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Biomedical subjects

I Os

Publications and source records attributed to I Os.

At least 37 records · Page 2Linked to original sources

Insulin resistance and sympathetic nervous system activity in hypertensive and normotensive premenopausal women.

The aim of the present study was to compare insulin sensitivity and catecholamine responses to insulin in lean, hypertensive (HT) and normotensive (NT) premenopausal women. HT (BP 149 5/99 +/- 2 mmHg, n = 14) and NT (BP 128 +/- 4/81 +/- 2 mmHg, n = 12) were matched for age (46 +/- 1 vs. 47 +/- 1 years) and body mass index. Insulin sensitivity was determined by fasting serum insulin, glucose disposal rate (GDR) and insulin sensitivity index (GDR/I) using euglycemic hyperinsulinemic glucose clamp technique. Sympathetic nervous system activity was assessed by plasma adrenaline and noradrenaline in arterialized venous blood at baseline and during euglycemic hyperinsulinemic glucose clamp. Insulin sensitivity index correlated negatively with total cholesterol in HT (r = -0.57, p < 0.05) and with body mass index (r = -0.42, p < 0.05, n = 26). The response in catecholamines to euglycemic hyperinsulinemia in HT differed from NT with an increase both in noradrenaline and adrenaline. Blood pressure and heart rate responses, however, did not differ between HT and NT. Fasting serum glucose did not differ between the two groups (4.7 +/- 0.1 mmol/l in HT vs. 4.9 +/- 0.1 mmol/l in NT), nor did fasting serum insulin (16 2 mU/l vs. 13 mU/l). Glucose disposal rate (8.8 +/- 0.5 vs. 8.7 +/- 0.7 mg kg-1 body weight min-1) and insulin sensitivity index were similar (7.3 +/- 0.8 vs. 7.6 +/- 0.8 arbitrary units). We conclude that in lean, premenopausal hypertensive women insulin sensitivity is not reduced compared with age- and weight-matched normotensive women, but the hypertensives respond to hyperinsulinemia with increased plasma catecholamines, i.e. sympathetic nervous systemic activity. Also, insulin sensitivity correlates negatively with serum cholesterol. Thus, an insulin-hyperadrenergic interaction may possibly be involved as a pathogenetic factor in lean hypertensive women.

Analysis of Variance

Non-responders.

Non-responders are frequently encountered in clinical practice, and different strategies have to be considered as well as diagnostic approaches. Nearly 50% of all hypertensive patients will require more than one drug to control blood pressure. The complexity of high blood pressure is reflected in the different responses to antihypertensive agents with varied mode of action. White coat hypertension may coexist with sustained hypertension and complicate interpretations of blood pressure measurements. Noncompliance is a challenge for the doctor, and may be difficult to solve. It depends not only on the patient-doctor relationship, but also on the patient's perception of own health and the side effect profile of the drugs. Patient education is crucial. Secondary hypertension should be excluded in truly resistant hypertension. Volume overload is frequent in essential hypertension, and volume expansion follows an excessive dietary sodium intake. These and other possibilities should be sought for when explaining failure to respond to antihypertensive therapy.

Antihypertensive Agents

Risk factors and differential antihypertensive therapies.

A less pronounced reduction in the incidence of coronary heart disease than in cerebrovascular events has been observed during antihypertensive therapy. Hypertension may not be the dominant risk factor for coronary heart disease as it is for cerebrovascular disease, and metabolic factors gain more importance. The reason for the differential effect of antihypertensive therapy could partly be explained by the adverse metabolic effects of some antihypertensive drugs which may thus attenuate the beneficial effects. When decision is made concerning antihypertensive treatment, it is imperative to assess the overall cardiovascular risk of the patient and take into account the possible impact on these factors of the different antihypertensive drugs.

Antihypertensive Agents

[Lisinopril and nifedipine have neutral effects on lipids].

In a randomized, double blind, parallel-group, multicentre study in Norway, 97 patients with mild to moderate hypertension (mean blood pressure 159/104 mm Hg) were treated with either lisinopril 10-40 mg or nifedipine 20-80 mg and the effects on blood lipids were evaluated. Complete results of laboratory analyses are given for 80 patients. After a 4 week run-in and placebo period, antihypertensive treatment was given for the next 10 weeks. During treatment with lisinopril the changes in lipids were +2.1% for total cholesterol, +0.7% for HDL-cholesterol, +3.8% for triglycerides and -6.1% for ratio HDL/cholesterol-HDL. For nifedipine the corresponding values were -2.4% for cholesterol, -5.8% for HDL-cholesterol, +8.0% for triglycerides and +3.2% for ratio. None of these changes was statistically significant. Both lisinopril and nifedipine lowered the blood pressure significantly, 18.1/12.0 mm Hg with lisonopril (p < 0.01 for both systolic and diastolic pressure) and 8.0/8.5 mm Hg with nifedipine (p < 0.01 for both respectively). Both drugs were well tolerated. In conclusion, neither lisinopril nor nifedipine had any negative impact on lipid levels.

Adult

[Treatment of hypertension in 1994. Comments on the 1993 guidelines of the Norwegian Society of General Practitioners concerning the treatment program for hypertension].

An absolute reduction of 2.5% per year in cardiovascular risk among persons treated with drugs indicates that elderly persons should also be treated for hypertension in this way. Today, ambulatory assessments of blood pressure and detection of organ damage using both traditional and new methods (echo-cardiography, microalbuminuria) are useful in identifying high-risk patients in need of treatment. Non-pharmacological treatment of hypertension (changes in lifestyle) has not been proved to have any effect on the clinical manifestations of high blood pressure, and is only a supplement to treatment with drugs. The assertion that diastolic pressure should not be brought down to below 85 mm Hg is based on small numbers and retrospective data. It is our impression that the Society of General Practitioners emphasizes economic savings to an extent that tends to conflict with current scientific knowledge.

Family Practice

[Antihypertensive treatment and risk of coronary disease. How significant is the antihypertensive effect for metabolic factors?].

A recent meta-analysis of hypertension treatment trials showed a marked reduction in cerebrovascular disease and a less pronounced reduction in coronary heart disease. Treatment has consisted of diuretics and betablockers, and this paper discusses the possible influence of their metabolic side effects as compared with the new vasodilating agents (angiotensin converting enzyme inhibitors, alpha receptor antagonists and calcium channel blockers). Several studies have now been started to compare the effect of these compounds with diuretics and betablockers with respect to long-term cardiovascular morbidity and mortality. Until the results of these studies are available, young patients (i.e. < 60-65 years) at high risk of coronary heart disease, especially patients with the insulin resistance syndrome or diabetes mellitus, should in our opinion be treated with ACE-inhibitors, alpha receptor blockers or calcium channel blockers.

Age Factors

Relationship between hemorrheologic factors and insulin sensitivity in healthy young men.

The present study aimed at testing a possible relationship between hemorrheologic factors, such as hematocrit, fibrinogen, and whole-blood viscosity, and insulin sensitivity in healthy humans. Twenty-one 21-year-old men were studied with the hyperinsulinemic euglycemic glucose clamp technique. We found statistically significant negative correlations between the glucose disposal rate (GDR) and calculated whole-blood viscosity at both high (r = -.55, P = .01) and low (r = -.51, P = .01) shear rates. We observed negative associations between GDR and fibrinogen (r = -.66, P = .002), GDR and hematocrit (r = -.63, P = .002), GDR and body mass index (r = -.51, P = .007), and GDR and resting heart rate (r = -.46, P = .04). Using stepwise multiple regression considering whole-blood viscosity, body mass index, mean arterial blood pressure, and heart rate as independent variables, we found that only whole-blood viscosity and body mass index were independent explanatory variables of the GDR. Together they accounted for 63% of the variability in the GDR in our subjects. These results suggest hemorrheologic, and therefore indirectly hemodynamic, factors as correlates to insulin sensitivity.

Adult

Female preponderance for lisinopril-induced cough in hypertension.

In a double-blind double-dummy multicenter study, patients with mild to moderate essential hypertension were randomized to receive either nifedipine (n = 416, 47.6% women) or lisinopril (n = 412, 50% women), and side effects were registered by specific questioning, by spontaneous reports, and by use of visual analog scales. Cough was spontaneously reported to occur in 8.5% with lisinopril compared to 3.1% with nifedipine. Women treated with lisinopril reported cough spontaneously three times more often than men, 12.6% v 4.4%, whereas no differences between the sexes were observed during the placebo period or during nifedipine treatment. Similar gender differences were observed during specific questioning. Furthermore, nonsmokers reported an increase in cough more often than did smokers.

Adult

Quality of life in hypertension.

Mild to moderate hypertension is usually asymptomatic and therefore the impact on quality of life and side-effects of the antihypertensive treatment can have a negative effect on treatment compliance. A number of comparative studies have addressed quality of life issues with various antihypertensive agents, and the results of these studies are summarised in this article with particular reference to ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors

[White coat hypertension and blood pressure measurement at home].

"White-coat" hypertension, i.e. high readings in the clinic but normal readings at home, has been demonstrated in 21-58% of hypertensive subjects without end-organ injury. The condition can be diagnosed by means of home blood pressure monitoring, which should therefore be used as a supplement to monitoring by the physician. Owing to the low blood pressure readings at home, these patients should not be treated with drugs. In the event of anti-hypertensive treatment, home blood pressure monitoring is useful in helping to decide the minimum required dose, thus reducing risk of side effects, and in monitoring the response to therapy. White coat hypertension is associated with overweight, lipid abnormalities and high fasting insulin. Owing to the high risk of developing sustained hypertension, the patients' blood pressure must be measured regularly both at the clinic and at home.

Adult

[Physical activity and the metabolic syndrome].

Hypertension may be accompanied by decreased insulin sensitivity, lipid abnormalities and increased haemostatic risk, all of which, constitute risk factors for coronary artery disease. Modifications of lifestyle, including more physical exercise, are important, and may reduce the coronary risk profile. Physical activity has been shown to lower blood pressure, reduce hypertriglyceridemia, improve insulin sensitivity and increase the fibrinolytic capacity. Hypertensive patients should be encouraged to increase physical activity as an adjuvans to both pharmacological and non-pharmacological treatment of high blood pressure.

Cardiovascular Diseases

Effect and tolerability of combining lovastatin with nifedipine or lisinopril.

Single cardiovascular risk factor intervention is probably not sufficient to prevent atherosclerosis progression. There is a lack of data on concomitant use of hypocholesterolemic agents and antihypertensive drugs with respect to possible interactions and adverse experiences. We studied 293 patients (below 65 years of age) under treatment with either lisinopril (n = 144) or nifedipine (n = 149) for mild to moderate hypertension for 10 weeks, and with serum cholesterol above 6.5 mmol/L, who were randomized to either lovastatin 20 mg every day or placebo in a double-blind, double-dummy design for 6 weeks. Lovastatin effectively lowered cholesterol by 16% and 15% in the lisinopril and nifedipine group respectively (P < .01 compared to placebo for both groups) without any negative impact on the antihypertensive efficacy of either lisinopril or nifedipine. The drugs in combination were well tolerated and did not affect the well-being of the patients, and did not cause any more adverse effects than the antihypertensive agents alone. Liver enzymes increased slightly during lovastatin therapy, while no case of myopathy was reported. Combined therapy with lovastatin and antihypertensive therapy can be safely undertaken.

Double-Blind Method

Sex differences in essential hypertension.

A group of 41-year-old hypertensive men (n = 35, blood pressure (BP) 149.9 +/- 2.1/98.9 +/- 1.1 mmHg, mean +/- SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 +/- 4.3/98.1 +/- 1.6 mmHg) with comparable body mass index (BMI, 25.9 +/- 0.5 vs. 24.9 +/- 4.5 kg m-2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 +/- 0.04 vs. 1.38 +/- 0.06 mmol l-1, P = 0.04), higher total cholesterol (6.04 +/- 0.14 vs. 5.54 +/- 0.18 mmol l-1, P = 0.04) and triglycerides (1.80 +/- 0.16 vs. 0.96 +/- 0.10 mmol l-1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = -0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m-2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m-2 (28 +/- 5 vs. 78 +/- 16 pg ml-1, P < 0.01 and 101 +/- 17 vs. 206 +/- 33 pg ml-1, P < 0.01 respectively). A negative curvilinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P = 0.05). These results suggest a male propensity for athero-thrombogenic risk factors in otherwise comparable hypertensive subjects. A close relationship between metabolic risk factors within the normal range seems to exist even in hypertensive women. The decreased sympathetic activity at rest in the obese hypertensive women indicates different pathophysiological mechanism for hypertension in lean and obese. Decreased sympathetic activity and thus reduced energy expenditure, promotes a risk for weight gain, and could explain the inverse relationship between insulin and adrenaline.

Adult

Regional differences of atrial natriuretic factors in humans.

During sinus coronarius catheterization in humans undergoing diagnostic right-sided cardiac catheterization, levels of atrial natriuretic factor (ANF) measured in sinus coronarius (n = 12) were four times higher than in peripheral arterial blood. Atrial natriuretic factor underwent average extractions of 0.57, 0.40, and 0.28 in the kidneys (n = 14), liver (n = 15), and forearm (n = 15) respectively. However, a close relationship was observed between arterial and peripheral venous concentrations. The substantial clearance of ANF even over the forearm indicates that arterial sampling may be preferred in conditions with altered peripheral vascular resistance, since an uptake of ANF in the peripheral vascular bed is likely to have occurred.

Aged

Plasma vasopressin, catecholamines and atrial natriuretic factor during hemodialysis and sequential ultrafiltration.

In 13 patients with chronic renal failure on maintenance hemodialysis, plasma vasopressin, atrial natriuretic factor, catecholamines and renin activity were measured during ordinary hemodialysis with fluid removal, and during isolated isoosmotic ultrafiltration and a subsequent isovolemic hemodialysis. Concomitant with a significant fall in serum osmolality, plasma vasopressin decreased significantly from 6.3 +/- 0.8 to 3.8 +/- 0.4 pg/ml (p < 0.05). Predialytic plasma vasopressin was significantly correlated to serum osmolality (r = 0.62, p = 0.001). No such relationship was observed after dialysis. During isolated ultrafiltration (1.25 +/- 0.13 L) through 1 hour, no change in either osmolality or vasopressin was observed, whereas atrial natriuretic factor decreased (700 +/- 136 to 564 +/- 115 pg/ml, p < 0.05). Atrial natriuretic factor was excessively high at all times, and may explain the low plasma renin activity observed in these patients even after fluid removal. No consistent changes were observed in the catecholamines during hemodialysis or ultrafiltration alone, despite marked changes in blood pressure and heart rate. Thus, even in patients with chronic renal failure osmotic regulation of vasopressin seems intact, and volume reduction through ultrafiltration causes a decrease in atrial natriuretic factor.

Arginine Vasopressin

Effect of cold pressor test and awareness of hypertension on platelet function in normotensive and hypertensive women.

Plasma beta-thromboglobulin (beta-TG) concentration, reflecting platelet function in vivo, was compared in fertile women with untreated essential hypertension and age-matched normotensives, in two separate studies. In the first study, hypertensives and normotensives were aware of their blood pressure status. Blood was sampled through arterial and venous indwelling catheters, and no difference in beta-TG was found between the groups. Arterial beta-TG was significantly lower than venous concentration (p < or = 0.05). Cold pressor test increased arterial beta-TG significantly in both groups (p < 0.05). In the second study, both women and investigator were unaware of blood pressure status, and beta-TG concentration, platelet count, and mean platelet volume obtained by venipunctures were similar in the hypertensive and normotensive group. Thus, platelet function in vivo seems to be normal in fertile hypertensive women, in contrast to the platelet dysfunction previously reported in hypertensive men. In women, as in men, platelet release occurred during venous catheter blood sampling and during cold pressor test. However, at variance from men, platelet function was not influenced by awareness of blood pressure status in the hypertensive females.

Adult

[Cough during treatment with angiotensin-converting enzyme inhibitors is gender related].

In a Norwegian, double-blind, double-dummy multicenter study, 828 patients with mild to moderate hypertension were randomized to treatment by either lisinopril or nifedipine. One of the aims of the study was to specifically investigate the frequency of side effects. Spontaneously reported coughing reached 8.5% for lisinopril, as against 3.1% for nifedipine. In two patients coughing led to withdrawal from the study, and in another three it contributed partially to discontinuation of the treatment. A significant sex difference was found for spontaneously reported coughing among patients on lisinopril; 12.6% of the women and 4.4% of the men. A similar difference between the sexes was found for specific questioning about coughing. Use of a visual analogue scale by both patient and spouse revealed similar frequency of coughing as when reported spontaneously. The reason for sex being an important determinant for lisinopril-induced coughing remains obscure.

Angiotensin-Converting Enzyme Inhibitors