Antianginal Efficacy of Ivabradine in Patients With History of Coronary Revascularization.

Although coronary revascularization procedures are widely performed in patients with coronary artery disease (CAD), angina is often reported, even after such procedures. This study evaluated the antianginal efficacy and effect of ivabradine treatment on quality of life (QOL) in patients with CAD and history of coronary revascularization. This is a post hoc analysis (926 post-revascularization patients) of a prospective, noninterventional study, which included 2403 patients with CAD and stable angina. The data were recorded at baseline, at 1 month and 4 months after inclusion. After ivabradine administration, mean number of anginal events decreased from 2.2 ± 2.3 (median: 2.0, minimum: 0.0, maximum: 21.0, range: 21.0) to 0.3 ± 0.6 (median: 0.0, minimum: 0.0, maximum: 7.0, range: 7.0) times/week (P < .001), while nitroglycerin consumption decreased from 1.5 ± 2.2 (median: 1.0, minimum: 0.0, maximum: 20.0, range: 20.0) to 0.1 ± 0.4 times/week (median: 0.0, minimum: 0.0, maximum: 5.0, range: 5.0; P < .001). Quality of life improved at study completion compared to baseline (P < .001). Ivabradine addition on top of optimal individualized dose of ß-blockers is associated with decreased anginal events and improvement in QOL in patients with stable angina and history of coronary revascularization.

Effect of magnetic seizure therapy on regional brain glucose metabolism in major depression.

Currently electroconvulsive therapy (ECT) is one of the only available therapies for treatment resistant depression (TRD). While effective, ECT is complicated by side effects, including cognitive impairment. One promising potential alternative is magnetic seizure therapy (MST). To date, no research has explored the effects of 100Hz MST on brain activity or the brain changes associated with response to treatment. Therefore the aim of this study was to determine the effects of a treatment course of 100Hz MST on regional brain glucose metabolism. Ten patients with treatment resistant depression underwent positron emission tomography with fluorodeoxyglucose before and after a treatment course of MST. Changes in the relative metabolic rate of a priori brain regions were investigated. Areas of increased relative metabolism after treatment were seen in the basal ganglia, orbitofrontal cortex, medial frontal cortex and dorsolateral prefrontal cortex. A secondary analysis showed trend-level differential findings in brain activation between responders and non-responders, namely in the ventral anterior cingulate. These results primarily indicate that MST is affecting regions consistent with the limbic-cortical dysregulation model of depression. Exploratory analysis indicated some differential findings in brain activation between responders and non-responders were also evident; however, the small sample size precludes any firm conclusions.

Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project.

Abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial function [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and thrombogenesis [plasminogen activator inhibitor (PAI), and fibrin D-dimer] are common in cardiovascular disease. We investigated changes in these markers in 86 patients (58 males) presenting with acute stroke (all age < 75 years, with ictus < 12 h), and sequential changes at six time points (baseline on admission, 48 h, 1 week, 2 weeks, 3 months and 6 months following the onset of stroke). Baseline plasma viscosity, haematocrit, fibrinogen, vWf, PAI, soluble P-selectin and fibrin D-dimer levels were increased in the acute stroke patients compared with 35 age-matched and sex-matched controls. Following admission, there were significant increases in haematocrit at 2 weeks, vWf at 48 h and 1 week, fibrinogen at 1 week, PAI at 48 h and 1 and 2 weeks, soluble P-selectin at 48 h, and fibrin D-dimer at 48 h and 1 week following admission. Using univariate 'time to event' analysis, high (> median) mean age (log-rank test, P = 0.0262), diastolic blood pressure (P = 0.01), haematocrit (P = 0.0234), PAI-1 (P = 0.0066) and fibrin D-dimer levels (P = 0.0356) were associated with a shortened event-free survival. Using a multivariate Cox survival analysis, only PAI-1 levels remained an independent predictor of survival (P = 0.0349). We conclude that acute stroke patients have marked baseline abnormalities of haemorheology, endothelial disturbance, thrombogenesis, platelet activation and abnormal fibrinolysis, with further changes over the subsequent follow-up period. Abnormal thrombogenesis and fibrinolysis may significantly influence survival in patients with acute stroke. These changes may have potential implications for the pathogenesis of stroke and its complications, although the possibility remains that we are documenting an acute phase response that previous studies, which included stroke patients with a wide time range since ictus onset, have neglected to consider.

Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project.

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.

Acute admissions with heart failure to a district general hospital serving a multiracial population.

To assess te incidence, clinical characteristics and current strategies in the management of patients with acute heart failure, we conducted a prospective survey of all acute medical admissions with heart failure to a district hospital serving a city centre population of 300,000 people in a multiracial community. Of 7451 such admissions, 348 (4.7%) were diagnosed as having acute heart failure: 265 Caucasian (76.1%), 27 black/Afro Caribbean (7.7%), 56 Indo-Asian (16.1%). Complete clinical data were available from 260 patients. The main presenting symptom was dyspnoea in 233 patients (89.6%) and chest pain in 60 patients (23.1%); 139 patients (53.5%) had a history of ischaemic heart disease, 87 (33.5%) hypertension and 49 (18.8%) had diabetes; 103 patients (39.6%) had a previous history of heart failure; 75 patients (28.8%) were in atrial fibrillation. An echocardiogram was performed in 89 patients (34.2%). On admission, ACE inhibition was prescribed to only 78 patients (30.0). The diagnosis of heart failure was stated on the hospital inpatient data sheet (KMR-1) in only 170 patients (65.4%). Following admission, 50 patients (19.2%) died while in the wards. Heart failure is a common problem among acute medical admissions and has a poor prognosis. The KMR-1 diagnosis may underestimate the prevalence of heart failure.

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)

Ambulatory blood pressure monitoring in acute stroke. The West Birmingham Stroke Project.

BACKGROUND AND PURPOSE: Ambulatory blood pressure monitoring (ABPM) devices are increasingly used in the assessment of hypertension, but their value in patients after a stroke is unknown, despite the fact that hypertension is an important cause of stroke and many patients have relatively high blood pressure (BP) levels at presentation. We therefore investigated the clinical use of a 24-hour oscillometric ABPM device in patients after acute stroke. We also investigated ABPM in different types of stroke (thrombosis, hemorrhage, and transient ischemic attack) and ethnic and sex differences. METHODS: BP was measured manually with a standard mercury sphygmomanometer, and ABPM measurements were made with an oscillometric device. The first reading obtained with the ABPM device was compared with simultaneous manual BP measurements. Mean daytime and nighttime pressures were also analyzed to determine the frequency of nocturnal BP falls ("dipping"). RESULTS: We studied 86 patients (48 men; mean +/- SD age, 64.2 +/- 9.2 years) admitted with acute-onset stroke (ictus within 12 hours) in a district general hospital. Thirty-one patients (36.0%) had a previous history of hypertension. The median percentage of successful BP readings by ABPM was 92% (interquartile range, 72 to 98). There was no significant difference in manual BP levels compared with the first simultaneous systolic or diastolic ABPM measurements. Systolic BPs recorded by ABPM were significantly higher in black patients with acute stroke and in patients with intracerebral hemorrhage, who also showed a trend toward higher nocturnal BPs. There was no difference in BPs between men and women and those who were alive or dead 6 months later (P = NS). There was also no difference between mean day and night systolic BP (mean difference, 1.9 mm Hg; P = .08), although mean daytime diastolic BP was higher than mean nighttime diastolic BP (mean difference, 2.4 mm Hg; P = .01). Patients with stroke therefore demonstrated a loss of diurnal BP rhythm and may be considered "nondippers"; there was also a trend toward "reverse dipping" in patients with intracranial hemorrhage. CONCLUSIONS: This study demonstrates higher systolic BPs as recorded by ABPM (but not manually) in patients with intracerebral hemorrhage than in those with cerebral infarcts; higher levels were also found in blacks. ABPM recordings are useful in the assessment of BP in patients with stroke, who may be considered nondippers.

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy.

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.

Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin and aspirin.

BACKGROUND: Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels. CONCLUSIONS: Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.

Ambulatory blood pressure monitoring in atrial fibrillation.

Ambulatory blood pressure monitoring (ABPM) devices are increasingly used in the assessment of hypertension, but patients with atrial fibrillation are usually excluded because device accuracy in this patient group is unproved. The present study investigates the clinical use of the Spacelabs 90207 oscillometric ABPM device in outpatients with chronic atrial fibrillation and suggests that such devices can be used in clinical practice to assess blood pressure in stable outpatients with chronic atrial fibrillation.

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.

Physician variation in the management of patients with atrial fibrillation.

OBJECTIVE: To investigate variations in the management of patients with atrial fibrillation among consultant physicians. DESIGN: Questionnaire survey. SUBJECTS: Consultant physicians in England, Wales, and Scotland. RESULTS: 214 consultant physicians (88 cardiologists and 126 non-cardiologists) were surveyed between May and July 1994. Most physicians (47.7%) reported that they saw one to five patients with atrial fibrillation weekly. Some 52% of cardiologists and 40% of non-cardiologists considered that the main factor influencing their decision of whether or not to anticoagulate was the clinical history--that is, heart failure, valve disease, or stroke. When encountering a patient admitted acutely with new onset atrial fibrillation, significantly more cardiologists (66% v 52%, chi 2 = 6.89, P = 0.03) would immediately start anticoagulant treatment, most favouring intravenous heparin. Most physicians would also introduce antiarrhythmic treatment or digoxin, but more cardiologists would attempt immediate pharmacological (39% v 18% of non-cardiologists, P < 0.001) or later electrical (86% v 69%, chi 2 = 11.7, P = 0.003) cardioversion to sinus rhythm, while non-cardiologists tended to prefer "rate control" with digoxin. Although many physicians would not continue antiarrhythmic treatment post-cardioversion, more cardiologists than non-cardiologists would do so (the commonest choice being class III agents) (31% v 17%, P = 0.04). Fewer non-cardiologists would continue anticoagulant treatment post-cardioversion (27% v 69% of cardiologists, chi 2 = 39.8, P < 0.0001). When treating patients with atrial fibrillation, decisions about anticoagulation were usually related to the perceived relative risk of thromboembolism versus haemorrhage derived for each of six case management scenarios in the questionnaire. There was, however, general agreement between cardiologists and non-cardiologists in the use of antithrombotic treatment in the management of lone atrial fibrillation, paroxysmal atrial fibrillation, and patients with atrial fibrillation and mitral valve disease or thyrotoxicosis. CONCLUSION: There is considerable variation in the management of atrial fibrillation, with more cardiologists than non-cardiologists considering cardioversion to sinus rhythm (and the use of antiarrhythmic and anticoagulant treatment post-cardioversion) and thrombo-prophylaxis with anticoagulation. Guidelines on the management of this common arrhythmia are clearly required.

Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report.

OBJECTIVE: Patients with essential hypertension are at high risk of atherosclerotic vascular disease. To investigate this further, we measured levels of the soluble adhesion molecule P-selectin, which is associated with platelet activity/function and atherosclerosis, von Willebrand factor, which is a marker of endothelial dysfunction, and plasma fibrinogen. PATIENTS AND METHODS: We studied 104 consecutive patients (47 males, 57 females; mean +/- SD age 54.8 +/- 14.1 years) with essential hypertension compared with 47 normotensive healthy controls (55.0 +/- 19.2 years). Levels of soluble adhesion molecule P-selectin and von Willebrand factor were measured by enzyme-linked immunosorbent assay, and plasma fibrinogen by a clotting method (CLAUSS). RESULTS: Compared with normotensives, the hypertensives showed significant increases in soluble P-selectin (300 versus 228 ng/ml; median difference 55 ng/ml, Mann-Whitney test P = 0.03), von Willebrand factor (114 versus 96 IU/I; unpaired t-test P < or = 0.001) and fibrinogen (3.3 versus 2.9 g/l; unpaired t-test P < or = 0.001). There were significant correlations between fibrinogen and P-selectin (r = 0.16; P = 0.02) and von Willebrand factor (r = 0.39; P<0.001), but not between P-selectin and von Willebrand factor. There were no differences in these factors between patients with (n = 53) and without (n = 51) antihypertensive therapy or between those with good blood pressure control (systolic/diastolic < or = 160/90 mmHg; n = 17) and those with poor control. A stepwise multiple regression analysis showed that diastolic blood pressure was a significant predictor for soluble P-selectin levels; diastolic blood pressure and von Willebrand factor levels were significant predictors for fibrinogen levels (P<0.05). CONCLUSIONS: This study suggests that hypertensives have high plasma fibrinogen levels, platelet dysfunction (which could contribute to atherogenesis, as indicated by raised soluble P-selectin levels) and endothelial dysfunction (as indicated by high von Willebrand factor levels), which are related to diastolic blood pressure. These factors may act synergistically to increase atherogenesis and may explain the high risk of atherosclerotic vascular disease in hypertensives.