Biomedical subjects
M Middeke
Publications and source records attributed to M Middeke.
[Antihypertensive therapy is successful as hardly any other]. Interview by Dr. rer. nat. S. Kressenstein].
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[Choice of drug and indications are deciding factors].
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[Chronopathology: from hypertension in general practice to manifest hypertension].
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[Long-term ambulatory blood pressure measurement].
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The effects of antihypertensive combination therapy on lipid and glucose metabolism: hydrochlorothiazide plus sotalol vs. hydrochlorothiazide plus captopril.
Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.
Drug effects on BP rhythm in secondary hypertension.
Antihypertensive drug treatment is necessary in most patients with secondary hypertension. Only a small percentage of cases can be cured by operation or angioplasty. Because blunted or reversed nocturnal blood pressure fall is frequently found in patients with secondary hypertension, time of day of drug application is of special interest in these patients. The time structure of blood pressure over 24 hours or even longer can be obtained using ambulatory blood pressure monitoring. This is a prerequisite for individualization of antihypertensive therapy and for achievement of optimal drug effects. Chronopharmacologic aspects are playing an increasingly important role in the treatment of secondary hypertension, especially in renal forms. Recently, the first studies in this field were completed, isradipine and doxazosin in chronic renal failure and trandolapril in hypertensive diabetic subjects. Results show that restoration of normal nocturnal blood pressure fall and constitution of normal circadian rhythm are possible in patients with mild to moderate renal hypertension after evening dosing as compared to morning dosing with monotherapy. In more severe hypertension combination therapy including multiple dosing with special attention to evening application is necessary. In conclusion, optimal drug effects and individualization of antihypertensive treatment in patients with secondary forms of hypertension can be achieved using a stepped care program including chronopharmacologic regimens to restore normal circadian rhythm on a normotensive level.
Office hypertension: abnormal blood pressure regulation and increased sympathetic activity compared with normotension.
BACKGROUND: The percentage of patients with office or white-coat hypertension has been reported in international studies to be 20-30% of the hypertensive population. These patients can be identified and distinguished from patients with established hypertension by ambulatory blood pressure monitoring (ABPM) or self-measurement. There is still no satisfactory explanation for the phenomenon of 'office hypertension' and there are no data available to show how the blood pressure behaviour of office hypertensives differs from that of normotensive subjects away from the physician's office or clinic environment. OBJECTIVE: To investigate the blood pressure behaviour of patients with office hypertension away from the clinical setting over a 24 h period and to compare it with that of normotensive subjects. DESIGN AND METHODS: The blood pressure and heart rate of 36 patients with office hyhpertension and 33 normotensive subjects matched for age and sex were measured in a hypertension outpatient clinic and over 24 h using ABPM. The ambulatory data were subjected both to conventional and to modern rhythm analysis. Urinary catecholamine excretion was measured as a marker of sympathetic activity. RESULTS: In the clinic, the patients with office hypertension had significantly (P < 0.01) higher blood pressure values (146/97 mmHg) than did the normotensive controls (128/81 mmHg). The conventional analysis as well as the rhythm analysis of the ABPM data revealed no difference between the two groups with respect to the 24 h, daytime or night-time mean values and SD. However, the rhythm analysis showed a higher maximum and a lower minimum value for systolic and diastolic blood pressures in the patients with office hypertension, resulting in a greater amplitude both of systolic and of diastolic blood pressure due to a significantly (P < 0.005 and P < 0.05) higher maximum minus minimum value (38/32 mmHg) compared with those of normotensive controls (29/28 mmHg). The early morning rise in systolic and diastolic blood pressures was significantly (P < 0.008 and P < 0.03) greater in the patients with office hypertension (11/9 versus 7/7 mmHg) and intersected the curve of the normotensive controls at approximately 0600 h. No significant differences in heart rate at any time were observed between the groups. The urinary excretion of noradrenaline and dopamine was significantly (P < 0.01 and P < 0.05) increased during daytime for the office hypertensives. CONCLUSION: Patients with office hypertension, who by definition do not yet have established hypertension, already exhibit abnormal regulation both of systolic and of diastolic blood pressure during the morning period and daytime, with a significantly greater early morning rise compared with normotensive subjects and a greater blood pressure amplitude (amplitude hypertension) due to lower blood pressure during night-time and higher blood pressure during the day with increased sympathetic activation. Office hypertension seems to be the earliest manifestation of hypertension.
Effect of nocturnal blood pressure measurement on sleep and blood pressure during sleep.
Nocturnal hypertension is of diagnostic interest and has important prognostic and therapeutic implications. Nighttime blood pressure can easily be measured using ambulatory blood pressure monitoring (ABPM). However, during nocturnal ambulatory blood pressure measurement pump noise, tactile stimuli and pressure produced by cuff inflation may alter the quality of sleep and subsequently influence the physiological fall of night time blood pressure. Eight studies were performed to determine whether non-invasive automated blood pressure monitoring during day and/or night provokes alert reaction, arousal, sleep disturbances and changes in blood pressure and/or heart rate. From these studies it can be concluded: 1) Nighttime blood pressure can be evaluated properly using ABPM. 2) Nocturnal blood pressure is not overestimated by ABPM. 3) ABPM does not induce an alarm reaction and a blood pressure rise when monitored with a silently operating recorder. 4) Sleep is often disturbed by blood pressure measurement without provoking a blood pressure increase. 5) In older patients blood pressure measurement and age-related alterations in sleep quality may influence each other. A patient's protocol has to be carried out and sleep quality should be recorded to provide a proper interpretation of nocturnal blood pressure behavior. ABPM is an important and valuable method to record nocturnal blood pressure for diagnostic and therapeutic purposes.
Double-blind comparison of antihypertensive treatment with ramipril and piretanide, given alone or in combination.
In a double-blind, randomized, multicenter trial, we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)
Nocturnal blood pressure in normotensive subjects and those with white coat, primary, and secondary hypertension.
OBJECTIVE: To compare the mean nocturnal blood pressure of patients with various forms of renal and endocrine hypertension with that in patients with primary and white coat hypertension, and normal blood pressure. DESIGN: Ambulatory monitoring of blood pressure over 24 hours in a prospective study. SETTING: Two German centres for outpatients with hypertension and kidney diseases. SUBJECTS: 176 normotensive subjects, 490 patients with primary hypertension including mild and severe forms, 42 with white coat hypertension, 208 patients with renal and renovascular hypertension, 43 with hypertension and endocrine disorders, and three with coarctation of the aorta. MAIN OUTCOME MEASURES: Fall in nocturnal blood pressure. RESULTS: Blood pressure in normotensive subjects fell by a mean of 14 mm Hg (11%) systolic and 13 mm Hg (17%) diastolic overnight (2200 to 0600). The falls in patients with primary and white coat hypertension were not significantly different. In all patients with renal and renovascular hypertension, however, the fall was significantly reduced (range of fall from 3/3 mm Hg to 7/9 mm Hg). In patients with hypertension and endocrine disorders the pattern of night time blood pressure was not uniform: patients with hyperthyroidism, primary hyperaldosteronism, and Cushing's syndrome had significantly smaller reductions in blood pressure (6/8, 4/7, 3/6 mm Hg, respectively). In patients with phaeochromocytoma the mean night time blood pressure increased by 4/2 mm Hg. In patients with hypertension, primary hyperparathyroidism, and unoperated coarctation of the aorta the falls in blood pressure were normal. CONCLUSIONS: In normotensive subjects and those with primary hypertension there is usually a reduction in blood pressure at night. In all renal forms of secondary hypertension and in most endocrine forms the reduction in blood pressure is only a third to a half of normal. Patients with primary hyperparathyroidism and unoperated coarctation of the aorta show a normal reduction.
Effects of perindopril on serum lipids in hypertensive patients with hyperlipidemia.
The effect of the angiotensin-converting enzyme (ACE)-inhibitor perindopril on serum lipids and apolipoprotein concentrations were assessed in a multicenter, randomized, double-blind, placebo-controlled study in 51 hyperlipidemic patients treated for mild hypertension. Perindopril was given as a single morning dose (4 mg) for 6 weeks. During the treatment period, blood pressure (BP) was significantly (p < 0.001) reduced from 159/99 to 148/90 mm Hg by verum treatment and from 158/101 to 151/95 mm Hg (NS) by placebo treatment. Neither total cholesterol and triglycerides nor high-density-lipoprotein and apolipoprotein AI and B levels were significantly altered by drug treatment as compared with placebo. Although perindopril had good antihypertensive effect in patients with mild hypertension and hyperlipidemia, it had no adverse effects on lipid metabolism in these patients. Therefore, perindopril is recommended for antihypertensive treatment, especially in hypertensive patients with concomitant hyperlipidemia.
Regulation of the beta-adrenoceptor-cAMP-system during dynamic exercise in patients with primary hypertension after acute beta-blockade.
Beta-adrenoceptors on lymphocytes are acutely increased after dynamic exercise in normotensive subjects, but not in hypertensives. It was thus of interest to evaluate the acute regulation of the lymphocyte beta-adrenoceptor-adenylate-cyclase-cAMP-system (BAAS) in patients with primary hypertension during dynamic stress after acute beta-blockade. Density and affinity of beta 2-adrenoceptors, and intracellular cAMP concentrations (baseline and isoprenaline stimulated values) were measured on the peripheral mononuclear cells in 8 male patients with primary hypertension before and immediately after dynamic exercise on a bicycle (50-200 W) at baseline and after acute beta-blockade (2 h following 100 mg atenolol). Dynamic exercise causes no significant changes in receptor density and affinity, nor in basal cAMP values. After acute beta-blockade the dynamic stress-induced rise in mean arterial blood pressure was significantly (p < 0.01) reduced from 33 to 24 mmHg, and beta-adrenoceptor density significantly (p < 0.05) increased from 1320 to 2102 molecules/cell, whereas affinity remained unchanged. Baseline and stimulated cAMP concentrations increased significantly (p < 0.05) from 5.3 to 7.0 and from 2.1 to 3.5 pmol/10(6) cells, respectively. These findings suggest that in primary hypertension the regulation of the beta 2-adrenoceptor-adenylate-cyclase-cAMP-system is impaired on exercise and can be normalised by acute beta-blockade. Since atenolol predominantly blocks beta 1-adrenoceptors, the observed normalisation of the lymphocyte BAAS may reflect only an unspecific effect of antihypertensive therapy per se.
[Ambulatory long-term blood pressure measurement].
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Deposits of paraprotein in small vessels as a cause of skin ulcers in Waldenström's macroglobulinemia.
A 71-year-old man presented with epistaxis and large ulcers on arms and legs. A monoclonal IgM-kappa gammopathy and high levels of cryoglobulins were found. Histology of the affected skin showed deposits of paraprotein in the small vessels, causing luminal obstruction. This in turn caused ischemic skin lesions, which were successfully treated with cortisone (fluocortolone 100 mg/day every second day) and cyclophosphamide (100 mg/day).
Erythromelalgia unmasked during norephedrine therapy: a case report.
A thirty-eight-year-old woman presented with typical signs of erythromelalgia: burning, redness, and warm congestion of the extremities. These symptoms occurred after cessation of obesity drug therapy with norephedrine (250 mg/day) continuously over six years. The condition was refractory to treatment with acetylsalicylic acid. It is suggested that erythromelalgia in this case was unmasked by the vasoactive properties of norephedrine. Continuous drug therapy with norephedrine may have led to adaptive adrenergic subsensitivity of vascular smooth muscles. The pathomechanism of primary erythromelalgia is still unknown. Their observations suggest that an enhanced vasodilatation due to an abnormal adrenergic sensitivity may play an important role in the pathogenesis of primary erythromelalgia.
Treatment of hypertension in the elderly.
Since 1967, results from well controlled long term studies have provided convincing evidence of the benefit of antihypertensive therapy in middle-aged patients. However, many physicians have hesitated to apply these findings to patients over 60 years of age. Recently, the results of several prospective randomised long term trials investigating the treatment of hypertension in elderly patients have been published. An analysis of the results of 5 major trials shows that antihypertensive treatment reduces overall mortality by 20%, cardiovascular mortality by 33%, the incidence of fatal and nonfatal cerebrovascular events by 40%, and complications as a result of coronary heart disease (i.e. fatal and nonfatal myocardial infarction and sudden cardiac death) by 15%. On the basis of trials undertaken in elderly patients with either high systolic and diastolic blood pressure or isolated systolic hypertension, antihypertensive therapy was more beneficial, in absolute terms, in elderly patients than in middle-aged patients with mild hypertension. Treatment was withdrawn as a result of adverse effects in about 2% of middle-aged and elderly hypertensive patients per year. Therefore, it is clear that elderly hypertensive patients should be treated.
[Ultrasound of incidental tumors of the adrenal gland and endocrine hypertension].
We report on a retrospective analysis of 1,500 hypertensive patients who underwent a sonographic examination of the abdomen. 8 'incidentalomas' of the adrenal gland (0.6%) were thereby found. Endocrinological analysis showed that only 1 of the incidentalomas was active (pheochromocytoma). The other tumors had no endocrine activity. On the other side, 7 patients without any sonographic abnormality had hyperaldosteronism, 1 patient suffered from an adrenomedullary hyperplasia. Those patients had been thought to have endocrine hypertension from clinical suspicion. We conclude that a thorough sonographic examination of the adrenal area is an important part of the diagnostic workup in hypertensive patients, although most of the incidentally discovered tumors are endocrinologically inactive. Adrenocortical and adrenomedullary hyperplasias and adrenocortical adenomas are detected clinically while they are still not visible by ultrasound.