[Antihypertensives always evenings-absolutely not or sensible?] / Antihypertensiva immer abends ­ bloß nicht oder sinnvoll?

The Spanish Hygia study has led to considerable irritation due to the general recommendation to prescribe antihypertensives preferably to be taken in the evening, especially since the lay press as well as medical media made enthusiastic comments. The discussion about the optimal time to take antihypertensive drugs shows once again how dangerous the uncritical handling of study data can be. No possible risks were pointed out. The Hygia study compared 19,084 patients with morning and evening intake of antihypertensive drugs under the control of a 48­h blood pressure measurement (!). There was a significantly better reduction in blood pressure and the rate of cardiovascular and cerebrovascular events with evening intake. The data are scientifically valuable; however, the conclusions are incomprehensible based on the data, contradict many other studies and are dangerous for certain patient groups. There are also methodological shortcomings. Therefore, a general evening intake is not justified and nonsensical due to the diverse, individually very different pathophysiological findings of the nocturnal blood pressure behavior. Basically, the outpatient 24­h blood pressure measurement (ABPM) enables a better assessment of the individual cardiovascular and cerebrovascular risks and prevents an incorrect assessment of the blood pressure and thus unnecessary or sufficient treatment. Instead of a general recommendation, the ABPM offers the option of an individually tailored treatment. Taking antihypertensive drugs in the evening should always be preceded by an ABDM in the case of prognostically unfavorable nocturnal hypertension in order to avoid the risk of nocturnal ischemic risks due to excessive drops in blood pressure.

[Antihypertensive drug therapy : Where do we stand?]. / Medikamentöse antihypertensive Therapie : Wo stehen wir?

Antihypertensive drug therapy is one of the most successful medical measures ever, at all levels. The treatment situation in Germany has clearly improved in recent years. Nowadays, a wide range of very effective and well-tolerated hypertensive substances is available. Combination therapy has a long and successful tradition in hypertensive treatment, especially with suitable fixed combinations. Furthermore, the administration of fixed combinations is very beneficial to therapy adherence because it is essentially dependent on the number of drugs to be taken. The value of beta blockers and the double blockade of the renin-angiotensin-aldosterone system are under discussion and the interpretation of corresponding studies must be conducted very carefully. The hypertensive effect of a substance cannot be comprehensively assessed without taking the time of day, the time point of measurement and the time point of intake into consideration. This is particularly important with respect to the effect over 24 h. Optimal antihypertensive therapy must also take into consideration the individual blood pressure rhythm with respect to the dose and dosing intervals. The importance of the central (aortic) blood pressure as target blood pressure will increase.

[Telemedicine in chronic heart failure: patient selection is a prerequisite for success]. / Telemedizin bei chronischer Herzinsuffizienz: Patientenselektion ist entscheidend für den Erfolg.

The two biggest studies worldwide on telemedicine in chronic heart failure were conducted in Germany. The study design, patient selection and equipment as well as the mode of therapeutic intervention varied between the two studies as much as their outcomes. A comparison of the two studies allows conclusions to be drawn as regards achieving effective telemedical intervention in chronic heart failure. Patient age, medication and degree of heart failure and the telemedical program itself are decisive factors in attaining a successful approach. It is best to induct patients into the program after hospitalisation for decompensated heart failure, especially in cases where the maximum drug therapy could not be administered.

[Salt consumption and cardiovascular risk : a plea for salt reduction]. / Salzkonsum und kardiovaskuläres Risiko : Plädoyer für eine Salzreduktion.

High salt intake over long term is associated with increased incidence of arterial, predominantly systolic, hypertension and increased risk of cardiovascular diseases, e.g., stroke, heart failure, and renal insufficiency. High salt consumption is a vascular risk factor generating aortic stiffness and decreased vascular compliance leading to central blood pressure augmentation, higher cardiac load, and diminished diastolic perfusion. The development of heart failure can be a consequence of this sequelae. Randomized trials show a reduction in blood pressure with lower sodium intake. In long-term clinical trials, a reduction in cardiovascular morbidity and mortality has been demonstrated. Recommendations should emphasize the simultaneous reduction in sodium intake and increase in potassium intake.

Current practice in nutrition after allogeneic hematopoietic stem cell transplantation - Results from a survey among hematopoietic stem cell transplant centers.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period. METHODS: To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018. RESULTS: All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18). CONCLUSION: The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT.

Prevalence of hypertension-attributed symptoms in routine clinical practice: a general practitioners-based study.

The objective of the present study was to determine the prevalence of symptoms generally attributed to hypertension and the relationship between symptoms and blood pressure categories. Routine office blood pressure measurement in the morning was obtained and morning symptoms were reported using a standardized questionnaire in a multicenter study from general practitioners in Germany. Dizziness and headaches were significantly (P<0.001) more prevalent in 2154 untreated hypertensives (19.6 and 17.0%) as compared with 1399 normotensives (13.6 and 7.4%), whereas tiredness was less in hypertensives (12.0 vs 17.0%, P<0.01). In untreated and in 52 469 treated hypertensives, the overall prevalence of symptoms increased constantly with blood pressure levels from 26.1% in untreated male patients with mild hypertension to 54.3% of female patients with severe treated hypertension, with a higher prevalence in women (+7% vs men) and in patients with concomitant diseases (+13% vs patients without concomitant diseases). The prevalence of symptoms in older patients with untreated isolated systolic hypertension was not different from younger normotensives. There was a tight positive correlation between systolic and diastolic blood pressure and dizziness (R=0.73 and 0.76) as well as headaches (R=0.83 and 0.90) for all blood pressure levels in all patient groups. Typical hypertension-attributed symptoms like dizziness and headaches are more prevalent in hypertensives and they are closely related to blood pressure levels in untreated and treated hypertensives. Morning symptoms in hypertensives may suggest that there is inadequate control of blood pressure. More attention should be paid to perceived symptoms in hypertensives.

The influence of sex, age, blood pressure and physical stress on beta 2-adrenoceptor density of mononuclear cells.

The influence of sex, age, blood pressure and physical stress on beta 2-adrenoceptor density on intact mononuclear cells was investigated in normotensives and in patients with essential hypertension using (+/-) 125-iodocyanopindolol as radio-ligand. The intra-individual receptor status under basal conditions at rest was fairly constant. The mean individual deviation of beta 2-adrenoceptor density was 11% after a time period of 3 +/- 1.9 months. The receptor number increased with age: there was a positive correlation (r = 0.59) between age and beta 2-adrenoceptor density. No significant difference existed between men and women matched for age and mean arterial blood pressure (548 +/- 179 versus 481 +/- 246 maximal binding sites per cell). A highly significant positive correlation (r = 0.73) existed between the mean arterial blood pressure and the beta 2-adrenoceptor density over a wide range of normal and increased blood pressure. A factorial analysis revealed a significant correlation between mean arterial pressure and beta 2-adrenoceptor density, but not between age or sex and beta 2-adrenoceptor density. Physical stress led within 15 min to a significant increase in beta 2-adrenoceptors followed by a fall to or even below the starting values after 15 to 30 min rest. It is concluded that beta 2-adrenoceptor density on intact mononuclear cells correlates significantly with mean arterial blood pressure and with age. However, factorial analysis revealed a significant positive correlation only between mean arterial blood pressure and the receptor number but not between age and the receptor number. Sex has no significant influence on the receptor density.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

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)

Comparison of the efficacy and safety of losartan (50-100 mg) with the T-type calcium channel blocker mibefradil (50-100 mg) in mild to moderate hypertension.

The objective of this study was to compare the antihypertensive efficacy and safety of losartan and mibefradil. 324 outpatients (57 +/- 9.2 years) with mild to moderate hypertension were randomly allocated in a double-blind fashion to receive 50 mg of losartan or mibefradil once daily p.o. for 6 weeks after 2 weeks of placebo run-in. Titration was then forced to 100 mg of losartan or mibefradil for an additional 6 weeks. Patients were assessed at baseline, 6 and 12 weeks. The primary efficacy variable was change in predose sitting diastolic (SDBP) and systolic (SSBP) blood pressure at 12 weeks. Secondary variables included change in mean 24-hour ambulatory blood pressure and comparison of safety and tolerability. Both treatments lowered SSBP and SDBP at 6 and 12 weeks (week 6: mibefradil -14/-9 mm Hg; losartan -12/-7 mm Hg) (P <0.001). The primary objective, a difference between treatments in reduction of SSBP and SDBP at week 12 could be demonstrated (mibefradil -22/-16 mm Hg; losartan -16/-10 mm Hg) (P=0.003 and P=0.001, respectively). Twenty-four-hour SBP and 24-hour DBP were reduced (P<0.001) within each treatment group at weeks 6 and 12. The secondary objective, a difference between treatments in reduction of 24-hour blood pressure at week 12 could be demonstrated (P<0.001). Twenty-four-hour heart rate was lowered in the mibefradil group at weeks 6 and 12 (P < 0.001). Responder rates at 6 and 12 weeks were 56.2% and 78.5% for mibefradil versus 56.1% and 55.3% for losartan (P = 0.001). Both treatments were equally well tolerated. This study demonstrates that 50 mg losartan is comparably effective to 50 mg mibefradil in the treatment of mild to moderate hypertension with 100 mg mibefradil being more potent than losartan.

Long time incubation of monocytic U 937 cells with LDL increases specific paf-acether binding and the cellular acetylhydrolase activity.

Besides the well established role of low density lipoproteins (LDL), the phospholipid PAF-acether (paf) seems to be involved in atherogenesis. The effect of LDL (10 micrograms/ml for 24 h, n = 3) on paf binding characteristics of monocyte/macrophage-like U 937 cells was investigated using the radioligand [3H]paf, unlabeled paf and the paf receptor antagonist WEB 2086. The specific [3H]paf binding significantly increased at 1.4 nM (P less than 0.02) and 2.8 nM (P less than 0.01) added [3H]paf with an increased number of paf binding sites in the Scatchard plot analysis of the data. Specific paf binding was functionally active since paf mediated a cellular [Ca2+]i rise. The protein kinase C (PKC) activator PMA (1 nM, 37 degrees C) expressed specific [3H]paf binding already after a 15-min incubation period, indicating a PKC activation as the decisive step of paf receptor expression. LDL also stimulated the paf degrading cellular acetylhydrolase significantly by increasing both Km (9.4 +/- 1.9 vs. 2.0 +/- 0.5 microM, P less than 0.02) and vmax (0.5 +/- 0.2 vs. 0.2 +/- 0.0 nmol/min per mg cell protein, P less than 0.02). The data demonstrate that LDL increases the number of paf receptors on monocyte/macrophage-like U 937 cells and interferes with the dynamics and/or synthesis of the cellular acetyl hydrolase. These effects could be of importance in the pathogenesis of atherosclerosis.

In vitro and in vivo angiogenesis in PC12 pheochromocytoma cells is mediated by vascular endothelial growth factor.

Angiogenesis, the formation of new blood vessels from existing vascular endothelium, is essential for tumor growth. Vascular endothelial growth factor (VEGF) is an endotheliumspecific mitogen and regulator of angiogenesis. Angiogenesis has been associated to the malignant phenotype of pheochromocytomas and is readily observed in experimental pheochromocytomas. Although VEGF gene expression has already been demonstrated in the rat PC12 cell line, the detailed mechanisms of action are not known. We have, therefore, studied angiogenesis in the rat PC12 pheochromocytoma cell line in vitro and in vivo. VEGF gene expression and accumulation of VEGF protein in cytoplasm and conditioned medium of PC12 cells was found. Conditioned medium from PC12 cells significantly increased proliferation of VEGF-dependent endothelial cells from human umbilical veins, and this effect reversed upon addition of a neutralizing anti-VEGF antibody. Dexamethasone and nerve growth factor (NGF) increased VEGF mRNA expression and accumulation of VEGF protein of PC12 subclones with established metastatic activity in vivo. PC12 cells xenotransplanted to nude mice had marked VEGF expression and induced host angiogenesis, confirmed by the presence of CD34-positive endothelial cells in the experimental PC12 tumors. When NGF-primed PC12 cells were immobilized in Matrigel supplemented with rising concentrations of the growth factor and xenotransplanted, increasing NGF resulted in tumors with smaller areas of necrosis and increased vital tumor volume. These results suggest that VEGF is a mediator of angiogenesis in the PC12 pheochromocytoma cell line, and that dexamethasone and NGF affect VEGF expression. Our data further suggest that NGF may contribute to angiogenesis in experimental pheochromocytoma.

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)

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.

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.