PubMed Health⌕ Search

Biomedical subjects

N Sharpe

Publications and source records attributed to N Sharpe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.

OBJECTIVES: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). CONCLUSIONS: The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effects of carvedilol on left ventricular regional wall motion in patients with heart failure caused by ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: Beta-blocker therapy has been shown to improve left ventricular (LV) ejection fraction and reduce LV volumes in patients with heart failure caused by ischemic heart disease. However, the possible mechanisms of this improvement and the effects of such treatment on regional wall motion have not been established. In a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure caused by ischemic heart disease, the effects of treatment on LV regional wall motion were assessed using 2-dimensional echocardiography. METHODS AND RESULTS: One hundred nineteen patients from 10 centers were included on this substudy. Patients were randomly assigned to treatment with carvedilol or placebo. Echocardiography was performed before randomization and after 6 and 12 months of treatment. LV regional wall motion was assessed using a semiquantitative scoring system. LV wall motion score index (WMSI) was reduced from 2.40 to 2.29 after 6 and 12 months in the carvedilol group and remained unchanged in the placebo group (2-tailed P = .005, carvedilol vs placebo). The percentage of myocardium with normal function also significantly improved with carvedilol treatment. CONCLUSIONS: Carvedilol improved LV regional WMSI in patients with heart failure caused by ischemic heart disease. These results indicate a mechanism by which beta-blocker therapy may benefit patients with heart failure and are consistent with an intrinsic improvement in LV function after treatment with carvedilol.

Adrenergic beta-Antagonists↗
PubMed2000

Does a glass of red wine improve endothelial function?

AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease.

Adult↗
PubMed2000

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers.

BACKGROUND: Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role. AIMS: The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects. METHODS: Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19-35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD). RESULTS: Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p<0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia (p<0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different (p=0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%). CONCLUSIONS: These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.

Acute Disease↗
PubMed1999

Reliability of echocardiographic assessment of left ventricular structure and function: the PRESERVE study. Prospective Randomized Study Evaluating Regression of Ventricular Enlargement.

OBJECTIVES: The study was done to evaluate reliability of echocardiographic left ventricular (LV) mass. BACKGROUND: Echocardiographic estimation of LV mass is affected by several sources of variability. METHODS: We assessed intrapatient reliability of LV mass measurements in 183 hypertensive patients (68% men, 65 +/- 9 years) enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial after a screening echocardiogram (ECHO) showed LV hypertrophy. A second ECHO was repeated at randomization (45 +/- 25 days later). Two-dimensional (2D)-guided M-mode or 2D linear measurements of LV cavity and wall dimensions were verified by one experienced reader. RESULTS: Mean LV mass was similar at first and second ECHO (243 +/- 53 vs. 241 +/- 54 g) and showed high reliability as estimated by intraclass correlation coefficient (RHO) = 0.93. Within-patient 5th, 10th, 90th and 95th percentiles of between-study difference in LV mass were -32 g, -28 g, +25 g and +35 g. Mean LV mass fell less from the first to the second ECHO than expected from a formula to predict regression to the mean (2 +/- 19 vs. 17 +/- 12 g, p < 0.001). Reliability was also high for LV internal diameter (RHO = 0.87), septal (RHO = 0.85) and posterior wall thickness (RHO = 0.83). Substantial or moderate reliability was observed for measures of LV systolic function and diastolic filling (RHO from 0.71 to 0.57). CONCLUSIONS: Left ventricular mass had high reliability and little regression to the mean; between-study LV mass change of +/-35 g or +/-17 g had > or = 95% or > or = 80% likelihood of being true change.

Aged↗
PubMed1999

Relations of diastolic left ventricular filling to systolic chamber and myocardial contractility in hypertensive patients with left ventricular hypertrophy (The PRESERVE Study).

Abnormalities of left ventricular (LV) diastolic filling and stress-corrected midwall shortening (MWS) have been described in hypertensive patients with normal ejection fraction (EF). However, whether stress-corrected MWS parallels LV diastolic filling better than EF does remains uncertain. Blood pressure, body mass index, echocardiographic LV mass and LV geometry, EF and stress-corrected MWS, LV diastolic filling (peak E- and A-wave velocities, E-wave deceleration time, and atrial filling fraction) were evaluated in 212 hypertensive patients with LV hypertrophy enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement study. LV structure, geometry, as well as LV diastolic filling, were compared between patients with reduced EF (<55%, n = 39, 18%) and those with normal EF (>55%) as well as between patients with reduced stress-corrected MWS (<89.2%, n = 31, 15%) and those with normal stress-corrected MWS (>89.2%). Patients with reduced EF had higher LV mass, eccentric LV geometry, and higher heart rate than those with normal EF, although they did not differ in age, blood pressure, or body mass index. LV filling pattern was also similar in those 2 groups. Patients with reduced stress-corrected MWS had higher atrial filling fraction, body mass index, heart rate, LV mass, and concentric geometry than those with normal stress-corrected MWS. Atrial filling fraction was negatively associated with stress-corrected MWS, but not with EF in multivariate models, independently of age, gender, heart rate, and body mass index. Thus, in hypertensive patients with LV hypertrophy, abnormal LV diastolic filling is more closely related to impaired myocardial contractility than to LV chamber EF.

Aged↗
PubMed1999

Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.

BACKGROUND: Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo. METHODS AND RESULTS: Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P<0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P<0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4. 0%; P<0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% (P<0.001). CONCLUSIONS: Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of beta-blockade in heart failure.

Arginine Vasopressin↗
PubMed1999

Symptomatic systolic ventricular failure.

Over the past 20 to 30 years there have been significant advances in the management of heart failure related to improved understanding of pathophysiology, better methods of assessment, and improved drug treatments. The aims of treatment have broadened, with increased emphasis on earlier intervention. Clinical research activity in this area has been considerable, increasingly allowing an evidence-based approach to management. Most earlier trials of treatment were relatively short-term, small-group studies with various clinical end points, including severity of symptoms, exercise performance, and left ventricular function assessment; however, increasingly a higher standard of evidence has been required, including a provision of reliable, large-scale mortality trial data. This has been further encouraged, if not mandated, by the relatively recent appreciation that some agents may demonstrate dissociation of treatment effects, possibly dose related, with improved short-term outcomes but adverse effects on survival with prolonged treatment. The general principles of management of congestive heart failure encompass patient evaluation and confirmation of the diagnosis, consideration, and correction of underlying remediable causes and precipitating factors, pharmacological treatment, patient education and counseling, and planned follow-up, as summarized in recently published guidelines. This review focuses primarily on the available randomized controlled clinical trial evidence related to the pharmacological treatment of the clinical congestive heart failure syndrome. Other aspects of management, such as patient education, counseling, and planned follow-up, should be regarded as complementary to pharmacological treatment and important to ensure compliance and optimal long-term outcomes.

Adrenergic beta-Antagonists↗
PubMed1999

Impact of a shared decision-making program on patients with benign prostatic hyperplasia.

OBJECTIVES: To determine patient views about the Shared Decision-Making Program (SDP), an interactive videodisk program designed to inform patients with benign prostatic hyperplasia (BPH) about their condition and treatment options and to determine its impact on perceived knowledge and treatment preference. METHODS: Six hundred seventy-eight patients with symptomatic BPH from eight Canadian centers viewed the SDP. Before and after viewing the video, patients answered questionnaires designed to assess treatment preference, knowledge gained, and satisfaction with this educational format. A 1-year follow-up survey was also conducted. RESULTS: Most patients showed a high desire for information and high satisfaction with the SDP; this satisfaction persisted at 1 year. Patients' self-reported knowledge increased significantly (P <0.0001). However, the SDP did not alter initial treatment preferences among those with already formed preferences, although it aided almost half of those initially undecided in forming a preference. Viewing the SDP also appeared to enhance the physician-patient relationship. CONCLUSIONS: Patients saw the SDP as an effective method for teaching patients about BPH and the risks and benefits of various treatments, clarifying particular areas about which many patients appear to have a desire for more information than is often provided. Patients were enthusiastic about the educational value of the program, and their active participation in the decision-making process may actually enhance the physician-patient relationship. Contrary to other studies, we found no significant alterations in treatment preferences. Problems relating to the cost and timely updating of the software need to be addressed for these kinds of programs to realize their full potential.

Aged↗
PubMed1999

Left ventricular mass correlates with fat-free mass but not fat mass in adults.

BACKGROUND: Left ventricular mass is associated with body size, obesity and blood pressure. Echocardiography is routinely used to estimate this parameter, which is usually indexed to body surface area to allow comparisons to be made between individuals and groups of different body size. However, in obese subjects, using left ventricular mass indexed to body surface area may inappropriately normalize left ventricular mass. OBJECTIVES: The aim of this study was to investigate the relationships between left ventricular mass and body composition and to determine the best determinants of left ventricular mass. SUBJECTS AND METHODS: Echocardiography and dual-energy X-ray absorptiometry were performed in 106 subjects under primary care. Half were hypertensive subjects and the others were normotensive age- and sex-matched control subjects. Univariate correlations were studied between left ventricular mass and height, height1.5, height2.7, weight, body surface area, body mass index, waist: hip ratio, fat-free mass, bone mineral content and fat mass. Stepwise multiple linear regression was performed to determine the best determinants of left ventricular mass. RESULTS: Fat-free mass was correlated with left ventricular mass (r = 0.53, P = 0.0001) and was the only independent predictor of left ventricular mass (R2 = 0.30, P= 0.0001) by multivariate analysis. Fat mass did not correlate with left ventricular mass (r= -0.005, P= 0.96). Other measures of body size, including body surface area, waist: hip ratio, bone mineral content, weight, height, height 1.5, height2.7 and body mass index all were correlated with, but were not independent determinants of, left ventricular mass. CONCLUSIONS: Left ventricular mass is independently determined by fat-free mass but by no other measures of body size or composition. Specifically, left ventricular mass was neither correlated with nor determined by fat mass. None of the other measures of body size determined left ventricular mass. It may be more appropriate to index left ventricular mass to fat-free mass rather than to measures of body size which include fat mass.

Aged↗
PubMed1999

Handgrip exercise increases postocclusion hyperaemic brachial artery dilatation.

OBJECTIVE: To examine the effect of handgrip exercise induced ischaemia on non-invasive assessment of endothelial function in the brachial artery. DESIGN AND SETTING: High frequency ultrasound was used to measure brachial artery diameter at rest and after reactive hyperaemia induced by forearm cuff occlusion with and without handgrip exercise induced ischaemia. SUBJECTS: 10 healthy subjects, < 40 years, without known cardiovascular risk factors. MAIN OUTCOME MEASURES: Brachial artery dilatation and blood flow. RESULTS: Hyperaemia following forearm occlusion with handgrip exercise induced ischaemia increased brachial artery diameter significantly more than hyperaemia following occlusion alone, 6.9 (3.2)% and 4.5 (1.6)%, respectively (95% confidence interval 0.3% to 4.5%). There was no difference in peak blood flow with and without exercise induced ischaemia CONCLUSIONS: Handgrip exercise induced ischaemia with forearm occlusion caused more pronounced brachial artery dilatation than occlusion alone without change in peak blood flow. This suggests continued brachial artery responsiveness to the stimulus of ischaemia despite maximum blood flow and peripheral vasodilatation with occlusion alone.

Adult↗
PubMed1998

Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group.

BACKGROUND: Cholesterol lowering in patients with above-average cholesterol levels has been shown to reduce the progression of atherosclerosis and lower the risk of coronary heart disease events. However, there has been uncertainty about the effects of cholesterol lowering in patients with average or below-average cholesterol levels. METHODS AND RESULTS: In this study, 522 patients with a history of myocardial infarction or unstable angina and with baseline levels of total cholesterol between 4 and 7 mmol/L (mean, 5.7 mmol/L) were randomized to treatment with a low fat diet plus pravastatin (40 mg daily) or to a low fat diet plus placebo. Treatment with pravastatin reduced the levels of total cholesterol by 19%, LDL cholesterol by 27%, apolipoprotein B by 19%, and triglycerides by 13% (all 2P<.0001) and increased apolipoprotein A1 and HDL cholesterol levels by 4% (both 2P<.0005), in comparison with placebo. Carotid atherosclerosis was assessed from B-mode ultrasound measurements of the common carotid artery. After 4 years, mean carotid wall thickness had increased by 0.048 mm (SE=0.01) in the placebo group and declined by 0.014 mm in the pravastatin-treated group (SE=0.01) (2P for difference <.0001). The effect of treatment on wall thickness was similar in three groups classified by tertiles of total cholesterol at baseline, with mean levels of 4.8, 5.7, and 6.6 mmol/L, respectively (2P for interaction >.8). CONCLUSIONS: Treatment with pravastatin reduced the development of carotid atherosclerosis among patients with coronary heart disease and a wide range of pretreatment cholesterol levels. Treatment with this agent prevented any detectable increase in carotid wall thickening over 4 years of follow-up.

Adult↗