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S MacMahon

Publications and source records attributed to S MacMahon.

At least 91 records · Page 5Linked to original sources
PubMed1994

Beta-blockers in heart failure: promising or proved?

Despite recent improvements in the management of congestive heart failure, the prognosis of many patients with this condition remains poor. The level of neurohormonal activation appears to be predictive of survival, and clinical studies indicate that inhibition of overactivated neurohormonal systems may be beneficial. Activation of the renin-angiotensin-aldosterone system is well documented in heart failure, and angiotensin-converting enzyme inhibition now has an established role in treatment based on evidence of hemodynamic, symptomatic and mortality benefit. Sympathetic nervous system activation also occurs as a compensatory mechanism in heart failure but with long-term deleterious effects. Increasing evidence suggests that beta-adrenergic blockade can produce hemodynamic and symptomatic improvement in heart failure of idiopathic or ischemic etiology. Trials of beta-adrenergic blocking agents in patients after myocardial infarction suggest a beneficial effect on mortality, even among those with heart failure. However, there remains uncertainty as to how generalizable are the results from the postinfarction trials, particularly in the current therapeutic environment with routine angiotensin-converting enzyme inhibitor therapy. Appropriately powered randomized, controlled trials are required to determine precisely the balance of benefit and risk resulting from long-term beta-blocker therapy in patients with heart failure of ischemic and other etiology.

Adrenergic beta-Antagonists↗
PubMed1994

Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease.

Most evidence about the effects of blood pressure on the risks of cardiovascular disease derives from two principal sources: prospective non-randomised observational studies of the associations between blood pressure and the incidence of stroke and of coronary heart disease, and randomised trials of antihypertensive drug therapy. The focus of the first part of this chapter concerns the evidence from observational studies, which--despite the possibility of confounding by other risk factors--may be more relevant to the eventual effects of prolonged blood pressure differences on stroke and coronary heart disease risk. The focus of the second part concerns the evidence from randomised trials of antihypertensive drug treatment, which are more relevant to assessing how rapidly, and to what extent, the epidemiologically expected reductions in stroke or in coronary heart disease are produced by suddenly lowering blood pressure in middle and old age.

Adult↗
PubMed1994

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study.

We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Pharmacological thromboprophylaxis in hip and knee surgery: a survey of New Zealand orthopaedic surgeons.

A survey was conducted of the attitudes and practices of New Zealand orthopaedic surgeons on the use of pharmacological thromboprophylaxis (PT) for patients undergoing major hip or knee surgery. A questionnaire was sent to all 106 consultant surgeons known to perform hip or knee surgery and a response rate of 89% was obtained. The results suggested that while almost all surgeons used PT at some time, only about one-third of elective surgery patients and just a few per cent of patients with neck of femur fracture (NOFF) receive PT. For about three-quarters of surgeons, heparin (usually low molecular weight) was the most frequently used PT. About half of the surgeons began prophylaxis pre-operatively and about half stopped it when the patients were mobile postoperatively. Previous venous thromboembolism was felt by almost all surgeons to be a very important indication for PT; gross obesity, prolonged pre-operative immobility and active malignancy were thought to be very important factors by approximately one-half of the surgeons. The presence of a major bleeding diathesis or active peptic ulcer was cited as a contraindication to PT by more than two-thirds of all surgeons. Fear of bleeding complications and the rarity of thromboembolic complications were cited as reasons for limited use of PT by about one-third of surgeons. The results suggest that most surgeons usually rely on non-pharmacological methods of thromboprophylaxis, particularly for NOFF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroplasty↗
PubMed1994

Cholesterol reduction and death from non-coronary causes: evidence from randomised controlled trials.

An overview of randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction approximately 10%) provides clear evidence of a reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the observed reduction in CHD death (9% +/- 3) was only half as large as the reduction in non-fatal myocardial infarction (19% +/- 4), although both were statistically significant (2p < 0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 9%, the expected reduction in total deaths was about 5-6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases individually statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations suggest that the small excesses of non-coronary deaths observed in the cholesterol reduction trials may have occurred by chance. Evidence from ongoing longer-term studies of treatments producing larger cholesterol reductions will be useful in further delineating the effects, if any, of such treatments on non-coronary mortality.

Cholesterol↗
PubMed1994

Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound measurements of the common carotid artery.

BACKGROUND AND PURPOSE: Arterial stiffness may indicate early vascular changes that predispose to the development of major vascular disease. The repeatability of a variety of indices of arterial stiffness calculated from a standard carotid arterial M-mode ultrasound image was investigated. METHODS: Twenty-six asymptomatic normal subjects were imaged and had blood pressure recordings on each of two separate occasions at least 1 day apart. Using a computer-assisted method, the maximum and minimum internal diameter and average wall thickness of the right common carotid artery were measured over several cardiac cycles, and the following indices of arterial stiffness and distensibility (compliance) were derived: the pressure-strain elastic modulus (Ep), Young's modulus (E), cross-sectional compliance (CC), and the distensibility coefficient (DC). RESULTS: The repeatability of these measures, expressed as coefficients of variation, was as follows: Ep, 18%; E, 24%; CC, 14%; and DC, 13%. In another group of 20 subjects, the coefficient of variation for repeat examination by different sonographers was Ep, 19%; E, 20%; CC, 14%; and DC, 17% and for the one sonographer using two ultrasound machines was Ep, 13%; E, 13%; CC, 11%; and DC, 13%. These values indicate a moderate level of repeatability. In a univariate analysis each of these indices was significantly related to increasing age (Ep = 1.0 + 12.9 x AGE, r = .80; E = 314.5 + 13.9 x AGE, r = .48; CC = 22.6-0.26 x AGE, r = -.63; DC = 64.0-0.65 x AGE, r = -.78) but not to wall thickness (all P > .47). Using multiple regression techniques to adjust for age, wall thickness is a significant predictor of distensibility (P = .017), cross-sectional compliance (P < .001), and the pressure-strain elastic modulus (P = .019). Because Young's modulus is calculated from wall thickness, it could not be included in the multivariate analysis. CONCLUSIONS: We conclude that estimates of carotid artery distensibility and cross-sectional compliance derived from M-mode ultrasound recordings are moderately repeatable and may provide useful additional end points for trials of atherosclerotic progression.

Adult↗
PubMed1994

Blood pressure, antihypertensive treatment and stroke risk.

ASSOCIATION BETWEEN BLOOD PRESSURE AND STROKE: Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. The strength of this association has been substantially underestimated by many previous analyses that have not taken account of the regression dilution bias; correction for this increases the strength of the association between blood pressure levels and stroke risk by about 60%. From corrected analyses it is apparent that a prolonged difference in usual systolic/diastolic blood pressure levels of just 9/5 mmHg would eventually confer about a one-third difference in stroke risk, with similar proportional effects in hypertensives and normotensives. RESULTS OF CLINICAL TRIALS: The results of randomized trials of antihypertensive drugs suggest that much or all of the long-term potential stroke avoidance associated with this level of prolonged blood pressure difference can be achieved within just a few years of beginning treatment. Overall, in 17 randomized trials of antihypertensive treatment, a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic conferred a reduction in stroke incidence of 38% (SD 4), with similar reductions in fatal and non-fatal strokes. Additionally, the sizes of the reductions were similar in trials in mild, moderate and more severe hypertension, in trials in older and younger patients and in trials in patients with a history of cerebrovascular disease and in patients without such a history. CONCLUSIONS: Because the proportional effects of treatment were similar in all these groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. Thus the greatest benefits were observed among those with a history of cerebrovascular disease, those above the age of 60 years and those with more severe hypertension.

Adult↗
PubMed1993

Management of raised blood pressure in New Zealand: a discussion document.

A report to the National Advisory Committee on Core Health and Disability Support Services, New Zealand, on the management of raised blood pressure recommends that decisions to treat raised blood pressure should be based primarily on the estimated absolute risk of cardiovascular disease rather than on blood pressure alone. In general, patients with a blood pressure of 150-170 mm Hg systolic or 90-100 mm Hg diastolic, or both, should be given treatment to lower blood pressure if the risk of a major cardiovascular disease event in 10 years is more than about 20%. The results of clinical trials indicate that, at this level of absolute risk, 150 people would require treatment to reduce the annual number of cardiovascular events by about one. Implementation of these recommendations may result in a smaller proportion of people aged under 60, particularly women, receiving treatment but an increased proportion of older people treated. In the absence of specific contraindications, low dose diuretics and low dose beta blockers should be considered for first line treatment, since for only these drug groups is there direct evidence of reduced risk of stroke and coronary disease in people with raised blood pressure.

Blood Pressure↗
PubMed1993

B-mode ultrasound images of the carotid artery wall: correlation of ultrasound with histological measurements.

B-mode ultrasound is being used to assess carotid atherosclerosis in epidemiological studies and clinical trials. Recently the interpretation of measurements made from ultrasound images has been questioned. This study examines the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and in situ in cadavers. Twenty-seven segments of human carotid artery were collected at autopsy, pressure perfusion fixed in buffered 2.5% glutaraldehyde and 4% paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical probe). Each artery was then frozen, sectioned and stained with van Gieson or elastin van Gieson. The thickness of the intima, media and adventitia were measured to an accuracy of 0.01 mm from histological sections using a calibrated eye graticule on a light microscope. Shrinkage artifact induced by histological preparation was determined to be 7.8%. Digitised ultrasound images of the artery wall were analysed off-line. The distance from the leading edge of the first interface (LE1) to the leading edge of the second interface (LE2) was measured using a dedicated programme. LE1-LE2 measurements were correlated against histological measurements corrected for shrinkage. Mean values for the far wall were: ultrasound LE1-LE2 (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm, S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18), intima (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall thickness, rather than elastin or the intima-media complex. Excision of part of the intima plus media or removal of the adventitia resulted in a corresponding decrease in the LE1-LE2 distance of the B-mode image. Furthermore, increased wall thickness due to intimal atherosclerotic thickening correlated well with LE1-LE2 distance of the B-mode images. B-mode images obtained from the carotid arteries in situ in four cadavers also corresponded best with total wall thickness measured from histological sections and not with the thickness of the intima plus media. In conclusion, the LE1-LE2 distance measured on B-mode images of the carotid artery best represents total wall thickness of intima plus media plus adventitia and not intima plus media alone.

Adult↗
PubMed1993

The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives.

Direct evidence about the effects of antihypertensive treatment on vascular disease in older patients is available from five randomized trials conducted exclusively in patients over the age of 60 years. These trials involved a total of 12,483 individuals with systolic or diastolic hypertension (mean age = 72 years, mean entry blood pressure = 181/88 mmHg). Over an average follow-up period of 4.7 years, a 15/6 mmHg difference in blood pressure between study and control groups was achieved. Among those patients assigned active treatment, stroke incidence was reduced by 34% SD6 and coronary heart disease incidence was reduced by 19% SD7. These proportional reductions were of similar size to those observed in trials in predominantly younger patients. However, the absolute benefits observed in older patients were more than twice as great as those observed in younger patients. The results suggest that over 10 years, treatment would prevent at least one major vascular event among every 10 elderly patients at similar risk to those enrolled in the trials.

Aged↗
PubMed1992

Lowering cholesterol: effects on trauma death, cancer death and total mortality.

Randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction approximately 10%) have demonstrated a clear reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the reduction in CHD death was only half as large as the reduction in non-fatal myocardial infarction (MI), although both were statistically significant (2P < 0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 10%, the expected reduction in total deaths was about 6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations are consistent with the hypothesis that the small excesses of cancer and trauma deaths observed in the cholesterol reduction trials occurred by chance.

Anticholesteremic Agents↗
PubMed1991

Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations.

OBJECTIVE: To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN: Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING: Urban Shanghai, China. SUBJECTS: 9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE: Death from coronary heart disease and other causes. RESULTS: The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION: Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death.

Cerebrovascular Disorders↗
PubMed1991

Long-term antiplatelet therapy for the prevention of vascular disease.

OBJECTIVE: To estimate the effects of prolonged antiplatelet therapy on the primary and secondary incidence of vascular disease. DATA SOURCES: Twenty-five randomised trials in 29,000 patients with a history of vascular disease (the Antiplatelet Trialists' Collaboration) and two randomised trials in 27,000 individuals without a history of vascular disease (the British doctors' and American physicians' studies). STUDY SELECTION: The Antiplatelet Trialists' Collaboration obtained data from all randomised trials of secondary prevention completed before January 1988. The British doctors' and American physicians' studies are the only two completed randomised trials of primary prevention. DATA EXTRACTION: Data from the secondary prevention trials were provided by the Antiplatelet Trialists' Collaboration. Data from the primary prevention trials were extracted from the final published reports of these studies. DATA SYNTHESIS: In the secondary prevention trials, antiplatelet therapy reduced the rate of vascular disease by about 15% and the incidence of non-fatal myocardial infarction and stroke by about 30%. In the American physicians' study, but not the British doctors' study, the incidence of non-fatal myocardial infarction was also reduced. In neither primary prevention trial was there evidence of reduced rates of non-fatal stroke or vascular death; overall, fatal or disabling strokes were slightly more frequent among those assigned aspirin. CONCLUSIONS: For patients with a history of vascular disease, the benefits of antiplatelet therapy appear to outweigh any risks. Among 100 such patients, antiplatelet therapy for two years would prevent one death and two major non-fatal events. The balance of benefits and risks for individuals without a history of vascular disease is less clear because there is no firm evidence of a net reduction in either vascular death or disabling non-fatal vascular events among those treated with aspirin.

Aspirin↗
PubMed1991

Blood pressure reduction and the prevention of stroke.

Observational epidemiological studies demonstrate a direct continuous relationship between the level of usual blood pressure and the incidence of stroke. The level of blood pressure appears to be an important determinant of stroke risk in normotensives as well as hypertensives. Clinical trials of blood pressure reduction in hypertensive patients suggest that much or all of the stroke avoidance associated with prolonged blood pressure differences are achieved within a few years of beginning treatment. In this regard, the effects of diuretics and beta-blockers have not been shown to be clearly different. Two important areas for future research in the prevention of stroke concern the effects of blood pressure reduction in high risk normotensive individuals (e.g. those with a history of transient cerebral ischaemia) and the effects of antiplatelet therapy in hypertensive individuals.

Adrenergic beta-Antagonists↗
PubMed1991

Effects of antihypertensive treatment on coronary artery disease: directions for future research.

Previous trials have shown that a 5-6 mm Hg reduction in diastolic blood pressure produced by antihypertensive treatment (mainly diuretics) reduces the risk of coronary artery disease (CAD) by 14% SD5 (2p less than 0.01). However, the 95% confidence limits for this estimate of treatment effect are wide and consistent, with true reductions as small as 4% or as large as 22%. For this reason, it is not possible to determine whether the treatment benefit is of a worthwhile magnitude. Because CAD remains the leading cause of death in hypertensive patients (and normotensive patients) in most Western populations, further studies are required to determine more precisely the effect of blood pressure reduction on the incidence of CAD. This could be achieved by further large-scale studies comparing antihypertensive treatment with no treatment. It could also be achieved by comparing the effects of more and less intensive antihypertensive treatment regimens. Additional relevant information might also be generated by studies comparing the effects on CAD of new classes of antihypertensive drugs (such as angiotensin-converting enzyme inhibitors and calcium antagonists) with those of older classes (in particular diuretics). In all such studies, the detection of plausible treatment effects or of plausible treatment differences requires the recruitment of large study populations with follow-up continued for several years. This is only feasible if study methods are kept simple to insure the widest possible collaboration.

Animals↗