Experimental hypertensive retinopathy: circulatory changes.
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Biomedical subjects
Publications and source records attributed to C J Bulpitt.
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BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.
The causes of death and associated risk factors are compared in young and old diabetic patients attending a retinopathy clinic. Mortality in those diagnosed under and over the age of 30 years is also examined in order to compare insulin-dependent with non-insulin-dependent patients. A defined cohort attending the Hammersmith Hospital Retinopathy Clinic was followed for an average of 11 years. Main outcome measures were standardized mortality ratios (SMRs) in different age/sex groups and relative hazard rates (RHRs) for possible risk factors related to mortality. The patients were divided into those aged under and over the age of 60 years at attendance at the clinic. The RHRs were smaller in the elderly for plasma urea [1.015 versus 1.107 (p < 0.01)]. Attenuation of risk was also suggested for systolic blood pressure (RHR of 1.005 in the elderly versus 1.015 in the younger patients) and for the effects of smoking [RHR of 1.17 (elderly patients) and 1.35 (younger patients)]. In those diagnosed under the age of 30 years, there were very high SMRs for renal disease, cerebrovascular disease (men only), ischemic heart disease, other heart disease, and respiratory disease (men only), but increased SMRs were also demonstrated in those diagnosed over the age of 30 years. The risk factors associated with poor survival were similar for those diagnosed over and under the age of 30 years: poor diabetic control, high systolic and diastolic blood pressure, and increased plasma urea. In conclusion, there was no evidence that blood sugar control or diastolic blood pressure were less important in older age groups. Plasma urea, systolic pressure, and being on insulin were less useful as predictors of mortality in the elderly, but were still important in patients diagnosed over the age of 30 years.
The 15-year survival of a group of 205 patients who started treatment in the period 1962 through 1966 and who received methyldopa for two-thirds or more of the time has been investigated. At entry these patients had severe hypertension with an average pretreatment pressure of 216/126 mm Hg. Twenty-one percent had retinal hemorrhages, cotton-wool spots, or papilledema. Blood pressure showed a large fall in the first year, followed by a small, progressive, further fall up to the sixth year. After 5 years of treatment the blood pressure averaged 144/90 mm Hg in men and 151/91 mm Hg in women. The average daily dose of methyldopa was approximately 1500 mg and changed little over the 15-year period. Survival was analyzed by life tables. Approximately 81% of men and women aged 30 to 49.9 years at entry were still alive 10 years later. In the age group 60 to 69.9 years, 53.8% of men and 63.2% of women were still alive 10 years later. Seventy-nine of the patients died during the follow-up period, 89% from cardiovascular or renal disease. Ischemic heart disease (40%) was the major cause of death, followed by stroke (19%). No patients died from drug toxicity.
One hundred and seventy-six patients who were newly referred to two diabetic clinics completed an initial questionnaire and a second questionnaire 1 yr later. Over the 1-yr period the average 2-h postprandial blood sugar was reduced from 13.8 to 8.8 mmol/L. The questionnaire included 33 questions on symptoms, and four symptoms improved by more than 10%: increased thirst (reduced by 29%), dry mouth (reduced by 24%), pruritus (17%), and weakness in the limbs (10%). No symptom was increased by more than 7%. The changes in five symptoms were significantly related to the changes in blood sugar observed, the improvement in symptoms being associated with reductions in blood sugar. These results are contrasted with newly referred hypertensive patients in whom marked improvements in symptoms were not observed and an increased frequency of certain symptoms was observed owing to drug side effects.