Metabolic risk is associated with sociodemographic characteristics in adolescents from both rural and urban regions from southern Brazil.

BACKGROUND: The prevalence of several cardiovascular metabolic disorders are increasingly cause for concern in adolescents worldwide. Given the complex interrelations between metabolic risk (MR) and sociodemographic variables, the present study aims to examine the association between the presence of MR with sociodemographic characteristics (sex, skin color, residential area, and parental socioeconomic status) in adolescents from Southern Brazil. METHODS: Cross-sectional study conducted with 1,152 adolescents (507 males) aged between 12 and 17 years. MR was assessed using a continuous score (cMetS; sum of Z-scores of the following variables: waist circumference, systolic blood pressure (SBP), glucose, high-density lipoprotein cholesterol [HDL-C, inverse], triglycerides [TG], and estimated cardiorespiratory fitness [CRF, inverse]). Poisson regression was used to examine associations between sociodemographic variables with the dichotomized cMetS and separate metabolic variables. The results were expressed with prevalence ratios (PR) and 95% confidence intervals (CI). RESULTS: The presence of MR (evaluated by the cMetS) was observed in 8.7% of adolescents. Higher MR was less prevalent among non-white adolescents (PR: 0.96; 95% CI: 0.93; 0.99). Adolescents living in rural areas had a lower prevalence of the following metabolic variables; low HDL-C (PR: 0.95; 95% CI: 0.94; 0.97), elevated TG (PR: 0.95; 95% CI: 0.92; 0.99), elevated glucose (PR: 0.96; 95% CI: 0.95; 0.98), and low CRF levels (PR: 0.88; 95% CI: 0.85; 0.92). Whereas, SBP was higher in those living in rural areas (PR: 1.11; 95% CI: 1.05; 1.17). In girls, there was a higher prevalence of raised TG (PR: 1.06; 95% CI: 1.02; 1.10) and lower levels of CRF (PR: 1.20; 95% CI: 1.16; 1.24), but a lower prevalence of elevated glucose (PR: 0.97; 95% CI: 0.97; 0.99). CONCLUSION: Higher MR prevalence was lower in those self-reporting non-white skin color and selected MR factors were less prevalent in those living in rural areas. The identification of groups at higher MR is important for early prevention and monitoring strategies for both Type 2 diabetes and later cardiovascular disease. Future studies should be conducted to assess the socio-cultural aspects of the relationships between MR and socio-cultural and lifestyle variables.

FTO gene polymorphism and longitudinal changes in nutritional/obesity status in children and adolescents: Schoolchildren's health cohort study.

The fat mass and obesity-associated gene (FTO) has been extensively reported in the literature related to nutritional status, but there has been limited description of the genetic contribution to obesity risk during childhood and adolescence, especially in Latin Americans. This study aims to associate the rs9939609 polymorphism, of the FTO gene, with changes in nutritional status in Brazilian schoolchildren followed for 3 years. A longitudinal study was conducted with 355 schoolchildren, aged 7-15 years in 2011/2012 and subsequently re-evaluated in 2014/2015. Nutritional (obesity) status was classified by identifying those exceeding recommended thresholds for waist circumference (WC), waist-to-height ratio (WHtR), body mass index (BMI), and body fat percentage (BF%). The rs9939609 polymorphism was genotyped by a real-time polymerase chain reaction. Relative risk (RR with 95% confidence interval) of obesity status by FTO gene polymorphism was calculated by Poisson regression. The risk group was determined for genotypes with the allele A polymorphism, and regression models were adjusted for age, sex, height, ethnicity, and geographical location. Considering the longitudinal changes in status over the 3-year follow-up, the RR of developing a WC exceeding the threshold recommended (WC >75th age and sex-standardized percentile), or remaining with this condition, was higher in children with AT/AA genotype. For WC, the RR was 1.66 (1.07; 2.58) in crude analysis and 1.17 (1.01; 1.35) following adjustment for age (years), gender, ethnicity, and geographical location. The comparative risk of abdominal obesity, assessed by WHtR (not recommended threshold ≥0.50), was 53% and 8%, respectively, higher in AT/AA compared to TT genotype.Conclusion: This is one of the first longitudinal investigations to show a significant association between the A allele of the rs9939609 polymorphism and individuals with higher than recommended WC and WHtR measures in Brazilian children and adolescents. What is known: • The FTO has an effect on increases in body mass index (BMI) among children and adolescents. • It established the association between FTO and overweight/obesity in Caucasians. What is new: • The presence of the risk allele of rs9939609 (FTO gene) polymorphism is associated with increased abdominal fat in Brazilian schoolchildren. • Was detected an association between FTO gene polymorphism (rs9939609) with WC in follow-up cohort and changes in WC and WHtR follow-up over 3 years, during childhood and adolescence growth.

Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.

BACKGROUND: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. METHODS AND RESULTS: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. CONCLUSIONS: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

Delivering effective, comprehensive, multi-exercise component cardiac rehabilitation (CR) for chronic heart failure patients in low resource settings in sub-Saharan Africa: Queen Elizabeth Central Hospital-(QECH-CR) randomised CR study, Malawi.

BACKGROUND: The delivery of Cardiac Rehabilitation (CR) and attaining evidence-based treatment goals are challenging in developing countries, such as Malawi. The aims of this study were to (i) assess the effects of exercise training/ CR programme on cardiorespiratory and functional capacity of patients with chronic heart failure (CHF), and (ii) examine the effectiveness of a novel, hybrid CR delivery using integrated supervised hospital- and home-based caregiver approaches. METHODS: A pre-registered (UMIN000045380), randomised controlled trial of CR exercise therapy in patients with CHF was conducted between September 2021 and May 2022. Sixty CHF participants were randomly assigned into a parallel design-exercise therapy (ET) (n = 30) or standard of care (n = 30) groups. Resting hemodynamics, oxygen saturation, distance walked in six-minutes (6MWD) and estimated peak oxygen consumption (VO2 peak) constituted the outcome measures. The exercise group received supervised, group, circuit-based ET once weekly within the hospital setting and prescribed home-based exercise twice weekly for 12 weeks. Participants in both arms received a group-based, health behaviour change targeted education (usual care) at baseline, 8-, 12- and 16-weeks. RESULTS: Most of the participants were female (57%) with a mean age of 51.9 ±15.7 years. Sixty-five percent (65%) were in New York Heart Association class III, mostly with preserved left ventricular ejection fraction (HFpEF) (mean Left Ventricular Ejection Fraction 52.9 ±10.6%). The 12-weeks ET led to significant reductions in resting haemodynamic measures (all P <0.05). The ET showed significantly higher improvements in the 6MWD (103.6 versus 13.9 m, p<0.001) and VO2 peak (3.0 versus 0.4 ml·kg-1·min-1, p <0.001). Significant improvements in 6MWD and VO2 peak (both p<0.001), in favour of ET, were also observed across all follow-up timepoints. CONCLUSION: This novel, randomised, hybrid ET-based CR, delivered to mainly HFpEF patients using an integrated hospital- and home-based approach effectively improved exercise tolerance, cardiorespiratory fitness capacities and reduced perceived exertion in a resource-limited setting.

Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure.

BACKGROUND: Prevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown. METHODS AND RESULTS: Of 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0-22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41-75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction. CONCLUSIONS: In patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.

Outcomes following coronary artery bypass surgery in diabetic treatment sub-groups. A propensity matched analysis of >7000 patients over 18 years.

BACKGROUND: European System for Cardiac Operative Risk Evaluation II incorporates insulin-controlled diabetes whilst omitting tablet-controlled diabetes. Differences in adverse clinical outcomes following coronary artery bypass graft between these groups are poorly established. Therefore, a propensity matched comparison of short and longer term mortality and morbidity in insulin-controlled diabetes, tablet-controlled diabetes and non-diabetic patients was undertaken. METHODS: Isolated first-time coronary artery bypass graft surgeries between April 1999 and April 2017 were propensity score matched by pre- and intra-operative variables. RESULTS: 8241 patients; 23.5% diabetics and 76.5% non-diabetics. The groups' demographical and clinical characteristics were comparable after matching. Insulin-controlled diabetes patients had significantly higher in-hospital mortality (3.8% vs. 1.7%, p < 0.05), multisystem failure (2.6% vs. 1.8%, p < 0.05), sternal wound infections requiring debridement (3.6% vs. 1.3%, p < 0.05), respiratory complications (25.6% vs. 21.9%, p < 0.05), new dialysis (4.7% vs. 0.9%, p < 0.05) and longer hospital stays (13.5 ± 13.3 vs. 10.6 ± 8.0, p < 0.05) compared to non-diabetic patients.Tablet-controlled diabetes patients had significantly higher strokes (2.9% vs. 1.2, p < 0.05), superficial sternal wound infections (6.7% vs. 5.4%, p < 0.05), respiratory complications (25.7% vs. 22.7%, p < 0.05), new dialysis (1.7% vs. 0.6%, p < 0.05), post-operative atrial fibrillation (37.1% vs. 33.9%, p < 0.05) and readmission with myocardial infarction (22.4% vs. 19.6%, p < 0.05) compared to non-diabetic patients. CONCLUSION: Diabetic treatment sub-groups are an independent risk factor for sternal wound infection, new dialysis requirement, multisystem failure and readmission with myocardial infarction after isolated first coronary artery bypass graft surgery. The findings suggest the need for better risk stratification of diabetic groups prior to cardiac surgery and for improved cardiovascular risk management post-surgery in tablet-controlled diabetes patients.

Moderating Role of Physical Fitness in the Association Between TV Time and Adiposity Parameters in Adolescents.

PURPOSE: To identify whether physical fitness (PF) components play a moderating role in the relationship between TV time and adiposity levels. DESIGN: Cross-sectional study. SETTING: Few studies have examined if different PF levels modify the association between TV time and adiposity in adolescents. Studies often focus on the isolated relationships between obesity and TV time, or obesity and PF levels. SUBJECTS: 1071 adolescents (617 girls), aged 12 to 17 years. MEASURES: Cardiorespiratory fitness (CRF), abdominal muscular endurance, and lower limb strength were evaluated using the protocols of the Projeto Esporte Brasil fitness testing battery. TV time was obtained using a self-reported questionnaire. Body mass index (BMI) and waist circumference (WC) were also assessed. Moderation analyses were conducted through multiple linear regression models with the following associations tested in different models: PF components, TV time, and interaction (PF component x TV time) with adiposity parameters (BMI and WC). RESULTS: A significant interaction term was found for CRF and TV time in the association with both WC (ß: -.005; 95% CI: -.009; -.001; P = .012) and BMI (ß: -.002; 95% CI: -.004; -.001; P = .009). CONCLUSION: CRF moderates the relationship between TV time and adiposity measures in this cross-sectional analysis. These data support strategies looking at increasing physical activity levels to improve CRF and avoid the development of excess abdominal obesity and excess weight.

Differential improvements in lipid profiles and Framingham recurrent risk score in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation.

OBJECTIVE: To determine whether lipid profiles and recurrent coronary heart disease (CHD) risk could be modified in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation (CR). DESIGN: Retrospective analysis of patient case records. SETTING: Community-based phase 4 CR program. PARTICIPANTS: Patients without diabetes (n=154; 89% men; mean ± SD age, 59.6 ± 8.5y; body mass index [BMI], 27.0 ± 3.5 kg/m²) and patients with diabetes (n=20; 81% men; mean age, 63.0 ± 8.7y; BMI, 28.7 ± 3.3 kg/m²) who completed 15 months of CR. INTERVENTIONS: Exercise testing and training, risk profiling, and risk-factor education. MAIN OUTCOME MEASURES: Cardiometabolic risk factors and 2- to 4-year Framingham recurrent CHD risk scores were assessed. RESULTS: At follow up, a significant main effect for time was evident for decreased body mass and waist circumference and improved low-density lipoprotein cholesterol (LDL-C) level and submaximal cardiorespiratory fitness (all P<.05), showing the benefits of CR in both groups. However, a significant group-by-time interaction effect was evident for high-density lipoprotein cholesterol (HDL-C) level and total cholesterol (TC)/HDL-C ratio (both P<.05). TC/HDL-C ratio improved (5.0 ± 1.5 to 4.4 ± 1.3) in patients without diabetes, but showed no improvement in patients with diabetes (4.8 ± 1.6 v 4.9 ± 1.6). CONCLUSIONS: We showed that numerous anthropometric, submaximal fitness, and cardiometabolic risk variables (especially LDL-C level) improved significantly after long-term CR. However, some aspects of cardiometabolic risk (measures incorporating TC and HDL-C) improved significantly in only the nondiabetic group.

Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure.

AIMS: The epidemiology of pulmonary arterial hypertension (PAH) in patients with heart failure (HF) is poorly described. Our aim was to investigate the determinants and prognostic significance of PAH in a large representative outpatient population with HF. METHODS AND RESULTS: Routine measurement of right ventricular tricuspid pressure gradient (RVTG) was attempted among unselected, consecutive referrals to an HF clinic. The diagnosis of HF was based on symptoms, signs, echocardiography, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of 2100 patients referred, 1380 were diagnosed as HF, of whom 1026 had left ventricular systolic dysfunction (LVSD) and 354 did not. Right ventricular tricuspid pressure gradient could be measured in 270 (26%) patients with and 143 (40%) without LVSD. The highest RVTG quartile [RVTG > 35 mmHg equivalent to an estimated PA systolic pressure (PASP) > 45 mmHg] constituted 7% of all those with HF and was associated with higher LV filling pressures, LV end-diastolic volume, LVSD, and more severe mitral regurgitation (MR). During a median (inter-quartile range) follow-up of 66 (56-74) months, mortality was 40.3%. Mortality was similar in the lowest quartile of RVTG and in those in whom RVTG could not be measured and rose with increasing RVTG quartile (log-rank: 26.9; P < 0.0001). The highest RVTG quartile, age, blood pressure, and log NT-proBNP independently predicted mortality. Right ventricular tricuspid pressure gradient >35 mmHg had a 96% specificity to discriminate between those with and without HF in patients without LVSD. CONCLUSION: Using a definition of PASP > 45 mmHg, 7% of the patients with HF have PAH, which is associated with worse LV function, MR, and prognosis. Whether PAH is a target for therapy in this population remains to be elucidated.

Anthropometric and Metabolic Responses in FTO rs9939609 Gene Polymorphism after a Multidisciplinary Lifestyle Intervention in Overweight and Obese Adolescents.

Few studies show the potential changing effect of fat-mass and obesity-associated ( FTO ) rs9939609 gene on cardiometabolic risk after a lifestyle intervention. This study aims to evaluate whether overweight and obese adolescents, carriers of the risk genotypes for obesity of the FTO rs9939609 gene polymorphism, have different anthropometric and biochemical responses to an interdisciplinary intervention program. The quasi-experimental study involved 34 adolescents aged 10 to 15 years. Schoolchildren with AA/AT genotype decreased glucose, total cholesterol, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. However, there were no differences between the genotypes, suggesting that the "A" allele did not modify the subject's response to the intervention program.

The Effect of Atorvastatin (and Subsequent Metformin) on Adipose Tissue Acylation-Stimulatory-Protein Concentration and Inflammatory Biomarkers in Overweight/Obese Women With Polycystic Ovary Syndrome.

Background: Atorvastatin has been shown to improve cardiovascular risk (CVR) indices in women with polycystic ovary syndrome (PCOS). Low-grade chronic inflammation of adipose tissue may link PCOS and adverse CVR. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index. Methods: The objective of this study was to determine the effect of atorvastatin on markers of adipose tissue dysfunction and inflammation; acylation-stimulating-protein (ASP), interleukin-6 (IL-6), and monocyte-chemoattractant-protein-1 (MCP-1) in PCOS. This was a randomized, double-blind, placebo-controlled study where 40 medication-naive women with PCOS and biochemical hyperandrogenaemia were randomized to either atorvastatin 20 mg daily or placebo for 12 weeks. Following the 12 week randomization; both group of women with PCOS were subsequently started on metformin 1,500 mg daily for further 12 weeks to assess whether pre-treatment with atorvastatin potentiates the effects of metformin on markers of adipose tissue function We conducted a post-hoc review to detect plasma ASP and the pro-inflammatory cytokines IL6 and MCP-1 before and after 12 and 24 weeks of treatment. Results: There was significant reduction in ASP (156.7 ± 16.2 vs. 124.4 ± 14.8 ng/ml p <0.01), IL-6 (1.48 ± 0.29 vs.0.73 ± 0.34 pg/ml p = 0.01) and MCP-1 (30.4 ± 4.2 vs. 23.0 ± 4.5 pg/ml p = 0.02) after 12 weeks of atorvastatin that was maintained subsequently with 12 weeks treatment with metformin. There was a significant positive correlation between ASP levels with CRP (p < 0.01), testosterone (p < 0.01) and HOMA-IR (p < 0.01); IL-6 levels with CRP (p <0.01) and testosterone (p < 0.01) and MCP-1 with CRP (p < 0.01); testosterone (p < 0.01) and HOMA-IR (p < 0.02). Conclusions: This post-hoc analysis revealed that 12 weeks of atorvastatin treatment significantly decreased the markers of adipose tissue dysfunction and inflammation, namely ASP, IL-6 and MCP-1 in obese women with PCOS. Changes in adipose tissue markers were significantly associative with substantial improvements in HOMA-IR, testosterone and hs-CRP levels. ISRCTN Number: ISRCTN24474824.

Low-density lipoprotein sub-fraction profiles in obese children before and after attending a residential weight loss intervention.

AIM: Small dense LDL particles are associated with an increased risk of coronary heart disease and are prevalent in obesity related dyslipidaemia. This study evaluated the effect of weight loss in nine children (BMI 33.4 +/- 8.4 kg.m(-2) and age 15.1 +/- 2.9 years) on LDL peak particle size, and cholesterol concentrations within particular LDL sub-fractions. METHODS: Each child undertook fun based physical activity, dietary restriction and modification and lifestyle education classes in a residential summer weight loss intervention. Blood was drawn before and after intervention and LDL heterogeneity measured by ultracentrifugation. RESULTS: The mean change in body weight were -6.8 +/- 4.9 kg, BMI units -2.5 +/- 1.4 kg.m(-2), and waist circumference -6.3 +/- 6.3 cm (all p < 0.01). Absolute LDL-c concentration reduced from 106.2 mg/dL to 88.3 mg/dL (p < 0.01). The cholesterol contained within the small dense LDL sub-fraction (LDL-c III) reduced from 54.1 mg/dL to 40.4 mg/dL (p < 0.01). Peak particle density decreased from 1.041g/mL to 1.035g/mL (p < 0.01). At pre intervention 50.9% of absolute cholesterol was within LDL-c III particles, changing to 46.2%. CONCLUSION: Mean weight loss of -6.8 +/- 4.9 kg lowers absolute LDL-c and the cholesterol specifically within LDL-c III particles. LDL peak particle size increased and a degree of LDL particle remodelling occurred. These favourable adaptations, accrued in a matter of 4 weeks, maybe associated with a reduction in CHD risk.

Vitamin D3 supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR-/- and LDLR+/+ mice.

INTRODUCTION: Fatty liver disease is prevalent in populations with high caloric intake. Nutritherapeutic approaches are being considered, such as supplementary Vitamin D3 , to improve aspects of metabolic syndrome, namely fatty liver disease, hyperlipidemia, and insulin resistance associated with obesity. METHODS: We analyzed female LDLR-/- and LDLR+/+ mice on a 10-week diabetogenic diet for markers of fatty liver disease, metabolic strain, and inflammation. RESULTS: The groups on a high fat high sugar diet with supplementary Vitamin D3 , in comparison with the groups on a high fat high sugar diet alone, showed improved transaminase levels, significantly less hypertriglyceridemia and hyperinsulinemia, and histologically, there was less pericentral hepatic steatosis. Levels of non-esterified fatty acids and lipid peroxidation products were significantly lower in the group supplemented with additional Vitamin D3 , as were systemic markers of inflammation (serum endotoxin and IL-6). M2 macrophage phenotype predominated in the group supplemented with additional Vitamin D3 . Beneficial changes were observed as early as five weeks' supplementation with Vitamin D3 and extended to restoration of high fat high sugar diet induced decrease of bone mineral density. CONCLUSION: In summary, Vitamin D3 was a significantly beneficial dietary additive to blunt a prediabetic phenotype in diet-induced obesity of female LDLR-/- and LDLR+/+ mice.

In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity?

Low grade endotoxemia is a feature of obesity which is linked to development of steatohepatitis in non-alcoholic fatty liver disease. In this study, macrophages (J774) and hepatocytes (HepG2) were stimulated with lipopolysaccharide (LPS) from E. coli 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D3 or docosahexaenoic acid (DHA) over a time period of 1 and 5 days. Pro-inflammatory TNFα and pro-fibrotic TGFß released into the supernatants were measured by ELISA; qPCR was performed for Srebp-1c and PPARα mRNA (genes for products involved in fatty acid synthesis and catabolism, respectively). Vitamin D3 and DHA exerted a consistent, dose dependent anti-inflammatory effect, and increased PPARα relative to Srebp-1c in both cell types. By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. Our results argue in favor of dietary supplementation of Vitamin D3 or DHA (and avoidance of monounsaturated/saturated fatty acids) to alleviate development of fatty liver disease.

Exploring quality of life in patients with and without heart failure.

AIMS: The EuroHeart Failure Survey Questionnaire (EHFSQ-1) has 39 questions on symptoms and quality of life (QoL); many items are related. We sought to identify underlying clusters amongst EHFSQ-1 questions, construct an overall "QoL score" and investigate its relationship to a single question asking patients to self-rate QoL. METHODS AND RESULTS: Factor analysis based on the principal component technique was used to identify patterns amongst responses to QoL questions from patients referred with symptoms suggesting heart failure (HF). Of 1031 patients, median age 71 (IQR: 63-77) years, 64% were men and 626 had confirmed HF. For patients with HF, seven symptom-clusters were identified: "breathlessness", "psychological distress", "sleep quality", "frailty", "cognitive/psychomotor function", "cough" and "chest pain". These clusters accounted for 65% of the total variance in QoL score. Cluster pattern was similar in patients with and without HF. A summary factor score was tightly correlated with summary QoL score (correlation coefficient: r=0.96; p<0.0001). Both summary factors and QoL scores were highly correlated with patient self-rating of overall health (r1=0.61 and r2=0.66 respectively, p<0.0001) or overall QoL (r1=0.60 and r2=0.66, p<0.0001). The medians (IQR) of the summary QoL score for patients with HFrEF, HFnEF and no-HF were, respectively, 83 (60-106), 82 (59-104) and 71 (51-94). CONCLUSIONS: EHFSQ-1, comprises seven symptom clusters in patients with HF. Either summary factors or QoL scores can be used as a QoL outcome measure. However, if the key question is 'what is this patient's QoL?' rather than the reason why it is impaired, then a single, direct question may suffice.

Hypertension and Different Levels of Body Mass Index and Cardiorespiratory Fitness Amongst Adolescents

Abstract Background Hypertension is an increasingly common problem in adolescents; amongst the associated factors, physical inactivity and obesity are increasing the risk of developing cardiovascular diseases. Objective To verify whether there is an association between higher blood pressure levels amongst adolescents with the relationship between different levels of body mass index (BMI) and cardiorespiratory fitness (CRF). Method Cross-sectional study consisting of 860 adolescents. Higher blood pressure (BP) was considered as borderline and hypertension as the classification. BMI was categorized as low-normal weight and overweight-obesity. The CRF was assessed by a nine-minute run/walk test and classified into low or appropriate levels (less and more favorable to health, respectively). Later, BMI and CRF were grouped into one categorical variable: (I) low/normal weight and appropriate CRF levels; (II) low/normal weight and low CRF levels; (III) overweight/obesity and appropriate CRF levels; and (IV) overweight/obesity and low CRF levels. Data were analyzed using Poisson regression, through the prevalence ratio (PR) and 95% confidence intervals (CI). The p-values of p <0.05 were considered significant. Results Adolescents with overweight/obesity and low CRF levels had a 22% higher BP prevalence. Moreover, children with overweight/obesity, but with appropriate CRF levels, have a 15% higher BP prevalence. Conclusion Adolescents with overweight/obesity had a higher prevalence of BP, regardless of CRF levels. It is suggested that maintaining normal BMI is a protective factor for less favorable BP.

On the Functional Overlap between Complement and Anti-Microbial Peptides.

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C3 involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C3 is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia).

Effects of reducing inspired oxygen concentration for one hour in patients with chronic heart failure: implications for air travel.

AIMS: The objective of this study was to establish the acute effects of hypoxia on clinical, spirometric, haemodynamic, and echocardiographic variables. Reducing inspired oxygen to 15%, as experienced during commercial air travel, decreases arterial oxygen saturation, increases respiratory rate and pulmonary artery pressure in healthy subjects. The effect on patients with chronic heart failure is unknown. METHODS AND RESULTS: Seventy-two patients with chronic heart failure and an LVEF <40%, in NYHA functional class II (74%) or III (26%), on stable treatment were studied and compared with 18 age-matched controls (65 ± 11 vs. 62 ± 12 years, respectively). Clinical, spirometric, haemodynamic, and echocardiographic measurements were performed in patients and controls before and after one hour inspiring 15% oxygen. Inspired 15% oxygen for 1 h was tolerated in all subjects and caused no worsening of symptoms. Arterial oxygen saturation decreased to a similar extent in patients (from 97 ± 2% to 86 ± 4%) and controls (from 97 ± 2% to 86 ± 3%). Mean arterial pressure increased from 81 ± 13 mmHg to 87 ± 12 mmHg in patients, but did not change in controls. There was no effect on heart rate, but systolic pulmonary artery pressure rose from 30.2 ± 14.0 mmHg to 34.0 ± 15.2 mmHg in patients, and from 22.4 ± 5.5 mmHg to 24.1 ± 6.9 mmHg in controls. CONCLUSIONS: Inspiring 15% oxygen was tolerated and caused no worsening of symptoms despite reductions in arterial oxygen saturation and increases in mean arterial pressure and systolic pulmonary artery pressure.

The predictive ability of triglycerides and waist (hypertriglyceridemic waist) in assessing metabolic triad change in obese children and adolescents.

BACKGROUND: The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak particle density] is characteristic of increased intra-abdominal adipose tissue and insulin resistance and can be predicted by the simple and adoptable screening tool, the hypertriglyceridemic waist. The associations between hypertriglyceridemic waist components [fasting triglycerides (TG) and waist circumference cut-points derived from a child-specific metabolic syndrome definition] with the metabolic triad were examined in obese youth before and after weight loss. METHODS: A continuous metabolic triad score (MTS) was calculated as a cumulative and standardized residual score of fasting insulin, apolipoprotein B, and LDL peak particle density (z-scores of the metabolic triad variables regressed onto age and sex). The predictive ability of TG and waist in assessing metabolic triad change was undertaken in 75 clinically obese boys and girls, aged 8-18, body mass index (BMI) 34.2±6.4 kg/m(2) before and after weight loss. RESULTS: Fasting TG concentrations (r(2)=0.216, P<0.0001) and waist circumference (r(2)=0.049, P=0.019) were both significant independent predictors of the cumulative MTS, together accounting for 26.5% of its total variance. All cardiometabolic risk factors [except a reduction in high-density lipoprotein cholesterol (HDL-C)] were favorably modified following weight loss. Fasting TG change was the only significant predictor of the MTS change (r(2)=0.177, P<0.0001). Waist circumference was not a significant predictor of MTS change. CONCLUSION: The reduction in fasting TG concentration (but not waist circumference) was the only significant predictor of MTS change. Fasting TG may be the most important metabolic syndrome component to best characterize the metabolic heterogeneity in obese cohorts and the changes in metabolic risk in clinically obese youth.