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I Os

Publications and source records attributed to I Os.

At least 37 records · Page 2Linked to original sources

The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins.

OBJECTIVES: To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. SETTING: In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. SUBJECTS: Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. INTERVENTIONS: The women were randomized to HRT, i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. MAIN OUTCOMES: Effects on lipids and lipoproteins. RESULTS: After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. CONCLUSIONS: In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Administration, Cutaneous↗

Reduced expression of endothelial cell markers after long-term transdermal hormone replacement therapy in women with coronary artery disease.

The effects of 12 months hormone replacement therapy (HRT) on biochemical markers associated with endothelial function were studied in 98 postmenopausal women with CAD, who were randomized to transdermal HRT or a control group. A significant reduction in the levels of von Willebrand factor in the HRT-group compared to controls was seen after 3 months, maintained after 12 months (p <0.001). Significant reduction in the HRT-group compared to controls was also seen in VCAM-1 after 3 months, sustained after 12 months (p = 0.013 and p = 0.045, respectively), and E-selectin was reduced by about 20% after 3 months on HRT, the reduction being statistically significant after 12 months (p <0.001). Significantly reduced levels of ICAM-1 were also seen after 12 months (p = 0.048). No effects could be observed on tPA-antigen or thrombomodulin. The reduction in procoagulant and proinflammatory markers of endothelial function after long-term transdermal HRT could indicate a beneficial effect on the endothelium and thus a potentially modulating effect on the progression of atherosclerosis in women with CAD.

Administration, Cutaneous↗

[An overview of hypertension studies with calcium antagonists].

Calcium antagonists are widely used in the treatment of hypertension. However, few endpoint studies with calcium antagonists have been done to prove reduction in hypertensive complications. Results of the STONE, SYST-EUR and SYST-CHINA studies show that long-acting calcium antagonists are effective compared to placebo, especially in patients with isolated systolic hypertension and diabetes. Ongoing prospective and randomized trials like STOP II, INSIGHT, NORDIL, ALLHAT and ASCOT will clarify whether calcium antagonists are more effective than well-proven diuretics and betablockers. ASCOT will test the hypothesis that amlodipine is more efficacious than atenolol in preventing cardiac complications in 18,000 hypertensive patients with high coronary risk including diabetes (among them, 2,000 in Norway). The study is also randomizing the patients in a factorial design to either atorvastatin or placebo, testing the so-called lipid hypothesis.

Antihypertensive Agents↗

Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension.

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.

Adult↗

Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group.

The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.

Adult↗

[Pregnancy, essential hypertension and chronic renal disease].

Women with chronic hypertension or renal disease are at a particular high risk of developing pre-eclampsia or eclampsia. Pre-eclampsia is associated with an increased risk of fetomaternal complications. In women with uncomplicated mild and moderate hypertension, pregnancy is usually normal. Treatment of high blood pressure aims at reducing maternal cardio- and cerebrovascular catastrophies, and the benefit of the treatment must be weighed against possible harmful effects on the foetus. In some cases, antihypertensive treatment can be discontinued, or medication changed. Preconceptional counselling is important both for women with chronic hypertension and, even more so, for women with renal disease, since the outcome of the pregnancy may be affected by the underlying disease.

Female↗

Evidence of excess hereditary predisposition in women with angiographically documented coronary artery disease.

In a hospital-based case-control study including women and men with angiographically documented coronary artery disease (CAD) admitted to a university hospital during a 6-month period, we observed an excessive hereditary predisposition in women. Clustering of risk factors was more pronounced in women than in men. Thus, the results suggest that hereditary factors as well as multiple risk factors are essential when CAD is expressed in women.

Angiography↗

Comparison of the combination of enalapril and a very low dose of hydrochlorothiazide with atenolol in patients with mild-to-moderate hypertension. Scandinavian Study Group.

The blood pressure lowering effect and tolerability of the angiotensin-converting enzyme inhibitor enalapril combined with a very low dose of hydrochlorothiazide (HCTZ) were compared with the selective betareceptor blocker atenolol in patients with mild-to-moderate hypertension. Three hundred seventy-four patients were randomized into a triple-blind, parallel, active-controlled 12-week study period comparing enalapril/HCTZ (20/6 mg) with atenolol (50 mg) after a 4-week placebo baseline period. Blood pressure (BP), clinical and laboratory safety, and metabolic laboratory variables were assessed. Enalapril/HCTZ as well as atenolol reduced both sitting and standing diastolic and systolic BP (P < .001), but enalapril/HCTZ had a more pronounced effect than atenolol on sitting systolic BP (P = .019); there was a trend toward more patients achieving target diastolic BP (<90 mm Hg, P = .053). No clinically important differences in safety and tolerability were observed.

Adolescent↗

Alpha-1-antitrypsin deficiency associated with hepatic cirrhosis and IgA nephritis.

The association between alpha1-antitrypsin (A1AT) deficiency and glomerulonephritis has only sporadically been reported, and mostly based upon autopsy findings, as opposed to the more frequent linkage between A1AT deficiency and lung emphysema with or without hepatic cirrhosis. The present case report describes a 30-year-old man with A1AT deficiency, without evidence of lung disease, who developed hepatic cirrhosis in early childhood and IgA glomerulonephritis and hypertension in adult life. The IgA nephritis followed an unusual course, with a sudden deterioration of the renal function, possibly induced by uncontrolled hypertension or the possible occurrence of vasculitis. After 6 months of hemodialysis, the patient successfully underwent living-related-donor kidney transplantation.

Adult↗

[How to combine antihypertensive drugs?].

Many hypertensive patients do not respond adequately to single-drug therapy and may therefore require two or more drugs to reach the treatment goal. The drugs used in combination therapy should have additive or synergistic effects on blood pressure. A potential benefit of combinations is to use lower doses of each drug, which may attenuate or abolish the occurrence of side effects. Different combinations are discussed, as well as the inhibition of compensatory mechanisms that may otherwise counteract the antihypertensive effect.

Antihypertensive Agents↗

[Alpha 1-antitrypsin deficiency--not only pulmonary and hepatic involvement].

The association between deficiency of alpha-1-antitrypsin (A1AT) and glomerulonephritis has been only sporadically reported on, as opposed to the linkage between A1AT-deficiency and lung emphysema or hepatic cirrhosis. We describe the case of a 30-year-old man with A1AT deficiency who developed hepatic cirrhosis in early childhood, and IgA glomerulonephritis and hypertension in adult life. The IgA nephritis followed an unusual course. After three years of slight elevation of serum creatinine levels, the patient rapidly developed renal failure necessitating acute hemodialysis. The deterioration of the renal function was preceded by eruption of skin lesions, believed to represent a vasculitis. After six months of hemodialysis, the patient successfully received a transplanted kidney from his mother. The literature is reviewed with respect to the association between A1AT-deficiency and renal disease. We discuss possible underlying causes for the rapid deterioration of renal function in this patient.

Adult↗

[Refractory hypertension].

Resistant hypertension is a common disorder in general practice, and poses a challenge to clinicians. It is generally defined as failure to reduce blood pressure adequately despite the use of at least three different antihypertensive agents with different modes of action. The importance of recognizing expansion of plasma volume as a mediator of resistance to therapy is emphasized. Some patients may have white-coat hypertension. An even larger group of patients may fail to comply with the prescribed medication. A good physician-patient relationship is vital, and education of the patient is crucial for obtaining better adherence to the medication.

Antihypertensive Agents↗

Mental stress increases glucose uptake during hyperinsulinemia: associations with sympathetic and cardiovascular responsiveness.

Infusion of epinephrine and norepinephrine reduces insulin-mediated glucose disposal, ie, induces insulin resistance. Mental stress increases concentrations of both plasma catecholamines. However, the effect of acute mental stress on insulin-mediated glucose uptake has not been examined. We observed in pilot studies that a mental stress test (MST) during a euglycemic glucose clamp decreased blood glucose concentration. In a prospective study, euglycemic hyperinsulinemia was established during 120 minutes of glucose clamping; the subjects (N = 74) then underwent 5 minutes of intense mental arithmetics with infusion rates of glucose and insulin kept constant. During MST, plasma epinephrine and norepinephrine increased (by 0.23 +/- 0.02 and 0.50 +/- 0.05 nmol/L) together with blood pressure ([BP] by 18 +/- 8/9 +/- 1 mm Hg) and heart rate ([HR] by 21 +/- 1 beats per minute), with P less than .0001 for all changes. During mental stress, blood glucose concentration decreased by 0.4 +/- 0.1 mmol/L (P < .0001), followed by full recovery after another 10 minutes. Serum insulin was unchanged, indicating an acute but transient increase in glucose uptake. This finding was unrelated to age, sex, body mass, and BP status. Fifty-nine subjects with a decrease in glucose concentrations during MST were characterized by accentuated epinephrine response to MST (a change of 0.25 +/- 0.03 v 0.12 +/- 0.02 nmol/L, P = .001), increase in systolic BP (by 20 +/- 2 v 10 +/- 3 mm Hg, P = .008), and increase in HR (by 23 +/- 2 v 15 +/- 2 beats per minute, P = .008) as compared with 15 subjects with unchanged/increased glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between hemorheological factors and insulin sensitivity in normotensive and hypertensive premenopausal women.

The present study aimed at testing a possible relationship between hemorheologic factors such as hematocrit and whole blood viscosity, and insulin sensitivity in premenopausal, hypertensive (HT), and normotensive (NT) women. Fourteen HT and 12 NT women were studied with the hyperinsulinemic euglycemic glucose clamp technique. Insulin sensitivity was similar in NT and HT (8.7 +/- 0.8 v 7.6 +/- 0.8 arbitrary units). Whole blood viscosity did not differ between the two groups at any shear rate (shear rate 5.2 sec-1: 7.5 +/- 0.4 in NT and 8.0 +/- 0.3 in HT, P = NS). Statistically significant negative correlations were observed between the insulin sensitivity index and calculated whole blood viscosity at both high (r = -0.49, P < .01) and low shear rates (r = -0.50, P < .01, n = 26). Insulin sensitivity index was also negatively correlated to body mass index in the combined groups (r = -0.40, P = .04), and to both systolic and diastolic blood pressure (r = -0.44, P = .02 and r = -0.38, P = .05, respectively). In multiple regression analysis, whole blood viscosity, body mass index, systolic, and diastolic blood pressure accounted for 39% of the variation in insulin sensitivity index, but only whole blood viscosity was an independent explanatory variable for the insulin sensitivity index. These results suggest hemorheologic, and therefore indirectly hemodynamic factors as correlates to insulin sensitivity.

Blood Glucose↗

The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistent to enalapril monotherapy.

The antihypertensive efficacy and tolerability of formulations of enalapril and low (12.5 mg) and very low (6 mg) doses of hydrochlorothiazide (HCTZ) were compared with enalapril and placebo. Four hundred and two patients with mild to moderate essential hypertension were treated with 20 mg enalapril for 8 weeks. Patients (n = 296) with persistent supine diastolic blood pressure > 95 mm Hg after enalapril monotherapy were randomized to receive enalapril/placebo (group I), 6 mg enalapril/HCTZ (group II), or 12.5 mg enalapril/HCTZ (group III) for another 8 weeks in a double-blind design. The mean reductions in blood pressure were significantly larger in groups II and III compared to group I, 7.3 (95% CI, -9.0; -6.2), 7.7 (-9.2;-6.3), and 4.1 (-5.9;-2.9) mm Hg, respectively P < .01 for groups II and III compared to group I). No difference in side effects was observed between the three groups. A very low dose of 6 mg HCTZ acts synergistically when given together with enalapril, but is devoid of adverse metabolic effects.

Adolescent↗

Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension.

There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension.

Adult↗