Influence of proteinuria on vascular disease,blood pressure,and lipoproteins in insulin dependent diabetes mellitus.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.     

Erythrocyte sodium-lithium countertransport and blood pressure in identical twin pairs discordant for insulin dependent diabetes.

OBJECTIVE--To investigate whether insulin dependent diabetes is responsible for the abnormal behaviour of the carrier in sodium-lithium countertransport and whether the diabetic state is associated with rise in blood pressure. DESIGN--Case-control study. SETTING--London teaching hospital. SUBJECTS--44 twin pairs discordant for insulin dependent diabetes living in United Kingdom and 44 healthy control subjects matched for age, sex, and body mass index. None of the twin pairs or the controls had evidence of microalbuminuria. MAIN OUTCOME MEASURES--Sodium-lithium countertransport activity in erythrocytes and arterial blood pressure. RESULTS--The mean (95% confidence interval) sodium-lithium countertransport activity (mmol Li per litre of red blood cells per h) of the diabetic twins (0.291 (0.244 to 0.338)) was similar to that of their non-diabetic cotwins (0.247 (0.204 to 0.290)); both values were significantly higher than that of the controls (0.187 (0.157 to 0.216); p < 0.05). In addition, systolic blood pressure was higher in those twins with diabetes (127 (122 to 133) mm Hg) than in the non-diabetic cotwins (122 (117 to 127) mm Hg; p < 0.01). There were no significant differences in mean diastolic blood pressure between any of the groups studied. CONCLUSIONS--The raised erythrocyte sodium-lithium countertransport activity in the diabetic twins compared with the controls seems to be inherited rather than a consequence of overt diabetes. The higher systolic blood pressure in diabetic twins than non-diabetic cotwins indicates that insulin dependent diabetes does exert a small influence on systolic blood pressure.     

Prognosis in diabetic nephropathy.

OBJECTIVE--To assess the effect of long term antihypertensive treatment on prognosis in diabetic nephropathy. DESIGN--Prospective study of all insulin dependent diabetic patients aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Memorial Hospital. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Forty five patients (20 women) with a mean age of 30 (SD 7) years and a mean duration of diabetes of 18 (7) years at onset of persistent proteinuria were followed until death or for at least 10 years. INTERVENTIONS--Antihypertensive treatment was started a median of three (0-13) years after onset of nephropathy. Four patients (9%) received no treatment, and 9 (20%), 13 (29%), and 19 (42%) were treated with one, two, or three drugs, respectively. The median follow up was 12 (4-15) years. MAIN OUTCOME MEASURES--Arterial blood pressure and death. RESULTS--Mean blood pressure at start of antihypertensive treatment was 148/95 (15/50) mm Hg. Systolic blood pressure remained almost unchanged (slope -0.01 (95% confidence interval -0.39 to 0.37) mm Hg a year) while diastolic blood pressure decreased significantly (0.87 (0.65 to 1.10) mm Hg a year) during antihypertensive treatment. The cumulative death rate was 18% (8 to 32%) 10 years after onset of nephropathy, in contrast to previous reports of 50% to 77% 10 years after onset of nephropathy. As in previous studies, uraemia was the main cause of death (9 patients; 64%). CONCLUSIONS--The prognosis of diabetic nephropathy has improved during the past decade largely because of effective antihypertensive treatment.     

Contrasting effects of enalapril and metoprolol on proteinuria in diabetic nephropathy.

OBJECTIVE--To assess whether angiotensin converting enzyme inhibition reduces proteinuria in diabetic nephropathy more than blood pressure reduction with other antihypertensive treatment. DESIGN--Prospective, open randomised study lasting eight weeks in patients with diabetic nephropathy. SETTING--Outpatient nephrology clinics. PATIENTS--40 Patients with type I diabetes and diabetic nephropathy with reduced renal function. INTERVENTION--Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURES--Arterial blood pressure and urinary excretion of albumin and protein. RESULTS--Arterial blood pressure after eight weeks was 135/82 (SD 13/7) mm Hg in the group given enalapril and 136/86 (16/12) mm Hg in the group given metoprolol. Proteinuria and albuminuria were similar in both groups before randomisation. After eight weeks'' treatment, the geometric mean albumin excretion was 0.7 (95% confidence interval 0.5 to 1.2) g/24 h in the patients given enalapril and 1.6 (1.1 to 2.5) g/24 h in the patients given metoprolol (p less than 0.02). The proteinuria was 1.1 (0.7 to 1.7) and 2.4 (1.6 to 3.6) g/24 h respectively (p less than 0.02). CONCLUSIONS--Antihypertensive treatment with enalapril reduced proteinuria in patients with diabetic nephropathy more than an equally effective antihypertensive treatment with metoprolol. This points to a specific antiproteinuric effect of the angiotensin converting enzyme inhibitor independent of the effect on systemic blood pressure.     

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years'' duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.     

Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis

Objective To determine the accuracy of using systolic and diastolic blood pressure, mean arterial pressure, and increase of blood pressure to predict pre-eclampsia.Design Systematic review with meta-analysis of data on test accuracy.Data sources Medline, Embase, Cochrane Library, Medion, checking reference lists of included articles and reviews, contact with authors.Review methods Without language restrictions, two reviewers independently selected the articles in which the accuracy of blood pressure measurement during pregnancy was evaluated to predict pre-eclampsia. Data were extracted on study characteristics, quality, and results to construct 2×2 tables. Summary receiver operating characteristic curves and likelihood ratios were generated for the various levels and their thresholds.Results 34 studies, testing 60 599 women (3341 cases of pre-eclampsia), were included. In women at low risk for pre-eclampsia, the areas under the summary receiver operating characteristic curves for blood pressure measurement in the second trimester were 0.68 (95% confidence interval 0.64 to 0.72) for systolic blood pressure, 0.66 (0.59 to 0.72) for diastolic blood pressure, and 0.76 (0.70 to 0.82) for mean arterial pressure. Findings for the first trimester showed a similar pattern. Second trimester mean arterial pressure of 90 mm Hg or more showed a positive likelihood ratio of 3.5 (95% confidence interval 2.0 to 5.0) and a negative likelihood ratio of 0.46 (0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of 75 mm Hg or more at 13 to 20 weeks’ gestation best predicted pre-eclampsia: positive likelihood ratio 2.8 (1.8 to 3.6), negative likelihood ratio 0.39 (0.18 to 0.71). Additional subgroup analyses did not show improved predictive accuracy.Conclusion When blood pressure is measured in the first or second trimester of pregnancy, the mean arterial pressure is a better predictor for pre-eclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure.     

Blood pressure control by home monitoring: meta-analysis of randomised trials

Objective To determine the effect of home blood pressure monitoring on blood pressure levels and proportion of people with essential hypertension achieving targets.Design Meta-analysis of 18 randomised controlled trials.Participants 1359 people with essential hypertension allocated to home blood pressure monitoring and 1355 allocated to the “control” group seen in the healthcare system for 2-36 months.Main outcome measures Differences in systolic (13 studies), diastolic (16 studies), or mean (3 studies) blood pressures, and proportion of patients achieving targets (6 studies), between intervention and control groups.Results Systolic blood pressure was lower in people with hypertension who had home blood pressure monitoring than in those who had standard blood pressure monitoring in the healthcare system (standardised mean difference 4.2 (95% confidence interval 1.5 to 6.9) mm Hg), diastolic blood pressure was lower by 2.4 (1.2 to 3.5) mm Hg, and mean blood pressure was lower by 4.4 (2.0 to 6.8) mm Hg. The relative risk of blood pressure above predetermined targets was lower in people with home blood pressure monitoring (risk ratio 0.90, 0.80 to 1.00). When publication bias was allowed for, the differences were attenuated: 2.2 (-0.9 to 5.3) mm Hg for systolic blood pressure and 1.9 (0.6 to 3.2) mm Hg for diastolic blood pressure.Conclusions Blood pressure control in people with hypertension (assessed in the clinic) and the proportion achieving targets are increased when home blood pressure monitoring is used rather than standard blood pressure monitoring in the healthcare system. The reasons for this are not clear. The difference in blood pressure control between the two methods is small but likely to contribute to an important reduction in vascular complications in the hypertensive population.     

Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy.

STUDY OBJECTIVE--To assess whether long term inhibition of angiotensin converting enzyme with captopril and frusemide or bendrofluazide protects kidney function in diabetic nephropathy. DESIGN--Non-randomised controlled before-after trial of matched hypertensive insulin dependent diabetics with nephropathy treated with captopril and frusemide or bendrofluazide. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Treatment group of 18 hypertensive insulin dependent diabetics with nephropathy (mean age 33), who had not been treated previously. Control group of 13 patients (mean age 32) fulfilling the same entry criteria from a prospective study. INTERVENTIONS--Treatment group was given daily captopril 37.5-100.0 mg and frusemide (mean) 98 mg (10 patients) or bendrofluazide (mean) 4 mg (seven). Treatment was continued for about two and a half years. Controls were not treated. END POINT--Measurement of arterial blood pressure, albuminuria, and glomerular filtration. MEASUREMENTS AND MAIN RESULTS--Baseline values were identical in treated and untreated groups respectively: mean blood pressure 146/93 (SE 3/1) mm Hg v 137/95 (2/1) mm Hg; geometric mean albuminuria 982 (antilog SE 1.2) micrograms/min v 936 (1.2) micrograms/min; and mean glomerular filtration rate 98 (SE 5) ml/min/1.73 m2 v 96 (6) ml/min/1.73 m2. Mean arterial blood pressure fell by 8.7 (1.3) mm Hg with captopril and rose by 6.6 (1.5) mm Hg in controls, (p less than 0.001); Albumin excretion decreased to 390 (1.1) micrograms/min with captopril and rose to 1367 (1.3) micrograms/min in controls (p less than 0.001). The rate of decrease in glomerular filtration rate was lower with captopril (5.8 (0.7) ml/year v 10.0 (1.3) ml/year) (p less than 0.01). Rate of fall in glomerular filtration rate and mean arterial blood pressure were significantly correlated (n = 31, r = 0.37, p less than 0.05). CONCLUSIONS--Captopril is a valuable new drug for treating hypertension in insulin dependent diabetics with nephropathy.     

Paranormal healing and hypertension

A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37), and no paranormal healing (controls; n=38). Healing at a distance and no paranormal healing were investigated double blind. Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 (mean reduction (95% confidence interval) 17·1 (14·0 to 20·2)/8·3 (6·6 to 10·0) mm Hg). Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different. Each week diastolic pressure was consistently lower (average 1·9 mm Hg) after healing at a distance compared with control, but on paired comparison these differences were not significant. Probably week to week variations among the groups accounted for any differences noted.In this study no treatment was consistently better than another and the data cannot therefore be taken as evidence of a paranormal effect on blood pressure. Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself.     

Cardiovascular effects of training for a marathon run in unfit middle aged men.

The effects of a 30 week exercise programme on serum lipid values, blood pressure, and cardiac function were assessed in a group of sedentary men aged 35-50 training for their first marathon. Mean serum cholesterol concentration (n = 33) fell by 12% from 6.54 (SE 0.18) to 5.76 (0.15) mmol/l (mean fall 0.78 mmol/l; 95% confidence interval 0.52 to 1.04 mmol/l), serum triglyceride concentration (n = 33) by 22% from 1.56 (0.17) to 1.21 (0.09) mmol/l (mean fall 0.34 mmol/l; 95% confidence interval 0.12 to 0.56 mmol/l), and mean blood pressure (n = 27) by 10% from 102 (2) to 92 (2) mm Hg (mean fall 10 mm Hg; 95% confidence interval 7 to 13 mm Hg). These changes were not explained by changes in body composition. Peak exercise left ventricular end diastolic volume (n = 16) increased with training; as a result of this and an increased exercise left ventricular ejection fraction peak exercise cardiac output increased from 19.9 (1.2) to 23.1 (3.0) l/min (mean rise 3.2 l/min; 95% confidence interval 1.5 to 5.0 l/min). Maximum oxygen consumption increased from 33.9 (1.6) to 39.0 (1.3) ml/kg/min (mean rise 5.0 ml/kg/min; 95% confidence interval 1.8 to 8.2 ml/kg/min). This study showed favourable effects on coronary risk factors and cardiac function and supports the place of regular exercise in coronary prevention programmes.     

Sodium and potassium intake and blood pressure change in childhood.

OBJECTIVE--To assess the association between sodium and potassium intake and the rise in blood pressure in childhood. DESIGN--Longitudinal study of a cohort of children with annual measurements during an average follow up period of seven years. SETTING--Epidemiological survey of the population of a suburban town in western Netherlands. SUBJECTS--Cohort of 233 children aged 5-17 drawn at random from participants in the population survey. MAIN OUTCOME MEASURES--At least six annual timed overnight urine samples were obtained. The mean 24 hour sodium and potassium excretion during the follow up period was estimated for each participant and the sodium to potassium ratio calculated. Individual slopes of blood pressure over time were calculated by linear regression analysis. RESULTS--No significant association was observed between sodium excretion and the change in blood pressure over time. The mean systolic blood pressure slopes, however, were lower when potassium intake was higher (coefficient of linear regression -0.045 mm Hg/year/mmol; 95% confidence interval -0.069 to -0.020), and the change in systolic pressure was greater when the urinary sodium to potassium ratio was higher (0.356 mm Hg/year/unit; 95% confidence interval 0.069 to 0.642). In relation to potassium this was interpreted as a rise in blood pressure that was on average 1.0 mm Hg (95% confidence interval -1.65 to -0.35) lower in children in the upper part of the distribution of intake compared with those in the lower part. The mean yearly rise in systolic blood pressure for the group as a whole was 1.95 mm Hg. Urinary electrolyte excretion was not associated with diastolic blood pressure. CONCLUSION--Dietary potassium and the dietary sodium to potassium ratio are related to the rise in blood pressure in childhood and may be important in the early pathogenesis of primary hypertension.     

Comparison of monotherapy with enalapril and atenolol in mild to moderate hypertension. The Canadian Enalapril Study Group.

Therapy with 10 to 40 mg once daily of enalapril, a new angiotensin converting enzyme inhibitor, was compared with therapy with 50 to 100 mg once daily of atenolol in a double-blind randomized multicentre trial in 180 patients with a diastolic blood pressure (determined with the patient seated) of 95 to 115 mm Hg between March 1984 and April 1986. A total of 86 patients (61 men and 25 women with a mean age of 49.4 years and a mean blood pressure [and standard deviation] at entry into the trial of 155.5 [15.7]/101.0 [6.3] mm Hg) received enalapril, and 94 patients (63 men and 31 women with a mean age of 50.9 years and a mean blood pressure at entry of 156.6 [16.6]/101.2 [5.7] mm Hg) received atenolol. After a placebo run-in period the patients received increasing dosages of medication every 2 weeks until the target diastolic blood pressure of 90 mm Hg or less was achieved on two consecutive visits, the maximum dosage was reached, or the patient withdrew because of adverse effects. At 14 weeks the mean blood pressure was 141.6 (18.0)/90.1 (9.5) mm Hg in the enalapril group (61 patients) and 140.0 (17.1)/88.4 (8.7) mm Hg in the atenolol group (54 patients). The target diastolic blood pressure was achieved on completion of therapy (between weeks 10 and 14) in 67 (77%) of the patients receiving enalapril and 75 (79%) of the patients receiving atenolol. Compliance was similar in the two groups. Seven patients withdrew because of adverse effects, three in the enalapril group and four in the atenolol group. The results suggest that once-daily monotherapy with enalapril, 10 to 40 mg, is effective in the treatment of mild to moderate hypertension and is as effective as and tolerated as well as once-daily therapy with atenolol, 50 to 100 mg.     

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.     

Relaxation therapy and continuous ambulatory blood pressure in mild hypertension: a controlled study.

OBJECTIVE--To determine the long term effects of relaxation therapy on 24 hour ambulatory intra-arterial blood pressure in patients with mild untreated and uncomplicated hypertension. DESIGN--Four week screening period followed by randomisation to receive either relaxation therapy or non-specific counselling for one year. Ambulatory intra-arterial blood pressure was measured before and after treatment. SETTING--Outpatient clinic in Amsterdam''s university hospital. SUBJECTS--35 Subjects aged 20-60 who were being treated by general practitioners for hypertension but were referred to take part in the study. At three consecutive screening visits all subjects had a diastolic blood pressure without treatment of 95-110 mm Hg. Subjects were excluded if they had damaged target organs, secondary hypertension, diabetes mellitus, a cholesterol concentration greater than 8 mmol/l, or a history of malignant hypertension. INTERVENTIONS--The group allocated to relaxation therapy was trained for eight weeks (one hour a week) in muscle relaxation, yoga exercises, and stress management and continued exercising twice daily for one year with monthly visits to the clinic. The control group had the same attendance schedule but had no training and were requested just to sit and relax twice a day. All subjects were asked not to change their diet or physical activity. MAIN OUTCOME MEASURE--Changes in ambulatory intra-arterial blood pressure after one year of relaxation therapy or non-specific counselling. RESULTS--Mean urinary sodium excretion, serum concentration of cholesterol, and body weight did not change in either group. Diastolic pressures measured by sphygmomanometry were 2 and 3 mm Hg lower in subjects in the relaxation group and control group respectively at the one year follow up compared with initial readings. The mean diastolic ambulatory intra-arterial pressure during the daytime had not changed after one year in either group, but small treatment effects could not be excluded: the mean change for the relaxation group was -1 mm Hg (95% confidence interval -6 to 3.9 mm Hg) and for the control group -0.4 mm Hg (-5.3 to 4.6 mm Hg). Mean ambulatory pressure in the evening also had not changed over the year, and in both groups nighttime pressure was 5 mm Hg higher. The variability in blood pressure was the same at both measurements. CONCLUSIONS--Relaxation therapy was an ineffective method of lowering 24 hour blood pressure, being no more beneficial than non-specific advice, support, and reassurance--themselves ineffective as a treatment for hypertension.     

A controlled study of eight months of physical training and reduction of blood pressure in children: the Odense schoolchild study.

OBJECTIVE--To examine the effect of physical training on physical fitness and blood pressure in children aged 9-11 years. DESIGN--Prospective randomised controlled intervention study of a sample of children drawn from a population survey of coronary risk factors in children. SETTING--Odense, Denmark. SUBJECTS--69 children with mean blood pressure greater than or equal to 95th centile (hypertensive group) and 68 with mean blood pressure less than 95th centile (normotensive group), randomly selected from a population of 1369 children. INTERVENTION--67 children were randomised to receive three extra lessons a week of an ordinary school physical education programme for eight months. MAIN OUTCOME MEASURES--Physical fitness assessed by calculation of maximum oxygen uptake and blood pressure recorded by one unblinded observer. RESULTS--After three months neither blood pressure nor physical fitness had changed significantly. After adjustment for values in weight, height, heart rate, and the variable in question before training physical fitness rose significantly at the end of eight months'' training, by 3.7 mlO2/kg/min (95% confidence interval 2.2 to 5.3) in the normotensive training subgroup and by 2.1 mlO2/kg/min (0.1 to 4.2) in the hypertensive training subgroup compared with that in the controls. Systolic and diastolic blood pressures in the training subgroups fell significantly by 6.5 mm Hg (3.2 to 9.9) and 4.1 mm Hg (1.7 to 6.6) respectively in the normotensive group and by 4.9 mm Hg (0.7 to 9.2) and 3.8 mm Hg (0.9 to 6.6) respectively in the hypertensive group. CONCLUSIONS--Physical training lowers blood pressure and improves physical fitness in children and might have implications for an important non-pharmacological approach to primary prevention of essential hypertension.     

Atenolol in essential hypertension during pregnancy.

OBJECTIVE--To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN--Prospective, randomised, double blind, placebo controlled study. SETTING--Hospital clinic. PATIENTS--33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES--Blood pressure and birth weight. INTERVENTION--14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS--The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION--Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.     

Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.     

Vascular factors of the orthostatic responses in systemic haemodynamic

In anaesthetised rats, bending of the body for 30 degrees and 45 degrees entailed a reverse linear dependence between the systolic and diastolic pressures under conditions of initial blood pressure over 95 mm Hg, whereas in initial blood pressure lower than 95 mm Hg the dependence is direct. In bending of the body for 60 degrees the dependence was direct and only present in initial blood pressure lower than 95 mm Hg. Pressor effects of mesaton in orthostasis directly depended on the level of the initial blood pressure. Any dependence of the cardiac output shifts on the initial blood pressure was absent. The direction and the degree of the arterial system reactivity's changes in response to orthostasis and adrenergic effect of mesaton was found to depend on the bending angle and the initial blood pressure level.     

Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.     

Insulin resistance in offspring of hypertensive parents.

OBJECTIVE--To determine if insulin resistance is present in normotensive adults at increased risk of developing hypertension. DESIGN--Normotensive subjects with at least one hypertensive parent were paired with offspring of normotensive parents (controls), being matched for age, sex, social class, and physical activity. SETTING--Outpatient clinic. SUBJECTS--30 paired subjects (16 men and 14 women) with and without a family history of hypertension, aged 18-32, with a body mass index < 25 kg/m2, with blood pressure < 130/85 mm Hg, and not taking drugs. INTERVENTIONS--Euglycaemic glucose clamp (two hour infusion of insulin 1 mU/kg/min) and intravenous glucose tolerance test (injection of 100 ml 20% glucose). MAIN OUTCOME MEASURES--Insulin mediated glucose disposal and insulin secretion. RESULTS--The offspring of hypertensive parents had slightly higher blood pressure than did the controls (mean 117 (SD 6) v 108 (5) mm Hg systolic, p = 0.013; 76 (7) v 67 (6) mm Hg diastolic, p = 0.017). Their insulin mediated glucose disposal was lower than that of controls (29.5 (6.5) v 40.1 (8.6) mumol/kg/min, p = 0.002), but, after adjustment for blood pressure, the difference was not significant (difference 6.9 (95% confidence interval -1.5 to 15.3), p = 0.10). Insulin secretion in the first hour after injection of glucose was slightly but not significantly higher in the offspring of hypertensive patients (9320 (5484) v 6723 (3751) pmol.min/l). The two groups had similar concentrations of plasma glucose (5.2 (0.3) v 5.1 (0.4) mmol/l), serum cholesterol (4.4 (0.8) v 4.6 (0.8) mmol/l), serum triglyceride (0.89 (0.52) v 0.68 (0.27) mmol/l), and serum low density lipoprotein cholesterol (2.81 (0.65) v 2.79 (0.61) mmol/l). The offspring of hypertensive parents, however, had lower serum concentrations of high density lipoprotein cholesterol (1.24 (0.31) v 1.56 (0.35) mmol/l, p = 0.002) and higher serum concentrations of non-esterified fatty acids (0.7 (0.4) v 0.4 (0.4) mmol/l, p = 0.039). CONCLUSIONS--Young normotensive subjects who are at increased risk of developing hypertension are insulin resistant.