[Management of dementia and cognitive functions in patients after cerebrovascular stroke: new results from the PROGRESS study].
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Biomedical subjects
Publications and source records attributed to J Widimský.
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Endocrine (adrenal) hypertension (primary aldosteronism, hypercortisolism and pheochromocytoma) had been considered for a long time as a rare cause of arterial hypertension. However, recent studies have shown a frequent incidence of primary aldosteronism among hypertensive subjects and therefore it is necessary to exclude primary aldosteronism in all subjects with severe hypertension. On the contrary, pheochromocytoma and hypercortisolism may be often overlooked in patients with incidentally found adrenal tumor and thus they can cause unexpected per- and postoperative complications.
Primary hyperaldosteronism (PH) is frequently considered to be a secondary form of diabetes mellitus (DM). In our previous study we attempted to evaluate the prevalence of DM among patients with PH compared to control subjects with essential hypertension (EH). We have noted a relatively high prevalence of DM and impaired glucose tolerance in PH, but the differences between the PH and EH groups did not reach statistical significance. We performed this study to assess whether the effective treatment of PH (surgical and conservative) would improve the glucose tolerance. We have studied 24 patients with PH of the following two subtypes: aldosterone-producing adenoma (APA) treated with adrenalectomy and idiopathic hyperaldosteronism (IHA) treated with spironolactone. No significant changes of glucose levels were found in the 60th and 120th min of the oral glucose tolerance test (OGTT) in the APA group. On the other hand, fasting glucose levels were decreased significantly after adrenalectomy. Plasma glucose levels were significantly increased in the 60th min, but no differences were found in fasting values and in the 120th min in the IHA group. There was a significantly higher incidence of impaired glucose tolerance (36 per cent before, 45 per cent after treatment) and DM (9 per cent, 18 per cent) in the IHA group compared to the APA group (8 per cent, 32 per cent; DM 0 per cent, 0 per cent). In conclusion, the treatment of PH does not improve glucose tolerance. Mild worsening of glucose tolerance after treatment could be explained by an increase of the body mass index. These data, in accordance with our previous study, do not support the idea that PH is a secondary form of diabetes mellitus.
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BACKGROUND: Leptin is a protein hormone produced predominantly by adipocytes that plays a role in food intake regulation and a series of other physiological processes including blood pressure regulation. OBJECTIVES: The aim of our study was to compare serum leptin levels in patients with primary hyperaldosteronism (PA) with those of healthy subjects and to explore the relationship of serum leptin levels and the parameters of insulin action in these patients before and after surgical or pharmacological treatment. METHODS: Serum potassium, leptin, aldosterone, insulin levels and plasma renin activity were measured and hyperinsulinaemic euglycaemic clamp was performed in 11 patients with PA and 11 healthy age-, gender- and body mass index (BMI)-matched subjects. In eight of 11 patients the same measurements were repeated at least 6 months after surgical or pharmacological treatment. RESULTS: The basal serum leptin levels in PA patients did not significantly differ from those of healthy subjects (mean+/-s.e.m. 8.4+/-1.9 vs 11.2+/-1.8 ng/ml, P=0.30), although their insulin sensitivity was significantly impaired (PA patients vs control subjects: glucose disposal rate in the last 20 min of clamp (M) 18.7+/-1.8 vs 30.6+/-3.3 micromol/kg/min, metabolic clearance rate of glucose (MCR(g)) 3.9+/-0.5 vs 7.2+/-1.1 ml/kg/min, P<0.05). The surgical or pharmacological treatment of PA patients increased significantly their serum leptin levels (10.9+/-3.7 vs 8.4+/-1.9 ng/ml, P<0.05) and simultaneously improved their insulin sensitivity. Basal serum leptin levels in both groups correlated positively with BMI and serum insulin levels. The inverse relationship between serum leptin levels and the insulin sensitivity parameters was found in both PA patients before treatment and healthy subjects. These relationships disappeared after treatment of PA patients except for those between serum leptin levels and MCR(g). CONCLUSION: Basal serum leptin levels in untreated patients with PA do not significantly differ from those of healthy subjects, but increase significantly after surgical or pharmacological treatment. The increase in serum leptin levels is paradoxically accompanied by the improvement of insulin sensitivity in these patients.
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Laparoscopic adrenalectomy is considered the "gold standard" in adrenal surgery for benign functioning (and non-functioning) tumors. Laparoscopy meets criteria of miniinvasive surgery with minimal postoperative pain, short hospital stay and an outstanding cosmetic effect, the radicality of the procedure, open surgery and laparoscopy are equally effective. In cooperation with endocrinological department focused on detection of functioning adrenal tumors, the diagnostic and therapeutic procedure seems to be very efficient, so that the primary goal of rapid cure could be achieved. Patients after laparoscopic adrenalectomy mostly do not need chronic antihypertensive medication and only those after bilateral adrenalectomy (Cushing's disease) require life-long low dose hydrocortisone therapy. In pheochromocytomas, total excision of the tumor is considered to be a life-saving procedure, although up to 20% may recur as hereditary or as a part of von Hippel-Lindau's disease.
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AIM OF THE STUDY: To evaluate the efficacy and tolerability of rilmenidine (Tenaxum) in the dose of 1-2 mg in patients with mild to moderate hypertension. GROUP OF PATIENTS AND METHODS: 243 patients (53% men, 47% women, mean age 52 +/- 11 years with mild to moderate essential hypertension were included into the study. Several cardiovascular risk factors for CAD were reported in the investigated group of patients: dyslipidaemia in 54%, obesity in 29%, diabetes mellitus in 14% and smoking in 17% of subjects. 87% of patients were subjects with newly diagnosed untreated or shortly (< 3 months) treated hypertension. In remaining hypertensives the antihypertensive therapy was withdrawn two weeks before the beginning of rilmenidine treatment. The following parameters were studied: BMI, sitting and upright casual blood pressure, heart rate and basal laboratory tests. If necesary, additional therapy with indapamide or perindopril was allowed. RESULTS: Rilmenidine treatment resulted in normalisation of blood pressure (BP) or significant (decrease of SBP/DBP = 20/10 mm Hg) blood pressure decrease in 69%, 22% of subjects, respectively. At the end of 6-month period significant BP decrease was noted: 134 +/- 6/83 +/- 5 mm Hg vs. 161 +/- 12/99 +/- 6 mm Hg (p < 0.001). Marked BP decrease was observed already during first visit after active treatment for 3 weeks. Six months of rilmenidine treatment led to significant heart rate decrease (71/min. +/- 8 vs. 74/min. +/- 9, p < 0.01). No significant laboratory (plasma Na, K, creatinine, urea, glycemia, triglycerides, haematocrit) changes were reported after rilmenidine treatment with the only exception of mild, but significant plasma cholesterol decrease. Rilmenidine had very good acceptability and mild side effects were noted in small percentage of patients. CONCLUSION: Rilmenidine is a centraly acting drug of IInd generation (imidazoline I1 receptors agonist) with potent antihypertensive and mild negative chronotropic effect. Rilmenidine has very good clinical tolerability without negative influence on metabolic parameters.
BACKGROUND: Setback in insulin resistance has been described in patients with essential hypertension. The aim of our study was to verify at the receptor and postreceptor levels the presence of insulin resistance in patients with high or low renin activity. METHODS AND RESULTS: Six patients with the renal artery stenosis (20 to 65 years, average age was 51 +/- 12 years, BMI: 27 +/- 2.0 kg.m2) and six patients with primary hyperaldosteronism (28 to 61 years, average age was 50 +/- 13 years, BMI: 26.9 +/- 3.2 kg.m2) were investigated. Their diagnose was confirmed by laboratory examination, computer tomography, and duplex sonography. Blood pressure was monitored for 24 hours with Spacelab tonometer (SBP: 161 +/- 29 mmHg, DBP: 98 +/- 12 mmHg versus SBP: 168 +/- 21 mmHg, DBP: 103 +/- 9 mmHg; plasma renin activity was 8.1 +/- 5.6 versus 0.3 +/- 0.4 ng.ml-1.h-1, p < 0.001; recumbent plasma aldosterone level was 98 +/- 31 versus 358 +/- 103 pg.ml-1, p < 0.001, normal value till 150 pg/ml, serum potassium was 3.9 +/- 0.4 and 3.5 +/- 0.6 mmol/l). All patients had normal course of the oral glucose tolerance test. Six volunteers of corresponding age and BMI formed the control group. Patients had normal values of the basal morning glycemia (4.9 +/- 0.5 and 5.0 +/- 0.6 versus 4.9 +/- 0.6 mmol/l), basal insulinemia level was 28.8 +/- 12.4 and 21.0 +/- 10.2 versus 15.9 +/- 8.8 mU.l-1 in healthy controls. Insulin effect was tested using isoglycemic hyperinsulinemic clamp method on Biostator with insulin infusion of 1 mU.kg.min-1. Plasma potassium concentration was kept at constant physiological levels using linear infusion pump (in patients with primary hyperaldosteronism after the prior supplementation). In patients with high-renin or low-renin hypertension, the glucose consumption during clamping was lower than that of healthy controls (M, glucose disposal rate: 23.7 +/- 4.8 and 19.5 +/- 3.4 versus 33.0 +/- 5.7 mumol.kg.-1.min-1, p < 0.001), increase of the metabolic glucose clearance (MCRG: 5.1 +/- 1.5 and 3.9 +/- 0.7 versus 7.9 +/- 1.4 ml.kg-1.min-1, p < 0.001) and tissue insulin sensitivity index (M/I: 24.3 +/- 10.1 and 26.4 +/- 8.3 versus 38.4 +/- 10.1 mumol.kg-1.min-1 to mU.l-1 x 100, p < 0.001). CONCLUSIONS: Patients with high-renin and low-renin hypertension have the insulin effectiveness significantly impaired. Such insulin resistance probably does not depend on the renin activity, plasma aldosterone concentration or on serum potassium level. The ethiopathogenesis of the described changes will be the aim of our next study.
The aim of our study was to evaluate the potential differences in blood pressure (BP) profile in subjects with different forms of primary aldosteronism (PA). Simultaneously, we studied the effects of PA treatment on BP curve. We therefore monitored 24-hour ambulatory blood pressure values in 22 subjects with aldosterone-producing adenoma (APA), 22 subjects with idiopathic hyperaldosteronism (IHA) and 33 subjects with essential hypertension (EH) as controls. We found a significantly attenuated nighttime systolic BP decline in the APA group (P=0.02). Patients with IHA had lower nighttime systolic BP values (P=0.01) and also a diastolic BP decline (P=0.02) during the night in comparison with EH. We did not detect any significant differences in BP profile characteristics between APA and IHA. Specific treatment of primary aldosteronism (adrenalectomy, treatment with spironolactone) led to the normalization of the BP curve with a marked BP decline. Our study thus demonstrates a blunted diurnal BP variability in patients with primary aldosteronism the specific treatment of which normalized previously attenuated nocturnal BP fall.
Aldosterone-producing adenoma (aldosteronoma)--the most frequent form of primary hyperaldosteronism (PH)--is considered a specific form of diabetes mellitus (DM). In a previous study we demonstrated insulin resistance in patients with PH. We have therefore undertaken a study to evaluate the incidence of abnormalities of glucose metabolism in patients with PH (36 subjects) compared to control subjects with essential hypertension (EH) (21 patients). The following parameters were measured in all studied subjects: office blood pressure (by mercury sphygmomanometer in the sitting position), body mass index (BMI), plasma potassium, plasma glucose and insulin levels during oral glucose tolerance test (OGTT) (0, 60, 120 min), plasma renin activity and plasma aldosterone. Although patients with PH tended to have higher stimulated plasma glucose levels after 60 and 120 min compared to EH, these differences did not attain statistical significance. Patients with EH tended to have higher insulin levels at each measured interval, but due to a high variability these differences were again not significant. There were no significant differences between PH and EH in the proportion of diabetics (20% vs. 14%) or patients with impaired glucose tolerance (18% vs. 10%). In conclusion, we have found the absence of significant differences in the frequency of diabetes mellitus, impaired glucose tolerance and insulin resistance in patients with EH and PH. Our data thus do not support the idea of primary hyperaldosteronism as a specific type of diabetes mellitus. Furthermore, our results indicate that glucose metabolic characteristics in essential hypertension and primary hyperaldosteronism tend to be similar. The definitive conclusion with respect to the possible causal relationship between DM and PH, however, can be obtained only on larger groups of subjects, in particular after the evaluation of the effect of surgical/pharmacological treatment of primary hyperaldosteronism.
In our study, the circadian blood pressure (BP) rhythm was studied in subjects with asymptomatic and normotensive pheochromocytoma. We have therefore performed 24-hour BP monitoring not only in 6 subjects with asymptomatic pheochromocytoma, but also in 33 patients with symptomatic pheochromocytoma and in 10 normotensive subjects, who served as a control group. Circadian BP rhythm was expressed by assessing a relative night-time BP decline. We found a similar BP rhythm, catecholamine excretion and tumor size in subjects with both forms of pheochromocytoma. Subjects with asymptomatic pheochromocytoma had a significantly lower night-time systolic BP decline (P=0.01) and diastolic BP decline (P=0.006) than normotensive controls. We conclude that the attenuated night-time BP decline in normotensive and asymptomatic subjects with pheochromocytoma might be a possible sign of partial desensitization of the cardiovascular system to catecholamines.
The relationship between arterial hypertension and insulin resistance has long been established. We used primary hyperaldosteronism as a model of the relationship between secondary hypertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemic euglycaemic clamp technique was performed before and at least 6 months following the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rate of glucose (MCR(G)) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium concentrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 +/- 5.9 vs. 51.4 +/-12.2 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyperaldosteronism did not significantly influence insulin action (M/I: 24.5 +/- 7.3 vs. 18.7 +/- 7.6 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.198). Since plasma aldosterone concentrations have been normalised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of impaired insulin action.
Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll AG) have a significantly superior antihypertensive effect compared to equal dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination produces the best dose-response ratio of different dose combinations of these two drugs. Combination therapy has the most pronounced effect on blunting the early morning rise in blood pressure. Thus, verapamil SR/trandolapril combination therapy may be an appropriate treatment option in patients with moderate essential hypertension, particularly in those who have a tendency toward the early morning rise in blood pressure. The adverse effect profile of the fixed combination of verapamil SR/trandolapril includes the typical side effects of its monocompounds. The fixed combination of verapamil SR/trandolapril is also effective and safe in the treatment of hypertension in the elderly. The fixed low-dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable treatment option for patients with moderate essential hypertension and Type 2 diabetes mellitus, because it improves parameters of carbohydrate metabolism and uricaemia and does not alter the lipid profile. The insulin-sensitising effect of angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical risk of hypoglycaemia is completely neutralised in the combination with verapamil SR. Comparative studies have shown that the low-dose combination of verapamil SR/trandolapril may be a suitable alternative to combinations containing a thiazide diuretic or a beta-blocking agent for the long-term management of hypertensive patients for whom combination therapy is indicated. The combination of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces proteinuria to a greater extent than either agent alone. A combination of an ACE inhibitor and a calcium channel blocker may provide additional benefit in inducing the regression of left ventricular hypertrophy. Combination therapy leads to a significant increase in left ventricular ejection fraction, improvement of wall motion index and increases exercise duration time in patients with coronary heart disease and left heart failure. It also improves the ratio of exercise to rest rate-pressure product and decreases the number of angina attacks. These findings support the hypothesis that the combination of verapamil and trandolapril might be useful in patients with attenuated left ventricular function and angina pectoris. Thus, Tarka is an effective and well-tolerated antihypertensive agent with a good safety profile and positive metabolic effects.
The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, micromol/kg/min) (18.7+/-6 vs. 29.3+/-4), decreased tissue insulin sensitivity index (M/I, micromol/kg/min per mU/l x100) (23.7+/-9.8 vs. 37.5+/-11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8+/-1.5 vs. 7.0+/-1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension.
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