Fifteen-year survival of patients beginning treatment with methyldopa between 1962 and 1966.

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.

Mortality in patients who have their antihypertensive therapy changed.

Medical records were examined for 1935 patients who presented sequentially to a hypertension clinic between 1971 and 1981. Patients were classified according to whether they were on a beta-blocker, methyldopa, a potassium-losing diuretic, or whether they had discontinued any of these treatments. Age-standardized mortality rates were calculated and the relative risks of stopping compared with non-stopping were computed. Those stopping a beta-blocker had a significantly higher mortality in the following year than those who continued, both in men [relative risk (RR) = 5.91, 95% confidence interval (Cl) 2.78-12.56] and women (RR = 5.67, 95% Cl 1.75-18.41). Moreover, women also had a significantly higher mortality when stopping methyldopa, compared with those who continued on the drug (RR = 4.91, 95% Cl 1.82-13.20). However, analysis of data from the years following withdrawal indicated that a high RR was not limited to the first year after the withdrawal of beta-blockers, but was still apparent in the fourth year after stopping. This indicates that the high mortality was not an early function of withdrawal. The high initial RR of mortality in women stopping methyldopa was followed by a substantial decrease in risk over the later years of follow-up. The high mortality in patients stopping particular antihypertensive drugs was not explained by known cardiovascular risk factors.

Stroke death and unemployment in London.

STUDY OBJECTIVE: The aim was to investigate the relationship between social factors and stroke mortality in men and women aged between 45 and 74 years using census and mortality data from 32 London boroughs in 1971 and 1981. DESIGN: Census data from 1971 and 1981 on type of accommodation, density of room occupation, male unemployment rate, and proportion of households without a car were linked with stroke mortality available for each London borough. SETTING: 32 London boroughs excluding the City of London. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were the association between age adjusted mortality from stroke and the proportion of households with no car, non-ownership of home, in council housing or rented accommodation, male unemployment rate, and living density of more than 1.5 people per room. There was no strong correlation between social variables and stroke mortality in 1971, but strong correlations were found for male stroke mortality in 1981. The highest correlation was with male unemployment (r = 0.64, p less than 0.001) even after adjusting for the proportion of the population born in the Caribbean and Africa (r = 0.56, p less than 0.01). Other social variables were also highly correlated with male stroke mortality: households without a car (r = 0.63, p less than 0.001), living density of more than 1.5 people per room (r = 0.053, p less than 0.001), council housing (r = 0.45, p = 0.01), and rented accommodation (r = 0.36, p = 0.05). After regressing male mortality on unemployment rate the other social variables were no longer significantly correlated with male stroke mortality. In women, the only significant correlation was found in 1981 between stroke mortality and the proportion of families living in council housing (r = 0.34, p = 0.05). CONCLUSIONS: Social factors are important indicators of stroke mortality. The major increases in unemployment over the decade may explain the generally stronger association in 1981 compared with 1971. Male stroke mortality increased by 0.062/1000 for every one percent increase in male unemployment (0.054/1000 after adjusting for place of birth).

Myocardial infarction and stroke during treatment of hypertensive patients with different diuretic regimes.

A retrospective analysis of mortality and cardiovascular morbidity in patients being treated with a potassium losing diuretic alone or the combination of a potassium losing and sparing diuretic was performed in 1,935 patients attending a hypertension clinic between 1971 and 1981. In all, 713 patients were treated with a potassium losing diuretic and 472 patients were on a potassium sparing diuretic, usually in combination with a potassium loser. Presenting data on risk factors were similar between the two groups and age-adjusted cardiovascular morbidity and mortality was similar between the two groups. The relative risk (RR) for a myocardial infarction event on a potassium losing drug was 1.1 (95% CI 0.5-2.3) in men and 1.0 (0.4-2.5) in women. The corresponding risks for stroke were 0.8 and 0.7 respectively and total mortality was 1.3 and 1.1. However, following exclusion of patients with previous history of cardiovascular disease the risk of myocardial infarction in the potassium losing group was over three times that on a sparing diuretic, though the confidence intervals were wide. Total male mortality tended to be higher (RR = 2.4) but again failed to achieve statistical significance. An excess risk from potassium losing diuretics was found only in patients without cardiovascular disease and cannot be readily explained. This may be the result of treatment selection in different 'at risk' groups or chance in the performance of subgroup analyses.

Fifteen year survival of patients presenting with hypertension to a hospital clinic.

The survival has been determined for the 404 patients who presented to the Hammersmith Hospital Hypertension Clinic during the years 1962 to 1966 and in whom the untreated blood pressure was known. The fifteen year survival ranged from 72% for young men aged 30-49 at presentation to 27% for men aged 60-69. Sixty-eight percent of the deaths were cardiovascular or renal, 33% of all deaths were from ischaemic heart disease (IHD), 17% from stroke and 3% from renal causes. Death from any cause was predicted with statistical significance by age, the presence of accelerated or malignant hypertension, impaired renal function, smoking at presentation and systolic blood pressure. Death was not predicted by hypokalaemia, hyperuricaemia (after adjusting for renal function) and obesity.

Risk of serious morbidity associated with hydralazine versus methyldopa treatment in hypertensive patients.

The medical records of patients presenting to the Hammersmith Hospital hypertension clinic between 1971 and 1981 were examined to determine presenting clinical data, treatment regimes, and both cardiovascular and non cardiovascular mortality and morbidity. When compared with 1004 patients receiving treatment other than hydralazine 310 patients on hydralazine had a significantly higher risk of developing renal disease (RR = 2.71) in men, and severe weight loss in women (RR = 3.06). Renal disease risk also tended to be high in women on hydralazine (RR = 1.95) compared with all other treatments, but this was not statistically significant and could be explained by poorer renal function and significantly higher untreated blood pressure in the hydralazine treated group at presentation. The 422 patients who were treated with methyldopa but not hydralazine had similar risk factors for cardiovascular disease compared with a group of 167 who received hydralazine but not methyldopa. Comparisons of event rates failed to find significant differences in morbidity or mortality between these two groups. The age adjusted male mortality was 14/1000 patient years on hydralazine and 12/1000 on methyldopa and 13/1000 and 6/1000 years for women respectively. There was no evidence of an increased risk of either renal disease (RR = 0.3 in men, RR = 0.3 in women) on hydralazine or weight loss (RR = 0.7 in men, RR = 1.6 in women), with similar presenting data. Systemic lupus erythematosus was a rare complication (2 of 314) of treatment with hydralazine.

Malignant hypertension in general practice.

A diagnosis of malignant hypertension was recorded for 165 patients in the national morbidity study between 1970 and 1973. Three patients with benign hypertension were selected as age- and sex-matched controls for each case. The general practitioners in the study were asked to complete a further questionnaire about the patients and 66% of the practices agreed to take part. Information about the retinal findings for the patients was requested and less than half of those in the national morbidity study proved to have a strict diagnosis of accelerated or malignant hypertension although they were originally recorded as patients with malignant hypertension. Of those patients originally classified as having benign hypertension 5% had the retinal appearance of accelerated or malignant hypertension.Patients had been diagnosed as having hypertension for a mean of more than five years prior to entry into the national morbidity study and the survival of patients with both benign and accelerated or malignant hypertension was good. Thirtyfour per cent of those with confirmed benign hypertension and 62% of those with definite accelerated or malignant hypertension died in the follow-up period which was on average 10 years from entry into the national morbidity study.The survival of patients registered with doctors who did not collaborate and of patients whose clinical details were missing was similar to the survival of patients for whom full details were provided.Blood pressure control was only fair with a mean of 172/101 mmHg for the group with benign hypertension and 177/107 mmHg for the group with accelerated or malignant hypertension. Blood pressure control was the poorest for those who died from a stroke. A high proportion (78%) of deaths in association with accelerated or malignant hypertension were from cardiovascular or renal causes.

Potassium supplementation fails to lower blood pressure in hypertensive patients receiving a potassium losing diuretic.

Thirty-three patients with hypertension receiving drug treatment that included a potassium losing diuretic were randomly allocated to 64 mmol of potassium (14 patients) or to no additional potassium supplementation (19 patients). Potassium was administered as slow release potassium chloride. After 3 months, blood pressure fell by 5/1 mm Hg in the patients who received the supplements and by 7/4 mm Hg in those who did not receive them. The falls in pressure were not significantly different and the 90% confidence limits for the effect of supplementation on diastolic pressure were: a fall of 2 mm Hg and a rise of 11 mm Hg, thus excluding an important hypotensive effect in these patients. Conversely, plasma creatinine fell by 11% in the supplement group compared with a 6% rise in the control group (P less than 0.05). Potassium supplementation, either by pharmacological preparations or by dietary manipulation, may prove to be desirable in patients on a potassium losing diuretic but should not be expected to lower blood pressure in such patients.

Is low salt dietary advice a useful therapy in hypertensive patients with poorly controlled blood pressure?

In order to decide whether or not to advise a low Na trial routinely in a hypertension clinic, a randomised controlled 'management' trial was conducted to assess dietary compliance, well-being and changes in antihypertensive medication as a result of such a diet. Sixty-five out-patients on drug treatment for hypertension but with diastolic blood pressures greater than 95 mm Hg on two successive occasions were randomly allocated either to an index group on a 1 g Na (44 mmol) daily diet or to a reference group. Dietary advice was given in detail and repeated as necessary to ensure there was no misunderstanding. After three months 28% of the index group still added salt to their cooking and 13% sometimes added salt at the table. The difference between the groups in 24-hour Na excretion averaged 59 mmol at the end of the trial but 55% of the index group had a 24-hour Na excretion greater than 80 mmol. The average blood pressure at the end of the trial was only a 4 mm Hg systolic and 3 mm Hg diastolic lower in the index group. However, this modest benefit was achieved without any obvious deterioration in the quality of the lives of the patients on the low Na diet. The index group enjoyed their food as much as before and tended to require less drug treatment. On the debit side the index group complained more of transient unsteadiness (p less than 0.05) suggestive of postural hypotension. Low salt dietary advice is only marginally effective in patients poorly controlled on drug treatment. Non-compliance limits the usefulness of the advice.