Elevated Cardiometabolic Risk Research Articles

Increased Cardiometabolic Risk in Dynapenic Obesity: Results from the Study of Workers' Health (ESAT).

Background: The coexistence of obesity and low muscle strength-denoted dynapenic obesity (DO)-has been associated with an unhealthy metabolic profile and increased risk for metabolic syndrome. However, there is a lack on studies investigating if DO exhibits higher cardiometabolic risk than non-dynapenic obesity. Objectives: To assess if individuals with DO exhibit elevated cardiometabolic risk compared to non-dynapenic obesity. Methods: a cross-sectional study that analyzed the data of workers from a quaternary care hospital collected between November 2018 and March 2020. Participants were stratified into the following anthropometrical and peripheral muscle strength profiles: non-obese/non-dynapenic (NOND), non-obese/dynapenic (NOD), obese/non-dynapenic (OND), and obese dynapenic (OD). Cardiovascular risk was evaluated by Atherogenic Index (AI), Plasma Atherogenic Index (PAI), Hypertriglyceridemic Waist (HW), A Body Shape Index (ABSI), Atherogenic Dyslipidemia (AD), Castelli Indices I and II, and Framingham Score (FS). Results: the OD group had significantly lower HDL compared to all others (p = 0.009), and despite exhibited lower prevalence of HW compared to OND (p < 0.01), a higher cardiometabolic risk compared to OND profile was observed assessing AI (p = 0.05), Castelli I (p < 0.05) and Castelli II (p < 0.05) scores. Conclusions: in the studied population, individuals with DO exhibit elevated cardiometabolic risk compared to other anthropometrical and peripheral muscle strength profiles.

Disordered eating and cardiometabolic risk factors in Chinese women: evidence from the China Health and Nutrition Survey.

Disordered eating (DE) is associated with elevated cardiometabolic risk (CMR) factors, yet little is known about this association in non-Western countries. We examined the association between DE characteristics and CMR and tested the potential mediating role of BMI. This cross-sectional study included 2005 Chinese women (aged 18-50 years) from the 2015 China Health and Nutrition Survey. Loss of control, restraint, shape concern and weight concern were assessed using selected questions from the SCOFF questionnaire and the Eating Disorder Examination-Questionnaire. Eight CMR were measured by trained staff. Generalised linear models examined associations between DE characteristics with CMR accounting for dependencies between individuals in the same household. We tested whether BMI potentially mediated significant associations using structural equation modelling. Shape concern was associated with systolic blood pressure (β (95 % CI) 0·06 (0·01, 0·10)), diastolic blood pressure (DBP) (0·07 (95 % CI 0·03, 0·11)) and high-density lipoprotein (HDL)-cholesterol (-0·08 (95 % CI -0·12, -0·04)). Weight concern was associated with DBP (0·06 (95 % CI 0·02, 0·10)), triglyceride (0·06 (95 % CI 0·02, 0·10)) and HDL-cholesterol (-0·10 (95 % CI -0·14, -0·07)). Higher scores on DE characteristics were associated with higher BMI, and higher BMI was further associated with lower HDL-cholesterol and higher other CMR. In summary, we observed significant associations between shape and weight concerns with some CMR in Chinese women, and these associations were potentially partially mediated by BMI. Our findings suggest that prevention and intervention strategies focusing on addressing DE could potentially help reduce the burden of CMR in China, possibly through controlling BMI.

Do Children's Health Behaviors Buffer the Impact of Cumulative Environmental Stress on Emerging Cardiometabolic Risk?

Previous studies have found that exposure to childhood environmental stress is associated with cardiometabolic risk. However, it is not known whether individual health behaviors disrupt this relationship. This study prospectively evaluated the relationship between cumulative environmental stress in a low-income sample and cardiometabolic risk in middle childhood and examined whether child health behaviors attenuated this relationship. In a cohort of children (n=338; 57% Hispanic children; 25% Black children), environmental stressors (family and neighborhood factors representing disadvantage/deprivation) and child health behaviors (accelerometry measured physical activity; parent-reported screen time and diet recalls) were measured over 5 time points beginning when children were aged 2 to 4 years and ending when they were aged 7 to 11 years. Children's cardiometabolic risk factors (body mass index, blood pressure, triglyceride/high-density lipoprotein ratio, glucose, hemoglobin A1c, C-reactive protein) were measured at 7 to 11 years. Emerging cardiometabolic risk was defined as having ≥1 elevations that exceeded clinical thresholds. In adjusted path analyses, greater cumulative environmental stress was associated with higher likelihood of emerging cardiometabolic risk in middle childhood (P<0.001). Higher levels of moderate to vigorous physical activity and fewer sedentary minutes attenuated the positive relationship between stress and cardiometabolic risk (P<0.05). Children with >2 hours of average daily screen time had a higher likelihood of elevated cardiometabolic risk (P<0.01), but screen time did not moderate the stress-cardiometabolic risk relationship. Dietary intake was not related to cardiometabolic risk. Interventions that promote moderate to vigorous physical activity and limit sedentary behavior may have particular importance for the cardiometabolic health of children exposed to high levels of cumulative environmental stress.

24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study

BackgroundHigh-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals. ObjectivesWe aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. MethodsIn 1028 healthy older adults from the Women’s and Men’s Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. ResultsHigher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman’s rank correlation coefficient ρ = 0.27), C-peptide (ρ = 0.30), and triglyceride (ρ = 0.46), and negatively with adiponectin (ρ = −0.40), and high-density lipoprotein cholesterol (ρ = −0.42). ConclusionsWe discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardiometabolic risk.

Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023.

Cumulative environmental stress and emerging cardiometabolic risk during childhood.

To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal-axis activity, mediates this relationship. In a cohort of children from low-income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2-4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C-reactive protein) were measured at the final timepoint when children were 7-11 years of age. In adjusted logistic regression models, greater cumulative environmental stress was associated with a higher likelihood of elevated cardiometabolic risk in middle childhood (p = 0.01). Children from minoritized racial/ethnic groups had a higher prevalence of both stressors and cardiometabolic risk factors. Cumulative environmental stress was associated with higher hair cortisol concentrations (p < 0.01). However, hair cortisol was not directly associated with cardiometabolic risk factors and did not explain the association between environmental stress and cardiometabolic risk in causal mediation analysis. The influence of cumulative stress on cardiometabolic health can be observed in middle childhood and may contribute to cardiometabolic health disparities, highlighting the importance of public health interventions to mitigate disadvantage.

Abstract P274: Beyond MVPA: Machine Learning Insights Into Activity Patterns and Cardiometabolic Health in the National Health and Nutrition Examination Survey (NHANES) 2003-2004

Physical activity (PA) and sedentary behavior (SB) volumes and patterns may be useful in identifying individuals who are at elevated cardiometabolic risk. Identifying individuals at risk will facilitate early interventions for prevention of cardiovascular diseases. The objective of this project is to identify important free-living physical activity patterns to classify cardiometabolic markers including insulin, plasma glucose, and triglyceride. Methods: We used cross-sectional NHANES 2003-2004 accelerometer, blood exam and demographic data. We included adults age ≥18 years who wore a hip-worn ActiGraph 7164 during waking hours for at least 4 days of 10 hours/day of wear time. We included PA and SB predictors including minutes per day (min/d) in sedentary time (0-99 counts per minute, cpm), light intensity PA (100-759 cpm), Lifestyle PA (760-2019 cpm), moderate to vigorous PA (MVPA, ≥2019 cpm), number of breaks in SB, and number of 30-min and 60-min SB, 10-min MVPA bouts etc. The cut points for cardiovascular disease risk were defined based on literature as: fasting serum insulin ≤ 5 μU/mL, plasma glucose ≤ 100 mg/dL and triglyceride &lt; 150 mg/dL. Three random forest (RF) classification models were developed for each cardiometabolic marker using age, body-mass-index, general health, and PA variables as predictors. Models were trained and tested using a 60% training - 40% testing split. We tuned the hyperparameters (final selection: number of trees = 500 and variables = 3) to find the model with the highest testing accuracy based on the out-of-bag error. The importance of each predictor was measured and ranked by the mean decrease in GINI index. Results: The three datasets include insulin (n = 2810, age=34 ±23, 50% females), glucose (n = 1852, age = 49±20, 51% females) and triglyceride (n = 3180, age=36 ±24, 50% females). For insulin model, the PA variables with largest mean decrease in GINI index were SB time, light intensity PA, MVPA, and SB bouts of 30-min. Similarly, time spent in Lifestyle PA, light intensity PA, number of SB breaks and SB bouts of 30-min were the most important variables for abnormal fasting glucose prediction. The number of sedentary breaks, light intensity PA, SB time and SB bouts of 30-min were the most important PA predictors for risk of high triglyceride. Both BMI and age were important demographic variables for prediction of increased risk in each model. The prediction accuracy and precision are as following: Insulin(73%; 76%), Plasma Glucose(68%; 58%), and Triglyceride(64%; 46%). Conclusion: Cardiometabolic markers using free-living PA has the potential to provide insights for classifying the risk for cardiovascular disease based on given physiological marker cut-off points. The time spent lower intensity PA patterns and the number of sedentary breaks, and 30-minutes bouts are important predictors for identifying individuals who may have increased cardiometabolic risk.

Trajectories of lifestyle patterns from 2 to 8 years of age and cardiometabolic risk in children: the GUSTO study

BackgroundTracking combinations of lifestyle behaviours during childhood (“lifestyle pattern trajectories”) can identify subgroups of children that might benefit from lifestyle interventions aiming to improve health outcomes later in life. However, studies on the critical transition period from early to middle childhood are limited. We aimed to describe lifestyle patterns trajectories in children from 2 to 8 years of age and evaluated their associations with cardiometabolic risk markers at age 8 years in a multi-ethnic Asian cohort.MethodsTwelve lifestyle behaviours related to child’s diet, physical activity, screen use, and sleep were ascertained using questionnaires at ages 2, 5, and 8 years. Age-specific lifestyle patterns were derived using principal component analysis and trajectories were determined using group-based multi-trajectory modelling. Child cardiometabolic risk markers were assessed at age 8 years, and associations with trajectories examined using multiple regression, adjusted for confounders.ResultsAmong 546 children, two lifestyle patterns “healthy” and “unhealthy” were observed at ages 2, 5, and 8 years separately. Three trajectory groups from 2 to 8 years were identified: consistently healthy (11%), consistently unhealthy (18%), and mixed pattern (71%). Children in the consistently unhealthy group (vs. mixed pattern) had increased odds of pre-hypertension (OR = 2.96 [95% CI 1.18–7.41]) and higher levels of diastolic blood pressure (β = 1.91 [0.27–3.55] mmHg), homeostasis model assessment of insulin resistance (β = 0.43 [0.13–0.74]), triglycerides (β = 0.11 [0.00-0.22] mmol/L), and metabolic syndrome score (β = 0.85 [0.20–1.49]), but not with BMI z-score or any anthropometric measurements. The consistently healthy group showed no differences in cardiometabolic outcomes compared to the mixed pattern group.ConclusionThree distinct lifestyle pattern trajectories were identified from early to middle childhood. Children in the consistently unhealthy lifestyle group did not have a raised BMI but was associated with several elevated cardiometabolic risk markers. These findings suggest the potential benefits of initiating holistic lifestyle interventions to improve children’s health and well-being from an early age.Trial registrationTrial registration number: NCT01174875. Name of registry: ClinicalTrials.gov. URL of registry: https://classic.clinicaltrials.gov/ct2/show/NCT01174875. Date of registration: August 4, 2010. Date of enrolment of the first participant to the trial: June 2009.

The menopause-related gut microbiome: associations with metabolomics, inflammatory protein markers, and cardiometabolic health in women with HIV.

This study aimed to identify menopause-related gut microbial features, as well as their related metabolites and inflammatory protein markers, and link with cardiometabolic risk factors in women with and without HIV. In the Women's Interagency HIV Study, we performed shotgun metagenomic sequencing on 696 stool samples from 446 participants (67% women with HIV), and quantified plasma metabolomics and serum proteomics in a subset (~86%). We examined the associations of menopause (postmenopausal vs premenopausal) with gut microbial features in a cross-sectional repeated-measures design and further evaluated those features in relation to metabolites, proteins, and cardiometabolic risk factors. Different overall gut microbial composition was observed by menopausal status in women with HIV only. We identified a range of gut microbial features that differed between postmenopausal and premenopausal women with HIV (but none in women without HIV), including abundance of 32 species and functional potentials involving 24 enzymatic reactions and lower β-glucuronidase bacterial gene ortholog. Specifically, highly abundant species Faecalibacterium prausnitzii , Bacteroides species CAG:98 , and Bifidobacterium adolescentis were depleted in postmenopausal versus premenopausal women with HIV. Menopause-depleted species (mainly Clostridia ) in women with HIV were positively associated with several glycerophospholipids, while negatively associated with imidazolepropionic acid and fibroblast growth factor 21. Mediation analysis suggested that menopause may decrease plasma phosphatidylcholine plasmalogen C36:1 and C36:2 levels via reducing abundance of species F. prausnitzii and Acetanaerobacterium elongatum in women with HIV. Furthermore, waist-to-hip ratio was associated with menopause-related microbes, metabolites, and fibroblast growth factor 21 in women with HIV. Menopause was associated with a differential gut microbiome in women with HIV, related to metabolite and protein profiles that potentially contribute to elevated cardiometabolic risk.

An examination of the relationships between the neighborhood social environment, adiposity, and cardiometabolic disease risk in adolescence: a cross-sectional study

BackgroundDisadvantaged neighborhood environments are a source of chronic stress which undermines optimal adolescent health. This study investigated relationships between the neighborhood social environment, specifically, chronic stress exposures, adiposity, and cardiometabolic disease risk factors among 288 Louisiana adolescents aged 10 to 16 years.MethodsThis cross-sectional study utilized baseline data from the Translational Investigation of Growth and Everyday Routines in Kids (TIGER Kids) study. Adolescent data were obtained using self-reported questionnaires (demographics and perceived neighborhood disorder), anthropometry, body imaging, and a blood draw while objective neighborhood data for the concentrated disadvantage index were acquired from the 2016 American Community Survey five-year block group estimates, 2012–2016. Multilevel linear regression models were used to examine whether neighborhood concentrated disadvantage index and perceived neighborhood disorder were associated with body mass index, waist circumference, body fat, adipose tissue, blood pressure, and lipids. We performed multilevel logistic regression to determine the odds of elevated adiposity and cardiometabolic disease risk for adolescents living in neighborhoods with varying levels of neighborhood concentrated disadvantage and disorder.ResultsAdolescents living in neighborhoods with higher disadvantage or disorder had greater waist circumference and total percent body fat compared to those in less disadvantaged and disordered neighborhoods (p for trend < 0.05). Neighborhood disadvantage was also positively associated with percentage of the 95th Body Mass Index percentile and visceral abdominal adipose tissue mass while greater perceived neighborhood disorder was related to higher trunk fat mass and diastolic blood pressure (p for trend < 0.05). Living in the most disadvantaged was associated with greater odds of obesity (OR: 2.9, 95% CI:1.3, 6.5) and being in the top tertile of body fat mass (OR: 3.0, 95% CI: 1.4, 6.6). Similar results were found with neighborhood disorder for odds of obesity (OR: 2.1, 95% CI:1.1, 4.2) and top tertile of body fat mass (OR: 2.1, 95% CI:1.04, 4.1).ConclusionsNeighborhood social environment measures of chronic stress exposure were associated with excess adiposity during adolescence, and relationships were most consistently identified among adolescents living in the most disadvantaged and disordered neighborhoods. Future studies should account for the influences of the neighborhood environment to stimulate equitable improvements in adolescent health.Clinical Trials Registration# NCT02784509.

Gestational Diabetes: A Review

Gestational diabetes (GD) is a disorder of glucose tolerance resulting in hyperglycemia first diagnosed during pregnancy. Its worldwide prevalence is estimated at 14% but varies regionally. In 2008, new diagnostic criteria were adopted, leading to an increase in diagnosed cases. Biomarkers could potentially serve as an alternative to the current diagnostic criteria in the future, enabling the realization of a universally applicable GD screening program. Risk factors associated with GD encompass a range of factors, including epigenetic factors, inadequate vitamin D levels, family history of diabetes, prediabetes, obesity, fetal death, polycystic ovary syndrome (PCOS), and advanced maternal age. GD can have consequences for maternal health, increasing the risk of hypertensive disorders, premature labor, cesarean delivery, metabolic disorders, and later type 2 diabetes. In children, it may be associated with macrosomia, shoulder dystocia, respiratory insufficiency, and hospitalization in the neonatal intensive care. Offspring born to mothers with GD face heightened susceptibility to childhood and adult obesity, alongside elevated cardiometabolic risk. The consequences and risk factors of GD are not fully understood to this day. Therefore, Additional research is warranted to gain a deeper comprehension of the pathophysiology underlying the disease and to ascertain efficacious preventive and therapeutic approaches. Nutritional therapy is often sufficient to achieve normoglycemia objectives. An individualized nutritional program is recommended, providing the necessary nutrients to promote maternal and infant health, attain optimal gestational weight gain and uphold glycemic regulation. However, in some cases, additional antidiabetic therapy is necessary. Insulin remains the most commonly used treatment, but metformin may be a safe and effective alternative. This still needs to be validated by in-depth studies leading to better evaluation of its long-term effects on offspring.

Challenges and Opportunities in Diagnosis and Management of Cardiometabolic Risk in Adolescents.

This review aims to elucidate the limitations of diagnosing metabolic syndrome in adolescents as well as challenges and opportunities in the identification and reduction of cardiometabolic risk in this population. There are multiple criticisms of how we define and approach obesity in clinical practice and scientific research, and weight stigma further complicates the process of making and communicating weight-related diagnoses. While the goal of diagnosing and managing metabolic syndrome in adolescents would be to identify individuals at elevated future cardiometabolic risk and intervene to reduce the modifiable component of this risk, there is evidence that identifying cardiometabolic risk factor clustering may be more useful in adolescents than establishing a cutoff-based diagnosis of metabolic syndrome. It has also become clear that many heritable factors and social and structural determinants of health contribute more to weight and body mass index than do individual behavioral choices about nutrition and physical activity. Promoting cardiometabolic health equity requires that we intervene on the obesogenic environment and mitigate the compounding effects of weight stigma and systemic racism. The existing options to diagnose and manage future cardiometabolic risk in children and adolescents are flawed and limited. While striving to improve population health through policy and societal interventions, there are opportunities to intervene at all levels of the socioecological model in order to decrease future morbidity and mortality from the chronic cardiometabolic diseases associated with central adiposity in both children and adults. More research is needed to identify the most effective interventions.

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Endothelial-specific deletion of methyltransferase Set7 protects mice from obesity-induced endothelial dysfunction

Abstract Background The prevalence and incidence of obesity is alarmingly increasing worldwide. Among the constellation of weight-related comorbidities, cardiovascular disease (CVD) carries the largest burden. A large body of evidence supports the notion that endothelial dysfunction contributes to the pathogenesis of obesity-related CVD. Seminal work has revealed that oxidative stress is a key event preceding the development of endothelial dysfunction in this setting. Epigenetic connections underpinning oxidative stress and vascular dysfunction in experimental and human obesity are emerging. We and others have previously demonstrated that histone methyltransferase Set7 may participate to adverse vascular phenotypes in elevated cardiometabolic risk. Purpose To investigate whether Set7 contributes to endothelial dysfunction in a mouse model of diet-induced obesity. Methods Aortas were isolated from obese mice fed with high fat diet (HFD, 15.5% fat) for 12 weeks and control littermates fed with standard diet (STD, regular unrestricted diet). To specifically investigate Set7 role in obesity-driven endothelial dysfunction, endothelium-dependent (EDR) and independent relaxations were assessed in aortas isolated from control and obese mice, with or without endothelium-specific conditional genetic deletion of Set7. Endothelium-specific Set7 conditional knockout (mice have been generated in our facilities. Conditional Set7flox/flox mice were crossed with TekCre mice to generate E-Set7−/− mice. Set7 deletion was induced by tamoxifen. Body weight, glucose/insulin and lipid plasma levels were measured in all experimental groups. Set7 expression in endothelial cells isolated from mice aorta was assessed by RT-PCR and confocal microscopy. Reactive oxygen species (ROS) production was determined by electron spin resonance spectroscopy. Results Set7 was upregulated in endothelial cells isolated from aortas of obese WT mice as compared to lean controls. Confocal microscopy and RT-PCR of aortic tissue confirmed selective endothelial deletion of Set7 in the E-Set7−/− mice. Both WT and E-Set7−/− animals fed with HFD had similarly elevated body weight and plasma lipids (triglycerides, total and LDL cholesterol), as well as decreased HDL cholesterol. EDR to acetylcholine were impaired in aortas isolated from WT mice fed with HFD as compared to STD. Higher production of superoxide anion (O2-) was observed in aortas isolated from WT, but not in E-Set7−/−, HFD fed mice. Accordingly, apocynin and free radical scavenger TEMPOL rescued HFD-induced EDR in WT mice. Interestingly enough, E-Set7−/− HFD fed mice were protected against obesity-induced endothelial dysfunction. Conclusions Our findings demonstrate that chromatin-modifying enzyme Set7 is upregulated in obesity and involved in oxidative stress, and endothelial dysfunction. Targeting Set7 might represent a promising option to dampen oxidative stress and to prevent atherosclerotic vascular disease in this setting. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Research Council, the Swedish Heart &amp; Lung Foundation, and King Gustav V and Queen Victoria Foundation.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Effect of aerobic exercise on waist circumference in adults with overweight or obesity: A systematic review and meta-analysis.

SummaryExcess visceral adiposity contributes to elevated cardiometabolic risk, and waist circumference is commonly used as a surrogate measure of visceral adipose tissue. Although regular aerobic exercise is known to improve abdominal obesity, its effect on waist circumference is unclear. A systematic review and meta‐analysis was performed to determine (1) the effect of aerobic exercise on waist circumference in adults with overweight or obesity; (2) the association between any change in waist circumference and change in visceral adipose tissue and/or bodyweight with aerobic exercise interventions; and (3) if reductions in waist circumference with exercise are moderated by clinical characteristics or components of aerobic exercise prescription. Twenty‐five randomized controlled trials (1686 participants) were included. Regular aerobic exercise significantly reduced waist circumference by 3.2 cm (95% confidence interval [CI] −3.86, −2.51, p ≤ 0.001) versus control. Change in waist circumference was associated with change in visceral adipose tissue (β = 4.02; 95% CI 1.37, 6.66, p = 0.004), and vigorous intensity produced superior reduction (−4.2 cm, 95% CI −4.99, −3.42, p < 0.0001) in waist circumference compared with moderate intensity (−2.50 cm, 95% CI −3.22, −1.79, p = 0.058). These findings suggest regular aerobic exercise results in modest reductions in waist circumference and associated visceral adipose tissue and that higher intensity exercise may offer superior benefit to moderate intensity.

Neuroticism, Worry, and Cardiometabolic Risk Trajectories: Findings From a 40-Year Study of Men.

BackgroundAnxiety is linked to elevated risk of cardiometabolic disease onset, but the underlying mechanisms remain unclear. We examined the prospective association of 2 anxiety facets, neuroticism and worry, with cardiometabolic risk (CMR) trajectories for 4 decades.Methods and ResultsThe sample comprised 1561 men from an ongoing adult male cohort. In 1975, healthy men (mean age, 53 years [SD, 8.4 years]) completed the Eysenck Personality Inventory‐Short Form neuroticism scale and a Worries Scale. Seven CMR biomarkers were assessed every 3 to 5 years. The CMR score was the number of biomarkers categorized as high‐risk based on established cut points or medication use. Using mixed effects regression, we modeled CMR trajectories over age and evaluated their associations with neuroticism and worry. Using Cox regression, we examined associations of neuroticism and worry with risk of having ≥6 CMR high‐risk biomarkers through 2015. CMR increased at 0.8 markers per decade from age 33 to 65 years, at which point men had an average of 3.8 high‐risk markers, followed by a slower increase of 0.5 markers per decade. Higher neuroticism (B=0.08; 95% CI, 0.02–0.15) and worry levels (B=0.07; 95% CI, 0.001–0.13) were associated with elevated CMR across time, and with 13% (95% CI, 1.03–1.23) and 10% (95% CI, 1.01–1.20) greater risks, respectively, of having ≥6 high‐risk CMR markers, adjusting for potential confounders.ConclusionsBy middle adulthood, higher anxiety levels are associated with stable differences in CMR that are maintained into older ages. Anxious individuals may experience deteriorations in cardiometabolic health earlier in life and remain on a stable trajectory of heightened risk into older ages.

In search of measures to improve the detection of increased cardiometabolic risk in children using second-generation antipsychotic medications

Purpose Second-generation antipsychotic medications (SGAs) are widely used in child psychiatry. SGA-induced metabolic disturbances are common in children, but monitoring practices need systematisation. The study’s aims were to test an SGA-monitoring protocol, examine the distributions of metabolic measurements compared to reference values in child psychiatry patients, and determine whether using a homeostasis model for the assessment of insulin resistance (HOMA-IR) and triglyceride/high-density lipoprotein (TG/HDL) ratio could improve the detection of increased cardiometabolic risk. Materials and methods A systematic monitoring protocol was implemented. Weight and height, blood pressure, fasting glucose, insulin, HDL, and TG were measured at baseline and four times during follow-up. HOMA-IR, TG/HDL ratio and zBMI were calculated. Age-, gender- and BMI-specific percentile curves for HOMA-IR were used to define elevated cardiometabolic risk. Results The study patients (n = 55, mean age 9.9 years) were followed for a median of 9 months. A disadvantageous, statistically significant shift, often appearing within the reference range, was seen in zBMI, TG, HDL, glucose, insulin, HOMA-IR, and TG/HDL ratio. The increase in HOMA-IR appeared earlier than individual laboratory values and was more evident than the TG/HDL ratio increase. An HOMA-IR cut point of 1.98 resulted in a sensitivity and specificity of 83%. Compared to a previous study performed in the same location, the monitoring rates of metabolic parameters improved. Conclusion The monitoring protocol implementation improved the monitoring of metabolic parameters in child psychiatric patients using SGAs. Using HOMA-IR as part of systematic SGA monitoring could help detect metabolic adverse effects.

The risk factors potentially influencing risk of serious illness/death in people with diabetes, following SARS-CoV-2 infection: What needs to be done from here

Since early 2020 the whole world has been challenged by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus coronavirus disease 2019 (COVID-19) and the associated global pandemic [1]. People with diabetes are particularly at high risk of becoming seriously unwell after contracting this virus [2,3]. As yet we do not fully understand the underlying factors which contribute to such risk and their respective contributions to outcomes. In this regard, Barron et al. [4] reported an odds ratio (OR) for in-hospital COVID-19-related death of 2.03 (1.97–2.09) in people with type 2 diabetes mellitus (T2DM). A body of work is emerging in relation to the reasons why people with diabetes are more likely to become seriously unwell and in some cases die following a COVID-19 infection. Two recent landmark articles [5,6] have brought into sharp focus the factors that mediate increased risk of serious consequences of a COVID-19 infection in relation to hospital admission and mortality for vaccinated individuals and for nonvaccinated individuals in England. For the postvaccination study [6] the risk algorithm explained 74.1% of the variation in time to COVID-19 related death. An early COVID-19 pandemic study from Mexico [7] concluded that early-onset T2DM conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. The predictive score for COVID-19 lethality included age ≥65 years, diabetes, early-onset diabetes, obesity, age <40 years, chronic kidney disease, hypertension, immunosuppression and significantly discriminated lethal from nonlethal COVID-19 cases. We previously showed that in one area of the UK, the month-by-month mortality rate for people with T2DM was up to 2.2 times higher than that in the same month averaged over the previous 5 years in the early stages of the COVID-19 pandemic, with age the strongest independent predictor of death [8]. Work is continuing to understand how much a previous diagnosis of diabetes type 1 diabetes mellitus (T1DM) or T2DM increases the risk of becoming seriously unwell following a COVID-19 infection vs. absence of diabetes as a diagnosis. Since these early studies, the advent of treatment of hospitalized patients with Dexamethasone has significantly reduced mortality rates across the world. In patients hospitalized with COVID-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization [9]. Potential pathogenetic links between the SARS-CoV-2 virus and diabetes include the influence of glucose homeostasis and potentially altered immune status on the progression of the viral infection once established [10]. COVID-19 infection aggravates inflammation and alters immune system responses, leading to difficulties in blood glucose control. COVID-19 infection also increases the risk of thromboembolism and is more likely to induce cardiopulmonary failure in patients with diabetes than in patients without diabetes [11]. All of these mechanisms are now believed to contribute to the poor prognosis of some patients with preexisting diabetes and a COVID-19 infection. In conclusion, as the COVID-19 pandemic moves into a new phase in Europe and some other parts of the world, much remains to be determined about why having diabetes increases the risk of serious consequences of a COVID-19 infection. The COVID-19 global pandemic poses considerable health hazards, for patients with diabetes. The estimation of risk will require the combination of population based studies using primary and secondary care data and studies that evaluate the immunologic, metabolic and haematologic response following a COVID-19 infection at both a specific tissue and a whole body level, while keeping in mind that basic strategies such as optimizing pharmacologic management for patients at elevated cardiometabolic risk, with targeted choice of glucose lowering, antihypertensive and lipid lowering medications are as relevant to current and future research as to everyday clinical practice. Acknowledgements There was no external funding for this study. The data that support the findings of this study are available from the corresponding author upon reasonable request. Conflicts of interest There are no conflicts of interest.

Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans

ABSTRACT Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.