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Biomedical subjects

C Bulpitt

Publications and source records attributed to C Bulpitt.

At least 19 recordsLinked to original sources

Associations of orthostatic blood pressure fall in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVES: To investigate the associations of the orthostatic blood pressure changes in older patients with isolated systolic hypertension. METHODS: A total of 2716 patients, 917 men and 1799 women, aged > or = 60 years, were examined at three separate outpatient visits whilst receiving placebo during the single-blind run-in phase of the Syst-Eur trial. The orthostatic blood pressure changes were calculated by subtracting the average of two blood pressure readings with the patient in the supine position from the mean of two readings obtained after the patient had stood for 2 min. An orthostatic blood pressure drop by at least 20 mmHg systolic or 10 mmHg diastolic was considered exaggerated. RESULTS: For the three run-in visits combined, the supine blood pressure was 175 +/- 13 mmHg systolic and 86 +/- 6 mmHg diastolic (means +/- SD). With the patients standing the systolic blood pressure was 5 +/- 12 mmHg lower, whereas the diastolic blood pressure was 2 +/- 7 mmHg higher. An exaggerated fall in systolic blood pressure was observed on at least 1 visit in 21.0% of the patients and on all three visits in 2.5%. The corresponding values for diastolic blood pressure were 9.7 and 0.4%. The orthostatic fall in systolic blood pressure increased with previous antihypertensive treatment, age and smoking, but decreased with a higher sitting pulse rate and usual alcohol consumption versus none. The rise in diastolic blood pressure upon standing was higher in women than in men, was curvilinearly associated with age and increased with the sitting diastolic blood pressure. By multiple logistic regression analysis, the odds of having a persistent or occasional exaggerated orthostatic fall in systolic blood pressure were 22% higher in women than in men. The odds increased with previous antihypertensive treatment (by 42%), age (by 1.4%/year), electrocardiographic left ventricular mass (by 15%/mV) and sitting systolic blood pressure (by 0.9%/mmHg), but decreased with sitting pulse rate (by 1.9%/beat per min). An exaggerated orthostatic fall in diastolic blood pressure was 30% more likely in men; the likelihood increased with age (by 6.4%/year) and decreased with sitting diastolic blood pressure (by 6.6%/mmHg). CONCLUSION: An exaggerated orthostatic blood pressure fall in older patients with isolated systolic hypertension is associated mainly with gender, age and blood pressure level. Previous antihypertensive treatment, a lower pulse rate and a lower electrocardiographic left ventricular mass were also associated with an exaggerated orthostatic fall in systolic blood pressure.

Age Factors

Prevalence and persistency of orthostatic blood pressure fall in older patients with isolated systolic hypertension. Syst-Eur Investigators.

Postural hypotension in older people has been the subject of many studies, but there remains some doubt as to its true prevalence. This study investigated the prevalence and persistency of an exaggerated orthostatic blood pressure (BP) fall in a large group of older patients with isolated systolic hypertension. A total of 2716 patients, 917 men and 1799 women, whose age ranged from 60-100 years, were examined at three separate outpatient visits on a placebo in the single-blind run-in phase of the Syst-Eur Trial. The supine and standing BPs at each visit were the averages of two readings. An exaggerated BP fall was defined as a drop in systolic pressure by at least 20 mm Hg 2 min after assuming the standing from the supine position, or as a drop in the diastolic pressure by at least 10 mm Hg. The reproducibility of orthostatic BP changes was evaluated by the Bland and Altman technique. With the three run-in visits combined, the sitting pressure averaged ( +/- standard deviation) 174 +/- 11 mm Hg systolic and 86 +/- 6 mm Hg diastolic. Systolic pressure fell on average by 5 +/- 12 mm Hg from the supine to the standing position, whereas diastolic pressure increased by 2 +/- 7 mm Hg. The percentage of patients showing an exaggerated orthostatic BP fall was constant at each of the three run-in visits, ie 11-12% for systolic pressure and 4% for diastolic pressure. An exaggerated BP fall at each of the three run-in visits was only present in 3% of the patients for systolic pressure and in 0.4% for diastolic pressure. An exaggerated BP fall at the run-in visits was not associated with dizziness and syncope, which occurred in only 1% of the patients. The orthostatic fall in systolic, but not diastolic pressure, was greater (0.6 mm Hg; P < 0.05) at the second than at the first visit. The repeatability coefficients tended to be higher (60-65%), signifying lower reproducibility, than those for the BP levels (45-55%). An exaggerated fall in systolic or diastolic pressure may occasionally occur in nearly 10% of older patients with isolated systolic hypertension even without antihypertensive drug therapy, but a persistent orthostatic response in only rarely observed.

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Risk factors for ischaemic heart disease and stroke mortality in young and old hypertensive patients.

We investigated the predictors of cardiovascular mortality at different ages in a longitudinal study of 10186 hypertensive patients attending clinics in the UK. There were 7374 patients (51% were men) < 60 years of age and 2799 patients (44% men) were > or = 60 years. For IHD death the age-adjusted relative risks (RRs) and 95% confidence intervals (CI) for a 1 mmol/l increase in cholesterol were RR = 1.17 (1.07, 1.27) (men) and RR = 1.22 (1.12, 1.33) (women). The RRs for stroke were 0.99 (men) and 1.07 (women). In men and younger women, urea and smoking were important predictors of IHD and stroke death. Age differences were present in women for both urea and smoking. For IHD in women, smoking: RR = 2.65 (1.80, 3.89) (< 60 years) and RR = 1.38 (1.01, 1.88) (> or = 60 years). For stroke in women, smoking: RR = 2.03 (1.23, 3.35) (< 60 years) and RR = 1.06 (0.70, 1.61) (> or = 60 years). We conclude that urea and smoking are important risk factors for stroke and IHD death in hypertensive women aged < 60 years, but are less important in those aged over 60 years. Cholesterol predicted IHD death in all men and women, but did not predict stroke death.

Adult

Epidemiology of hypertension in the elderly.

DISTRIBUTION: Blood pressure tends to rise with increasing age. Six to eight per cent of people aged 60-69 years, and about 12-16% of those aged 70-79 years, are estimated to need treatment for raised systolic and diastolic blood pressures. DETERMINANTS: It seems likely that the rise in blood pressure with increasing age is partly explained by the determinants of blood pressure, such as sodium intake, body weight, physical exercise and alcohol consumption. MORTALITY: There is a linear relationship between the level of diastolic or systolic blood pressure and the risk of stroke or coronary heart disease. However, the relationship between blood pressure and mortality in later life may be obscured if concurrent illness lowers blood pressure; low blood pressure by itself may not be a risk factor for mortality. TREATMENT: Randomly allocated trials have consistently shown that the treatment of hypertension in men and women over 60 years of age reduces the incidence of stroke by about 40%, and some trials have also shown reductions in coronary events.

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Implications for trials in progress of publication of positive results.

It is not easy to decide, when results from similar trials appear, whether a trial still underway should be stopped or not. The weight of the other evidence has to be taken into account--as indeed it has to be for decisions by clinicians and by health service managers outside the settings of a trial. Taking the Systolic Hypertension in the Elderly Trial (SHEP) as an example, we show how its results are not unequivocal (ie, there is no proof beyond reasonable doubt). This verdict justifies the continuation of similar trials in progress. More generally--but again for individual clinicians and for trial organisers and again with SHEP as the example--we illustrate a bayesian approach to trial-termination decisions.

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Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society.

Several important new issues have arisen in the management of patients with hypertension. A working party of the British Hypertension Society has therefore reviewed available intervention studies on anti-hypertensive treatment and made recommendations on blood pressure thresholds for intervention, on non-pharmacological and pharmacological treatments, and on treatment goals. This report also provides guidelines on blood pressure measurement, essential investigations, referrals for specialist advice, follow up, and stopping treatment.

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Nitrendipine in older patients with isolated systolic hypertension: second progress report on the SYST-EUR trial.

This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older (> or = 60 years of age) subjects with isolated systolic hypertension (SBP 160-219 mmHg and DBP < 95 mmHg). Active treatment consisted of nitredipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), if necessary to reduce SBP to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. This analysis was restricted to 18 months of follow-up. The placebo (n = 456) and active treatment (n = 485) groups had similar characteristics at randomisation (sitting pressure 176/85 mmHg; age 73 years). SBP fell (P < 0.001) on average 10 mmHg more on active treatment than on placebo and DBP 4 mmHg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started earlier (P < 0.001). Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment (P < 0.001). In conclusion, a significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist (associated with a converting-enzyme inhibitor and a thiazide, where necessary). Whether this BP reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

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Management of elderly patients with sustained hypertension.

OBJECTIVE: To assess the clinical benefits of treating hypertension in elderly patients and to derive practical guidelines regarding indications, goals, and forms of treatment. DESIGN: Review of six published randomised trials. RESULTS: Active treatment of hypertension in elderly patients was associated with significant improvements in several indices of cardiovascular morbidity and mortality, particularly the incidence of fatal and non-fatal strokes. On the basis of the trial data, combined systolic and diastolic hypertension was defined as a sustained systolic pressure greater than 160 mmHg and diastolic pressure greater than 90 mmHg. There is convincing evidence that efforts should be made to reduce both systolic and diastolic pressures to below these levels in patients up to the age of 80 years. Isolated systolic hypertension was defined as a systolic pressure greater than 160 mmHg in the presence of a diastolic pressure less than 90 mmHg. Two trials reported benefit from the treatment of isolated systolic hypertension in patients up to the age of 80, and further trials are underway to support or refute this recommendation. Diuretics have an established role in the management of hypertension in elderly patients; beta adrenoceptor antagonists have given variable results, and the benefits are less impressive than with diuretic based regimens. Newer agents show promise in the treatment of elderly patients, particularly in the presence of coexisting disease, but their effects on morbidity and mortality have not been evaluated in large randomised trials. CONCLUSIONS: Diuretics rather than beta blockers are the treatment of choice for patients with uncomplicated hypertension, but combinations of drugs may be required in as many as 50% of patients.

Adrenergic beta-Antagonists

Quality of life in the treatment of hypertension. The effect of calcium antagonists.

The effects of calcium antagonists on psychological well-being, cognitive function, activity and physical symptoms in hypertensive patients are reviewed. Effects on these aspects of quality of life appear to differ according to whether a dihydropyridine calcium antagonist such as nifedipine is employed or verapamil, which is a phenylalkylamine derivative. Nifedipine has been associated with a self-assessment of impaired cognitive function in 2 clinical trials. Nifedipine was also associated with more symptomatic complaints than both atenolol and verapamil in different studies. The problems with nifedipine centred on oedema, flushing and palpitations. Verapamil was associated with constipation. Compared with other classes of antihypertensive drugs, the position of calcium antagonists with respect to the maintenance of patients' quality of life is presently unclear. Verapamil has been associated with improved quality of life compared with propranolol (a beta-blocker) and nifedipine. Verapamil appears to have similar effects on quality of life as atenolol and the angiotensin converting enzyme (ACE) inhibitor, captopril. The position of nifedipine remains unclear.

Calcium Channel Blockers

[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.

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Quality of life and antihypertensive drugs in the elderly.

Hypertension is common in the elderly with estimates of around 10-20% showing a sustained level of pressure, either systolic (greater than or equal to 160 mmHg), or diastolic (greater than or equal to 90 mmHg) or both. The benefits of treating subjects with raised diastolic pressure was shown by the trials of the European Working Party on High Blood Pressure in the Elderly (EWPHE), the Hypertension in Elderly Patients in Primary Care (HEP), and the Swedish Trial in Old patients with Hypertension (STOP-Hypertension). Evidence for the benefit of treating isolated systolic hypertension in the elderly was provided in one trial (SHEP: Systolic Hypertension in the Elderly Program), and the results of two others are awaited. However, it is important to provide data on all treatment effects, including adverse reactions as well as benefits. In addition to traditional measures of mortality, morbidity and side effects, the quality of life in patients on antihypertensive treatment should be considered. The methods of measuring quality of life in trials is discussed, and some results presented.

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Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly.

Hypertensive patients over the age of 60 years were admitted to a double-blind placebo-controlled trial. Patients in the actively treated group received a combined potassium-losing and -sparing diuretic (triamterene 50 mg plus hydrochlorothiazide 25 mg; n = 416); this dose could be doubled and methyldopa (up to 2 g, daily) was added in 35% of patients when blood pressure remained high. The placebo group (n = 424) received matching capsules and tablets. Adverse effects were assessed in the double-blind period of the trial by calculating the incidence of abnormal biochemical results, investigator reports of diseases and prescriptions of concomitant therapy and a self-administered symptom questionnaire completed by patients. In 1000 hypertensive subjects over 60 years of age, 1 year of active treatment would prevent 11 fatal cardiac events, 6 fatal and 11 non-fatal strokes and 8 cases of severe congestive heart failure. No unexpected adverse treatment effects were observed. A significant excess incidence rate (per 1000 person years) was found in the active group compared with placebo for: (1) impaired renal function, a serum creatinine greater than 180 mumol/l (2.0 mg/dl); (2) mild hypokalaemia, a serum potassium less than 3.5 mmol/l; (3) reports of gout; and (4) an elevated serum uric acid greater than 0.52 mmol/l in men or greater than 0.46 in women. Elevated blood sugar and prescriptions for hypoglycaemic drugs tended to be more frequent in the actively treated group, but this difference was not statistically significant. In both groups, there was a low incidence (less than 7 per 1000 person years) of anaemia and depression and diseases of the liver, gall bladder or pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

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[A comparison of the effects of verapamil and nifedipine on the quality of life].

Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 months randomized double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95 to 115 mm Hg was required for inclusion in the trial. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (p less than 0.01). The reporting of swollen ankles and flushing (p less than 0.05) increased on nifedipine, and nocturia (p less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (p = 0.05). There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (p less than 0.01). The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.

Adult

Is a high serum cholesterol level associated with longer survival in elderly hypertensives?

The relationship between serum total cholesterol, measured at randomization, and mortality was investigated in 822 patients, who were followed for an average of 3.1 years in a double-blind trial, conducted by the European Working Party on High Blood Pressure in the Elderly. Serum cholesterol, measured at randomization, was 0.54 mmol/l higher in women than in men, and declined with increasing age in both men (0.028 mmol/l per year) and women (0.036 mmol/l per year). During follow-up on randomized treatment, cholesterol fell by a similar amount with placebo (0.11 mmol/l per year) and with active treatment (0.14 mmol/l per year). Active treatment consisted of hydrochlorothiazide (25-50 mg/day) plus triamterene (50-100 mg/day) with the addition of alpha-methyldopa (0.5-2.0 g/day) in one-third of the patients. Serum total cholesterol, measured at randomization, was independently and inversely correlated with total (P = 0.03), non-cardiovascular (P = 0.03) and cancer (P = 0.04) mortality during follow-up on double-blind treatment. Total and non-cardiovascular mortality were also negatively correlated with haemoglobin and body weight at randomization.

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