[A 10-year follow-up of men with mild hypertension. Bendroflumethiazide and propranolol give equal effect in treatment of high blood pressure].
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Bendroflumethiazide↗
Biomedical subjects
G Berglund
Publications and source records attributed to G Berglund.
Economic evaluation of a Swedish medical care program for hypertension.
A Hypertension Care Program, developed in cooperation between physicians and nurses in both primary care and at the hospitals in the area, was implemented in the Skaraborg County, Sweden in 1977. The Program, which provided for the establishment of hypertensive clinics at outpatient units and referral to medical clinics, was clearly aimed towards giving nurses increased responsibility for hypertensive care. The Skaraborg Program has been evaluated from several important perspectives. A terminal population study showed better blood pressure control among the hypertensive patients within the program area than within the control area. The economic evaluation indicates that hypertensive care according to the Program is somewhat less resource demanding than conventional hypertensive care. Since the medical effects of hypertensive care were improved without increased demand for resources, the structured Care Program was more cost-effective than conventional care.
Cost-Benefit Analysis↗
Treatment of arterial hypertension with ketanserin in mono- and combination therapy.
We evaluated the long-term antihypertensive effects of ketanserin, a selective serotonin2-receptor blocker with weak adrenergic receptor blocker properties. Ketanserin was given alone, 40 mg o.d. or b.i.d., for 2 years to 12 patients with essential hypertension. Systolic and diastolic blood pressures (BPs) were significantly reduced 14 days after the start of therapy and remained lowered during the 2-year follow-up period. In a larger group of patients who received ketanserin monotherapy for 2 to 3 months, the response to therapy varied considerably between subjects, with an overall response rate (BP less than 165/95 mm Hg) of 60% to 75%. During steady-state conditions, the maximum and minimum ketanserin plasma concentrations varied from threefold to fourfold between subjects and did not correlate with individual reductions in BP, but for each individual there was a positive correlation between BP reduction and ketanserin plasma concentration throughout a study day. In combination with beta-blockers, ketanserin effectively reduced BP in the supine and standing positions. The plasma concentration profile was not altered as much during combination therapy as when ketanserin was given alone. Side effects were few and tolerable. Ketanserin effectively reduces BP both alone and in combination with beta-blockers and may be still another drug useful in the treatment of essential hypertension.
Adrenergic beta-Antagonists↗
Predictors of cardiovascular morbidity in treated hypertension: results from the primary preventive trial in Göteborg, Sweden.
Prognostic factors for cardiovascular disease (CVD) were studied in treated, middle-aged male hypertensives, derived from a random population sample and followed for more than 10 years. In multivariate analysis diastolic blood pressure, smoking, serum cholesterol, proteinuria, angina pectoris and previous stroke were found to be independent predictors of CVD morbidity (non-fatal myocardial infarction (MI), non-fatal stroke, or CVD death). Multivariate analyses for coronary heart disease (CHD), stroke and CVD mortality were also performed and the results are given. Life-table analyses showed a three times higher CVD incidence among smokers than amongst non-smokers and a doubled incidence for subjects with a serum cholesterol in the highest quartile, i.e. above 7.3 mmol/l, compared with those with levels below, and a three times higher incidence for subjects with proteinuria than those without. Non-smokers with a serum cholesterol below 7.3 mmol/l and free of any hypertensive organ manifestation at entry did not differ significantly in CVD morbidity from a normotensive comparison group that was derived from the same population sample. These findings in a well-defined population sample show that in spite of treatment for hypertension the CVD risk is still substantial if organ damage or other risk factors are present. These findings underline the importance of multiple risk intervention.
Angina Pectoris↗
A comparative and long-term evaluation of ketanserin in the treatment of essential hypertension.
Ketanserin is a serotonin (S2) blocker that reduces blood pressure (BP) in patients with essential hypertension preferentially by a reduction of peripheral vascular resistance. Heart rate is generally not affected or slightly reduced. When given in monotherapy on a 40 mg b.i.d. regimen, ketanserin reduces diastolic BP as effectively as metoprolol 100 mg b.i.d. or hydrochlorotiazide 25 mg b.i.d. The incidence of adverse reactions is low and comparable to these reference drugs. A satisfactory BP control is provided over a 24-h interval on a 40 mg b.i.d. dosage schedule, and the effect is maintained on a long-term basis, i.e., greater than 2 years. The response seems to be more marked in older patients, which may be due to an augmented platelet serotonin release and a vascular hypersensitivity in this age group. The future usefulness of ketanserin, as well as any other antihypertensive agent, will depend on its ability to prevent organ damage, as well as its ability to provide "quality of life" for the patient.
Adrenergic beta-Antagonists↗
Renal function and renal haemodynamics before and after 7 years' antihypertensive treatment in men with primary hypertension.
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Antihypertensive Agents↗
Effective dose range of enalapril in mild to moderate essential hypertension.
The dose-response relationship of enalapril was evaluated in a double-blind, balanced, two-period, incomplete-block study in 91 patients with mild to moderate essential hypertension. Patients were randomly assigned to two of six treatments: placebo, 2.5, 5, 10, 20 and 40 mg/day of enalapril maleate. There were two 3-week treatment periods, each preceded by a 4-week, single-blind placebo washout. Each dose of enalapril produced significant decreases in standing and supine systolic and diastolic blood pressure after 2 and 3 weeks of treatment. There were no significant changes on placebo. There was a significant linear dose response relationship for both mean blood pressure and mean change from baseline in blood pressure (P less than 0.01 for systolic and mean arterial pressure, and P less than 0.05 for diastolic pressure). Enalapril was associated with an increasing dose-response relationship across the 2.5-40 mg/day range. The 2.5 mg/dose is effective in some patients; however, doses greater than or equal to 10 mg/day may be necessary to achieve satisfactory blood pressure control.
Adult↗
A longitudinal study of growth in children with acute lymphoblastic leukemia.
Growth in terms of both height and weight was studied in a longitudinal sample consisting of ten children who all experienced the onset of acute leukemia between 18 months and 7 years of age. In spite of the lack of deviation in body size at birth, these children had somewhat higher values for attained size than the reference group one year before diagnosis. The information from this study showing a decrease in growth rate before the start of treatment, could suggest that the disease causes the growth failure. Growth rate for height increased with time from the first year of treatment, which could be correlated to a positive effect of medical treatment of the disease. These results indicate a very stable regulation of growth between 18 months and 12 years of age. The children dropped temporarily in mean one standard deviation (SD) corresponding to about 4 cm, from one year before the start of treatment to the end of the three years of treatment. It seems, however, that it is possible for the body to repair such a temporary growth inhibition as is seen in the catch-up growth during the following two years. Height measured in SD for the group two years after discontinuing treatment was practically the same as height at the time of the start of treatment. Children with leukemia during the first years of life and during the pubertal period may not show a similar growth pattern.
Age Factors↗
Prognostic factors in treated hypertension.
Prognostic factors for cardiovascular disease (CVD) were studied in 686 treated, middle-aged male hypertensives followed for 10 years at a hypertension clinic. The factors studied were all obtained from a standard clinical routine examination and both univariate and multivariate analyses were performed. Only entry characteristics were analysed. The 10-year incidence of any CVD event (CVD death, non-fatal myocardial infarction or non-fatal stroke) was 15.3% and of coronary heart disease (CHD) morbidity (fatal or non-fatal myocardial infarction) 12.3%. Independent predictors of CVD morbidity were diastolic blood pressure (DBP), smoking, cholesterol, proteinuria, angina pectoris and previous stroke. Except for a previous stroke the same variables were independent predictors of CHD. The findings show that in spite of treatment for hypertension, the CVD risk is still substantial if organ damage or other risk factors are present. The results underline the importance of multiple risk factor intervention in hypertensive patients.
Humans↗
Early results of a trial of the Oka-strain varicella vaccine in children with leukaemia or other malignancies in Sweden.
Nineteen children with acute lymphoblastic leukaemia or other malignancies, aged 3-13 years, with negative histories of varicella-zoster virus (VZV) and of whom 5 were still on regular maintenance chemotherapy, were vaccinated with the Oka-strain varicella vaccine. Mild systemic reactions, involving low-grade fever of a few days duration, were recorded in 4 of the vaccinees. Two of them also developed an extremely sparse rash. A mild local reaction at the vaccination site was observed in 1 child. Conversion rates for circulating VZV antibody, measured at 4-6 weeks and 4-6 months after vaccination using an indirect immunofluorescence test, were 8/12 (67%) and 5/9 (56%), respectively. Markedly lower antibody conversion rates of 5/18 (28%) and 5/14 (36%) were found by means of the enzyme-linked immunosorbent assay method. Corresponding conversion rates for cell-mediated immunity against VZV, determined using a specific lymphocyte stimulation technique, were 9/17 (52%) and 12/14 (86%), respectively.
Adolescent↗
Haemodynamics in young normotensive men with familial predisposition to hypertension. Studies on normal and increased salt intake.
Central and peripheral haemodynamics were studied noninvasively (echocardiography, plethysmography) in normotensive young men (mean age 30 years) with (n = 17) (H), and without (n = 15) (C) a positive history of hypertension during normal salt intake and after four weeks of ordinary diet plus 12 g NaCl daily. No changes in blood pressure were noted during the course of the study in either group. After three days of high salt an increased cardiac output and decreased total peripheral resistance was seen in H but not in C. The former might be due to a salt induced volume load occurring in a less distensible venous system. The difference in response disappeared during the course of the study. Both on normal and high salt intake resting resistance and resting vascular tone were significantly higher in H reflecting an increased contractile state of the smooth muscles of the resistance vessels. The increased smooth muscle tone of the resistance vessels and the less distensible venous system in these young men with family history of hypertension might be a genetically determined basis for a future increase in blood pressure.
Adolescent↗
Blood pressure and intra-erythrocyte sodium during normal and high salt intake in middle-aged men: relationship to family history of hypertension, and neurogenic and hormonal variables.
During 4 weeks 37 normotensive 50-year-old men identified by screening in a random population sample were given 12 g of NaCl daily, in addition to their usual dietary sodium intake. Blood pressure, heart rate, weight, urinary excretion of sodium, potassium and catecholamines, plasma aldosterone and noradrenaline and intra-erythrocyte sodium content were determined on normal and increased salt intake. The subjects were divided into those with a positive family history of hypertension (n = 11) and those without such a history (n = 26). Systolic blood pressure and weight increased significantly irrespective of a positive family history of hypertension. On normal salt intake intra-erythrocyte sodium content was significantly higher in those with a positive family history of hypertension. During high salt intake intra-erythrocyte sodium content decreased significantly in that group and the difference between the hereditary subgroups was no longer significant. In the whole group urinary excretion of noradrenaline, adrenaline and dopamine increased whereas plasma aldosterone decreased during the increased salt intake. Thus, in contrast to some earlier studies performed in young subjects, our results indicate that moderately increased sodium intake acts as a pressor agent in normotensive middle-aged men whether there was a positive family history of hypertension or not. We confirm that men with positive family history of hypertension have an increased intra-erythrocyte sodium content, and that an increase in salt intake seems to increase overall sympathetic activity.
Aldosterone↗
Blood pressure, intraerythrocyte content, and transmembrane fluxes of sodium during normal and high salt intake in subjects with and without a family history of hypertension: evidence against a sodium transport inhibitor.
Seventeen young normotensive men with a family history of hypertension in two generations (H) and 15 age-matched control subjects (C) were studied with respect to blood pressure (BP), intraerythrocyte sodium content (IeNa), sodium influx, and rate of sodium efflux. The investigations were done during normal salt intake and after 4 weeks of ordinary intake plus 12 g NaCl daily. BP did not increase significantly in either of the two groups during increased salt intake. During normal salt intake H had a significantly (p less than 0.01) higher IeNa (9.5 +/- 1.5 mmol/L) compared with C (8.2 +/- 1.4 mmol/L). During high salt intake IeNa in H decreased significantly to 8.1 +/- 1.2 mmol/L, the difference from C (7.6 +/- 1.2 mmol/L) not being significant. While the Na influx was similar in the two groups, the rate constant for Na efflux was significantly lower during normal salt intake in H (0.23 +/- 0.08 vs 0.29 +/- 0.1 h-1, p less than 0.05). Salt intake increased the efflux rate constant significantly in H (0.28 +/- 0.08 h-1, p less than 0.05), while it did not change significantly in C (0.32 +/- 0.08 h-1) compared with the value for normal salt intake. Our results suggest that young men with a hereditary predisposition to hypertension have a higher IeNa secondary to a lower rate of Na efflux, while a normal Na influx indicates normal cell permeability to Na. The findings in H during high Na intake--a decreased IeNa and an increased efflux rate of Na--do not favor the existence of a sodium transport inhibitor, in subjects predisposed to hypertension, increasing during high salt intake and volume expansion and acting through inhibition of the Na efflux.
Biological Transport, Active↗
Diuretics in long-term treatment of hypertension: a comparison to beta-blockers.
Diuretics are first-line drugs for treatment of hypertension in most parts of the world. Recently, however, beta-blockers have been increasingly used as drugs of first choice. The aim of this review is to describe advantages and disadvantages of diuretics in comparison to beta-blockers. The blood pressure (BP)-lowering effect of normally used doses of diuretics gives a useful decrease of BP equal to what can be achieved with beta-blockers in corresponding doses. Over 20 years of use has shown diuretics to be relatively safe for long-term treatment. The frequency of withdrawals and the subjective tolerability are comparable to those with beta-blockers. Diuretics do not seem to induce diabetes or impaired glucose tolerance when used in small doses. At higher doses and in elderly patients impairment of glucose tolerance might appear. The commonly encountered hypokalemia during diuretic treatment seems to be related to the dose and to the duration of the diuretic action. Diuretics can always be used once daily, and they are cheaper than beta-blockers, even when a greater need for laboratory check-ups is taken into account. While beta-blockers so far have not been shown to prevent or postpone hypertensive complications, diuretics have done so in several recent large-scale trials. Two multicenter trials are currently testing the hypothesis of whether beta-blockers are superior to diuretics in preventing coronary heart disease, the most common hypertensive complication. Until these studies are presented, there is little evidence to change the current use of diuretics as first-choice drugs in hypertension.
Adrenergic beta-Antagonists↗
Sodium elimination rate and blood pressure during normal and high salt intake in subjects with and without familial predisposition to hypertension.
We have assessed the elimination rate of 22Na (ER-22Na), total exchangeable sodium (NaE), blood pressure, plasma volume (PV), haematocrit, urinary noradrenaline (U-NA) and urinary 3-methoxy-4-hydroxymandelic acid (U-VMA) in normotensive men with (n = 17) and without (n = 15) familial predisposition to hypertension. All measurements were done during habitual salt intake and after four weeks of increased salt intake (ordinary intake + 12 g NaCl/daily). On ordinary salt intake, ER-22Na, NaE, blood pressure, PV, haematocrit, U-NA and U-VMA did not differ between the groups thus indicating a normal sodium turnover in both groups and a comparable activity of the sympathetic nervous system. After 10 days of high salt intake those without familial predisposition showed signs of volume expansion and decreased sympathetic activity and those with such predisposition showed insignificant changes in the same direction. After four weeks of increased salt intake, ER-22Na had increased significantly and equally in both groups, while blood pressure and NaE remained unchanged. This indicates that the predisposed individuals had a normal ability to cope with a prolonged increase in salt intake.
Adolescent↗
Intraerythrocyte sodium content and transmembrane sodium flux in hypertensive patients treated with diuretics or beta-adrenoceptorblockers.
Forty-seven male patients with essential hypertension were randomized to treatment with either a beta-adrenoceptorblocker (metoprolol), (n = 24), or a diuretic (hydrochlorothiazide), (n = 23). If their diastolic blood pressure was not lowered below 95 mm Hg by the maximum dose of either drug, hydralazine (15 patients) and in a few cases (6 patients) spironolactone was given. After five years of treatment all the patients were examined with respect to intraerythrocyte sodium (IeNa) and potassium (IeK), sodium influx and sodium efflux. Patients treated with the diuretic (D) tended to have a higher IeNa (9.8 +/- 0.4 mmol/l red cells) and sodium influx (0.044 +/- 0.002 mmol Na/l X min) compared with those taking the beta-adrenoceptorblocker (B) (8.9 +/- 0.3 mmol/l and 0.041 +/- 0.002 mmol Na/l X min), but neither of these differences was statistically significant. Sodium efflux, however, was significantly increased in D (0.073 +/- 0.003 mmol Na/l X min vs 0.061 +/- 0.003 mmol/l X min). No difference in IeK was noted between the two groups. Six patients taking spironolactone had a low IeNa (7.3 +/- 0.4 mmol/l), sodium influx (0.039 +/- 0.001 mmol Na/l X min) and sodium efflux (0.050 +/- 0.006 mmol Na/l X min).
Adrenergic beta-Antagonists↗
A simplified technique to estimate sodium influx and efflux in erythrocytes.
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Adult↗
Experience with ketanserin, a serotonin (S2) antagonist, in longterm treatment of essential hypertension.
Ketanserin ia a quinazoline derivative which acts selectively on serotonin (S2) receptors. The compound has been shown to possess antihypertensive properties. BP and HR were measured blindly on 14 patients with essential hypertension during one year. Ketanserin 40 mg, once or twice daily, reduced BP (and HR to a slight extent) largely unchanged from 14 days after initiation of therapy. Response rate varied from 57-77% at the regular control visits. During the one year follow up period the reduction in supine SBP was 9 +/- 3% (p less than 0.001) and DBP was 12 +/- 1% (p less than 0.001). The only side effect was a slight sedation that passed with time. It is concluded that ketanserin is effective in the chronic treatment of hypertension and may offer a new alternative to existing pharmacotherapy.
Adult↗