with one or more coronary vessel stenoses than in those without (9.9 microU/mL compared with 9.0 microU/mL, P < .0001). However, the association the presence of vessel stenoses was stronger in patients with a previous myocardial infarction than in those without. Insulin increased markedly (P < .0001) and independently of other risk factors with age body mass index, triglyceride concentration, and markers of inflammation, such as white blood cell count and C-reactive protein. The strongest relations between insulin and hemostatic factors were observed with fibrinolytic variables, particularly plasminogen activator inhibitor-1 (PAI-1) levels (r = .44, P < .0001). This relation decreased somewhat (r = .29) after simultaneous adjustment for markers of the insulin resistance syndrome, mainly body mass index and triglycerides, but not after adjustment for markers of inflammation. Therefore, we propose that increased PAI-1 levels, which are essentially related to the classic metabolic aspect of the insulin resistance syndrome, have to be included in this syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Favorable long-term effect of a low-fat/high-fiber diet on human blood coagulation and fibrinolysis.

In an 8-month strictly controlled dietary study of 16 healthy young men, the long-term effect of a low-fat (26% of energy) high-fiber (4.5 g/MJ) diet on cardiovascular risk markers of the hemostatic system was assessed. Fasting blood sampling was performed during a 4-week baseline period and then monthly during the intervention. A matched control group of 16 men on habitual diets was also monitored. Median fibrinolytic activity of tissue-type plasminogen activator (t-PA) in plasma was significantly elevated (twofold to fourfold) by the experimental diet. A significant increase in the systemic fibrinolytic activity of the euglobulin fraction of plasma was also observed. Median plasma factor VII coagulant activity (F VIIc) was depressed by 5-10% during the first 2 months and the last month of the study period. The dietary change did not significantly affect plasma levels of fibrinogen, t-PA antigen, or plasminogen activator inhibitor type I antigen. In conclusion, young men who were switched from a typical Danish diet high in saturated fat to a low-fat/high-fiber diet showed a permanent increase in plasma fibrinolytic activity and a biphasic decrease in F VIIc. The dietary change thus had a favorable effect on cardiovascular risk markers of the hemostatic system.

Adult↗
PubMed1993

The fibrinolysis and coagulation systems in ischaemic heart disease. Risk markers and their relation to metabolic dysfunction of the arterial intima.

This report reviews the major haemostatic deviations associated with the evolution of ischaemic heart disease (IHD) and also such deviations, which might be of importance for the evolution of the acute ischaemic heart syndrome. It is demonstrated that deviation in the t-PA/PAI-1 system indicate endothelial cell dysfunction in patients with IHD. Different factors which have the capability to induce such an endothelial cell dysfunction are proposed, i.e. hyperinsulinemia, mediators of chronic disease phase response, and thrombin. Finally, the intimate interrelation between coagulation and fibrinolysis in patients with IHD is discussed. The experimental and clinical studies reviewed provide good evidence that the endothelial cell response of t-PA and PAI-1 is coupled and that there is an intimate interrelation between generation of thrombin and production/release of t-PA and PAI-1 in IHD patients.

Blood Coagulation↗
PubMed1992

The variability of and associations between measures of blood coagulation, fibrinolysis and blood lipids.

Hemostatic variables are increasingly recognized as atherothrombotic risk markers and their susceptibility to lifestyle changes has therefore considerable interest. To study this subject knowledge of the spontaneous variability of measures of coagulation and fibrinolysis is required. We monitored 17 young male adults with constant lifestyles for a year and here present characteristics of the observed variability of factor VII coagulant activity (F VIIc), fibrinogen, fibrinolytic variables and blood lipids. The variables differed considerably with regard to total variability (range of CV (%): 13-54) and with respect to relative size of the inter- and intrapersonal components of variation. None of the variables showed seasonal changes of biological significance. Descriptive statistics of the same variables measured in 74 young healthy adults (19 women, 55 men) are also reported. These values may be used as a reference for comparable groups of individuals. Serum triglycerides were significantly associated with F VIIc (Spearman's Rs = 0.24, P < 0.05) and plasma concentrations fo the plasminogen activator inhibitor type I (Spearman's RS = 0.23, P = 0.05). An increased thrombotic tendency with elevated triglyceride levels was thus indicated. Serum cholesterol was not associated with hemostatic variables, except for plasminogen activator activity (Spearman's Rs = 0.31, P < 0.05).

Adult↗
PubMed1992

Increased fibrinolytic potential induced by gliclazide in type I and type II diabetic patients.

Despite the fact that the relationship between impaired diabetic control and the development of vascular complications now seems less controversial than before, we are still in a situation where interventions or strategies aimed at decreasing the complications of late diabetes have high priorities. It is believed that accelerated vascular disease in the diabetic population is caused by repeated intimal injury of the arteries, and there is also evidence that the accelerated vascular disease states cannot be attributed only to the hyperglycemic state. One factor of importance for delayed tissue repair and arteriosclerotic disease in diabetic patients might be a disordered endothelial cell-dependent fibrinolytic system. Here, we review the evidence of the relationship between increased fibrin deposition and defective fibrinolysis in diabetic patients, and, furthermore, we discuss the possible beneficial effects of an enhancement of endogenous endothelial cell-related fibrinolysis by sulphonylurea drugs.

Arteriosclerosis↗
PubMed1992

Lipoprotein profile of a Greenland Inuit population. Influence of anthropometric variables, Apo E and A4 polymorphism, and lifestyle.

Previously it has been reported that Greenland Inuit (Eskimos) from the Uummannaq district display low levels of plasma cholesterol and triglycerides and relatively high levels of high density lipoprotein (HDL) when compared with healthy Danish control subjects (Lancet 1971;1:1143-1146). Here we present data obtained in 1989 that show the following. In a group of 133 healthy adult Greenland Inuit from Nanortalik, the levels of plasma cholesterol and low density lipoprotein (LDL) cholesterol (6.39 and 4.39 mmol/l, respectively) were slightly higher than "normal" values found in western societies, whereas the HDL cholesterol level was markedly higher (1.64 mmol/l). Compared with most Caucasian populations, the Inuit population we studied exhibits a high apolipoprotein (APO)E*4 allele frequency (0.229), whereas the APOE*2 allele frequency was extremely low (0.015). In contrast to Caucasian populations, in the Inuit population the apoE polymorphism showed only a minor influence on the plasma lipid and (apo)lipoprotein levels, as evaluated by multiple regression analysis, with the exception of apoE levels. This absence of an effect could be explained by the low very low density lipoprotein (VLDL) plus intermediate density lipoprotein (IDL) cholesterol levels. The contributions of eicosapentaenoic acid and linoleic acid to the total amount of fatty acids in plasma cholesterol esters differed markedly from those reported in 1971 for another Greenland Inuit population (3.2% versus 15.8% and 49.5% versus 20.4%, respectively), thereby resembling values now found in the average western population. Even in those Inuit who reported exclusive consumption of the traditional Inuit diet (13% of the population), the fatty acid composition of the plasma cholesterol esters closely resembled the values measured in western populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Fasting blood coagulation and fibrinolysis of young adults unchanged by reduction in dietary fat content.

Low-fat, high-fiber diets may influence the variables of blood coagulation and fibrinolysis associated with cardiovascular morbidity. Dietary fat content has been suggested as the important determinant. This hypothesis was tested in a strictly controlled dietary study of 13 healthy individuals. They were fed two experimental diets in a 2 x 2-week crossover trial. The diets differed in fat content (39% versus 31% of total energy), whereas the fatty acid composition and the fiber content were virtually identical. We observed no significant differences between diets in terms of fasting plasma levels of factor VII coagulant activity, fibrinogen, euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) activity, t-PA antigen, plasminogen activator inhibitor type 1 (PAI-1) antigen, or PAI activity. Serum levels of total cholesterol, high density lipoprotein cholesterol, and triglycerides were also unaffected. In conclusion, a moderate reduction in dietary fat intake, at a fixed fatty acid composition and dietary fiber intake, did not significantly influence blood coagulation, fibrinolysis, or blood lipids in the fasting state.

Adult↗
PubMed1991

[Plasma fibrinogen and cardiovascular disease].

In prospective epidemiological studies the plasma fibrinogen level is correlated to cardiovascular diseases even after statistical correction for the major risk factors. The fibrinogen level is positively correlated with many risk factors such as life-style variables including smoking, lack of physical activity and high-fat diet. Psychosocial variables are in many studies closely correlated with the fibrinogen level even after adjustment for the traditional (established) risk factors.

Cardiovascular Diseases↗
PubMed1991

Increased fibrinolytic potential induced by gliclazide in types I and II diabetic patients.

This study examined the effect of gliclazide on tissue-type plasminogen activator (t-PA)-related fibrinolysis in 23 Type I diabetic patients without residual beta-cell function and 17 Type II diabetic patients initially treated with tolbutamide. The Type I diabetic patients received gliclazide for a period of 6 months; the Type II diabetic patients were shifted from tolbutamide to gliclazide. In Type I diabetic patients, after 2-3 months of treatment with gliclazide, we observed a significant increase in plasma concentrations of total t-PA antigen that remained stable until discontinuation of the drug (p less than 0.0002), whereas the plasma concentrations of plasminogen activator inhibitor (PAI) did not change significantly during the study. Next, we investigated the possibility of gliclazide inducing t-PA-related fibrinolysis in a subset of Type II diabetics without detectable concentrations of t-PA during treatment with tolbutamide. The concentrations of active t-PA increased significantly 3 months after a change in treatment to gliclazide, and active t-PA again decreased in one patient to undetectable levels after 12 months with gliclazide. Moreover, the plasma concentrations of total t-PA antigen increased significantly (p less than 0.02) in this group of diabetic patients while PAI remained unchanged. The changes in t-PA-related fibrinolysis could not be related in either Type I or Type II diabetics to changes in metabolic state evaluated by blood glucose, HbA1c, cholesterol, triglycerides, or apolipoproteins A and B. We conclude that gliclazide has the potential to exert extrametabolic non-insulin-mediated effects on t-PA-related fibrinolysis in diabetic patients.

Adult↗
PubMed1991

Long-lasting depression of the factor XII-dependent fibrinolytic system in patients with myocardial infarction undergoing thrombolytic therapy with recombinant tissue-type plasminogen activator: a randomized placebo-controlled study.

In a randomized placebo-controlled study, seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment. Seven patients with acute myocardial infarction treated intravenously with 1.5 million U of streptokinase were later studied during two sampling periods before and after treatment. The placebo group showed no significant deviations of endogenous factor XII-dependent fibrinolytic activity (p greater than 0.05). In the rt-PA group, this activity decreased significantly (p less than 0.001) after the infusion and remained depressed throughout the 1st 4 days. A significant decrease in activity (p less than 0.05) was also found in the streptokinase-treated patients. The depletion of factor XII-dependent fibrinolytic activity was not due to generation of inhibition or a depletion of factor XII, prekallikrein and plasminogen, but could be related to the proactivator of this system. It is concluded that rt-PA (and streptokinase) treatment in patients with acute myocardial infarction causes a prolonged depletion of factor XII-dependent fibrinolytic activity. This depression of endogenous fibrinolytic activity needs to be evaluated in relation to the enhanced risk of coronary reocclusion after thrombolytic therapy.

Depression, Chemical↗
PubMed1991

[Standardized prothrombin time determinations and optimal anticoagulant therapy].

WHO and other international organizations have recommended the introduction of a standardized prothrombin time determination. This would allow a universal scale for the intensity of oral anticoagulation therapy to be used. A prerequisite is the use of thromboplastin, calibrated against the international reference thromboplastin, standardized methodology etc. This permits every prothrombin time determination to be expressed as International Normalized Ratio (INR). The introduction of INR facilitates the implementation of optimal oral anticoagulation as defined by larged international studies.

Anticoagulants↗
PubMed1991

Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy.

Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction.

Aged↗
PubMed1991

Induction and possible role of fibrinolysis in diabetes mellitus.

This article reviews the evidence supporting a relationship between an enhanced tissue injury, increased fibrin formation, defective fibrinolysis, and the evolution of the complications of late diabetic disease. Particular attention is drawn to the role of a defective endothelial cell mediated fibrinolysis with respect to increased fibrin formation and a delayed tissue repair in diabetic patients. Reviewed are studies that indicate that it is possible in patients with diabetes by means of sulfonylurea compounds to increase endothelial cell-produced t-PA without affecting PAI-1. It is advocated that potent compounds should be searched for, with the capability to modify the hemostatic process of the diabetic endothelial cell in order to express more fibrinolytic activity independent of the patient's metabolic state in an attempt to delay the complications of late diabetes.

Diabetes Mellitus↗
PubMed1991

Possible role of vascular intima for generation of coagulant activity in patients undergoing coronary thrombolysis with recombinant tissue-type plasminogen activator. A randomized, placebo-controlled study.

In our present placebo-controlled study on recombinant tissue-type plasminogen activator (rt-PA) and heparin treatment of patients with acute ischaemic heart disease (IHD), we studied the extent of fibrin resolution and generation of coagulant activity. In rt-PA treated patients the lysis of fibrin in vivo (median 60 nmol of fibrin--estimated as fibrinogen equivalents) was significantly higher (p less than 0.02) than can be accounted for solely by lysis of a coronary thrombus (approximately 2 nmol) and circulating soluble fibrin (median 15 nmol). We observed a 200% increase of plasma concentrations of both prothrombin fragment 1 + 2 (p less than 0.001) and thrombin-antithrombin III complexes (p less than 0.001) as a consequence of rt-PA treatment, indicating that the coagulant activity is primarily caused by a physiological activation of the coagulation system. We conclude that an important contribution to the activation of coagulation in patients undergoing coronary thrombolysis is lysis of fibrin deposited widespread on the vascular intima, and that this process causes an intimal-dependent activation of the coagulation system.

Adolescent↗
PubMed1991

Effect of fish diet versus meat diet on blood lipids, coagulation and fibrinolysis in healthy young men.

Twelve healthy young men followed a 10-d controlled diet that included 210 g of fatty fish d-1. The diet was repeated after 18 d, but with lean meat substituted for fish. Blood samples were collected for assessment of serum lipids and haemostatic variables in the plasma. Both experimental diets caused serum triglycerides and plasma factor VIIc to decline to the same extent. The meat diet was also associated with significant changes in plasma levels of tissue plasminogen activator (t-PA) antigen. PA inhibitor type I (PAI-1) antigen, PAI activity, and t-PA activity of the euglobulin fraction of plasma. The fish diet left these variables unchanged from initial values. Thus, in a paired comparison of the two diets, the fish diet was associated with higher levels of t-PA antigen (5.4 vs. 4.7 g ml-1), which is considered to be beneficial with regard to prevention of cardiovascular disease. However, the fish diet was concurrently associated with the putative unfavourable higher levels of PAI-1 antigen (3.0 vs. 1.2 ng ml-1) and PAI activity (6.1 vs. 3.2 IU ml-1), and lower t-PA activity (80 vs. 140 mIU ml-1). Thus it is unclear which of the two diets has the greatest potential in the prevention of cardiovascular disease.

Adult↗