Biomedical subjects

V Burke

Publications and source records attributed to V Burke.

At least 19 recordsLinked to original sources

PubMed2006

Alcohol intake and incidence of coronary disease in Australian aborigines.

AIMS: To examine risk for coronary heart disease (CHD) and cardiovascular disease (CVD) in relation to alcohol in a cohort of Australian Aborigines. METHODS: In 1988-1989, alcohol intake, drinking pattern, and beverage preference were elicited by interviewer-administered questionnaire in Western Australian Aborigines (258 men, 256 women) and cardiovascular outcomes ascertained through linkage to mortality and hospital admission records to 2002. RESULTS: In proportional hazards models, risk for CHD, relative to lifetime abstainers, was significantly increased in ex-drinkers [Hazard ratio (HR) 2.29, 95% CL 1.23, 4.27], those drinking 41-60 g/day in men or 21-40 g/day in women (HR 2.80, 95% CL 1.04, 7.53), and those drinking >150 g/day for men or >100 g/day for women (HR 2.25, 95% CL 1.03, 4.90) with a J-shaped relationship. Low-to-moderate drinkers had lower waist girth, exercised more, and had a lower prevalence of overweight and smoking than at-risk drinkers. A preference for wine was associated with lower HR (0.28, 95% CL 0.10, 0.95). With CVD, only ex-drinkers showed significantly increased risk (HR 1.87, 95% CL 1.20, 2.91). CONCLUSIONS: More favourable health-related behaviours in low-to-moderate drinkers suggest that lower risk could be mediated by lifestyle, as proposed in other populations.

Adolescent↗

PubMed2006

Alcohol intake and incidence of coronary disease in Australian aborigines.

AIMS: To examine risk for coronary heart disease (CHD) and cardiovascular disease (CVD) in relation to alcohol in a cohort of Australian Aborigines. METHODS: In 1988-1989, alcohol intake, drinking pattern, and beverage preference were elicited by interviewer-administered questionnaire in Western Australian Aborigines (258 men and 256 women) and cardiovascular outcomes ascertained through linkage to mortality and hospital admission records to 2002. RESULTS: In proportional hazards models, risk for CHD, relative to lifetime abstainers, was significantly increased in ex-drinkers [Hazard ratio (HR), 2.29; 95% confidence intervals (CI), 1.23-4.27], those drinking 41-60 g/day in men or 21-40 g/day in women (HR 2.80; 95% CI, 1.04-7.53) and those drinking >150 g/day for men or >100 g/day for women (HR, 2.25; 95% CI, 1.03-4.90) with a J-shaped relationship. Low-to-moderate drinkers had lower waist girth, exercised more and had a lower prevalence of overweight and smoking than at-risk drinkers. A preference for wine was associated with lower HR (0.28; 95% CI, 0.10-0.95). With CVD, only ex-drinkers showed significantly increased risk (HR, 1.87; 95% CI, 1.20-2.91). CONCLUSIONS: More favourable health-related behaviours in low-to-moderate drinkers suggest that lower risk could be mediated by lifestyle, as proposed in other populations.

Adolescent↗

PubMed2006

Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines.

OBJECTIVE: To examine predictors of coronary heart disease (CHD) and all-cause mortality in Aboriginal Australians. METHOD: In 1988-89, a survey of Western Australian Aborigines (256 women, 258 men) aged 15-88 years documented diet, alcohol and smoking habits. Linkage to mortality and hospital admissions to the end of 2002 provided longitudinal data for modelling of coronary heart disease endpoints and all-cause mortality using Cox regression. RESULTS: Coronary heart disease risk increased with smoking (HR 2.62, 95% CI: 1.19, 5.75), consumption of processed meats >once/week (HR 2.21, 95% CI: 1.05, 4.63), eggs >twice/week (HR 2.59, 95% CI: 1.11, 6.04) and using spreads on bread (HR 3.14. 95% CI: 1.03, 9.61). All-cause mortality risk was lower with exercise >once/week (HR 0.51, 95% CI 0.26, 1.05), increased in ex-drinkers (HR 3.66, 95% CI: 1.08, 12.47), heavy drinkers (HR 5.26, 95% CI: 1.46, 7.52) and with consumption of take away foods >nine times/month (HR 1.78, 95% CI 0.96, 3.29). Greater alcohol intake, smoking and adverse dietary choices clustered in 53% of men and 56% of women and increased risk of coronary heart disease (HR 2.1, 95% CI: 1.1, 4.0) and all-cause mortality (HR 2.3, 95% CI: 1.2, 4.2). CONCLUSION: Lifestyle in Aboriginal Australians predicts coronary heart disease and all-cause mortality. Clustering of adverse behaviours is common and increases risk of coronary heart disease and death.

Adolescent↗

PubMed2006

Perinatal and childhood origins of cardiovascular disease.

BACKGROUND: Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children. METHODS AND RESULTS: Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05-3.2). Risk was lower if children were breast fed for >/=4 months (OR=0.6, 95% CI=0.37-0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8-51.1) compared to the nadir PEBW quintile of non-smokers. CONCLUSION: A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.

Birth Weight↗

PubMed2005

Predictors of body mass index and associations with cardiovascular risk factors in Australian children: a prospective cohort study.

OBJECTIVE: To examine predictors of body mass index (BMI) at the age of 8 y in a prospective study of Australian children. DESIGN: Longitudinal survey of a cohort of Australian children followed from the 16th week of gestation to 8 y. SUBJECTS: In total, 741 boys and 689 girls who attended the survey as 8 y olds. MEASUREMENTS: Weight and height, blood pressure measured by automated oscillometry, fasting blood lipids and glucose. Questionnaire assessment of activity and diet. RESULTS: Proportions of overweight including obesity in boys and girls were, respectively, 22 and 25% at 1 y, 14 and 14% at 3 y, 13 and 18% at 5 y and 15 and 20% at 8 y. At the age of 1, 3, 6 and 8 y, children with overweight including obesity showed significantly more adverse cardiovascular risk factors. Blood pressure (BP) was significantly higher by 2/3 mmHg (systolic/diastolic) at 1 y, 3/2 mmHg at 3 y, 4/2 mmHg at 5 y and 6/2 mmHg at 8 y; HDL was significantly lower (P=0.002) by 8% and triglycerides were significantly higher by 27% (P<0.001). In multivariate regression, BMI at the age of 8 y was significantly predicted positively by birth weight, mother's BMI and hours spent in watching television at the time of the survey of 6 y olds. Mothers being ex-smokers or non smokers and children being 'slightly active' and 'active' negatively predicted BMI in 8 y olds. In a subset of 298 children with information about fathers, paternal BMI was an additional independent predictor. Maternal or paternal overweight including obesity each independently increased risk of overweight including obesity at the age of 8 y three-fold. A food factor with consumption of cereals and breads as the major components derived from a Food Frequency Questionnaire in a subset of 340 children was also an independent negative predictor of BMI in multivariate models. CONCLUSION: The increasing rate of overweight including obesity, particularly in girls, is associated with an increase in cardiovascular risk factors very early in life. Improvement of health-related behaviours within the family and a focus on promotion of activity in children should be priorities in achieving weight control.

Birth Weight↗

PubMed2005

Cholesterol tracking from childhood to adult mid-life in children from the Busselton study.

AIM: To determine if subjects' cholesterol levels tracked relative to their peers from early childhood to adult mid-life. METHODS: Longitudinal study using subjects from the Busselton Population Study. Data were available from 1967 on a triennial basis until 1983, and a re-survey held in 1994. The study included 1764 subjects aged 5-18 y at first measurement. Pearson's correlation coefficient, adjusted for age and survey year, was used to examine cholesterol tracking. The proportion of children who persisted with cholesterol measurements in the extreme high quartile was assessed over time before and after adjusting data for regression to the mean. The variability of the children's cholesterol level was examined by track width using the method of Porkka. RESULTS: The correlation coefficients for tracking were from 0.35 to 0.55. Stronger correlations coincided with shorter time periods between measurements. Before adjustment for regression to the mean, 55-60% of children from the highest quartile at first measurement remained in the same quartile 27 y later. After adjustment for regression to the mean, the number of children with levels in the extreme high quartile decreased, but 80% of these persisted in that quartile. CONCLUSION: Intra-individual variations in cholesterol levels have an important influence on population tracking levels and need to be considered when interpreting tracking results from early childhood to adult mid-life. However, removing the effect of regression to the mean by taking multiple measurements of cholesterol will probably improve prediction for individuals.

Adolescent↗

PubMed2004

A randomized trial of interactive group sessions achieved greater improvements in nutrition and physical activity at a tiny increase in cost.

OBJECTIVE: Weight gain may follow altered eating habits and decreased physical activity in couples beginning to live together. Mutual support and willingness to accept changes in lifestyle at this stage may facilitate positive responses to health promotion. We aimed to compare the effects of a diet and physical activity program in couples using a randomized controlled trial. STUDY DESIGN AND SETTING: Couples were randomized to a control group or to one of two intervention groups in whom the program was either delivered mainly by mail or with a combination of mail-outs and interactive group sessions. RESULTS: Diets, physical fitness, and blood cholesterol improved up to 12 months after beginning the 4-month program, mainly in the interactive group. In that group, at the end of the program, the estimated cost was 445.30 dollars (111.33 dollars/month) per participant per unit change in outcome variables, only 0.03 dollars per participant per month more than the group receiving the program mainly by mail. One year after beginning the program, costs per participant per month were 38.37 dollars in the interactive group and 38.22 dollars in the group receiving the program mainly by mail-out. CONCLUSION: The changes observed in cardiovascular risk factors could translate to a substantial cost-savings relating to health.

Adult↗

PubMed2004

Associations between blood pressure and overweight defined by new standards for body mass index in childhood.

BACKGROUND: Using data from a longitudinal study of young Australians, we applied recent international standards for overweight and obesity to examine associations with blood pressure (BP) and to determine the prevalence and degree of tracking of overweight and obesity. We also aimed to examine socioeconomic status in relation to these variables. METHODS: BP, height, and weight were measured at 3-year intervals from age 9 to 18, and then at 25 years of age in a Western Australian cohort. At these stages, data were available for 1,036, 1,310, 618, 615 and 600 individuals, respectively. RESULTS: We found 10% of 9-year-old males to be overweight or obese, while among 12-year-olds, 13% were overweight or obese; at age 15, and still at age 18, overweight or obesity was registered in 17% of this population and it rose to 42% among the 25-year-old young men. The percentage of overweight or obese females at these stages was initially 8, then 12 (at age 12), 11 (at age 15), 14 (at age 18) and finally 32. Overweight or obesity tracked to young adult life in 16% of those overweight or obese at 9, 24% at 12, 34% at 15 and 35% at 18 years. Systolic BP was significantly higher in the overweight or obese except in 12-year-olds. At the age of 25 years, 53% of men had high normal BP or were hypertensive. CONCLUSIONS: Increasing overweight or obesity in young Australians, consistent with international trends, has serious health implications. Overweight and obesity show tracking and are predictors of higher blood pressure, except in early adolescence.

Adolescent↗

PubMed2003

Controlled comparison of retention and adherence in home- vs center-initiated exercise interventions in women ages 40-65 years: The S.W.E.A.T. Study (Sedentary Women Exercise Adherence Trial).

BACKGROUND: In an 18-month exercise intervention in previously sedentary older women (40-65 years), we examined whether an initial 6 months of supervised exercise leads to greater long-term retention and adherence to regular physical activity than an unsupervised home-based program and whether these outcomes are influenced by the exercise intensity. METHODS: Women (N = 126) were recruited from the community and randomly assigned to either center-based or home-based exercise three times/week. The center-based group attended supervised sessions for 6 months, while after 10 initial sessions the home-based group exercised at home. After 6 months both groups were home-based for a further 12 months. Within each arm, subjects were further randomized to exercise at either moderate or vigorous intensity. RESULTS: The center-based group had higher retention than the home-based (97, 94, 81 versus 87, 76, and 61%) at 6, 12, and 18 months, respectively (P < 0.05). At 6 months, adherence was higher in the center-based group (84 versus 63%, P < 0.001) and energy expenditure was higher at 6 (P < 0.05) and 12 (P < 0.01) months. At 18 months, retention was higher with moderate exercise (P < 0.05), while adherence was similar with both intensities. CONCLUSION: An initial 6 months of center-based exercise enhanced retention in both the short and the long term and promoted short-term adherence and energy expenditure. Long-term, moderate exercise retained more subjects, but had little influence on adherence.

Adult↗

PubMed2003

Effects of general practice-based nurse-counselling on ambulatory blood pressure and antihypertensive drug prescription in patients at increased risk of cardiovascular disease.

Lifestyle programmes delivered by academic nurse-counsellors in a primary care setting lowered blood pressure (BP) among at-risk patients. We examined whether the programmes could be successfully implemented by nurses employed in Australian general practices. In a randomised controlled trial, 212 of 591 eligible 20-75-year olds with hypertension, Type II diabetes or coronary disease from seven practices volunteered. Patients were randomised to: a 'Low' group with one face-to-face individual counselling session, then monthly telephone contacts for 1 year (n=69); a 'High' group with individual face-to-face counselling up to 1 h monthly for 1 year (n=74) or a control group receiving usual care only (n=69), and were evaluated at baseline and 12 and 18 months later; 164 individuals completed the study. Patients' usual doctors continued to prescribe in all groups. Changes in 24 h ambulatory BP did not differ significantly between groups at 12 months (Low, -2+/-2/1+/-1 mmHg; High, +4+/-2/1+/- 1 mmHg; usual care, +1+/-2/1+/-1 mmHg) or 18 months (-2+/-2/2+/-1 mmHg; -4+/-2/3+/-2 mmHg; -1+/-2/2+/- 1 mmHg, respectively). Antihypertensive drugs prescribed decreased by 12 months in 33% of the High, 5% of the Low and 13% of the control groups (P=0.008) and by 36, 7 and 16% at 18 months (P=0.018). After 18 months, targets for BP control were not met in about 60% of patients and almost 50% had clinic BP above 140/90 mmHg. Year-long interaction with nurse-counsellors may influence longer-term antihypertensive drug prescription, possibly by improving compliance. Suboptimal BP control suggests that continuing physician education on BP targets is needed.

Adult↗

PubMed2003

Waist circumference, waist-to-hip ratio and body mass index as predictors of adipose tissue compartments in men.

BACKGROUND: The accumulation of fat in visceral and posterior subcutaneous adipose tissue compartments is highly correlated with the metabolic abnormalities that contribute to increased risk of diabetes mellitus and cardiovascular disease. AIM: To determine which of waist circumference (WC), waist-to-hip ratio (WHR) and body mass index (BMI) was the best predictor of intraperitoneal and posterior subcutaneous abdominal adipose tissue mass in men. METHODS: We studied 59 free-living men with a wide range of BMI. WC, WHR and BMI were determined using standard methods. Intraperitoneal, retroperitoneal, anterior subcutaneous and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, ASAATM and PSAATM, respectively) were quantified using magnetic resonance imaging. RESULTS: In univariate regression analysis, WC, WHR and BMI were all significantly and positively correlated (all p < 0.05) with IPATM, RPATM, ASAATM and PSAATM. To assess the relative strength of these associations, we used non-nested regression models. There was no significant difference between WC and WHR in predicting IPATM and RPATM; WC was a stronger predictor of ASAATM (p < 0.001) and PSAATM (p < 0.001) than WHR; WC was also a stronger predictor of IPATM (p = 0.042) and RPATM (p = 0.045) than BMI, but the relative strengths of WC and BMI in predicting ASSATM and PSAATM did not different significantly (p > 0.05); there was no significant difference between BMI and WHR in predicting IPATM and RPATM (p>0.05), but BMI was a stronger predictor of ASAATM (p = 0.036) and PSAATM (p < 0.001) than WHR. DISCUSSION: In men WC is the anthropometric index that most uniformly predicts the distribution of adipose tissue among several fat compartments in the abdominal region, there apparently being little value in measuring WHR or BMI.

Abdomen↗

PubMed2003

Exercise behaviour change in 40 to 65-year-old women: The SWEAT Study (Sedentary Women Exercise Adherence Trial).

OBJECTIVE: The purpose of this study was to examine the relation between self-reported psychological processes and changes in exercise behaviour in an 18-month longitudinal stage-based intervention trial in 115 initially sedentary women aged 40-65 years. DESIGN: A two-way factorial design was used. METHODS: Participants were assigned randomly to either moderate or vigorous and either home or centre-based exercise. After six months, all participants exercised at home. Participants completed questionnaires at baseline, six, 12 and 18 months which assessed stage of exercise behaviour, self-efficacy, decisional balance and processes of change. RESULTS: 28 patterns of stage change were identified across the 18 months with 6.1% remaining sedentary and 45% demonstrating linear movement from contemplation to action to maintenance to continued maintenance. Two interpretable clusters were identified within both the contemplation (at baseline) and action (at six months) stages. Cluster membership, however, did not influence behaviour change. For participants demonstrating a linear pattern of change, self-efficacy for overcoming barriers and behavioural processes increased from contemplation to action. Self-efficacy for exercise competence increased from contemplation to action but was more pronounced for the vigorous exercise groups. Decisional balance showed a three-way interaction and there was no change for experimental processes. There was no change in any variable from action to maintenance. CONCLUSIONS: The intervention was seen to be effective regardless of location or intensity of exercise. The relevance of substages is questionable in stage-based interventions as women with a profile suggesting less readiness to change or sustain change were just as likely to adopt or maintain exercise.

Adult↗

PubMed2002

Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus.

AIM/HYPOTHESIS: We assessed whether dietary supplementation with coenzyme Q(10) improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. METHODS: A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q(10) or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F(2)-isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. RESULTS: The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q(10) and decreased by -0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q(10) treatment resulted in a threefold increase in plasma coenzyme Q(10) (p < 0.001) but did not alter plasma F(2)-isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. CONCLUSION/INTERPRETATION: Coenzyme Q(10) supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F(2)-isoprostane concentrations.

Antioxidants↗

PubMed2002

Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes.

OBJECTIVE: Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects. SUBJECTS AND DESIGN: Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention. SETTING: The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia. INTERVENTIONS: Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks. MAIN OUTCOME MEASURES: We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes. RESULTS: Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345). CONCLUSIONS: These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes. SPONSORSHIP: This study was supported by a grant from the NH&MRC, Australia.

Antioxidants↗

PubMed2002

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised, double-blind comparative trial in Asian patients.

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P<or=0.0001) and 2.4+/-6.3 vs 6.0+/-6.0 mmHg for diastolic BP (P<or=0.0002). Significant differences between the two drugs in mean 24-h ambulatory BP levels were already evident on day 1 after withdrawal, even though there were no significant differences on the final day of treatment. No differences in safety parameters were observed, and neither drug caused any serious or severe treatment-related adverse events. In conclusion, amlodipine provides greater protection than nifedipine GITS against loss of BP control following missed doses.

Amlodipine↗

PubMed2002

Relationship between sample size and the definition of equivalence in non-inferiority drug studies.

Statistical testing of clinical trial data leads to acceptance of a hypothesis if a test of the opposite (null) hypothesis (H0) fails to reach a critical probability value. The usual aim is to demonstrate that a new treatment is superior to a comparator, whence H0 is that the two treatments are the same. By contrast, in studies designed to show that a new treatment is equivalent to an existing therapy, the same principle is satisfied by an amended null hypothesis, that the treatments differ by more than a defined amount. This reversal entails subtle but important logical and practical problems which affect particularly the calculation of sample size. The choice of the limits used to define equivalence is critical to the calculation of sample size in a manner not previously discussed, and in the interpretation of data in relation to the probability of Type I and Type II errors. Investigators, regulatory bodies and institutional ethics committees must ensure that the range of values chosen to indicate equivalence is clinically appropriate and be aware of the effect of this decision on possible errors in accepting or rejecting H0.

Clinical Trials as Topic↗

PubMed2001

Red wine polyphenols, in the absence of alcohol, reduce lipid peroxidative stress in smoking subjects.

Phenolic compounds in red wine can exert antioxidant effects on in vitro lipoprotein oxidation. This has led to speculation that red wine consumption mediates unique anti-atherosclerotic effects compared to other alcoholic beverages. However, studies assessing the effects of red wine consumption on lipoprotein oxidation ex vivo have not been conclusive. The recent identification of the F2-isoprostanes as oxidative products of arachidonic acid has provided a reliable measure of in vivo lipid peroxidation. This randomized trial investigated changes in plasma and urinary F2-isoprostane concentrations following red wine, white wine, or dealcoholized red wine consumption in humans. Eighteen male smokers consumed, in random order, red wine, white wine, or dealcoholized red wine, for two weeks with one week washout between beverages. Plasma and urinary F2-isoprostane concentrations were measured before and after each beverage. Serum gamma-glutamyl transpeptidase (gamma-GT) and urinary 4-O -methylgallic acid were measured as markers of alcohol consumption and phenolic acid absorption, respectively. Plasma F2-isoprostanes (p < .05) decreased significantly with dealcoholized red wine but not with the alcohol-containing beverages. Urinary excretion of F2-isoprostanes showed a similar trend. gamma-GT decreased significantly with dealcoholized red wine and increased with both alcohol-containing beverages (p < .01). Urinary excretion of 4-O-methylgallic acid increased significantly (p < .001) in the 24 h urine samples following red wine or dealcoholized red wine ingestion, but not with white wine. Serum urate increased and beta-carotene decreased with both alcoholic beverages relative to dealcoholized red wine. There was no change in the antioxidants alpha- and gamma-tocopherol or vitamin C with any of the beverages. The results suggest that polyphenols in dealcoholized red wine can reduce in vivo lipid peroxidation as measured by F2-isoprostanes in smoking subjects. However, no reduction in lipid peroxidation was observed following red or white wine consumption, suggesting that any protective effects of wine drinking on cardiovascular disease are unlikely to be related to inhibition of lipid oxidation.

Adult↗

PubMed2001

Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids.

Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Three recently described exonic polymorphisms of the gene, D9N, N291S and S447X, have been variably found to influence plasma lipids while effects on coronary heart disease (CHD) are less well documented. Two predominantly Caucasian groups were studied: CHD patients <50 years of age, with angiographically documented CHD; and a randomly recruited community control group without a history of heart disease. The 9N allele of the D9N polymorphism was present in 25 of 428 (5.8%) of Caucasian males with CHD and in seven of 291 (2.4%) of corresponding community subjects (odds ratio, 2.5; 95% confidence interval (CI), 1.1-5.9; P=0.03) and was also significantly over-represented in the Caucasian males with myocardial infarction (MI) (21 of 308 or 6.8%; odds ratio, 2.6; 95% CI, 1.1-5.9; P=0.01). The distributions of the other two polymorphisms were similar in the CHD and community groups. In multivariate models adjusted for age, sex, diabetes, body mass index, smoking, lipid levels and race, the D9N polymorphism remained significantly related to both CHD and MI, with an odds ratio >2. There were, generally, trends to more adverse fasting plasma high-density lipoprotein (HDL) cholesterol and triglycerides in carriers of the 291S and 9N alleles, and the opposite trends for triglycerides in 447X carriers. In the community group, male carriers of 291S (n=13) had significantly (20%) lower HDL cholesterol than corresponding non-carriers (n=323), 0.98+/-0.07 mmol/l (mean+/-S.E.) versus 1.22+/-0.02 mmol/l (P<0.005), while HDL cholesterol was not different in male carriers (n=8) and non-carriers (n=296) of 9N (1.23+/-0.13 mmol/l versus 1.22+/-0.02 mmol/l). Multivariate analysis confirmed that the 291S allele carrier status conferred a significantly lower HDL cholesterol (P=0.001) and the 447X allele lower triglyceride (P<0.01) in the community group. In conclusion, LPL 9N carrier status was unequivocally related to premature CHD and to MI in males, strongly supporting recent results in older aged males. The somewhat different effects of the D9N and N291S polymorphisms on plasma lipids, and the absence of a clear effect of the N291S on CHD, raise the possibility that the effect of 9N carrier status might be mediated through effects on LPL function in addition to those influencing fasting plasma lipids.

Adult↗