Cardiometabolic Comorbidities Research Articles

Hypertension and cardiometabolic comorbidity in patients with different levels of blood glucose in the non-diabetic range

Objective. To study the prevalence of hypertension (HTN), concomitant and associated cardiovascular, metabolic diseases and disorders in people with different levels of blood glucose in the non-diabetic range.Design and methods. A content analysis of 1503 outpatient maps was carried out with the assessment of age, body weight, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol, low density lipoprotein cholesterol (LDL)), overweight/obesity, HTN, atherosclerotic diseases. The changes in carbohydrate metabolism were classified as following: highnormal FPG (5,6-6,0 mmol/l; n = 141; group 1), normoglycemia (FPG up to 5,5 mmol/l; n = 1227; group 2), previously diagnosed prediabetes (n = 54; group 3) and diabetes mellitus (n = 81).Results. Group 1 was characterized by higher body mass, BMI, FPG, total cholesterol, higher prevalence of dyslipidemia, atherosclerotic diseases, overweight/obesity, HTN (p < 0,001) compared with group 2. The presence of a “highnormal level of FPG” is associated with an increased risk of dyslipidemia (relative risk: RR 1,579; 95 % confidence interval (CI): 1,348-1,803), atherosclerotic diseases (RR2,095; 95 % CI 1,371-3,832), obesity (RR 1,766; 95 % CI 1,568-1,934), AH (RR 1,697; 95 % CI 1,45-1,93). Groups 1 and 3 did not differ by the general characteristics. HTN patients in group 1 compared with group 2 more often had dyslipidemia (p = 0,034) and overweight/obesity (p = 0,014). In patients with HTN, the presence of “highnormal FPG” is associated with an increased risk of dyslipidemia (RR 1,221; 95 % CI 1,005-1,429), overweight/obesity (RR 1,189; 95 % CI 1,0291,319). HTN patients in groups 1 and 3 did not differ in the frequency of dyslipidemia, atherosclerotic diseases, overweight/obesity.Conclusions. “Highnormal level of FPG” is associated with an increased risk of dyslipidemia, atherosclerotic diseases, HTN, obesity; among HTN patients—with an increased risk of dyslipidemia, overweight/ obesity. Patients with “highnormal FPG” and patients with prediabetes show similar cardiometabolic status.

Sarcopenia Is an Independent Risk Factor for NAFLD in COPD: A Nationwide Survey (KNHANES 2008-2011).

BackgroundNonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with chronic obstructive pulmonary disease (COPD) and is independently associated with cardiometabolic comorbidities and systemic inflammation. Although several factors are associated with NAFLD, the influence of sarcopenia on NAFLD has not been fully determined in patients with COPD. We explored whether sarcopenia is associated with NAFLD in a COPD population.MethodsData from the Korean National Health and Nutrition Examination Surveys 2008–2011 were analyzed. The subjects were defined as having NAFLD when they had a hepatic steatosis index (HSI) score >36, which is a previously validated NAFLD prediction score. Sarcopenia_BMI (=total appendicular skeletal muscle mass [kg]/body mass index [kg/m2]), sarcopenia_BW (=total appendicular skeletal muscle mass [kg]/body weight [kg] × 100), and sarcopenia_height (= total appendicular skeletal muscle mass (kg)/height2 (m)) measured using dual-energy X-ray absorptiometry was used to diagnose sarcopenia.ResultsNAFLD was identified in 124 (14.6%) of 850 COPD subjects using the HSI. Multivariable logistic analyses adjusted for age, sex, hypertension, diabetes mellitus (DM), forced vital capacity (FVC), and metabolic syndrome demonstrated that sarcopenia (sarcopenia_BMI, odds ratio [OR] = 1.95; 95% confidence interval [CI], 1.11–3.46, p = 0.022; sarcopenia_BW, OR = 2.25; 95% CI, 1.30–3.92, p = 0.004) was associated with NAFLD in patients with COPD. The proportion of sarcopenia_BMI was higher in patients with a high fibrotic burden from NAFLD (Q3, Q4) than in subjects with a low fibrotic burden from NALFD (Q1, Q2) (54.8% vs 24.2%, p = 0.024). The proportion of sarcopenia_BW was also higher in patients with a high fibrotic burden from NAFLD than in patients with a low fibrotic burden from NAFLD (51.6% vs 30.6%, p = 0.029).ConclusionSarcopenia was associated with an increased risk for NAFLD in patients with COPD, independent of age, sex, lung function, and metabolic factors. Sarcopenic COPD was also associated with a high fibrotic burden in NAFLD patients. Pulmonologists should be aware of possible liver comorbidities in the sarcopenic COPD phenotype.

Cardiometabolic comorbidities and epithelial ovarian cancer risk among African-American women in the African-American Cancer Epidemiology Study (AACES)

BackgroundStudies that have examined the association between cardiovascular comorbidities and epithelial ovarian cancer (EOC) have yielded inconsistent results. It remains unknown whether cardiometabolic disease is associated with EOC in African American (AA) women, who have a higher prevalence of cardiovascular disease and lower risk of EOC than White women. Here, we estimate the effect of cardiovascular comorbid conditions and EOC risk among AA women. MethodsData were available from 593 ovarian carcinoma patients and 752 controls enrolled in the African American Cancer Epidemiology Study (AACES). Participants were asked to self-report a history of hypertension, hyperlipidemia, and diabetes and any current medication use. The relationship between hypertension, hyperlipidemia, diabetes, and medications taken for these conditions was determined using multivariate logistic regression. ResultsHypertension was associated with an increased risk (adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.01, 1.73), whereas diabetes and hyperlipidemia were associated with a decreased risk (aOR = 0.67, 95% CI = 0.49, 0.91 and aOR = 0.61, 95% CI = 0.47, 0.80, respectively) of EOC. Use of anti-diabetic medication was inversely associated with EOC risk, as was use of lipid lowering medications (in the overall study population), which were predominantly statins. Among women with hypertension, use of anti-hypertensive medications was inversely associated with EOC risk, with associations that were most pronounced for diuretics, ARBs and ACE inhibitors. ConclusionHypertension was associated with an increased EOC risk in this patient population, whereas an inverse association was observed for diabetes and hyperlipidemia. The decreased risk of EOC identified with use of anti-hypertensive, anti-diabetes or lipid-lowering medications could have implications for risk reduction strategies.

Evidence for Use or Disuse of Renin-Angiotensin System Modulators in Patients Having COVID-19 With an Underlying Cardiorenal Disorder.

Coronavirus disease 19 (COVID-19) originated in Wuhan, China, in December 2019 has been declared pandemic by World Health Organization due to an exponential rise in the number of infected and deceased persons across the globe. Emerging reports suggest that susceptibility and mortality rates are higher in patients with certain comorbidities when compared to the average population. Cardiovascular diseases and diabetes are important risk factors for a lethal outcome of COVID-19. Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. This raises the question whether the use of RAS inhibitors, the backbone of treatment of cardiovascular, neurovascular, and kidney diseases could increase the susceptibility for coronavirus infection or unfortunate outcomes of COVID-19. Thus, currently, there is a lack of consensus regarding the effects of RAS inhibitors in such patients. Moreover, expert bodies like American Heart Association, American College of Cardiology, and so on have now released official statements that RAS inhibitors must be continued, unless suggested otherwise by a physician. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19. Moreover, we will discuss the potential effect of the use and disuse of RAS inhibitors in patients having COVID-19 with cardiometabolic comorbidities.

COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

Racial Disparities in Healthcare Utilization Among Individuals with Cardiometabolic Risk Factors and Comorbid Anxiety Disorder.

This study addresses racial/ethnic differences in adverse health care utilization among individuals with comorbid anxiety disorder and cardiometabolic syndrome (CMetS) risk factors. Utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data, logistic regression models were estimated to determine the likelihood of receiving CMetS-related medical treatment in the emergency department (ED) or via inpatient services and to determine if the likelihood is associated with race/ethnicity. Adjusted models controlled for age, sex, and insurance type. Significant racial-ethnic differences were observed for utilization (any emergency department and/or inpatient visit). The odds of non-Hispanic Black respondents reporting emergency department and/or inpatient utilization was 2.39 (p < 0.05) times the odds of non-Hispanic White respondents. Racial-ethnic variation in adverse healthcare utilization suggests an opportunity to improve care and outcomes for persons diagnosed with comorbid anxiety disorder and cardiometabolic syndrome. Integrated interventions could simultaneously improve mental health and facilitate CMetS disease self-management.

Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK

ObjectivesThe objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of...

Depression profilers and immuno-metabolic dysregulation: Longitudinal results from the NESDA study

BackgroundMajor depressive disorder (MDD) is linked to higher cardio-metabolic comorbidity that may in part be due to the low-grade inflammation and poorer metabolic health observed in MDD. Heterogeneity of MDD is however large, and immune-inflammatory and metabolic dysregulation is present in only part of the MDD cases. We examined the associations of four depression dimensional profilers (atypical energy-related symptom dimension, melancholic symptom dimension, childhood trauma severity, and anxious distress symptom dimension) with immuno-metabolic outcomes, both cross-sectionally and longitudinally. MethodsThree waves covering a 6-year follow-up (>7000 observations) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression profilers were based on the Inventory of Depressive Symptomatology, the Beck Anxiety Inventory, and the Childhood Trauma index. An inflammatory index (based on IL-6 and CRP), a metabolic syndrome index (based on the five metabolic syndrome components), and a combination of these two indices were constructed. Mixed models were used for cross-sectional and longitudinal models, controlling for covariates. ResultsOf the four depression profilers, only the atypical, energy-related symptom dimension showed robust associations with higher scores on the inflammatory, metabolic syndrome and combined inflammatory-metabolic indexes cross-sectionally, as well as at follow-up. The melancholic symptom dimension was associated with lower scores on the metabolic syndrome index both cross-sectionally and longitudinally. ConclusionThe atypical energy-related symptom dimension was linked to poorer immune-inflammatory and metabolic health, while the melancholic symptom dimension was linked to relatively better metabolic health. Persons with high atypical energy-related symptom burden, representing an immuno-metabolic depression, may be the most important group to target in prevention programs for cardiometabolic disease, and may benefit most from treatments targeting immuno-metabolic pathways.

Pretreatment serum GH levels and cardio-metabolic comorbidities in acromegaly; analysis of data from Iran Pituitary Tumor Registry.

Acromegaly is a rare chronic disabling disorder, in which growth hormone (GH) excess is associated with a range of clinical features and systemic complications. The present study aims to evaluate the association between pretreatment basal GH levels as well as GH levels after oral glucose tolerance test (OGTT) and cardio-metabolic comorbidities, including diabetes mellitus (DM), left ventricular hypertrophy (LVH) and hypertension (HTN) in patients with active acromegaly. A retrospective study of the medical records regarding 113 patients with acromegaly registered at two main centers of Iran Pituitary Tumor Registry during 2011-2018. The mean age of the patients was 42.76 ± 11.6 (range: 21-72) years. Mean GH level at baseline was 21 ng/ml while nadir GH levels at 60 and 120 min after glucose were 6.95 and 9.05 ng/ml, respectively. There was a negative correlation between age and basal serum GH level (r= -0.196, p = 0.038). Hypertension and diabetes mellitus were detected in 26.8% and 19.7% of the patients. A positive correlation was detected between serum GH values and systolic blood pressure. There was not any significant difference in basal GH and GH post OGTT regarding DM, Diastolic blood pressure and LVH. Our findings suggest that pretreatment basal GH levels are higher in younger patients with acromegaly. Furthermore, higher GH values (0, 60 and 120 min) during OGTT are associated with higher systolic blood pressure. A comprehensive evaluation of this population regarding comorbidities should be performed.

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers.

Psoriasis is a common inflammatory skin condition, affecting 2-4% of the worldwide population. Psoriasis remains an important public health challenge because there are many clinical forms of psoriasis in particular sites, probably related to the dysregulation of different cytokines. Therefore, there is a continuous need to improve treatment options with mechanisms of action different from those of the currently known therapies. Advances in knowledge of the molecular bases of pathogenesis lead to a better understanding of the disease, thus influencing the development and management of effective treatments. Moreover, data from recent published work indicate that psoriasis coexists with cardiovascular diseases, metabolic syndrome, diabetes mellitus and psychiatric disorders. We present results from our 52-week open-label trial in a cohort of psoriatic and psoriatic arthritis patients treated with daily p.o. doses of apremilast 60mg. We confirmed the efficacy and safety of the drug in favoring the improvement of skin and joint disease as well as the modulation of metabolic biomarkers in diabetic and non-diabetic psoriatic patients. Apremilast could be used successfully in psoriatic patients affected by cardiometabolic comorbidities, ensuring an improvement in both diseases.

Hypoxemic features of obstructive sleep apnea and the risk of mortality: a cluster analysis.

Patients with moderate to severe obstructive sleep apnea (OSA) have an increased risk of cardiovascular comorbidities and mortality. Although different subtypes of OSA have been described, data about oximetric parameters and their suitability to identify a different phenotype are scant. In this study, we evaluate the association between moderate to severe OSA and oximetric parameters included in the home sleep apnea test (HSAT) and the risks of all-cause mortality, cardiovascular mortality, and cancer mortality. Adult patients with moderate to severe OSA from a clinical cohort in Chile were included (SantOSA study). We developed a latent class analysis (LCA) incorporating oximetric measures commonly reported on HSAT. Differences between the groups were evaluated using ANOVA and the chi-squared test. Survival curves were constructed using a Kaplan-Meier (log-rank) model, and adjusted hazard ratios of mortality were calculated using a Cox regression model following a confounder analysis of cardiovascular comorbidities. A total of 889 patients were included in the analysis. LCA identified three different clusters: Cluster 1, "nonhypoxemic" (n = 591); cluster 2, "moderately hypoxemic" (n = 297); and cluster 3, "severely hypoxemic" (n = 115). The mean follow-up was 4.7years. The hypoxemic groups showed an increased risk of cardiometabolic comorbidities and an independent risk of all-cause mortality (adjusted HR 1.67 (CI 1.0-2.64) p value = 0.027). The moderately hypoxemic group had an adjusted HR of 2.92 (CI 1.00-8.58), p value = 0.05, while the severely hypoxemic group had an adjusted HR of 2.55 (CI 1.08-6.02), p value = 0.031. For cardiovascular mortality, we found an HR of 2.03 (CI 0.50-8.136), p value = 0.31, and for cancer mortality, we found an HR of 5.75 (CI 1.03-32.17), p value = 0.042. Oximetric parameters are useful for describing a different phenotype with a high risk of mortality among patients with moderate to severe OSA, beyond the apnea-hypopnea index.

Hepatic Function and Fibrosis Assessment Via 2D-Shear Wave Elastography and Related Biochemical Markers Pre- and Post-Gastric Bypass Surgery.

Nonalcoholic fatty liver disease (NAFLD) exhibits a worldwide distribution and encompasses a wider range of hepatic abnormalities that can culminate in serious clinical outcomes. The growing incidence of NAFLD necessitates more efficient management strategies particularly in clinically severe obese patients. Weight reduction is the cornerstone of NAFLD treatment; therefore, bariatric surgery could be a therapeutic approach in selected obese patients afflicted with NAFLD and other cardiometabolic comorbidities. The present study focused on the potential role of bariatric surgery on hepatic function and NAFLD-related histopathological features measured through a noninvasive method. Ninety patients entered to this study and underwent initial preoperative assessments including demographic profile, anthropometric measurements, standard laboratory tests, and hepatic biopsy. Liver stiffness was also evaluated via two-dimensional shear wave elastography (2D-SWE). All assessments were repeated over the subsequent 6months following surgery except for liver biopsy. Postoperative hepatic elasticity was lessened after 6months (p = 0/002).The levels of alanine aminotransferase, gamma-glutamyl transferase, total protein, lipid indices, glucose, and platelet count were also improved following surgery (p < 0/001). Further progression of fibrosis was observed in 25% of patients after surgery. Bariatric surgery was associated with a favorable impact on anthropometric and hepatic elasticity indices as well as metabolic parameters. The ideal target population for bariatric surgery should be thoroughly addressed, and the underlying risk factors for fibrosis progression need to be controlled before surgery. However, expanded research designed as comprehensive randomized controlled trials are recommended to confirm these findings.

The role of the interleukin-23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis.

Alterations in the innate and adaptive immunity underpin psoriasis pathophysiology, with the Th17 cells subset now recognized as the fundamental cells in the key controlling pathway involved in its pathogenesis. Since psoriasis is a systemic disease with important comorbidity, further knowledge on the interleukin (IL)‐23/Th17 axis led to the hypothesis that there may be shared pathogenic pathways between primary skin disease and comorbidity. Psoriasis has been identified as a risk factor for cardiovascular and metabolic disease, and increasing evidence gives support to this epidemiological observation from the clinical‐pathologically field. As an example, increased levels of IL‐23 and IL‐23R have been found in human atherosclerotic plaque, and levels correlated with symptom duration and mortality. Also, upregulation of IL‐23/IL‐17 seems to play an important role in both myocardial damage and stroke, with interesting reports on deleterious effect neutralization after administration of related anti‐bodies in both associated conditions. In diabetic patients, increased levels of IL‐23/IL‐17 have also been observed and available data support a synergistic role of IL‐23/IL‐17 in β‐cells damage. In obesity, signs of an expansion of Th17 subset in adipose tissue have been reported, as well as elevated concentrations of IL‐23 in obese patients. In non‐alcoholic fatty liver disease, closely related to metabolic syndrome, but also in other mentioned cardiometabolic disorders, a predominance of IL‐23 and other related pro‐inflammatory factors has been identified as participating in their pathogenesis. Thus, the involvement of the IL‐23/Th17 axis in these shared psoriasis‐cardiometabolic pathogenic mechanisms is reviewed and discussed in the light of the existing preclinical and clinical evidence, including that from comorbid psoriasis patients.

Abstract P326: Multilevel Analysis Of Concentrated Neighborhood Disadvantage And Cardiometabolic Factors In People Living With Hiv

Aging persons living with HIV (PLWH) are a vulnerable population at higher risk for chronic illnesses such as metabolic alterations, diabetes, cardiovascular disease, and cancer. Community and specifically, neighborhood, factors may play a key role in the development of comorbidities. Availability of healthy food stores, physical activity resources, walking/physical activity environment, and neighborhood socioeconomic status have all been individually associated with a higher odds of having ideal cardiovascular health scores. We hypothesized that exposure concentrated disadvantage at the community level impact cardio metabolic outcomes in PLWH. We examined this hypothesis in a cross-sectional analysis of the N ew O rleans A lcohol use in H IV [NOAH] Study of adult PLWH under care (n=365). Hypertension (HTN) was defined as a mean systolic ≥130-139 or diastolic blood pressure ≥80-89 mmHg. Metabolic syndrome (MS) was defined as having 3 of 5 conditions: HTN, low high-density lipoproteins (≤40 (men)/50 (women)), high triglycerides (≥ 150mg/dl), high glucose (≥100 mg/dl), waist circumference &gt;88(women)/102(men). Multivariable logistic regression and multilevel binomial regression analyses were performed adjusting for age, race, smoking, and viral load. The majority of participants were African American (83.6%) with a mean age 48.2 ±10.4, 68.8% male and 31.2% female. MS was prevalent in 36.1%, HTN 66.0%, diabetes 14%, dyslipidemia 28.2%, and 27.4% were obese. There was substantial clustering of cardiometabolic outcomes by neighborhood, with intra-class correlations (ICC) near or greater than 20% for BMI, diabetes, hypertension, and metabolic syndrome. Neighborhood concentrated disadvantage explained a significant proportion of the variance in diabetes (ICC drop from 18% to 8%) and the likelihood of having diabetes increases by 33% for each unit increase in neighborhood concentrated disadvantage (odds ratio = 1.33, 95% CI=1.02, 1.74). Our results suggest a significant role of environmental factors on cardio metabolic comorbidities among PLWH. There is a critical need for a deeper understanding of the roles that social determinants at the community and interpersonal levels play in chronic comorbidities in PLWH. Neighborhoods and social spaces are important contexts through which social determinants act to shape health and health behavior. (Supported by: NIH P60AA009803)

Abstract P407: Association of Obesity at Baseline and Change Over Time With 6 Minute Walk Distance: The Multi-ethnic Study of Atherosclerosis

Introduction: The 6 minute walk distance (6MWD) may be an indicator of frailty and is strongly associated with risk of mortality. Obesity is increasingly shown to be associated with decreased physical function, frailty, and disability, and is also associated with multiple major cardiometabolic comorbidities that cause early mortality. Studies of 6MWD have generally been limited in scope by the use of a single measurement of BMI for obesity, highly selected samples, and by lack of racial/ethnic diversity. Methods: 6MWD was measured in participants at Visit 6 (2016-2018) of the Multi-Ethnic Study of Atherosclerosis (MESA) who were able to ambulate without assistance. MESA participants were diverse with 62% non-white and 50% female, aged 45-84 and free of CVD at Visit 1 (2000-2002). We used multivariable linear regression with robust standard errors that account for within person correlation to investigate the association of baseline BMI categories and BMI change over time (from Visit 1 to Visit 6) with 6MWD. We used normal weight (BMI 18.5 - &lt;25.0kg/m 2 ) and no BMI change (-1 to +1 kg/m 2 ) as reference categories. Results: Among 2525 participants with 6MWD at Visit 6, mean Visit 1 BMI was 28.2 kg/m 2 , mean Visit 6 BMI was 28.4 kg/m 2 , mean BMI change was 0.22kg/m 2 , and mean 6MWD was 410 m. Average time between BMI measurements was 15.8 years. Baseline overweight and obesity were strongly and significantly associated with lower 6MWD, as was increase in BMI over time ( Figure ). Adjustment for potential confounders and mediators did not explain these associations, although significant interaction by age was found for BMI decrease ≥ -4kg/m 2 (p = 0.003) with those over 70 having lower 6MWD (-31.2 (-50.6, -11.8)) and younger participants having non-significantly higher 6MWD (17.2 (-8.2, 42.5)). There was no significant heterogeneity by sex or race/ethnicity. Conclusion: Even modest increase in BMI (1≤ change &lt;4 kg/m 2 ) with aging is associated with lower 6MWD in MESA. Consensus about the impact of weight loss in older adults remains a major challenge.

A Carbohydrate Beverage Reduces Monocytes Expressing TLR4 in Children with Overweight or Obesity

Background:Childhood obesity is increasing, with about one-third of children overweight or obese. Obesity is characterized by a state of chronic low-grade inflammation that is related to cardiometabolic comorbidities. Inflammatory monocytes, which are classified into 3 different groups—classical, intermediate, and nonclassical monocytes, with Toll-like receptor 4 (TLR4+) expression indicating a proinflammatory state—underlie several obesity-associated morbidities. Objectives:This study aimed to assess the responses of monocyte populations to beverages of differing macronutrient composition in children with healthy weight (HW) or overweight/obesity (OW/OB). Methods:Ten HW children (5th to 84.9th percentile; mean age 12.29±2.5 y) and 7 children with OW/OB (85th to 99.99th percentile; mean age 11.96±3.8 y) completed the study. Adiposity was determined via DXA. Using a double-blinded, randomized, crossover design, participants consumed either a high-carbohydrate (CHO; 210 kcal; 0g fat/56g carbohydrates/0g protein) or a whole-eggbased high-protein/fat (EGG; 210 kcal; 15g fat/0g carbohydrates/18g protein) beverage. Venous blood was collected at baseline and 2 h postprandially for evaluation of metabolic and inflammatory responses. Repeated measures ANOVA and Pearson correlations were conducted. Results:Consuming the CHO beverage significantly reduced the primary outcome: TLR4+expression on classical monocytes in children with OW/OB only (25.60% decrease from baseline in OW/OB compared with 1.61% increase in HW). Children with OW/OB had significantly less percentages of TLR4+nonclassical monocytes than HW (47.66% lower after CHO). Insulin and glucose (secondary outcomes), were significantly higher after the CHO condition compared with baseline (230.61% and 9.93% increase, respectively). Changes in glucose were significantly and negatively related to changes in monocyte populations in the CHO condition. Conclusions:These data suggest that high-carbohydrate beverages alter monocyte populations in the blood in children with OW/OB, which is related to glucose metabolism. These findings have implications for nutritional recommendations in children with overweight/obesity. National Clinical Trial registry trial number: NCT03597542.

Pathogenesis of Chronic Plaque Psoriasis and Its Intersection With Cardio-Metabolic Comorbidities.

Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic plaques on the skin. Psoriasis is frequently associated to comorbidities, including psoriatic arthritis, cardiovascular diseases, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and inflammatory bowel diseases. In this review, we discuss the pathophysiological relationship between psoriasis and cardio-metabolic comorbidities and the importance of therapeutic strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis. Pathogenesis of psoriasis and its comorbidities share both genetic predisposition and inflammatory pathways, which include the TNFα and the IL-23/IL-17 pathways. These pathways are selectively addressed by biological treatments, which have substantially changed the outcomes of psoriasis therapy and affect positively comorbidities including reducing cardiovascular risk, allowing a more comprehensive approach to the patient.

Abnormal weight gain with fatigue and stress in early survivorship after childhood brain tumor diagnosis.

Diagnosis and treatment for individuals with brain tumors during childhood involves sequelae, including abnormal weight gain. This symptom is commonly clustered with fatigue and increased risk for cardiovascular disease. Children's Oncology Group recommendations include annual surveillance of body mass index (BMI) and cardiometabolic comorbidities; however, there has been little emphasis on individualized screening early in survivorship. The primary purpose of this paper is to describe the findings of abnormal weight gain and its correlates in a sample of young childhood brain tumor survivors during early survivorship. This cross-sectional multi-site study included brain tumor survivors of ages 8-12 years who were less than 6 years posttreatment. Convenience sampling from two pediatric cancer centers in the southern United States was utilized. Data collected included BMI, parent report of sleep, and child report of fatigue and stress. The sample (N = 21) consisted of children who had received chemotherapy, radiation treatment, and surgery for childhood brain tumor. BMI in overweight and obese categories exceeded normative samples with 38% at or above the 85th percentile. There were clinically significant relationships with fatigue, stress about weight, tumor location, cranial radiation, chemotherapy, and recurrence PRACTICE IMPLICATIONS: Screening for abnormal weight gain and related factors, such as fatigue should begin early in survivorship after childhood brain tumor treatment completion with the aim of health promotion and disease prevention. Adiposity measurement techniques should be utilized in future clinical and research settings to improve assessment of cardiometabolic risk.

CPAP Effect on Cardiopulmonary Exercise Testing Performance in Patients with Moderate-Severe OSA and Cardiometabolic Comorbidities.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with daytime somnolence, cognitive impairment and high cardiovascular morbidity and mortality. Obesity, associated cardiovascular comorbidities, accelerated erythropoiesis and muscular mitochondrial energetic dysfunctions negatively influence exercise tolerance in moderate-severe OSA patients. The cardiopulmonary exercise testing (CPET) offers an integrated assessment of the individual’s aerobic capacity and helps distinguish the main causes of exercise limitation. The purpose of this study is to evaluate the aerobic capacity of OSA patients, before and after short-term continuous positive airway pressure (CPAP). Materials and Methods: Our prospective study included 64 patients with newly diagnosed moderate-severe OSA (apnea hypopnea index (AHI) 39.96 ± 19.04 events/h) who underwent CPET before and after CPAP. Thirteen patients were unable to tolerate CPAP or were lost during follow-up. Results: 49.29% of our patients exhibited a moderate or severe decrease in functional capacity (Weber C or D). CPET performance was influenced by gender but not by apnea severity. Eight weeks of CPAP induced significant improvements in maximal exercise load (Δ = 14.23 W, p = 0.0004), maximum oxygen uptake (Δ = 203.87 mL/min, p = 0.004), anaerobic threshold (Δ = 316.4 mL/min, p = 0.001), minute ventilation (Δ = 5.1 L/min, p = 0.01) and peak oxygen pulse (Δ = 2.46, p = 0.007) as well as a decrease in basal metabolic rate (BMR) (Δ = −8.3 kCal/24 h, p = 0.04) and average Epworth score (Δ = −4.58 points, p < 0.000001). Conclusions: Patients with moderate-severe OSA have mediocre functional capacity. Apnea severity (AHI) was correlated with basal metabolic rate, resting heart rate and percent predicted maximum effort but not with anaerobic threshold or maximum oxygen uptake. Although CPET performance was similar in the two apnea severity subgroups, short-term CPAP therapy significantly improved most CPET parameters, suggesting that OSA per se has a negative influence on effort capacity.

SRC-3/AIB-1 may Enhance Hepatic NFATC1 Transcription and Mediate Inflammation in a Tissue-Specific Manner in Morbid Obesity.

Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders. 50 morbidly obese patients participated in the present study. Biopsies were collected from visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, extra-myocellular adipose tissue and liver. We evaluated the differential protein expression of NFATc1, SRC-2/TIF-2, SRC-3/AIB-1 and inflammatory biomarkers CD68 and CD3 by immunohistochemistry. The current study was designed to determine any correlations between the transcription factor NFATc1 and the SRC coregulators, as well as any associations with the inflammatory biomarkers. We identified SRC-3 as a hepatic NFATc1 coactivator and we demonstrated its possible role in energy homeostasis and lipid metabolism. Moreover, we revealed a complex and extensive intraand inter-tissue network among the three main investigated proteins and the inflammatory biomarkers, suggesting their potential participation in the obesity-induced inflammatory cascade. Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead to numerous cardiometabolic diseases. Further on, our present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.