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.

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.

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.

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.

Acute admissions with atrial fibrillation in a British multiracial hospital population.

To assess the clinical characteristics and management of patients with atrial fibrillation (AF), we performed a prospective survey of all acute medical admissions over six months to our hospital. Of 7,451 such admissions, 245 had AF (110 male, 135 female; mean age 74.4 years). Of these, 213 were Caucasian, 10 black/Afro-Caribbean and 22 Asian. Complete data were available for 185 patients. Of these, 82 had newly diagnosed AF, 83 had previous chronic AF and 20 had paroxysmal AF. The main presenting features was dyspnoea, stroke and syncope. A history of ischaemic heart disease was present in 64, heart failure in 46, hypertension in 51 and rheumatic heart disease in 13, while 31 had a previous stroke. Chest X-ray showed cardiomegaly and pulmonary oedema in 121 patients, but was normal in 28. Echocardiography showed poor cardiac function in eight patients and enlarged left atria in five. Only 28% of those with previously diagnosed AF were on anticoagulation. Of the newly diagnosed patients, only 18% were started on anticoagulants. Cardioversion was attempted or planned in only 6%. The primary diagnosis on discharge was heart failure in 45, stroke in 24 and myocardial infarction in 12. AF remains a common arrhythmia among acute medical admissions and is commonly associated with heart failure and a high mortality. There is still a reluctance to start anticoagulant therapy or to perform cardioversion in such patients.

Acute admissions with atrial fibrillation in a British multiracial hospital population

To assess the clinical characteristics and management of patients with atrial fibrillation (AF), we performed a prospective survey of all acute medical admission over six months to our hospital. Of 7,451 such admissions, 245 had AF (110 male, 135 female; mean age 74.4 years). Of these, 213 were Caucasian, 10 black/Afro-Caribbean and 22 Asian. Complete data were available for 185 patients. Of these, 82 had newly diagnosed AF, 83 had previous chronic AF and 20 had paroxysmal AF. The main presenting features were dyspnoea, stroke and syncope. A history of ischaemic heart disease was present in 64, heart failure in 46, hypertension in 51 and rheumatic heart disease in 13, while 31 had a previous stroke. Chest x-ray showed cardiomegaly and pulmonary oedema in 121 patients, but was normal in 28. Echocardiography showed poor cardiac function in eight patients and enlarged atria in five. Only 28 percent of those with previously diagnosed AF were on anticoagulation. Of the newly diagnosed patients, only 18 percent were started on anticoagulants. Cardioversion was attempted or planned in only 6 percent. The primary diagnosis on discharge was heart failure in 45, stroke in 24 and myocardial infarction in 12. AF remains a common arrhythmia among acute medical admissions and is commonly associated with heart failure and a high mortality. There is still a reluctance to start anticoagulant therapy or to perform cardioversion in such patients.(AU)

Malignant hypertension in association with primary aldosteronism.

Primary aldosteronism is associated with low plasma renin levels, whilst malignant phase hypertension is generally associated with raised renin activity. These two conditions are therefore at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. We describe in detail 3 cases of primary hyperaldosteronism from a disease register of 315 cases of malignant hypertension seen in one medical centre over 29 years.

Ethnic differences in public health awareness, health perceptions and physical exercise: implications for heart disease prevention.

OBJECTIVES: To study whether the wide differences in heart disease incidence amongst ethnic groups in the UK, with the higher mortality and morbidity in peoples of south Asian descent, may be attributed to differences in public health awareness and life-style. DESIGN: Questionnaire-based survey of women from different ethnic groups attending an antenatal clinic in a city centre district general hospital. RESULTS: We surveyed 232 housewives from 3 different ethnic groups: 84 white (mean age 24.3 years +/- standard deviation (SD) 5.84), 76 Afro-Caribbean (mean age 24.7 years +/- SD 4.46) and 72 Asians (defined as people of south Asian or Indian subcontinent descent; mean age 25.7 years +/- SD 5.5). The proportions of smokers amongst the whites, blacks and Asians were 38.1%, 27.6% and 2.8% respectively. Proportions consuming alcohol regularly were 31.0%, 10.5% and 4.2% respectively. A higher proportion of blacks reported a change in dietary fibre intake, whilst a higher proportion of whites reported a change in dietary fat intake and sugar intake as a result of public health campaigns, publicity or advertising. There was a significantly lower proportion of reported regular exercise activity amongst the Asian women and their husbands or partners. CONCLUSION: This study demonstrates that Asian families were the least likely to take regular exercise, and had a lower awareness of cholesterol or dietary content (fibre, sugar, salt) despite public health campaigns and publicity. They were however the least likely to smoke cigarettes. These ethnic differences may in part explain the higher prevalence of coronary heart disease amongst the Asian population in the UK. This ethnic group should be targeted for intense public health intervention, education and other preventative measures to reduce the risks of heart disease.