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Biomedical subjects

H Arnesen

Publications and source records attributed to H Arnesen.

At least 55 records · Page 3Linked to original sources

Increased risk of recurrent venous thromboembolism during hormone replacement therapy--results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET).

Recent observational studies suggest a 2-4 fold increased risk of venous thromboembolism (VTE) in women taking hormone replacement therapy (HRT). The present study was started before publication of these studies, and the aim was to determine if HRT alters the risk of VTE in high risk women. The study was a randomized. double-blind, and placebo-controlled clinical trial with a double-triangular sequential design. Females with previously verified VTE were randomized to 2 mg estradiol plus 1 mg norethisterone acetate, 1 tablet daily (n = 71) or placebo (n = 69). The primary outcome was recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE). Between 1996 and 1998 a total of 140 women were included. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. Eight women in the HRT group and one woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. The sequential design did not stop the study, but strongly indicated a difference between the two groups. Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. The results also support those of recent epidemiological studies, which also indicate increased risk of VTE in non-selected female populations during HRT.

Actuarial Analysis↗

N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial.

OBJECTIVES: The aim of the study was to investigate whether omega-3 fatty acids (n-3 FA) reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND: Meta-analyses have shown significant reduction of restenosis after coronary angioplasty upon supplementation with n-3 FA. METHODS: In a prospective, placebo-controlled, double-blind study, 500 patients were randomly allocated to treatment with n-3 FA (Omacor, Pronova AS, Oslo, Norway) 5.1 g/day or corn oil (placebo) starting at least two weeks prior to elective coronary angioplasty. The treatment was continued until restenosis evaluation by quantitative coronary angiography after six months. Stenosis was defined as a minimal luminal diameter (MLD) < 40% of the reference diameter. Successful coronary angioplasty was defined as > or = 20% acute gain in MLD and a residual stenosis < 50%. Restenosis was defined as > or = 20% late loss of diameter and stenosis > 50% or an increase in stenosis of > or = 0.7 mm. Three-hundred ninety-two patients fulfilled the criteria for initial stenosis and successful coronary angioplasty, and, except four patients who died, none were lost for follow-up. RESULTS: Restenosis occurred in 108/266 (40.6%) of the treated stenoses in the Omacor group and in 93/263 (35.4%) in the placebo group (odds ratio [OR] 1.25, 95% confidence interval [CI] [0.87-1.80] p = 0.21). In the Omacor group one or more restenoses occurred in 90/196 (45.9%) patients as compared with 86/192 (44.8%) in the placebo group (OR 1.05, 95% CI [0.69-1.59] p = 0.82). CONCLUSIONS: Supplementation with 5.1 g n-3 FA/day for six months, initiated at least two weeks prior to coronary angioplasty did not reduce the incidence of restenosis.

Aged↗

Plasma homocysteine concentration related to diet, endothelial function and mononuclear cell gene expression among male hyperlipidaemic smokers.

BACKGROUND: Elevated plasma concentration of homocysteine is an independent risk factor for development of cardiovascular diseases. MATERIALS AND METHODS: We evaluated potential links between homocysteine and atherothrombogenesis by relating the plasma concentration of homocysteine to (i) dietary antioxidants and omega-3 fatty acids (and determined influence of intervention with antioxidants or omega-3 fatty acids); (ii) markers of endothelial cell function; and (iii) peripheral blood mononuclear cell mRNA levels. RESULTS: We observed an inverse relationship between the plasma homocysteine concentration and dietary intake of vegetables, vitamin C and beta-carotene and between homocysteine and the serum concentration of folate, vitamin B12 and omega-3 fatty acids. Intervention with antioxidants or omega-3 fatty acids did not affect plasma homocysteine concentration. The plasma levels of cysteinylglycine and vitamin B12 correlated positively with circulating E-selectin and VCAM-1, respectively, whereas folate in serum and blood correlated negatively with P-selectin. A negative correlation was found between the concentrations of homocysteine and von Willebrand factor. Negative and positive correlations were found between plasma homocysteine and the mononuclear cell mRNA levels of peroxisome proliferator activated receptor delta (PPAR delta) and c-myc respectively. A negative correlation was also found between plasma homocysteine and mononuclear cell mRNA levels of the proteoglycan serglycin. Homocysteine was not correlated with serum activity of glutathione peroxidase or with the mRNA level of glutathione peroxidase in mononuclear cells. CONCLUSION: The plasma homocysteine level was negatively correlated with dietary intake of vegetables, including vitamins C and E, and serum omega-3 fatty acids, whereas supplementation with antioxidants or omega-3 fatty acids did not affect plasma homocysteine concentration. Homocysteine was not associated with circulating adhesion molecules or increased procoagulant activity, but homocysteine may alter mononuclear cell gene expression. Cysteine showed no significant correlation with these parameters.

Adult↗

Panic disorder in chest pain patients referred for cardiological outpatient investigation.

OBJECTIVES: The aims of the study were to: (i) determine the prevalence of panic disorder (PD) in patients referred to cardiological outpatient clinics for evaluation of chest pain; (ii) compare psychiatric comorbidity, psychological distress, pain characteristics and suicidal ideation in PD and non-PD patients: (iii) compare the prevalence of coronary risk factors and medical comorbidity in PD and non-PD patients; and (iv) describe current PD treatment and need for PD treatment as expressed by PD patients. DESIGN: A cross-sectional study based on psychiatric and cardiological investigation. SETTING: Four cardiological outpatient clinics in Oslo, Norway. SUBJECTS: One-hundred and ninety-nine consecutive patients without known heart disease referred to out-patient clinics for investigation of chest pain. MAIN OUTCOME MEASURES: Psychiatric state diagnosis (axis I); scores on self-assessment rating scales of psychological factors and pain modalities; cardiological diagnosis. RESULTS: Thirty-eight per cent of the patients met criteria for current panic disorder (PD). Panic disorder was associated with psychological distress, comorbid psychiatric disorders, medical disorders and significantly higher prevalence of coronary risk factors (P<0.05). Furthermore. the results suggest that these patients were not identified and appropriately treated for panic disorder prior to cardiological investigation. The results indicate that the patients are positive to screening for psychiatric disorder and communicate a need for treatment early in the investigation process. CONCLUSION: PD commonly occurs in this chest pain population. Thus, there is a need to educate physicians caring for these patients about PD identification and treatment.

Adult↗

Prosthetic heart valve thrombosis during dicloxacillin therapy.

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.

Aged↗

Effects of doxazosin and atenolol on circulating endothelin-1 and von Willebrand factor in hypertensive middle-aged men.

Elevated levels of endothelin-1 (ET-1) and von Willebrand factor (vWF), both markers indicative of endothelial function, are associated with hypertension. In a randomized open study we investigated the effect of antihypertensive treatment with the alpha-blocker doxazosin (n = 23) or the beta-blocker atenolol (n = 22) for 22 weeks on circulating levels of ET-1 and vWF in middle-aged men with essential hypertension. Blood pressure reduction was satisfactorily achieved with both drugs, although the decrease in the atenolol group was larger than that in the doxazosin group. A reduction in the levels of vWF occurred in both groups, being more pronounced in the alpha-blocker group compared with the decrease on beta blockers, p = 0.004 and p = 0.056, respectively. In the alpha-blocker group, there was a significant correlation (r = 0.50, p = 0.022) between the reduction in diastolic blood pressure and the decline in vWF. A highly significant decrease in plasma ET-1 was obtained during beta blockade (p = 0.007), whereas no significant change occurred within the alpha-blocker group. There was, however, no correlation between the decrease in blood pressure and the reduction in ET-1. The different favorable effects of alpha and beta blockers on endothelial function expressed as vWF and ET-1, could indicate that the effects are probably related not only to the blood pressure per se, but also to the different pharmacologic mechanisms of the drugs.

Adrenergic alpha-Antagonists↗

Combined administration of dextran 70 and dalteparin does not increase perioperative blood loss compared to dextran 70 alone in major orthopedic surgery.

A prospective open-labeled clinical study was carried out to compare the safety of dextran 70 and low molecular weight heparin (dalteparin; DD group) versus dextran 70 alone (D group) in patients subjected to elective hip replacement surgery. Dalteparin, 5,000 IU/day and dextran 70, 500 ml during surgery and on the first postoperative day were administered to 214 patients. Dextran 70 alone was infused in 44 patients, 500 ml during surgery and on the 1st, 3rd and 5th postoperative day. Mean total blood loss during the operation and until the 2nd postoperative day was 1,708 ml in the DD group and 1,712 ml in the D group (p = 0.79). During the 1st postoperative week, no group differences were found in the relative number of patients that received packed red blood cells (p = 0.95), the amount of transfused packed red blood cells (p = 1.0) and changes in hemoglobin concentrations (p = 0.69). The present results suggest that dextran 70 and dalteparin can be combined in recommended doses without significantly increasing perioperative bleeding in patients undergoing hip replacement surgery. Bone traumatization and insufficient plugging of surgical traumatized bone surfaces with bone cement favor bleeding. Further well-designed studies are needed to evaluate the safety and efficacy of this regimen.

Aged↗

The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease.

During progression of atherosclerosis the overlying endothelial cells alter their expression of some surface molecules. Circulating levels of such molecules may be quantified. We investigated the effect of omega-3 fatty acids (n-3 FA) on the levels of tissue plasminogen activator antigen, von Willebrand factor, and the soluble forms of thrombomodulin, P-selectin, E-selectin, and vascular cell adhesion molecule-1 in 54 patients with coronary heart disease. Twenty-three of the patients had taken 5.1 g/d n-3 FA for 6 months (group I) and 31 were given corn oil as placebo (group II). For another 4 weeks ("the study period") they all got 5.1 g/d of n-3 FA. Compliance was confirmed by demonstration of changes in relevant fatty acids in serum phospholipids. At baseline, significant differences between the groups were found with lower median values of von Willebrand factor (128% versus 147%) and soluble thrombomodulin (24.9 versus 32.5 ng/mL) and higher median values of soluble E-selectin (41.4 versus 35.5 ng/mL) and soluble vascular cell adhesion molecule-1 (573 versus 473 ng/mL) in group I. During the study period differences in changes between the groups were found; tissue plasminogen activator antigen and soluble thrombomodulin decreased (P for difference between the groups 0.001 and 0.015, respectively), whereas soluble E-selectin and soluble vascular cell adhesion molecule-1 increased (P for difference between the groups <0.01 for both) in group II relative to group I. Our results indicate that n-3 FA supplementation decreases hemostatic markers of atherosclerosis, whereas markers of inflammation may be increased. The latter may be the result of lipid peroxidation as a simultaneous decrease of vitamin E and increase in thiobarbituric acid-reactive substances were observed.

Adult↗

Procoagulant activity and cytokine expression in whole blood cultures from patients with atherosclerosis supplemented with omega-3 fatty acids.

Omega-3 fatty acids (n-3 FA) may reduce atherogenesis and thrombosis. We investigated the effects of n-3 FAs on procoagulant activity and cytokine expression in whole blood cultures from patients with atherosclerosis. Eleven of the 23 included patients had received 5.1 g n-3 FA daily for 6 months (group I) whereas 12 patients had been on placebo (group II). All patients were then given 5. g n-3 FA daily for another 4 weeks. At baseline significantly lower levels of LPS-induced prothrombin fragment1+2 were found in group I (p = 0.010), this difference being eliminated after 4 weeks. Il-6 and TNFalpha were significantly higher at baseline in group I and the differences in changes from baseline between the groups were statistically highly significant with increasing values in group II(Il-6 p = 0.001, TNF alpha p = 0.002). The present results indicate a reduction in pro-thrombotic potential in patients receiving highly concentrated n-3 FA, whereas some proinflammatory responses might be adverse.

Adult↗

[Transient postischemic myocardial injury--a condition of practical clinical significance?].

After a brief ischemic period, a prolonged phase of cardiac dysfunction develops. This transient dysfunction is now known as myocardial stunning. In this article we list the pathophysiological conditions in which myocardial stunning is most likely to occur in humans, and we discuss how it can be diagnosed. Although stunning is a reversible condition, its clinical implications can be life threatening. However, knowledge of the mechanisms involved may help improve the treatment of patients with myocardial stunning where this occurs after revascularization procedures for instance, and after cardiac arrest.

Humans↗

Circulating levels of endothelin-1 during acute hyperinsulinemia in patients with essential hypertension treated with type 1 angiotensin receptor antagonist or placebo.

Insulin and angiotensin II (Ang II) are involved in the regulation of endothelin-1 (ET-1). This study investigates their possible influence on plasma levels of ET-1 in humans. Twenty patients with essential hypertension were included in a randomized, double-blind, placebo-controlled crossover study of 4 weeks' treatment with losartan, a selective type 1 angiotensin (AT1) receptor antagonist. The effect was evaluated in the fasting state and during acute hyperinsulinemia physiologically induced by oral glucose ingestion (OGTT) and by euglycemic glucose clamp. Losartan lowered blood pressure significantly, but did not influence plasma levels of ET-1 in the fasting condition (5.2 +/- 0.2 fmol/mL on placebo and 5.6 +/- 0.3 fmol/mL after losartan treatment). During both models of acute hyperinsulinemia, there was a significant decrease in plasma ET-1. In the OGTT the mean values after placebo treatment decreased from 5.2 +/- 0.2 fmol/mL at time 0 to 4.7 +/- 0.4 (P = .001) and 4.0 +/- 0.5 (P = .001) at 60 and 120 minutes, respectively. During the clamp the mean ET-1 values decreased from 5.7 +/- 0.4 fmol/mL at time 0 to 4.6 +/- 0.2 (P < .001) and 4.3 +/- 0.3 (P = .006) at 60 and 120 minutes, respectively. No differences in these profiles occurred after losartan treatment. Significant inverse correlation between fasting levels of ET-1 and insulin sensitivity index was found, r = -.51, P = .003. In conclusion, losartan did not influence the circulating levels of ET-1 in basal condition or during acute hyperinsulinemia, whereas a significant decrease in plasma ET-1 occurred during acute hyperinsulinemia. A significant inverse correlation demonstrated between basal levels of plasma ET-1 and the insulin-stimulated glucose uptake could point to a possible regulatory influence of ET-1 production on glucose metabolism or vice versa.

Adult↗

Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers.

BACKGROUND: Increased expression of cell adhesion molecules and increased procoagulant activity of the vascular endothelium have been postulated to characterize dysfunctional endothelium. The cellular effects of n-3 fatty acids (n-3 FAs) and antioxidants are still not clarified. METHODS: In a randomized, factorial two-by-two design study, we have investigated 41 male smokers with hyperlipidaemia before and after 6 weeks of supplementation with either n-3 FAs (4.8 g daily) or placebo with the addition of antioxidants (150 mg of vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene daily) or placebo with regard to the effects on some endothelial cell markers: thrombomodulin (sTM), von Willebrand factor (vWF), tissue plasminogen activator antigen (tPAag) and soluble forms of the cell adhesion molecules E-selectin, P-selectin and vascular cell adhesion molecule 1 (VCAM-1). RESULTS: In the n-3 FA group, significant reductions in the plasma levels of vWF (P = 0.034) and sTM (P < 0.001) were demonstrated compared with placebo, whereas increased levels were found for E-selectin (P = 0.001) and VCAM-1 (P = 0.010). In the antioxidant group, no differences in changes were noted for any of the variables. CONCLUSION: The reduction in the levels of sTM and vWF with n-3 FA supplementation could indicate an improvement with regard to the haemostatic markers of endothelial dysfunction, whereas the simultaneous increase in the soluble forms of E-selectin and VCAM-1 may suggest an adverse effect on the inflammatory system. The antioxidants seem to be neutral in their effect on these endothelial cell markers in our study population of smokers. The interpretation of the soluble forms of these molecules are, however, still debatable.

Adult↗

Myocardial damage during percutaneous transluminal coronary angioplasty as evidenced by troponin T measurements.

AIM: The present study was undertaken to assess the effect of balloon inflation during percutaneous transluminal coronary angioplasty on markers of myocardial damage. METHODS AND RESULTS: Seventy-five patients undergoing elective percutaneous transluminal coronary angioplasty were evaluated with serum creatine kinase MB and cardiospecific troponin T before and 1 and 4 days after the procedure. On day 1, 28% of the patients had increased cardiospecific troponin T values and 18% had increased creatine kinase MB values. On day 4, 24% had increased cardiospecific troponin T values, whereas all creatine kinase MB values were normal. A high degree of correlation between creatine kinase MB and cardiospecific troponin T on day 1, as well as between both markers on day 1 and cardiospecific troponin T on day 4 were found. The increased levels of cardiospecific troponin T on day 4 was significantly correlated with the total balloon inflation time (P < 0.001). CONCLUSION: We conclude that irreversible myocardial damage, as evidenced by increased cardiospecific troponin T values on day 4, occurs in an appreciable number of patients during percutaneous transluminal coronary angioplasty, and that this damage is strongly correlated with the total balloon inflation time.

Adult↗

Markers of myocardial injury in blood following PTCA: a comparison of CKMB, cardiospecific troponin T and troponin I.

In 74 patients undergoing elective PTCA, CKMB, cTnT, cTnI-Access (cTnI-Acc) and cTnI-Abbott (cTnI-Abb) were measured in serum before and days 1 and 4 after the procedure. Two of the patients had pronounced biochemical evidence of AMI. In addition, a minor to moderate increase in CKMB, cTnT, cTnI-Acc and cTnI-Abb were found on day 1 in 13, 22, 18 and 25 patients, respectively. Excluding the two with AMI, cTnT was also increased on day 4 in 16 patients and cTnI-Abb in 15 patients, whereas CKMB and cTnI-Acc levels were essentially normal in all. Thus, an unexpected discrepancy between the two methods for cTnI was revealed on day 4. In these 16 patients, there was no statistically significant relationship between the level of cTnT on day 4 and the levels of CKMB or cTnI-Acc on day 1. This is in contrast to a significant correlation to cTnT and cTnI-Abb on day 1. Based on these results, it is speculated that the marker levels on day 1 are due to reversible as well as irreversible damage, whereas cTnT and cTnI-Abb on day 4 more selectively reflect the degree of myocardial necrosis. cTnT and TnI-Abb on day 4 are therefore proposed as valuable markers for further study of the clinical implications of myocardial damage following PTCA and related interventions.

Angioplasty, Balloon, Coronary↗

The effect of different antithrombotic regimens on platelet aggregation after myocardial infarction.

Platelet aggregate ratio (PAR) was measured according to the method of Wu & Hoak in 143 patients after acute myocardial infarction (AMI) and in 54 controls. A PAR < 1 expresses the presence of platelet aggregates. The patients were randomized to aspirin 160 mg/d, or warfarin, or aspirin 75 mg/d + warfarin. In patients on aspirin, PAR was measured 24 h after aspirin intake, and in 76 patients also 2 h after aspirin. The median PAR in patients on warfarin was 0.85, on warfarin + aspirin 0.91 and on aspirin alone 0.94, all significantly lower than the median PAR of 0.97 in the controls. In 14 patients on aspirin the PARs were below a cut-off point of 0.82 (secondary aspirin non-responders). PAR increase significantly 2 h after aspirin intake. In two patients, however, PAR remained low (primary aspirin non-responders). It is concluded that some patients do not seem to respond to aspirin, the clinical implication of which has yet to be determined.

Adult↗

Effects of doxazosin and atenolol on atherothrombogenic risk profile in hypertensive middle-aged men.

The alpha-blockers prazosin and doxazosin reduce hypertriglyceridemia (HTG) and increase serum levels of high-density lipoprotein (HDL)-cholesterol, whereas beta-blockers such as atenolol have the opposite effect. As HTG is associated with reduced fibrinolysis and hypercoagulability, we investigated the effects of doxazosin and atenolol on serum lipids and hemostatic factors in hypertensive men with an atherothrombogenic risk profile. The study was randomized and open, but blinded to investigator of biochemical results. Forty-five men (mean age, 44.5 years) with central obesity [median body-mass index (BMI), 28 kg/m2] and moderate hypertension [median diastolic blood pressure (DBP), 104.5 mm Hg] were treated with atenolol (n = 22) or doxazosin (n = 23) for 22 weeks, after which changes in between-group differences from baseline were estimated. After intervention, significant between-group differences in favor of doxazosin were found: lower triglycerides (p = 0.008) and higher HDL cholesterol (p = 0.036); furthermore, improvement of fibrinolysis: lower plasminogen activator inhibitor-1 (PAI-1) activity (p = 0.012), higher tissue plasminogen activator (tPA) activity after venous occlusion (VO); and higher levels of serum D-dimer, both unstimulated (p = 0.0016) and after VO (p = 0.0032). In addition, lower levels of serum testosterone were found in the atenolol group (p = 0.0016). A profile with reduced HTG, increased HDL cholesterol, and improved fibrinolysis was obtained with doxazosin when compared with atenolol. Furthermore, the observed decrease in serum testosterone on atenolol treatment would rather favor long-term treatment with doxazosin in this study population.

Adult↗