The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

BACKGROUND: Neutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB4. OBJECTIVE: This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. DESIGN: In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. RESULTS: Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB5 (P < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. CONCLUSION: n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease.

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.

The effects of alcohol on ambulatory blood pressure and other cardiovascular risk factors in type 2 diabetes: a randomized intervention.

OBJECTIVE: Although prospective studies suggest light-to-moderate chronic alcohol intake protects against coronary artery disease in type 2 diabetic patients, the balance of effects on individual cardiovascular risk factors needs further assessment. We examined the effects of alcohol consumption on 24-h ambulatory blood pressure (BP) and heart rate (HR), high-density lipoprotein cholesterol, fibrinogen, C-reactive protein, homocysteine, and glycaemic control in well controlled type 2 diabetes. METHODS: Twenty-four participants aged 49-66 year were randomized to a three-period crossover study with women drinking red wine 230  ml/day (∼24  g alcohol/day) and men drinking red wine 300  ml/day (∼31  g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. Ambulatory BP and HR were monitored every 30  min for 24  h at the end of each period. Home blood glucose monitoring was carried out twice weekly throughout. RESULTS: Red wine increased awake SBP and DBP relative to water by 2.5 ±â€Š1.2 /1.9 ±â€Š0.7  mmHg (P = 0.033, P = 0.008, respectively), with a similar nonsignificant trend relative to DRW. Asleep DBP fell with red wine relative to DRW (2.0 ±â€Š0.8  mmHg, P = 0.016) with a similar nonsignificant trend relative to water. Red wine increased 24-h, awake and asleep HR relative to water and DRW. Relative to DRW, red wine did not affect glycaemic control or any other cardiovascular risk factor. CONCLUSION: In well controlled type 2 diabetic individuals 24-31  g alcohol/day (∼2-3 standard drinks) raises awake BP and 24-h HR and lowers asleep BP but does not otherwise favourably or adversely modify cardiovascular risk factors.

A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease.

BACKGROUND AND OBJECTIVE: The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD. METHODS: In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography-tandem mass spectrometry before and after intervention. RESULTS: Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased (P = 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively. CONCLUSION: SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD.

Randomized Controlled Intervention of the Effects of Alcohol on Blood Pressure in Premenopausal Women.

Alcohol has been consistently demonstrated to elevate blood pressure (BP) in intervention studies in men. There are uncertainties, however, as to the nature of the relationship in women. We, therefore, determined in healthy premenopausal women the dose-dependent effects of alcohol on ambulatory BP. Twenty-four participants aged 25 to 49 years, with a mean alcohol intake of 202±94 g alcohol/wk and mean 24-hour systolic and diastolic BP of 110.2±8.9/68.9±5.7 mm Hg, were randomized to a 3-period cross-over study. Each evening they consumed higher volume red wine (lower level drinkers, 146 g alcohol/wk; higher level drinkers, 218 g alcohol/wk), lower volume red wine (lower level drinkers, 42 g alcohol/wk; higher level drinkers, 73 g alcohol/wk), or dealcoholized red wine, each for a period of 4 weeks. Higher volume red wine significantly increased 24 hours systolic and diastolic BP relative to dealcoholized red wine (by 2.0±0.6/1.2±0.4 mm Hg; P=0.001 and P=0.028, respectively). There were similar changes for higher volume red wine relative to lower volume red wine (by 1.6±0.6/1.4±0.4 mm Hg; P=0.014 and P=0.005, respectively). These effects were predominantly on awake rather than asleep BP. There was no significant difference in BP between lower volume red wine and dealcoholized red wine. We conclude that in healthy premenopausal women regular consumption of alcohol as 200 to 300 mL red wine/d (146-218 g alcohol/wk) elevates 24 hours systolic and diastolic BP. The magnitude of the increase in BP is similar to that previously reported in intervention studies in men.

n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease.

BACKGROUND: Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. METHOD: We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. RESULTS: Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P < 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P < 0.0001) and DBP (P < 0.0001) after n-3 fatty acids. CONCLUSION: This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.

Clustering of metabolic and cardiovascular risk factors in the polycystic ovary syndrome: a principal component analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent condition with heterogeneity of clinical features and cardiovascular risk factors that implies multiple aetiological factors and possible outcomes. OBJECTIVE: To reduce a set of correlated variables to a smaller number of uncorrelated and interpretable factors that may delineate subgroups within PCOS or suggest pathogenetic mechanisms. MATERIALS AND METHODS: We used principal component analysis (PCA) to examine the endocrine and cardiometabolic variables associated with PCOS defined by the National Institutes of Health (NIH) criteria. Data were retrieved from the database of a single clinical endocrinologist. We included women with PCOS (N = 378) who were not taking the oral contraceptive pill or other sex hormones, lipid lowering medication, metformin or other medication that could influence the variables of interest. PCA was performed retaining those factors with eigenvalues of at least 1.0. Varimax rotation was used to produce interpretable factors. RESULTS: We identified three principal components. In component 1, the dominant variables were homeostatic model assessment (HOMA) index, body mass index (BMI), high density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL) cholesterol and triglycerides; in component 3, total testosterone and LH/FSH ratio. These components explained 37%, 13% and 11% of the variance in the PCOS cohort respectively. CONCLUSIONS: Multiple correlated variables from patients with PCOS can be reduced to three uncorrelated components characterised by insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering of risk factors is consistent with different pathogenetic pathways within PCOS and/or differing cardiometabolic outcomes.

Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment--a position paper of the The Obesity Society and The American Society of Hypertension.

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity-related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced-based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients.

Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment: a position paper of The Obesity Society and the American Society of Hypertension.

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and the American Society of Hypertension agreed to jointly sponsor a position paper on obesity-related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced-based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients.

The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes: Results from two placebo-controlled interventions.

Omega-3 (omega3) fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular disease. Despite these benefits, concern remains that omega3 fatty acids may increase lipid peroxidation. It has previously been shown that urinary F(2)-isoprostanes (F(2)-IsoPs) were reduced following omega3 fatty acid supplementation in humans. It is now determined whether EPA or DHA supplementation affects plasma F(2)-IsoPs. In two 6-week placebo-controlled interventions, Study A: overweight, dyslipidaemic men; and Study B: treated-hypertensive Type 2 diabetic, patients were randomized to 4 g daily EPA, DHA. Post-intervention plasma F(2)-IsoPs were significantly reduced by EPA (24% in Study A, 19% in Study B) and by DHA (14% in Study A, 23% in Study B) relative to the olive oil group. The fall in plasma F(2)-IsoPs was not altered in analyses that corrected for changes in plasma arachidonic acid, which was reduced with EPA and DHA supplementation. Neither F(3)- nor F(4)-IsoPs were observed in plasma in both studies. These results show that in humans, EPA and DHA reduce in vivo oxidant stress as measured in human plasma and urine.

A comparison of the effects of swimming and walking on body weight, fat distribution, lipids, glucose, and insulin in older women--the Sedentary Women Exercise Adherence Trial 2.

All types of aerobic exercise are assumed to affect cardiovascular risk similarly. There are few studies of swimming, but complex responses to water-based exercise suggest its potential for differential effects. The aim of the study was to compare the effects of swimming and walking on fitness, body weight, lipids, glucose, and insulin in older women. Sedentary women aged 50 to 70 years (N = 116), randomly assigned to swimming or walking plus usual care or a behavioral intervention, completed 3 sessions per week of moderate-intensity exercise, supervised for 6 months then unsupervised for 6 months. After 6 months, 1.6-km walk time decreased in walkers and swimmers, with greater improvement in walkers (1.0 vs 0.6 minute, P = .001). In swimmers, but not walkers, distance swum in 12 minutes increased (78.1 vs -2.2 m, P = .021). Waist and hip circumferences (80.8 vs 83.1 cm and 101.8 vs 102.4 cm; P = .023 and P = .042, respectively) and insulin area under the curve (oral glucose tolerance test) (5128 vs 5623 µU/[L 120 min], P < .05) were lower with swimming. Lipids did not differ between groups. At 12 months, fitness was maintained. Relative to walking, swimming reduced body weight by (1.1 kg, P = .039) and resulted in lower total and low-density lipoprotein cholesterol (0.3 and 0.2 mmol/L; P = .040 and P = .049, respectively). The magnitude of the difference in the reduction of insulin area under the curve between swimming and walking was greater at 12 months; however, the significance was attenuated (4677 vs 5240 µU/[L 120 min], P = .052). Compared with walking, swimming improved body weight, body fat distribution, and insulin in the short term and, in the longer term, body weight and lipid measures. These findings suggest that the type of exercise can influence health benefits.

A cohort study of missed and new cancers after esophagogastroduodenoscopy.

OBJECTIVES: Little is known about missed rates of upper gastrointestinal cancer (UGC) in Western populations, with most data originating from Japanese centers quoting high missed rates of 23.5-25.8%. The objective of this study was to better define missed rates of esophagogastroduodenoscopy (EGD) and the natural history of UGC in a Western population that underwent an initial EGD without cancer, but were subsequently diagnosed with a UGC. Our hypothesis was that a normal EGD rarely misses the detection of UGC. METHODS: This is a retrospective cohort study. A prospectively maintained electronic database was used to identify all patients who underwent EGD between 1990 and 2004 at the study institution. Patients in this cohort who were diagnosed with UGC before 2006 were identified through the Western Australian Cancer Registry. We defined missed cancers as those diagnosed within 1 year of EGD, possible missed cancers as those diagnosed 1-3 years after EGD, and new cancers as those diagnosed more than 3 years after EGD. This study had no interventions and was conducted at a tertiary referral center. The main outcome measurement included UGC. RESULTS: Of the 28,064 EGDs performed, UGC was diagnosed subsequent to the procedure in 116 cases (0.41%). There were 29 missed cancers, 26 possible missed cancers, and 75 new cancers. Of the missed cancers, 11 were esophageal, 15 were gastric, and 3 were duodenal. In 69% (n=20) of the missed cancers, an abnormality was described at the site of malignancy. In 59% (n=17) of the missed cancers, the indication for EGD was an alarm symptom of dysphagia or suspected blood loss. In an univariate analysis, the presence of an alarm symptom was related to missed cancers, whereas operator experience, trainee participation, and usage of newer equipment were not. One of the main limitations of this study is that it was a retrospective review. CONCLUSIONS: UGC is rare after normal EGD, confirming the high accuracy of EGD. Institutional approval was granted for the conduct of this study.

A score test for assessing the cured proportion in the long-term survivor mixture model.

The long-term survivor mixture model is commonly applied to analyse survival data when some individuals may never experience the failure event of interest. A score test is presented to assess whether the cured proportion is significant to justify the long-term survivor mixture model. Sampling distribution and power of the test statistic are evaluated by simulation studies. The results confirm that the proposed test statistic performs well in finite sample situations. The test procedure is illustrated using a breast cancer survival data set and the clustered multivariate failure times from a multi-centre clinical trial of carcinoma.

The effects of [omega]3 fatty acids and coenzyme Q10 on blood pressure and heart rate in chronic kidney disease: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) associates with increased cardiovascular disease (CVD) risk. Hypertension is a major determinant of progression of CKD. Omega-3 fatty acids (omger3FA) protect against CVD via improvements in blood pressure, heart rate, vascular reactivity and serum lipids. Coenzyme Q(10) (CoQ) may improve blood pressure and vascular function. This study determined whether omega3FA and CoQ have independent or additive effects in improving the cardiovascular profile, particularly blood pressure and heart rate, in nondiabetic patients with CKD stages 3-4. METHODS: In a double-blind, placebo-controlled intervention, patients were randomized to either omega3FA (4 g), CoQ (200 mg), both supplements or control (4 g), daily for 8 weeks. RESULTS: Eighty-five patients aged 56.5 +/- 1.4 years; BMI 27.3 +/- 0.5 kg/m(2); supine blood pressure 125.0/72.3mmHg; and glomerular filtration rate 35.8 +/- 1.2 ml/min/1.73m(2), were randomized. Seventy-four completed the study. omega3FA, but not CoQ, reduced 24-h ambulatory heart rate (P<0.0001) and blood pressure (P<0.0001). Main effects for omega3FA on 24-h measurements were -3.3 +/- 0.7/ -2.9 +/- 0.5mmHg and -4.0 +/- 0.5 bpm. Postintervention blood pressure showed significant interactions between treatments. omega3FA reduced triglycerides 24% (P<0.001). There were no changes in glomerular filtration rate, urinary albumin or total protein excretion, cholesterol, HDL-cholesterol (C), LDL-C, glucose, insulin, or high-sensitivity C-reactive protein. CONCLUSION: This study has shown that omega3FA reduce blood pressure, heart rate and triglycerides in patients with CKD. CoQ had no independent effect on blood pressure but increased heart rate. These results show that omega3FA lower blood pressure and may reduce cardiovascular risk in nondiabetic patients with moderate-to-severe CKD.

Synergy between adiposity, insulin resistance, metabolic risk factors, and inflammation in adolescents.

OBJECTIVE: The purpose of this study was to investigate relationships between inflammatory markers and components of a metabolic syndrome cluster in adolescents. RESEARCH DESIGN AND METHODS: This was a cross-sectional analysis of an Australian childhood cohort (n = 1,377) aged 14 years. Cluster analysis defined a "high-risk" group similar to adults with metabolic syndrome. Relevant measures were anthropometry, fasting insulin, glucose, lipids, inflammatory markers, liver function, and blood pressure. RESULTS: Of the children, 29% fell into a high-risk metabolic cluster group compared with 2% by a pediatric metabolic syndrome definition. Relative to the "low-risk" cluster, they had higher BMI (95% CI 19.5-19.8 vs. 24.5-25.4), waist circumference (centimeters) (95% CI 71.0-71.8 vs. 83.4-85.8), insulin (units per liter) (95% CI 1.7-1.8 vs. 3.5-3.9), homeostasis model assessment (95% CI 1.7-1.8 vs. 3.5-3.9), systolic blood pressure (millimeters of mercury) (95% CI 110.8-112.1 vs. 116.7-118.9), and triglycerides (millimoles per liter) (95% CI 0.78-0.80 vs. 1.25-1.35) and lower HDL cholesterol (millimoles per liter) (95% CI 1.44-1.48 vs. 1.20-1.26). Inflammatory and liver function markers were higher in the high-risk group: C-reactive protein (CRP) (P < 0.001), uric acid (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and gamma-glutamyl transferase (GGT) (P < 0.001). The highest CRP, GGT, and ALT levels were restricted to overweight children in the high-risk group. CONCLUSIONS: Cluster analysis revealed a strikingly high proportion of 14 year olds at risk of cardiovascular disease-related metabolic disorders. Adiposity and the metabolic syndrome cluster are synergistic in the pathogenesis of inflammation. Systemic and liver inflammation in the high-risk cluster is likely to predict diabetes, cardiovascular disease, and nonalcoholic fatty liver disease.

Interferon-induced thyroid dysfunction in chronic hepatitis C.

BACKGROUND: Treatment of chronic hepatitis C with interferon is known to be associated with thyroid dysfunction (TD) in 5-14% of patients. We studied the incidence, types, outcome and risk factors predictive of thyroid dysfunction. METHODS: A retrospective analysis was performed on all patients treated with interferon alpha (IFN) or pegylated interferon alpha (PEG-IFN) +/- ribavirin (RBV), who developed abnormal thyroid function tests (TFTs). These cases were compared with treatment-matched controls to identify factors predictive of thyroid dysfunction. Statistical methods consisted of: chi(2) test, Fischer's exact test, Welch's t-test, and multivariate analysis. RESULTS: From a total of 511 patients, 45 cases with TD were identified (8.8%). Pegylated interferon alpha was associated with higher rates of TD than IFN (14.1% vs 6.0%, P = 0.0029). Female sex (OR 5.6, 95% CI 1.1-7) and Asian ethnicity (OR 2.7, 95% CI 1.4-22) were independent predictors of developing TD. Cytology was obtained in 13 patients: benign follicular pattern (8); thyroiditis (3); and normal (2). Thyroid peroxidase (TPO) antibodies (P = 0.004) and earlier onset of dysfunction (P = 0.03) were associated with need for treatment. Sixteen patients had persistent TD by the end of the follow-up period, predicted by female sex, non-Asian ethnicity, prior history of TD and TPO antibodies. CONCLUSIONS: Pegylated interferon alpha, female sex and Asian ethnicity are independent risk factors for TD. Thyroid peroxidase antibodies and earlier TD within the course of IFN are associated with the requirement for treatment. Thyroid function tests should be monitored during and after IFN-based therapy. The most common cytological finding is a benign follicular pattern.

Barriers and motivators for owners walking their dog: results from qualitative research.

ISSUE ADDRESSED: This qualitative research explored the relationship between dog ownership and dog-related, social environmental and physical environmental factors associated with walking with a dog. METHODS: Seven focus groups with dog owners (n=51) were conducted. A pre-determined discussion guide was used and transcripts were analysed as group data, using content analysis to identify common themes. RESULTS: Many of the physical environmental barriers and facilitators that influenced dog owners to walk were similar to those found in the literature for general walking. However, a number of key motivators for walking, specific to dog owners, were identified. Dog owners reported that their dog was a strong source of motivation, companionship and social support that encouraged them to walk with their dog. The availability and accessibility of public open space (POS) for dogs and the provision of dog-related infrastructure within POS were also important environmental factors that affected whether owners walked with their dog. CONCLUSIONS: Results from this qualitative study were used to develop the Dogs and Physical Activity (DAPA) tool which is now being used to measure the walking behaviour of dog owners.

Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population. METHODS: Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. RESULTS: Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P < 0.001). MetS by WHO criteria was not calculated in the AusDiab population. Age was an independent predictor of MetS in PCOS and controls. The prevalence of MetS was significantly higher among those with PCOS (P = 0.027) in obese women (BMI > 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011). CONCLUSIONS: An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction.

OBJECTIVE: To investigate the effects of fenofibrate and coenzyme Q(10) (CoQ) on diastolic function, ambulatory blood pressure (ABP), and heart rate (HR) in type 2 diabetic subjects with left ventricular diastolic dysfunction (LVDD). RESEARCH DESIGN AND METHODS: We randomized, double-blind, 74 subjects to fenofibrate 160 mg daily, CoQ 200 mg daily, fenofibrate 160 mg plus CoQ 200 mg daily, or matching placebo for 6 months. Echocardiography (including tissue Doppler imaging) and 24-h ABP and HR monitoring were performed pre- and postintervention. RESULTS: Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E'), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time, or the ratio of early mitral flow velocity to early diastolic mitral annular myocardial relaxation velocity (E/E') compared with placebo (P > 0.05). Fenofibrate and CoQ interactively (P = 0.001) lowered 24-h systolic blood pressure (-3.4 +/- 0.09 mmHg, P = 0.010), with a prominent nocturnal effect (-5.7 +/- 1.5 mmHg, P = 0.006). Fenofibrate (-1.3 +/- 0.5 mmHg, P = 0.013) and CoQ (-2.2 +/- 0.5 mmHg, P < 0.001) independently lowered 24-h diastolic blood pressure. Fenofibrate reduced 24-h HR (-3.3 +/- 0.5 beats/min, P < 0.001), but CoQ had no effect on HR. CONCLUSIONS: In type 2 diabetic subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-h blood pressure, and fenofibrate alone reduced 24-h HR.

Short and long-term adherence to swimming and walking programs in older women--the Sedentary Women Exercise Adherence Trial (SWEAT 2).

OBJECTIVE: To examine in previously sedentary older women the effects of exercise mode and a behavioural intervention on short and long-term retention and adherence. METHODS: Healthy, sedentary women aged 50-70 years (N=116) were randomly assigned to a supervised 6-month swimming or walking program 3 sessions a week. They were further randomised to usual care or a behavioural intervention. The same program was further continued unsupervised for 6 months. We assessed retention, adherence, stage of exercise behaviour and changes in fitness. RESULTS: One hundred women (86%) completed 6 months and 86 (74%) continued for 12 months. Retention rates were similar for both exercise modes at 6 and 12 months. Adherence to swimming or walking was similar after 6 months (76.3 (95% CI: 69.5, 83.1)% vs. 74.3 (67.7, 80.9)%) and 12 months (65.8 (57.9, 73.8)% vs. 62.2 (54.6, 70.0)%). The behavioural intervention did not enhance retention or adherence. Fitness improved for both exercise modes after 6 months and was maintained at 12 months. CONCLUSIONS: Either swimming or walking programs initiated with careful supervision over 6 months resulted in similar high retention and adherence rates by highly motivated older women over 12 months. Behavioural intervention in this setting did not improve these rates further.