Monitoring clinical trials.
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Clinical Protocols↗
Biomedical subjects
S MacMahon
Publications and source records attributed to S MacMahon.
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↗
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↗
Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group.
BACKGROUND: The beta-blocker/vasodilator carvedilol is found to have beneficial effects in patients with chronic heart failure. However, the safety and efficacy of this agent in the presence of concomitant amiodarone therapy has not been previously determined. METHODS AND RESULTS: We retrospectively analyzed the Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study of 415 patients with mild to moderate ischemic heart failure where amiodarone was administered as part of the treatment therapy (in 52 patients). After the open-label carvedilol run-in, patients received carvedilol (target dose 25 mg twice daily) or placebo for an average of 19 months. The main adverse events during this double-blind period were worsened heart failure, hypotension/dizziness, bradycardia/atrioventricular block, and aggravation of angina. By Chi square analysis, carvedilol and amiodarone together were not associated with a greater overall incidence of adverse effects than either drug alone. The beneficial effects of carvedilol on left ventricular ejection that were observed in the main trial were preserved in the presence of amiodarone. CONCLUSIONS: Carvedilol is a useful additional therapy for patients with chronic heart failure already receiving amiodarone. Carvedilol can be added to amiodarone in these patients without expectation of increased adverse effects or loss of clinical efficacy.
Adrenergic beta-Antagonists↗
The determinants of fat intake in a multi-ethnic New Zealand population. Fletcher Challenge--University of Auckland Heart and Health Study Management Committee.
BACKGROUND: The New Zealand diet is high in total and saturated fat and this is likely to be contributing to the increasing prevalence of obesity and relatively high rates of coronary heart disease in New Zealand. The identification of subgroups with a high-fat intake will enable nutrition-related public health strategies to be better targeted. METHODS: Subjects from two surveys were included in the study: 7574 employees from a large multinational workforce survey and 2447 people aged 35-84 years selected from a stratified random sample of the electoral roll in central Auckland. Fat and saturated fat intake were assessed by short questionnaire which gave a dietary fat habits (DFH) score and supplemented by a six-item food frequency questionnaire. RESULTS: The DFH scores were higher in males than in females at all ages, and there was an inverse relationship with age which was stronger for males. Age-adjusted scores showed significantly higher DFH scores for Maori than for Europeans. Lower socioeconomic status was associated with higher DFH scores in males. Current smoking and heavy drinking (in males) were associated with significantly higher DFH scores after controlling for socioeconomic status. The results of the limited food frequency questionnaire supported the trends in DFH scores. CONCLUSIONS: The subgroups with high total and saturated fat intakes which should be a priority for public health action are young and middle-aged males, Maori and lower socioeconomic status males. The clustering of high-fat intake with smoking and heavy drinking should be considered when developing preventative strategies.
Adult↗
Atherosclerosis and left ventricular hypertrophy: persisting problems in treated hypertensive patients.
OBJECTIVES: First, to determine whether hypertensive patients managed in general practice have more advanced atherosclerosis and left ventricular hypertrophy than matched normotensive patients from the same practices. Second, to investigate the associations of several potentially modifiable factors with these vascular and cardiac outcomes. DESIGN AND METHODS: We performed a case-control study of 500 hypertensive cases (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or receiving treatment) and 506 age- (mean 61 years) and sex- (54% female) matched normotensive controls recruited from general practices. Carotid artery far wall thickness (CWT), assessed by B-mode ultrasound, and left ventricular mass (LVM), assessed by M-mode echocardiography, were the main study outcome measures. RESULTS: Mean systolic/diastolic blood pressure levels in the 399 treated cases (145/87 mmHg) were lower than those in untreated cases (158/94 mmHg) but higher than those in controls (133/82 mmHg, all P < 0.0001). Mean body mass index (BMI) and total triglyceride levels were higher and high-density lipoprotein cholesterol was lower in cases than in controls (all P < 0.0004). Mean CWT was 10% greater in cases than in controls and LVM was 14% greater (both P < 0.001), but both were similar in treated and untreated cases (P > 0.05). In multivariate analyses, blood pressure and BMI were both directly and independently related to CWT and LVM (both P < 0.0001). CONCLUSIONS: In this study, hypertensive patients managed in general practice - whether treated with antihypertensive drugs or not - had more advanced atherosclerosis and left ventricular hypertrophy than did matched normotensive patients. Efforts to lower blood pressure further and to reduce BMI could potentially reduce these differences, and this might lead to a reduction in the risk of major cardiovascular events.
Aged↗
Association of environmental tobacco smoke exposure with socioeconomic status in a population of 7725 New Zealanders.
OBJECTIVE: To test the hypothesis that environmental tobacco smoke (ETS) exposure is inversely associated with socioeconomic status. DESIGN: Survey. SETTING: General community, New Zealand. PARTICIPANTS: 7725 non-smoking adults (volunteer sample of a multi-industry workforce, n = 5564; and a random sample of urban electoral rolls, n = 2161), including 5408 males; mean age 45 years. MAIN OUTCOME MEASURES: ETS exposure was assessed as self-reported number of hours per week spent near someone who is smoking, and as prevalence of regular exposure to some ETS. Socioeconomic status was assessed as educational level, occupational status, and median neighbourhood household income. RESULTS: Both measures of ETS exposure were steeply and inversely associated with all three indicators of socioeconomic status (all p < 0.0001). Geometric mean ETS exposure ranged from 16 minutes per week among university-educated participants to 59 minutes per week in the second lowest occupational quintile (95% confidence intervals: 14-18 minutes per week and 54-66 minutes per week). The associations with occupational status and educational level were steeper than those with neighbourhood income. The socioeconomic gradients of ETS exposure were steeper among participants aged less than 35 years than among participants aged over 50 years, among men than women, and among Maori than Europeans. CONCLUSIONS: In this study population, ETS exposure was inversely associated with socioeconomic status. Greater ETS exposure might therefore contribute to the higher risks of disease and death among low socioeconomic groups. These results provide a further rationale for targeting tobacco control measures to people in low socioeconomic groups.
Adult↗
Socioeconomic distribution of smoking in a population of 10,529 New Zealanders.
AIMS: This study aimed to investigate the associations of several smoking variables with socioeconomic status. METHODS: Cross-sectional analyses of data about smoking behaviour and socioeconomic status (education, occupation and neighbourhood income) were performed using baseline data from the Fletcher Challenge-University of Auckland Heart and Health Study (10,529 participants). RESULTS: After adjustment for age and sex, lower educational level was associated with: (1) higher frequency of ever having smoked (65% of participants who had attended secondary school for fewer than two years, versus 43% of participants who had attended university; 2p < 0.0001); (2) lower likelihood of having quit (46% versus 71%; 2p < 0.0001); (3) higher likelihood of being a current smoker (35% versus 12%; 2p < 0.0001); (4) higher tobacco consumption per smoker (13 manufactured cigarettes/day versus 8 manufactured cigarettes/day; 2p < 0.0001); and (5) higher tobacco consumption per participant (1980 cigarette-equivalents/year versus 450 cigarette-equivalents/year; 2p < 0.0001). Similar, but shallower, associations of these smoking variables were observed with occupation and neighbourhood income (with the exception that tobacco consumption per smoker was not associated with neighbourhood income). The socioeconomic gradients of tobacco consumption per study participant with all three socioeconomic indicators were particularly steep among younger participants, men and Maori. CONCLUSIONS: Participants of low socioeconomic status consumed a disproportionately large amount of tobacco. Policies that prevent smoking initiation and promote smoking cessation in low socioeconomic groups are therefore needed. These should include targeting of mass media messages to low socioeconomic groups, public subsidisation of nicotine replacement therapy and higher taxes on tobacco.
Adult↗
Regional variation in the incidence of hip fracture in New Zealand.
AIM: To determine the regional incidence of hip fracture among individuals aged 60 years or older in New Zealand. METHODS: New Zealand Health Information Service inpatient morbidity data for the years 1988-92 were examined by area health board region to identify all hip fractures (ICD N820) among individuals aged 60 years or older. RESULTS: Substantial regional variation exists in the incidence of hip fractures among older people in New Zealand. Among both men and women, similar regional variations were observed with the age-standardised rates being consistently highest in the West Coast (790 per 100,000 for women and 360 per 100,000 in men) and lowest in Northland (540 per 100,000 in women and 185 per 100,000 in men). CONCLUSION: These findings have implications for resource allocation, both in terms of targeting prevention initiatives and in providing acute and long term management of hip fracture patients. In addition, they raise questions as to why such variations in hip fracture incidence exist in New Zealand.
Aged↗
Migraine: a risk factor for motor vehicle driver injury?
To test the hypothesis that migraine is associated with motor vehicle driver injury, data collected from 10,529 individuals on personal history of migraine and motor vehicle injury were analysed cross-sectionally. In multiple logistic regression analyses, the adjusted odds ratio for motor vehicle driver injury associated with migraine was 2.3 [95% confidence interval (CI) 1.9-2.7]. After excluding those who also had a history of head injury, the odds ratio was 1.5 (95% CI: 1.2-2.0). These results suggest that migraine may be associated with a 50% increase in the risk of motor vehicle driver injury and that in this population may account for as many as one in every 20 motor vehicle driver injuries. These findings require confirmation in prospective studies of motor vehicle driver injuries.
Accidents, Traffic↗
Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.
OBJECTIVES: The aim of this study, a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure due to ischemic heart disease, was to determine the effects of this treatment on left ventricular size and function with the use of quantitative two-dimensional (2D) echocardiography. BACKGROUND: Beta-adrenergic blocking drugs have been shown to improve left ventricular ejection fraction in patients with heart failure due to either ischemic heart disease or idiopathic dilated cardiomyopathy. However, the effects of such treatment on left ventricular size remain uncertain. METHODS: One hundred twenty-three patients from 10 centers in New Zealand and Australia participated in the 2D echocardiographic substudy. Echocardiography was performed before randomization and was repeated after 6 and 12 months of treatment. Left ventricular end-diastolic and end-systolic volumes were measured from apical four- and two-chamber views with the use of a modified Simpson's rule method. RESULTS: After 12 months, heart rate was 8 beats/min lower in the carvedilol than in the placebo group, whereas left ventricular end-diastolic and end-systolic volumes were increased in the placebo group but reduced in the carvedilol group. At 12 months, left ventricular end-diastolic volume index was 14 ml/m2 less in the carvedilol than in the placebo group (p = 0.0015); left ventricular end-systolic volume index was 15.3 ml/m2 less (p = 0.0001), and left ventricular ejection fraction was 5.8% greater (p = 0.0015). CONCLUSIONS: In patients with heart failure due to ischemic heart disease, carvedilol therapy for 12 months reduced left ventricular volumes, increased left ventricular ejection fraction and prevented progressive left ventricular dilation. These changes demonstrate a beneficial effect of carvedilol on left ventricular remodeling in heart failure. The observed changes may explain in part the improved clinical outcomes produced by treatment with carvedilol.
Adrenergic beta-Antagonists↗
Effect of treatment with simvastatin on serum cholesteryl ester transfer in patients on dialysis. PERFECT Study Collaborative Group.
BACKGROUND: Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on dialysis who have elevated levels of apolipoprotein B (apoB)-containing lipoproteins. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, reduces levels of these lipoproteins but the effect of treatment on cholesteryl ester transfer activity in patients on dialysis remains to be determined. METHODS: We measured serum newly synthesized cholesteryl ester transfer (NCET) activity, lecithin:cholesterol acyltransferase (LCAT) activity and serum lipid, lipoprotein and apolipoprotein concentrations before and immediately after 6 months treatment with simvastatin (10 mg daily, n = 24) or placebo (n = 29) in 53 patients with chronic renal failure receiving haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). RESULTS: Simvastatin therapy significantly reduced serum cholesterol, LDL cholesterol, apoB concentrations, and both NCET (P = 0.001) and LCAT (P = 0.012) rates. The decrease in NCET activity was correlated significantly with the corresponding decrease in apoB concentration (r = 0.715, P < 0.001) and LCAT activity (r = 0.715, P < 0.001) during simvastatin therapy and was no longer significant when apoB concentration (P = 0.14) or LCAT activity (P = 0.07) were controlled. CONCLUSIONS: These data show that simvastatin therapy reduces serum NCET rates, and suggest that this may be linked to the concomitant decrease in levels of apoB-containing lipoproteins which are acceptors of transferred cholesteryl esters, and to the decrease in serum LCAT rates in patients with chronic renal failure with treatment.
Adolescent↗
Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.
AIMS: Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. METHODS AND RESULTS: Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. CONCLUSIONS: Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.
Administration, Oral↗
Reliable and unbiased assessment of the effects of calcium antagonists: importance of minimizing both systematic and random errors.
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Calcium Channel Blockers↗
Blood pressure lowering for the secondary prevention of myocardial infarction and stroke.
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Adrenergic beta-Antagonists↗
Use of the Friedewald formula to estimate LDL-cholesterol in patients with chronic renal failure on dialysis.
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Cholesterol, LDL↗
The Cochrane Collaboration: New Zealand gets involved.
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Humans↗
Ethnic differences in blood pressure: findings from the Fletcher Challenge-Auckland University Heart and Health Study.
AIMS: To investigate the determinants of ethnic differences in blood pressure, hypertension and the prevalence of additional risk factors for cardiovascular disease among a New Zealand population. METHODS: Baseline data from the Fletcher Challenge-University of Auckland Heart and Health Study were analysed for ethnic differences in blood pressure, and the likelihood of those with hypertension having other major cardiovascular disease risk factors was estimated. RESULTS: Maori and Pacific Islands participants had mean diastolic blood pressure up to 3 mmHg higher than Europeans, but Pacific Islands people had mean systolic blood pressure 3-4 mmHg lower than Europeans and Maori respectively. After adjustment for age and gender almost 20% of Maori, 16% of Pacific Islands and 11% of European people were classified as hypertensive. Adjustment for body mass index and alcohol consumption almost eliminated ethnic differences in blood pressure, and body mass index was found to be the single most important modifiable determinant of raised blood pressure. Greater proportions of Maori (15%) and Pacific Islands people (14%) with hypertension had multiple additional cardiovascular risk factors compared with Europeans (8%), but similar proportions were on antihypertensive drug treatment. CONCLUSIONS: Efforts to reduce obesity have the potential to significantly reduce raised blood pressure among Maori and Pacific Islands people. Overall cardiovascular risk is more likely to be higher in Maori and Pacific Islands people than in Europeans with hypertension, indicating that greater proportions of Maori and Pacific Islands people with high blood pressure should be receiving treatment.
Adult↗