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Biomedical subjects

S MacMahon

Publications and source records attributed to S MacMahon.

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

Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration.

BACKGROUND: This programme of overviews of randomised trials was established to investigate the effects of angiotensin-converting-enzyme (ACE) inhibitors, calcium antagonists, and other blood-pressure-lowering drugs on mortality and major cardiovascular morbidity in several populations of patients. We did separate overviews of trials comparing active treatment regimens with placebo, trials comparing more intensive and less intensive blood-pressure-lowering strategies, and trials comparing treatment regimens based on different drug classes. METHODS: The hypotheses to be investigated, the trials to be included, and the outcomes to be studied were all selected before the results of any participating trial were known. Individual participant data or group tabular data were provided by each trial and combined by standard statistical techniques. FINDINGS: The overview of placebo-controlled trials of ACE inhibitors (four trials, 12,124 patients mostly with coronary heart disease) revealed reductions in stroke (30% [95% CI 15-43]), coronary heart disease (20% [11-28]), and major cardiovascular events (21% [14-27]). The overview of placebo-controlled trials of calcium antagonists (two trials, 5520 patients mostly with hypertension) showed reductions in stroke (39% [15-56]) and major cardiovascular events (28% [13-41]). In the overview of trials comparing blood-pressure-lowering strategies of different intensity (three trials, 20,408 patients with hypertension), there were reduced risks of stroke (20% [2-35]), coronary heart disease (19% [2-33]), and major cardiovascular events (15% [4-24]) with more intensive therapy. In the overviews comparing different antihypertensive regimens (eight trials, 37,872 patients with hypertension), several differences in cause-specific effects were seen between calcium-antagonist-based therapy and other regimens, but each was of borderline significance. INTERPRETATION: Strong evidence of benefits of ACE inhibitors and calcium antagonists is provided by the overviews of placebo-controlled trials. There is weaker evidence of differences between treatment regimens of differing intensities and of differences between treatment regimens based on different drug classes. Data from continuing trials of blood-pressure-lowering drugs will substantially increase the evidence available about any real differences that might exist between regimens.

Aged↗
PubMed2000

Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.

BACKGROUND: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. METHODS: 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model. FINDINGS: Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group). INTERPRETATION: Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin.

Adult↗
PubMed2000

Pravastatin therapy and the risk of stroke.

BACKGROUND: Several epidemiologic studies have concluded that there is no relation between total cholesterol levels and the risk of stroke. In some studies that classified strokes according to cause, there was an association between increasing cholesterol levels and the risk of ischemic stroke and a possible association between low cholesterol levels and the risk of hemorrhagic stroke. Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have suggested that these agents may reduce the risk of stroke. METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in Ischaemic Disease study), we compared the effects of pravastatin on mortality due to coronary heart disease (the primary end point) with the effects of placebo among 9014 patients with a history of myocardial infarction or unstable angina and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per liter). Our goal in the present study was to assess effects on stroke from any cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There were 419 strokes among 373 patients over a follow-up period of six years. A total of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of unknown type. Among the patients given placebo, the risk of stroke was 4.5 percent, as compared with 3.7 percent among those given pravastatin (relative reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent; P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given placebo, as compared with 3.4 percent of those given pravastatin (reduction in risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS: Pravastatin has a moderate effect in reducing the risk of stroke from any cause and the risk of nonhemorrhagic stroke in patients with previous myocardial infarction or unstable angina.

Adult↗
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

Reducing the global burden of blood pressure-related cardiovascular disease.

OBJECTIVE: To assist in prioritisation for strategies for the control of cardiovascular disease (CVD) worldwide, by estimating the size of the contribution of elevated blood pressure and, more importantly, the likely effects of its modification. DESIGN: We estimated the size of the disease burden attributable to increased blood pressure in Eastern Asia and describe a method for estimating the likely effects of blood pressure lowering strategies. METHODS: Attributable risk estimates were calculated to assess the likely contribution of increased blood pressure to death from CVD in Asia. Estimates were also made of the possible effects of population-wide (2% lower diastolic blood pressure [DBP] for all) and targeted (7% lower DBP for those with DBP > or =95 mm Hg) blood pressure lowering interventions. These estimates were based on data from several sources, including surveys of blood pressure values in Asian populations, estimates of the incidence of cardiovascular disease in Asia, studies of the associations of blood pressure with cardiovascular disease risks in Asia and elsewhere, and randomized trials of blood pressure lowering treatments. RESULTS: The results suggest that DBP values of 80 mm Hg or more account for about 57% of all stroke deaths and about 24% of all coronary heart disease deaths in Eastern Asian populations. The two intervention strategies proposed would each be expected to avert about 1 in 6 stroke deaths and about 1 in 20 coronary heart disease deaths. This would amount to about 1 million deaths per year throughout Asia by 2020, with about half of those deaths averted in the People's Republic of China. The benefits of the two different approaches would be approximately additive. CONCLUSIONS: Increased blood pressure levels are directly responsible for the majority of stroke deaths (more than 50%) and a substantial minority of deaths from coronary heart disease (about 25%) in Eastern Asia. Both modest population-wide blood pressure reductions and more moderate targeted reductions in those with hypertension could be expected to produce large reductions in the burden of cardiovascular disease in these and other Asian regions.

Adolescent↗
PubMed2000

PROGRESS (Perindopril Protection Against Recurrent Stroke Study): regional characteristics of the study population at baseline. PROGRESS Management Committee.

OBJECTIVE: To determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure lowering regimen on the risk of stroke among patients with a history of cerebrovascular disease. Secondary aims include investigation of the effects of treatment on other cardiovascular events, dementia, and disability. DESIGN AND METHODS: PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a double-blind, placebo-controlled, randomized trial being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden, and the United Kingdom). Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication for or contraindication to treatment with a diuretic) or matching placebo(s). Both hypertensive and normotensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. RESULTS: Of 6105 patients randomly allocated to study groups on completion of recruitment in November 1997, 1110 were recruited from Australia and New Zealand, 1520 from China, 713 from France and Belgium, 557 from Italy, 815 from Japan, 675 from Sweden, and 715 from the UK and Ireland. Regional differences in the baseline characteristics included a greater rate of diabetes, lacunar infarction, and cerebral haemorrhage in patients from China and Japan, and a more frequent history of myocardial infarction in Australia and New Zealand. Previous treatment with calcium antagonists was very frequent in Japan and China, whereas diuretic treatment was most often documented in the UK and Ireland. CONCLUSIONS: Analysis of baseline characteristics of patients recruited from seven distinct geographic regions revealed some interesting differences, but more striking was the consistency of characteristics of patients recruited from many different countries across the world.

Aged↗
PubMed1999

Mortality after hip fracture: regional variations in New Zealand.

AIM: To determine the 35-day and one-year mortality rates following a hospital admission for hip fracture, among individuals aged 60 years or older in New Zealand. METHODS: New Zealand Health Information Service mortality data for the years 1988 to 1992 were examined to determine the case fatality rate among individuals aged 60 years or older admitted to hospital for fractures of the neck of femur (ICD-9 N-code 820). Case fatality rates assessed at 35 days and one year after admission to hospital were examined by age, gender, year of admission, place of residence, area health board region and cause of death. RESULTS: Between 1988 and 1992, the case fatality rate was 8% within 35 days of admission to hospital and 24% within one year of admission. Case fatality rates were found to be twice as high in men compared to women and four to five times higher in individuals aged 85 years and older, compared to people aged between 60 and 64 years. The only regional difference in hip fracture mortality was found in the Canterbury area health board region, which had a 30% higher rate of hip fracture mortality compared to all regions combined. The two main cited underlying causes of death after hip fracture were accidental falls (ICD E880-E888) and ischaemic heart disease (ICD 410-414). CONCLUSION: Over three-quarters of individuals aged 60 years or older who are hospitalised with a hip fracture in New Zealand survive for at least one year after admission. However, significant variations in mortality exist with age and gender. These data highlight the importance of preventive strategies for hip fracture in older people and the need to identify ways of improving post-admission care.

Age Distribution↗
PubMed1999

The World Health Organization--International Society of Hypertension Blood Pressure Lowering Treatment Trialists' Collaboration: prospective collaborative overviews of major randomized trials of blood pressure-lowering treatments.

Clear evidence shows that decreasing blood pressure reduces risks for major cardiovascular events in patients with hypertension. However, there is considerable uncertainty about the separate effects of the various classes of blood pressure-lowering agents and the effects of blood pressure lowering in patients at high risk, particularly in the absence of hypertension. Several new randomized controlled trials have been started in the past few years in an effort to address these questions. However, individually, these studies are unlikely to resolve all current uncertainties. For this reason, systematic overviews and meta-analyses of the major ongoing trials are planned. The overviews will be conducted as a collaboration among the principal investigators of the participating trials and will involve about 270,000 patients and 1.1 million patient-years of follow-up. The combined trial results should provide good statistical power to detect even modest differences in the effects of various treatments on major cardiovascular outcomes.

Adrenergic beta-Antagonists↗
PubMed1999

Blood pressure, cholesterol, and common causes of death: a review. Prospective Studies Collaboration.

Many prospective observational studies have reported on associations of blood pressure and blood cholesterol with cardiovascular disease, but few have been large enough to provide reliable estimates of the nature of these associations in different circumstances (or on the associations with nonvascular causes of death). Moreover, almost all such reports have related risk of disease to baseline measurements of the risk factor of interest, which can lead to substantial underestimation of the importance of the risk factor due to the regression dilution bias. By appropriate combination of individual participant data from all such studies in a systematic meta-analysis, with correction for regression dilution, the Prospective Studies Collaboration will characterize more precisely than has previously been possible the age- and gender-specific relevance of blood pressure and blood cholesterol to particular causes of death.

Age Factors↗
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↗
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↗
PubMed1998

Selection bias in clinical research when subjects are excluded because of failure to estimate left ventricular mass by echocardiography.

Quantitative echocardiographic imaging often is used in clinical research, but the method is not successful in all patients. The goals of this study were as follows: (1) to determine the frequency with which left ventricular mass (LVM) could be estimated by echocardiography, (2) to characterize persons in whom LVM could not be estimated from echocardiography, and (3) to determine whether failure to estimate LVM was independently related to any common cardiovascular risk factors, thereby suggesting a potential for selection bias. This research was part of a community-based case-control study of risk factors in hypertension. Five hundred hypertensive subjects and 506 normotensive age- and sex-matched control subjects were studied prospectively. The mean age was 61 years (range: 39 to 76 years), the mean weight was 74 kg (range: 37 to 127 kg), 46% of the subjects were men, and 56% had a history of smoking. Two-dimensionally guided M-mode echocardiography was attempted in all subjects for determination of LVM (Penn convention). LVM was estimated when the endocardial borders could be accurately identified from a true radial cavity diameter. LVM was estimated in 803 subjects (79.8%). Subjects in whom estimates of LVM could not be obtained were older and had the following characteristics: higher systolic blood pressure; larger chest, waist, and abdominal circumferences; higher waist/hip ratio; and larger body mass index (all P <.02). In multivariate analysis the only independent predictors of failure to estimate LVM by echocardiography were advanced age (P =.0001), larger chest size (P =.0001), and history of smoking (P =.004). The inability to estimate LVM in 20% of subjects has important implications to our understanding the strength of association between potential risk factors and LVM, an independent measure of cardiovascular risk. LVM is more likely to be missing in older subjects who have a large chest and a history of smoking. The effects of such a selection bias should be considered in any analysis, and a characterization of the excluded subjects should be developed.

Adult↗