Diuretics for preventing pre-eclampsia.

BACKGROUND: Diuretics are used to reduce blood pressure and oedema in non-pregnant individuals. Formerly, they were used in pregnancy with the aim of preventing or delaying the development of pre-eclampsia. This practice became controversial when concerns were raised that diuretics may further reduce plasma volume in women with pre-eclampsia, thereby increasing the risk of adverse effects on the mother and baby, particularly fetal growth. OBJECTIVES: To assess the effects of diuretics on prevention of pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2) and EMBASE (2002 to April 2005). SELECTION CRITERIA: Randomised trials evaluating the effects of diuretics for preventing pre-eclampsia and its complications. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. We analysed and double checked data for accuracy. MAIN RESULTS: Five studies (1836 women) were included. All were of uncertain quality. The studies compared thiazide diuretics with either placebo or no intervention. There were no clear differences between the diuretic and control groups for any reported pregnancy outcomes including pre-eclampsia (four trials, 1391 women; relative risk (RR) 0.68, 95% confidence interval (CI) 0.45 to 1.03), perinatal death (five trials,1836 women; RR 0.72, 95% CI 0.40 to 1.27), and preterm birth (two trials, 465 women; RR 0.67, 95% CI 0.32 to 1.41). There were no small-for-gestational age babies in the one trial that reported this outcome, and there was insufficient evidence to demonstrate any clear differences between the two groups for birthweight (one trial, 20 women; weighted mean difference 139 grams, 95% CI -484.40 to 762.40). Thiazide diuretics were associated with an increased risk of nausea and vomiting (two trials, 1217 women; RR 5.81, 95% CI 1.04 to 32.46), and women allocated diuretics were more likely to stop treatment due to side-effects compared to those allocated placebo (two trials, 1217 women; RR 1.85, 95% CI 0.81 to 4.22). AUTHORS' CONCLUSIONS: There is insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications. However, from this review, no clear benefits have been found from the use of diuretics to prevent pre-eclampsia. Taken together with the level of adverse effects found, the use of diuretics for the prevention of pre-eclampsia and its complications cannot be recommended.

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

RATIONALE: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. DESIGN: The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. SETTING: Acute stroke and medical units in teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

The failure of malignant hypertension to decline: a survey of 24 years' experience in a multiracial population in England.

INTRODUCTION: The widespread use of antihypertensive medication and the increasing frequency of diagnosis of mild-to-moderate hypertension should mean that malignant-phase hypertension should be becoming less common, and this trend has been reported elsewhere. No decline in the incidence of malignant hypertension has been apparent in our practice in a district general hospital in a city centre. OBJECTIVE AND METHODS: To investigate the incidence and mode of clinical presentation of patients presenting with malignant hypertension, we performed a retrospective survey of the number of patients presenting with malignant hypertension to our hospital, over the 24-year period from 1970 to 1993. We identified a total of 242 patients (155 male, 87 female; mean +/- SD age 50.1 +/- 13.3 years) with malignant hypertension. RESULTS: There were no significant differences in the number of patients presenting each year, the mean age or the presenting systolic and diastolic blood pressures over the period surveyed. At presentation, 131 patients (54.1%) had no previous history of hypertension; 161 (66.5%) were receiving no antihypertensive therapy and only 70 (28.9%) were receiving antihypertensive treatment (with no record of therapy in 11 patients). The most common presenting symptoms included visual disturbance in 62 (25.6%), headaches in 29 (12.0%), headaches and visual disturbance in 24 (9.9%), heart failure in 19 (7.9%), stroke or transient ischaemic attack in 17 (7.0%) and dyspnoea in 13 (5.4%), although 23 patients (9.5%) were asymptomatic. The most common presenting complications were heart failure [27 patients (11.1%)], stroke [23 patients (9.5%)], angina [10 patients (4.1%)], myocardial infarction [nine patients (3.7%)] and chronic renal failure [77 patients (31.7%)]. In the whole group the majority (147 patients, 60.5%) had no complicating clinical features. Primary or essential hypertension was the most common underlying cause in 137 patients (56.4%). Secondary causes of hypertension (mainly renal disease) were identified in 97 patients (39.9%). CONCLUSION: Our experience suggests that malignant hypertension is still common, with a small proportion of hypertensives presenting each year. In particular, the incidence has failed to decline in Birmingham. The incidence rate in the population served by our hospital is approximately 1-2 cases per 100,000 per year. An awareness of the different presenting clinical features is required to allow better recognition and management of this life-threatening condition.

Mortality in patients of the Glasgow Blood Pressure Clinic.

The mortality of 3783 non-malignant hypertensive patients attending the Glasgow Blood Pressure Clinic between 1968 and 1983 and followed for an average of 6.5 years was compared with that in three control groups: the general population of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen in a blood pressure clinic based on general practice in Renfrew. Average blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling to 158/96 mmHg during treatment. Corresponding values for women were 185/109 mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males) died during follow-up, the commonest causes of death in both sexes being myocardial infarction and stroke. All-cause age-adjusted mortality (deaths per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages in both sexes and for all levels of initial blood pressure mortality was less in patients whose blood pressure was reduced most. Without a randomized control group it is not certain that lower mortality in those with well controlled blood pressure was due to treatment, although this is the most likely explanation. Cigarette smoking, a history of myocardial infarction, angina or stroke, retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram (ECG) and secondary hypertension were associated with increased risk, but heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia and social class were not. Life table analysis showed that, despite some reduction of mortality by treatment, the relative risk to men and women in the clinic remained two- to five-times that of the general population. The benefits of treatment were not such as to restore normal expectation of life even when blood pressure was well controlled. Excess mortality in the clinic could not be explained by difference of smoking habit or social class. This suggests that there is in the hypertensive patients of the Glasgow Clinic an element of irreducible risk, that treatment may be beneficial in some respects but harmful in others, or that patients at particularly high risk are selectively referred to the clinic.

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Body fat and stroke: unmasking the hazards of overweight and obesity.

STUDY OBJECTIVE: It has been frequently noted that overweight and obesity have a stronger relationship to hypertension and diabetes mellitus than to the risk of stroke. The reason for this observation has not been clear. This study aimed to examine the lifelong relation between body fat and stroke to shed light on why the public health risks of overweight and obesity have tended to be obscured in previous epidemiological studies. DESIGN: Case-control study. SETTING: Eleven general practices in west Birmingham. PARTICIPANTS: Altogether 125 men and women who had just had their first stroke and were aged 35-74 years and 198 controls frequency matched for age and sex were recruited over 24 months during 1988-90. MAIN RESULTS: Those in both the thinnest and fattest quartiles of subscapular skinfold thickness were at increased risk of stroke compared with those in the middle quartiles (age adjusted odds ratios 2.12 (95% confidence interval (CI) 1.2, 3.9) and 2.08 (1.1, 3.8) respectively). When lifelong maximum reported body mass index was assessed the hazards of obesity but not leanness were seen (odds ratio for the highest versus the lowest quartile were--age adjusted, 1.54 (0.8, 3.0) and multiple risk factor adjusted, 2.25 (1.1, 4.5). This lifelong pattern of risk seemed to be established early, the odds ratios for the highest versus the lowest quartile of reported body mass index aged 21 years were--age adjusted, 2.18 (1.1, 4.4) and multiple risk factor adjusted 2.13 (1.1, 4.2). The risks of both maximum reported body mass index and reported body mass index aged 21 years were more clear in those who had never smoked cigarettes (test for trend in odds ratio, p = 0.009 and p = 0.02 respectively). CONCLUSIONS: Potentially important risks of excessive body fat for stroke can be obscured by both a history of cigarette smoking and thinness associated with deteriorating health. The results seem to explain why excess body fat has previously been consistently related to hypertension and diabetes mellitus but less consistently to stroke. Avoiding overweight and obesity during adult life offers protection against stroke.

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.

Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study.

The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.

Dietary fat purchasing habits in whites, blacks and Asian peoples in England--implications for heart disease prevention.

The mortality and morbidity from coronary heart disease (CHD) is higher in people of South Asian origin than in whites, but is significantly lower in the black (Afro-Caribbean origin) community in the United Kingdom. To investigate whether this may be related to differences in fatty food intake, we performed a questionnaire survey of the weekly food purchasing habits and preparation methods in white, black (Caribbean) and Asian households in Birmingham. We interviewed 224 housewives from three ethnic groups (84 white, 76 black/Afro-Caribbean and 72 Asian). The highest quantity of fat in foods purchased per week was found in the Asian population (median 1409 g/week per person, interquartile range (IQR) 850-1952), which was significantly greater than black subjects, who had the lowest quantity of fat in foods purchased (1012 g/week per person, IQR 835-1388) (Mann-Whitney test:median differences 300.5, 95% C.I. 23.3-600.4, P = 0.029). The median quantity of fat in foods purchased by the white households was intermediate, at 1186 g/week per person (IQR 861-1711). There was a higher quantity of fat in foods purchased in the lower social classes (IV and V) in both the white and Asian populations. Butter, egg and milk consumption was significantly greater in Asians; with ghee consumption almost exclusive amongst this group (98%). Amongst whites and blacks, the commonest food preparation methods were grilling, boiling or poaching; whilst amongst Asians, frying was more common (chi 2 = 81.25, d.f. = 4, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Meta-analysis of relation between cigarette smoking and stroke.

There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.

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.