Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women.

BACKGROUND AND AIMS: Pre-clinical studies suggest that sesame and its lignans induce beneficial changes in risk factors related to cardiovascular disease and increase the bioavailability of mammalian lignans. However, only very few intervention trials have investigated the potential bioactivities of sesame in humans. We aimed to investigate the effects of sesame supplementation in humans on blood lipids, blood pressure, systemic oxidative stress, inflammatory biomarkers and mammalian lignan metabolism. METHODS AND RESULTS: We conducted a randomized, placebo-controlled cross-over intervention trial at a university research centre. Overweight or obese men and women (n=33) consumed 25g/d of sesame ( approximately 50mg/d of sesame lignan) and an iso-caloric placebo matched for macronutrient composition for 5 wks each. Each intervention period was preceded by a 4-wk washout period. Blood lipid profiles, day time ambulatory blood pressure, oxidative stress and inflammatory biomarkers and urinary mammalian lignans were measured before and after each intervention. Results are presented as the effect of sesame supplementation relative to placebo. Urinary excretion of the mammalian lignans, enterolactone and enterodiol, increased by approximately 8-fold (P<0.001). Blood lipids and blood pressure were not altered. In addition, markers of systemic inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) and lipid peroxidation (F(2)-isoprostanes) were not affected. CONCLUSION: Supplementation with 25g/d of sesame can significantly increase the exposure to mammalian lignans. However, this did not cause any improvement in markers of cardiovascular disease risk in overweight or obese men and women.

Hospital admissions and length of stay for coronary disease in an Aboriginal cohort.

BACKGROUND AND AIMS: Coronary disease (CHD)-related hospital admission is more common among indigenous than non-indigenous Australians. We aimed to identify predictors of hospital admission potentially useful in planning prevention programs. METHODS AND RESULTS: Length of stay (LOS), interval between, and number of recurrent admissions were modelled with proportional hazards or negative binomial models using lifestyle data recorded in 1988-1989 among Aborigines (256 women, 258 men, aged 15-88years) linked to hospital records to 2002. Among 106 Aborigines with CHD, hypertension (hazard ratio (HR) 1.69, 95% CI 1.05-2.73); smoking (HR 1.90, 95% CI 1.02-3.53); consuming processed meat >4 times/month (HR 1.81, 95% CI 1.01-3.24); >6 eggs/week (HR 1.73, 95% CI 1.03-2.94); and lower intake of alcohol (HR 0.54, 95% CI 0.35-0.83) predicted LOS. Eating eggs (HR 1.05, 95% CI 1.01-1.09) and bush meats > or =7 times/month (HR 0.46, 95% CI 0.23-0.92) predicted interval between recurrent admissions. Hypertension (IRR 4.07; 95% CI 1.32-12.52), being an ex-drinker (IRR 6.60, 95% CI 2.30-19.00), eating red meat >6 times/week (IRR 0.98, 95% CI 0.97-0.99), bush meats >7 times/month (IRR 0.26, 95% CI 0.10-0.67), and adding salt to meals (IRR 3.16, 95% CI 1.12-8.92) predicted number of admissions. CONCLUSION: Hypertension, alcohol drinking, smoking, and diet influence hospital admissions for CHD in Aboriginal Australians.

The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized.

A retrospective review of the prevalence of intraepithelial neoplasia (IN) in surgically removed perianal/anal warts from December 1995 to December 2004 was undertaken in patients referred to the Sexual Health Clinic at Royal Perth Hospital. Data were analysed from 115 men and 38 women, 29 of whom had HIV infection (27 men and two women). Perianal/anal IN within the warts was found in 78% (52% high grade) of men with HIV infection. In men without HIV infection, the overall rate of IN within warts was 33% (20% high grade). The IN rate was 8.3% for HIV-negative women (2.8% high grade). Rates of IN within perianal/anal warts in men with or without HIV infection are higher than previously reported, and suggest the likelihood of a substantial increase in the future incidence of anal cancer. The association between IN and genital warts needs to be further studied.

Quality of life and psychological morbidity in women with polycystic ovary syndrome: body mass index, age and the provision of patient information are significant modifiers.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has clinical features and implications for long-term health that may lead to decreased quality of life (QoL) and psychological morbidity. We studied QoL in women with PCOS, compared the findings with population norms and assessed whether they correlated with reported quality of patient information received. DESIGN: Cross-sectional study. PATIENTS: Women with PCOS by National Institutes of Health (NIH) criteria, diagnosis confirmed by one endocrinologist. MEASUREMENTS: Four questionnaires were mailed: the Short Form-36 (SF-36), the Quality-of-Life Questionnaire for Women with Polycystic Ovary Syndrome (PCOSQ), the General Health Questionnaire-28 (GHQ-28) and an assessment of information quality and sources, the Patient Information Questionnaire (PIQ). RESULTS: Questionnaires were sent to 443 women with PCOS from one endocrinologist's database; 203 women aged 15-65 years agreed to participate. To compare with Australian population norms, data from those women aged 18-44 years (n = 173) were used. Of these, 64% were obese, 18% overweight and 18% of normal weight. The demographics, socioeconomic status and untreated biochemistry of the responders and the total patient group were not significantly different. SF-36 scores were significantly lower than the age- and sex-matched Australian population (P < 0.01), including the overweight subset (P < 0.01). Health-related QoL by PCOSQ was similar to other published studies. GHQ-28 identified psychological morbidity in 62.4%, compared with 26.4% in a matched Australian population (P < 0.0001). Body mass index (BMI) was negatively correlated with QoL (P < 0.01). There was a positive association between the psychological domain of QoL and the subjective assessment of the quality of health-related information in general (P < 0.001), for hirsutism (P < 0.01) and for menstrual irregularity (P < 0.05). CONCLUSIONS: We have shown impaired QoL and increased prevalence of psychological morbidity in PCOS compared with population norms. The perception of inadequate information about the condition correlated with poorer QoL scores. Improved information delivery may lead to an improvement in QoL and needs to be tested with an intervention study.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.