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Biomedical subjects

H Holzgreve

Publications and source records attributed to H Holzgreve.

At least 19 recordsLinked to original sources
PubMed1992

Where now the diuretics in antihypertensive treatment?

The ultimate aim in treating hypertension is to reduce cardiovascular mortality and morbidity, especially from coronary heart disease and strokes. In several long-term trials this goal has been achieved with antihypertensive therapy in the form of diuretics. Subsequently, diuretics and betablockers, compared as single agents or with the addition of other agents, did not appear to affect overall cardiovascular morbidity and mortality differentially. Therefore, recommended first-line therapy for hypertension was initially diuretics, followed later by beta blockers as alternatives. Recently, calcium antagonists and ACE inhibitors have been accepted as equally valuable in the treatment of hypertension because they similarly lower blood pressure, lack any adverse metabolic effects and may be more beneficial than diuretics or beta-blockers on the long-term prognosis of hypertensive patients. Such recommendations are, however, highly speculative and are not supported by trials using cardiovascular mortality and morbidity as endpoints. In order to solve the conflict between proven facts and sound theory, long-term trials comparing older (mainly diuretics) and newer (calcium antagonists, ACE inhibitors, alpha-adrenoceptor blockers) antihypertensive agents are needed. Until such trials are completed, the debate surrounding first-line drugs for antihypertensive treatment will not be resolved.

Adrenergic beta-Antagonists↗
PubMed1992

Risk-benefit aspects of antihypertensive drugs.

Several long term trials using traditional antihypertensive therapy with diuretics and beta-blockers have shown that antihypertensive therapy reduces the overall risk of cardiovascular complications. However, even after several years of therapy the cardiovascular risk in hypertensive patients cannot be lowered to that in the normotensive population. Antihypertensive therapy can reduce the incidence of cerebrovascular complications in patients with hypertension by about 65%. However, the effect of such therapy in preventing coronary events has been disappointing, as these events are 3 to 4 times more common than cerebrovascular complications in hypertensive patients. It is now apparent that adverse pharmacological effects of diuretics and beta-blockers on lipid metabolism persist for many years. Thus, treatment with these agents constitutes a new risk factor for coronary heart disease and may, at least in part, explain the failure of traditional antihypertensive therapy to reduce the incidence of myocardial infarction and sudden death as effectively as that of cerebrovascular accidents. On the other hand, titration of these antihypertensive agents to the lowest possible dose in order to avoid metabolic alterations and subjective adverse effects has frequently resulted in the administration of subtherapeutic doses, particularly for hydrochlorothiazide. Until comparative long term clinical trials with older and newer antihypertensive agents and morbidity and mortality as end-points are completed, the debate on first-line drugs for antihypertensive treatment will not be satisfactorily resolved.

Antihypertensive Agents↗
PubMed1991

Circadian blood pressure rhythm in primary and secondary hypertension.

Circadian blood pressure variability was recorded in patients with primary hypertension and with different forms of secondary hypertension using ambulatory 24-h blood pressure measurement. A group of 20 patients with different forms of secondary hypertension was compared with a matched group of patients with primary hypertension. Although the mean 24-h blood pressure was not different between the two groups, the patients with secondary hypertension had significantly higher systolic blood pressure during sleep and higher systolic and diastolic blood pressure in the early morning, compared with the primary hypertension group. This nocturnal blood pressure fall was then investigated in various groups of patients with different forms of secondary hypertension and compared with normotensives and patients with primary hypertension. Patients with mild primary hypertension (n = 152) and with severe primary hypertension (n = 30) had the same blood pressure fall (14-16 mm Hg systolic and diastolic) during the night (23:00-05:00 h) as normotensives (n = 20). However, in patients with renoparenchymal hypertension (n = 29), renovascular hypertensions (n = 20), hyperaldosteronism (n = 6), and hyperthyroidism (n = 14), the nocturnal blood pressure fall was significantly (p less than 0.01) reduced. One patient with coarctation of the aorta and nine patients with primary hyperparathyroidism and elevated blood pressure had a normal circadian blood pressure profile with a normal nocturnal blood pressure fall. The heart rate decrease during the night was equal in all patient groups. Ambulatory blood pressure measurement allows blood pressure recording under everyday conditions, including nighttime. In primary hypertension the blood pressure variability exhibits the same circadian variation as in normotension, showing a marked nocturnal fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Chronopharmacology of captopril plus hydrochlorothiazide in hypertension: morning versus evening dosing.

Blood pressure follows a strong circadian rhythm in normotensive people and in patients with primary hypertension. This may have several implications for antihypertensive therapy, including the time of dosing. For this reason we studied the influence of different dosing times on the antihypertensive effect over 24 h using ambulatory blood pressure monitoring (ABPM). We studied 13 male patients with moderate hypertension with controlled blood pressure over 12 months under a fixed combination of captopril and hydrochlorothiazide. The dosage of the combination therapy was then halved and given as one evening and then as one morning dose, each for 3 weeks. The combination therapy given twice daily showed a good 24-h antihypertensive effect after 12 months of treatment. During the following 6 weeks the mean 24-h blood pressure did not increase under half dosage, irrespective of whether under evening or morning dosing. However, mean daytime values (systolic and diastolic) of ABPM were significantly higher with evening dosing when compared both with full dosage and with half dosage given in the morning. The mean arterial blood pressure over 24 h showed the same differences as systolic and diastolic blood pressure, whereas heart rate was not significantly different between the three therapeutic regimens. ABPM seems to be an ideal method for chronopharmacological investigations under everyday conditions. Our study demonstrated significant differences in daytime blood pressure but not in 24-h blood pressure between morning and evening dosing of a fixed antihypertensive combination therapy.

Blood Pressure↗
PubMed1991

Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group.

The efficacy and tolerability of hydrochlorothiazide, sustained-release verapamil, and their combination was compared in patients with mild to moderate hypertension. The design was a multicenter, randomized, double-blind clinical trial with a single-blind placebo baseline period of 2 weeks. Three hundred sixty-nine patients with a diastolic blood pressure of 95-120 mm Hg were included. Treatment consisted of 12.5 mg of hydrochlorothiazide once daily, then 25 mg once daily, and finally 25 mg twice daily; the other group received verapamil at a dose of 120 mg once daily, then 240 mg once daily, and finally 240 mg twice daily. Patients not achieving target blood pressure (less than 90 mm Hg diastolic) were given the combination of hydrochlorothiazide and verapamil, that is, 25 and 240 mg once daily and twice daily. During all time points during the study patients receiving verapamil achieved target blood pressure more often than patients receiving hydrochlorothiazide (after 8 weeks, 57.7 and 42.7%; after 24 weeks, 46.8 and 26.4%; and after 48 weeks, 44.8 and 24.7%, respectively). Adding verapamil to hydrochlorothiazide was more effective in lowering blood pressure than adding hydrochlorothiazide to verapamil. The number of treatment withdrawals was essentially the same with the two drugs. Therefore, in the doses currently used in antihypertensive treatment, verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension.

Adult↗
PubMed1991

[Value of ambulatory 24-hour blood pressure monitoring in diagnosis of mild hypertension].

Ambulatory blood-pressure monitoring (ABPM) is the best method to identify causal blood-pressure increases, and for differentiating between white-coat (office) blood pressure and sustained hypertension. This differentiation is necessary because 20% of patients with mild hypertension (90-104 mmHg diastolic, without end-organ damage) have white-coat hypertension. Thus, using conventional blood-pressure measurements (repeated measurements on at least two different occasions) for diagnosing mild hypertension (85% of all hypertensives!) many persons will be overtreated. The results of intervention in mild hypertension will improve through a better identification of patients at risk. ABPM correlates best with end-organ damage. The introduction of ABPM for diagnosing mild hypertension seems to be the best way to differentiate between white-coat hypertension without increased cardiovascular risk and sustained hypertension with increased cardiovascular risk. This procedure allows a better treatment of patients at risk and it avoids overtreatment. The ABPM diastolic blood-pressure range for mild hypertension is 85-92 mmHg (mean values during the active phase).

Antihypertensive Agents↗
PubMed1990

Systemic malignant lymphoma presenting as bilateral exudative retinal detachment.

A 52-year-old male patient presented with a sudden painful loss of vision in both eyes. Ophthalmological examination revealed bilateral uveitis and marked bilateral nonrhegmatogenous retinal detachment near the optic disk. Systemic workup demonstrated IgM paraproteinemia. Abdominal ultrasound and computed tomographic studies revealed enlarged adrenal glands and irregular masses in the right hepatic lobe. Immune electrophoresis and multiple biopsy specimens established the diagnosis of systemic polymorphous immunocytoma. Polychemotherapy of this B-cell-derived type of non-Hodgkin's lymphoma led to a rapid remission and fast reduction of serous retinal detachment. We believe this is the first case of bilateral exudative retinal detachment as the initial ocular manifestation of systemic malignant B-cell lymphoma.

Adrenal Gland Neoplasms↗
PubMed1990

[Diuretic-induced edema].

The diagnosis of "diuretic-induced oedema" was made in 17 women (mean age 42.4 [23-60] years) who had developed generalized oedema after stopping their (chronic) intake of diuretics. Five patients were between 11 and 32% overweight, five of them were unusually old. A further four patients had severe concomitant diseases, such as primary lymphoedema, mitral valve defect and lupus erythematosus. In 10 of the 17 discontinuation was successful: the initial weight gain averaged 3.9 (1.5-7.5) kg. The maximal weight-gain, in a woman in the course of weaning her of the diuretic, was reversed within 20 days. Diuretic withdrawal after more than 20 years in a woman with mitral valve disease caused heart failure. Diuretic abuse caused prerenal failure in one women, but renal function became normal again after stopping of the diuretic and rehydration.

Adult↗
PubMed1990

Concomitant considerations in long-term antihypertensive treatment.

Even with antihypertensive therapy, the risks in hypertensive patients, especially the incidence of coronary events, cannot be lowered to that of the normotensive population. Therefore, the metabolic effects of long-term therapy on lipid metabolism and the efficacy of antihypertensive drugs to lower blood pressure were studied as possible explanations for this partial therapeutic failure. Hypertensive patients who participated in a long-term trial provided a unique opportunity to observe the effects of long-term treatment and of then discontinuing antihypertensive therapy. During treatment, increases in total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides following hydrochlorothiazide, and increases of LDL-C and triglycerides and a decrease of high-density lipoprotein cholesterol (HDL-C) following atenolol were observed up to 42 months. After 5.2 +/- 1.4 years of randomised antihypertensive treatment, cessation of hydrochlorothiazide led to a decrease of total cholesterol from 6.40 to 5.98 mmol/l and of LDL-C from 4.33 to 3.89 mmol/l. After discontinuation of atenolol, LDL-C decreased from 4.20 to 3.89 mmol/l and triglycerides from 2.21 to 1.91 mmol/l, whereas HDL-C increased from 0.96 to 1.17 mmol/l (all differences significant). Thus the adverse effects of both agents persisted for more than five years and were reversible after medication was discontinued. In recent years titration to the lowest possible dose of antihypertensive agents has been suggested to avoid adverse metabolic alterations and subjective side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE: To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial of 48 weeks' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING: Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS: 369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS: Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE: Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS: After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS: In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.

Adult↗
PubMed1989

[Ambulatory indirect long-term blood pressure measurement in primary and secondary hypertension].

Ambulatory 24 hour blood pressure measurements were performed in 21 patients with various forms of secondary hypertension and were compared with the blood pressure profile of a matched group of patients with primary hypertension. Patients with renovascular (n = 8) and renoparechymal hypertension (n = 8), and with primary hyperaldosteronism (n = 4) showed no significant fall in systolic blood pressure during the sleeping period (00-03 a.m.) and in systolic and diastolic blood pressure in the early morning (06 a.m.) as compared with essential hypertensives. However, in a single case of hypertension due to coarctation of the aorta the 24 hour blood pressure profile is not different from essential hypertension. Thus, ambulatory 24 hour blood pressure recording is a good method for screening secondary forms of hypertension.

Ambulatory Care↗
PubMed1988

Acute regulation of lymphocyte beta-adrenoceptor activity in pheochromocytoma.

The effect of an acute endogeneous catecholamine stimulation on the regulation of lymphocyte beta-adrenoceptor activity was studied in a patient with pheochromocytoma. Baseline blood pressure, heart rate, adrenoceptor density, and plasma concentrations of epinephrine, norepinephrine, and cyclic adenosine monophosphate were normal. Excessive spontaneous increases of catecholamine concentrations were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of beta-adrenoceptors. Plasma concentrations of cyclic adenosine monophosphate paralleled the increase in receptor density and blood pressure. After normalization of catecholamine plasma levels, blood pressure, and beta-adrenoceptor density returned to baseline values. This observation adds support to the theory that an acute catecholamine stimulation leads to an acute sensitization of the beta-adrenoceptor-adenylatecyclase-cyclic-adenosine-monophosphate system leading to blood pressure elevation.

Adrenal Gland Neoplasms↗
PubMed1987

Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.

Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.

Adrenergic beta-Antagonists↗
PubMed1985

Adrenergic hyposensitivity during long-term diuretic therapy--a possible explanation for the antihypertensive effect of diuretics?

The long-term effect of hydrochlorothiazide on beta 2-adrenoceptor density on mononuclear cells was investigated in 10 male patients with essential hypertension. There was a 40% reduction in beta 2-adrenoceptor density but no change in receptor affinity. This down-regulation of beta 2-adrenoceptors may explain the observed adrenergic hyposensitivity after long-term diuretic therapy. If lymphocytic beta 2-adrenoceptors represent presynaptic beta-adrenoceptors, a down-regulation of presynaptic beta 2-receptors may occur too, and result in a decrease of adrenergic transmitter release. Under this assumption long-term diuretic treatment causes its antihypertensive effect by modulating adrenergic sensitivity at the receptor level on the presynaptic side leading to an attenuated response to pressor hormones on the postsynaptic vascular side.

Adult↗