Adverse Cardiometabolic Risk Research Articles

Identification of glucose and insulin patterns during A 5-H glucose tolerance test and association with cardiometabolic risk factors.

Insulin resistance is key in the pathogenesis of the metabolic syndrome and cardiovascular disease. We aimed to identify glucose and insulin patterns after a 5-h oral glucose tolerance test (OGTT) in individuals without diabetes and to explore cardiometabolic risk factors, beta-cell function, and insulin sensitivity in each pattern. We analyzed the 5-h OGTT in a tertiary healthcare center. We identified classes using latent class trajectory analysis and evaluated their association with cardiometabolic risk factors, beta-cell function, and insulin sensitivity surrogates by multinomial logistic regression analysis. We included 1088 5-h OGTT performed between 2013 and 2020 and identified four classes. Class one was associated with normal insulin sensitivity and secretion. Class two showed hyperglycemia, dysinsulinism, and a high-risk cardiometabolic profile (obesity, hypertriglyceridemia, and low high-density lipoprotein [HDL] cholesterol). Class three included older individuals, a higher proportion of males, and a greater prevalence of hypertension, hyperglycemia, hyperinsulinemia, and postprandial hypoglycemia. Finally, class four showed hyperglycemia, dysinsulinism, and hyperinsulinemia; this class had the worst cardiometabolic profile (a high proportion of males, greater age, hypertension, obesity, hypertriglyceridemia, and low HDL cholesterol, p < 0.001 vs. other classes). The latent class analysis approach allows the identification of groups with an adverse cardiometabolic risk factor, and who might benefit from frequent follow-ups and timely multidisciplinary interventions.

Neither Resistance Or Aerobic Training Improve Postprandial Lipemia Or Glycemia In Post-menopausal Women.

Introduction: Cardiovascular disease is the leading cause of death for women. Post-menopausal (PM) women are particularly vulnerable in terms of adverse cardiometabolic risk factors, including impairments in glucose and lipid metabolism. Acute resistance and aerobic exercise are efficacious for improving postprandial metabolic glucose (GLU) and triglycerides (TG), however it is unclear if chronic training elicits improvements in postprandial metabolism in PM women. Purpose: To determine if 16 weeks of progressive resistance (RT) or aerobic (AT) training improve postprandial GLU and TG in PM women. Methods: Forty-eight PM women (56 ± 5 y) completed 16 weeks of RT (n = 18), AT (n = 16), or no exercise (control (CON; n = 14)). PM women in the RT group completed 2-4 sets of 9 exercises for the major muscle groups at 50-70% of one repetition maximum on 3 d·wk-1. PM women in the AT group walked, jogged, or cycled at 50-65% of heart rate reserve on 5 d·wk-1. PM women in the CON group maintained habitual physical activity and dietary habits. Before and after the intervention period, participants arrived to the lab after a 10-h fast and having abstained from exercise for at least 72 h. Participants’ GLU and TG were measured while fasted (BL), and 2 h and 4 h after consuming a standardized high-fat, high-sugar meal (12 kcal/kg body weight; 61% fat, 25% carbohydrate). Metabolic load index (MLI) was calculated as the sum of GLU and TG at each time point. Trapezoidal area under the curve (tAUC) and incremental area under the curve (iAUC) were calculated for GLU, TG, and MLI. Non-normally distributed data were log-transformed for analyses, which included two-way mixed effects models (group * time). Results: The GLU tAUC decreased (p = 0.025) from pre- to post-intervention independent of group (539.7 ± 53.6 vs. 520.0 ± 59.63 mg/d x 4 hr). No significant interactions or main effects were observed for any other outcome (p = 0.134 - 0.814). Conclusions: Neither 16 weeks of RT or AT influenced postprandial TG or GLU in PM women. These data may suggest that chronic exercise training does not modify postprandial metabolic response to mixed meals independent of acute exercise, or otherwise that PM women are resistant to the potential beneficial effects of chronic training on postprandial metabolism. Future studies are needed to examine these possibilities.

The cardiometabolic depression subtype and its association with clinical characteristics: The Maastricht Study

BackgroundIndividuals with depression often show an adverse cardiometabolic risk profile and might represent a distinct depression subtype. The aim of this study was to investigate whether a cardiometabolic depression subtype could be identified and to investigate its association with demographics and clinical characteristics (severity, symptomatology, anti-depressant use, persistence and cognitive functioning). MethodsWe used data from The Maastricht Study, a population-based cohort in the southern part of The Netherlands. A total of 248 participants with major depressive disorder were included (mean [SD] age, 58.8 ± 8.5 years; 121 [48.8 %] were men). Major depressive disorder was assessed at baseline by the Mini-International Neuropsychiatric Interview. Cardiometabolic risk factors were defined as indicators of the metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. We measured severity and persistence of depressive symptoms by use of the 9-item Patient Health Questionnaire. ResultsLatent class analysis resulted in two subtypes, one with cardiometabolic depression (n = 145) and another with non-cardiometabolic depression (n = 103). The cardiometabolic depression subtype was characterized by being male, low education, more severe depressive symptoms, less symptoms of depressed mood and more symptoms of loss of energy, more use of antidepressant medication and lower cognitive functioning. LimitationsNo conclusions can be made about causality. ConclusionsLatent class analysis suggested a distinct cardiometabolic depression subtype. Participants with cardiometabolic depression differed from participants with non-cardiometabolic depression in terms of demographics and clinical characteristics. The existence of a cardiometabolic depression subtype may indicate the need for prevention and treatment targeting cardiometabolic risk management.

0214 Effects of Simulated Night-Shiftwork Induced Circadian Misalignment on the Human Plasma Metabolome

Abstract Introduction Circadian misalignment occurs when behaviors such as food intake and sleep happen at inappropriate endogenous circadian times, is common among shift-workers, and is a risk factor for cardiometabolic disease. Identifying mechanisms underlying adverse cardiometabolic risk linked to circadian misalignment could help develop new countermeasure strategies to mitigate health consequences of shiftwork. Thus, we analyzed 24-hour profiles of plasma metabolites during circadian alignment and misalignment in a night-shiftwork protocol. Methods 14 healthy adults (6M/8F), aged 26.4±1.2y (mean±SD), completed a 6 day in-laboratory simulated night-shiftwork study. The protocol comprised 2 baseline days (circadian alignment) followed by a transition day to shiftwork, and then 2 simulated night-shiftwork days (circadian misalignment). Participants consumed energy-balanced diets throughout the protocol, starting 3 days prior to laboratory admission. Plasma was collected every 4h during circadian alignment and misalignment conditions and was analyzed via untargeted metabolomics (liquid chromatography/mass-spectrometry). A model selection approach (best fit) with circadian and behavioral cosine models identified metabolites influenced by circadian (central circadian clock measured via dim-light melatonin onset) versus behavioral cycles (food intake/sleep). Results 5,171 metabolites were detected with average abundance of 424 (~8%) changing between conditions (false discovery rate (FDR)&amp;lt;0.05). 380 metabolites had significant (FDR&amp;lt;0.05) 24-h time-of-day patterns. Of these 380 metabolites, 248 had 24-h time-of-day patterns during circadian alignment, 283 had 24-h time-of-day patterns during misalignment, and 141 had 24-h time-of-day patterns during both conditions. Of the metabolites with 24-h time-of-day patterns in both conditions, 50 were circadian-influenced (e.g., arachidinoyl-serine) and 91 were behaviorally-influenced (e.g., propionylcarnitine). Conclusion Almost twice as many metabolites were influenced by the behavioral versus circadian cycle suggesting altered timing of behaviors like food intake and sleep have a significant impact on 24-h time-of-patterns in the human plasma metabolome. For example, propionylcarnitine is involved in energy metabolism and likely reflects 24h time-of-day patterns altered by food intake. Alternatively, arachidinoyl-serine was circadian influenced, is involved in vasodilation, and thus may contribute to circadian regulation of blood pressure. Further understanding circadian and behavioral regulation of the metabolome could have application in identifying mechanisms of physiological dysregulation and targets for intervention to mitigate health consequences of circadian misalignment. Support (If Any) NIH-DK092624, NIH-TR001082, NIH-DK048520, NIH-HL132150, NIH-HL145099, NIH-DK111161

Menopause Is Associated with an Altered Gut Microbiome and Estrobolome, with Implications for Adverse Cardiometabolic Risk in the Hispanic Community Health Study/Study of Latinos.

ABSTRACTMenopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial β-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups.IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.

Abstract P177: Resistance Training Improves Cardiorespiratory Fitness And Maximal Fat Oxidation Similarly To Aerobic Training, But Uniquely Decreases Visceral Adipose Tissue In Previously Sedentary Postmenopausal Women

Introduction: Cardiovascular disease is the leading cause of death for women, and postmenopausal (PM) women are a particularly vulnerable population in terms of adverse cardiometabolic (CM) risk. Progressive aerobic exercise training (AT) is efficacious for improving CM risk factors such as cardiorespiratory fitness (CRF), body composition (e.g., relative body fat (BF%)), and metabolic flexibility. However, there are large clinical gaps regarding the efficacy of progressive resistance training (RT) to reduce CM risk in PM women. Hypothesis: We hypothesized that 16 weeks of RT would (a) improve CRF, (b) decrease body weight, BF%, and visceral adipose tissue (VAT) volume, and (c) improve metabolic flexibility (as evidenced by an increase in maximal fat oxidation (MFO) during exercise) in a manner similar to AT, but greater than habitual activity control (CON). Methods: Forty-eight PM women (aged 56 ± 5 years) were randomized into RT (n=18), AT (n=16), or CON (n=14) and completed the study per protocol. Women in the RT group performed 2 - 4 sets of 9 resistance exercises using all major muscle groups on 3 d·wk -1 at 50-70% of one repetition maximum. Women in the AT group walked or biked 5 d·wk -1 at 50-65% of heart rate reserve. Women in the CON group maintained habitual physical activity levels and dietary habits. All exercise was progressive in nature. Pre- and post-intervention, participants arrived to the laboratory following a 10-h fast, and had body weight and VAT assessed using a medical-grade bioelectrical device and BF% determined by dual-energy x-ray absorptiometry. CRF (relative VO 2 in mL/kg/min), exercising whole body MFO (g/min), and the intensity at which MFO occurred (Fat max , %CRF) were determined using indirect calorimetry during a graded exercise test to volitional exhaustion on a cycle ergometer. Two-way mixed factorial ANOVAs and follow-up Holm-Sidak-corrected comparisons were used for statistical analyses. Changes are reported as mean ± SE of difference. Results: CRF and MFO increased similarly in the RT (+4.2 ± 1.0 mL/kg/min and +0.17 ± 0.05 g/min) and AT (+4.9 ± 1.0 mL/kg/min and +0.19 ± 0.05 g/min) groups (all p holm ≤ 0.001), and these changes were greater than in the CON group (+0.4 ± 1.0 ml/kg/min and -0.06 ± 0.05 g/min). There was similar improvement in Fat max among groups from pre- to post-intervention (+2.4 ± 1.7%; p = 0.01). Despite no observed changes in bodyweight ( p = 0.25), BF% decreased similarly in the RT (-1.21 ± 0.3%) and AT (-0.9 ± 0.3%) groups (all p holm ≤ 0.03), and to a greater extent than in CON (-0.49 ± 0.4%). However, only RT decreased VAT (-0.40 ± 0.14 l; p = 0.02). Conclusions: Sixteen weeks of RT was similarly efficacious to AT for improving CRF, reducing BF%, and increasing MFO in previously sedentary PM women. Interestingly, we demonstrate that RT may provide a unique benefit in reducing VAT.

Animal-based food choice and associations with long-term weight maintenance and metabolic health after a large and rapid weight loss: The PREVIEW study

Low-energy diet replacement is an effective tool to induce large and rapid weight loss and improve metabolic health, but in the long-term individuals often experience significant weight regain. Little is known about the role of animal-based foods in weight maintenance and metabolic health. We aimed to examine longitudinal associations of animal-based foods with weight maintenance and glycaemic and cardiometabolic risk factors. We also modelled replacement of processed meat with other high-protein foods. In this secondary analysis, longitudinal data were analysed from 688 adults (26-70 years) with overweight and prediabetes after 8-week low-energy diet-induced weight loss (≥8% of initial body weight) in a 3-year, multi-centre, diabetes prevention study (PREVIEW). Animal-based food consumption, including unprocessed red meat, processed red meat, poultry, dairy products, fish and seafood, and eggs, was repeatedly assessed using 4-day food records. Multi-adjusted linear mixed models and isoenergetic substitution models were used to examine the potential associations. The available-case analysis showed that each 10-g increment in processed meat, but not total meat, unprocessed red meat, poultry, dairy products, or eggs, was positively associated with weight regain (0.17kg⋅year-1, 95% CI 0.10, 0.25, P<0.001) and increments in waist circumference, HbA1c, and triacylglycerols. The associations of processed meat with HbA1c or triacylglycerols disappeared when adjusted for weight change. Fish and seafood consumption was inversely associated with triacylglycerols and triacylglycerol-glucose index, independent of weight change. Modelled replacement of processed meat with isoenergetic (250-300kJ·day-1 or 60-72kcal·day-1) dairy, poultry, fish and seafood, grains, or nuts was associated with-0.59 (95% CI -0.77,-0.41),-0.66 (95% CI -0.93,-0.40),-0.58 (95% CI -0.88,-0.27), and-0.69 (95% CI -0.96,-0.41) kg·year-1 of weight regain, respectively (all P<0.001) and significant improvements in HbA1c, and triacylglycerols. Higher intake of processed meat, but not total or unprocessed red meat, poultry, dairy products, or eggs may be associated with greater weight regain and more adverse glycaemic and cardiometabolic risk factors. Replacing processed meat with a wide variety of high-protein foods, including unprocessed red meat, poultry, dairy products, fish, eggs, grains, and nuts, could improve weight maintenance and metabolic health after rapid weight loss. This study was registered as ClinicalTrials.gov, NCT01777893.

Sex-specific associations of adiposity with cardiometabolic traits in the UK: A multi-life stage cohort study with repeat metabolomics.

BackgroundSex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages.Methods and findingsData were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B–containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required.ConclusionsThe results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

Consider the Source: Noise-Stroke Association Varies by Transportation Type.

Consider the Source: Noise-Stroke Association Varies by Transportation Type.

Childhood obesity and adverse cardiometabolic risk in large for gestational age infants and potential early preventive strategies: a narrative review.

Accumulating evidence indicates that obesity and cardiometabolic risks become established early in life due to developmental programming and infants born as large for gestational age (LGA) are particularly at risk. This review summarizes the recent literature connecting LGA infants and early childhood obesity and cardiometabolic risk and explores potential preventive interventions in early infancy. With the rising obesity rates in women of childbearing age, the LGA birth rate is about 10%. Recent literature continues to support the higher rates of obesity in LGA infants. However, there is a knowledge gap for their lifetime risk for adverse cardiometabolic outcomes. Potential factors that may modify the risk in early infancy include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. The early postnatal period may be a critical window of opportunity for active interventions to mitigate or prevent obesity and potential adverse metabolic consequences in later life. A variety of promising candidate biomarkers for the early identification of metabolic alterations in LGA infants is also discussed. IMPACT: LGA infants are the greatest risk category for future obesity, especially if they experience rapid postnatal growth during infancy. Potential risk modifying secondary prevention strategies in early infancy in LGA infants include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. LGA infants may be potential low-hanging fruit targets for early preventive interventions in the fight against childhood obesity.

Measuring Visceral Adipose Tissue Metabolic Activity in Sleep Apnea Utilizing Hybrid 18F-FDG PET/MRI: A Pilot Study.

PurposeVisceral adipose tissue (VAT) is proinflammatory and is associated with cardiovascular (CV) disease. We investigated the relationship between obstructive sleep apnea (OSA) and visceral adipose tissue (VAT) metabolic activity in a pilot group of patients using positron-emission tomography/magnetic resonance imaging (PET/MRI) with 18F-fluorodeoxyglucose (FDG) tracer as a novel marker of adipose tissue inflammation.Patients and MethodsWe analyzed patients from an ongoing study, recruiting those with newly diagnosed, untreated OSA (Respiratory Disturbance Index [RDI] ≥ 5), using home sleep apnea testing (WatchPAT-200 Central-Plus). PET/MRI scans were acquired before continuous positive airway pressure (CPAP)-initiation, and after 3 months of CPAP therapy. Adipose tissue metabolic activity (18F-FDG-uptake) was measured using standardized uptake values (SUV) within the adipose tissue depots. The primary outcome was VAT SUVmean, and secondary outcomes included VAT volume, and subcutaneous adipose tissue (SAT) volume/SUVmean. Reproducibility and reliability of outcome measures were analyzed using intraclass correlation coefficients (ICC). Multivariable linear regression was used to evaluate the association between OSA and primary/secondary outcomes.ResultsOur analytical sample (n = 16) was 81% male (mean age 47 ± 15 years, mean BMI of 29.9 ± 4.8kg/m2). About 56% had moderate to severe OSA (mean RDI 23 ± 6 events/hour), and 50% were adherent to CPAP. We demonstrated excellent inter/intra-rater reliability and reproducibility for the primary and secondary outcomes. Patients with moderate-to-severe OSA had a higher VAT SUV mean compared to those with mild OSA (0.795 ± 0.154 vs 0.602 ± 0.19, p = 0.04). OSA severity was positively associated with VAT SUVmean (primary outcome), adjusted for age and BMI (B [SE] = 0.013 ± 0.005, p = 0.03). Change in VAT volume was inversely correlated with CPAP adherence in unadjusted analysis (B [SE] = −48.4 ± 18.7, p = 0.02).ConclusionDerangements in VAT metabolic activity are implicated in adverse cardiometabolic outcomes and may be one of the key drivers of CV risk in OSA. Our results are hypothesis-generating, and suggest that VAT should be investigated in future studies using multi-modal imaging to understand its role as a potential mediator of adverse cardiometabolic risk in OSA.

Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Importance of adverse childhood experiences

As we learn more about the life-course approach to chronic disease development, it has become clear that a range of exposures during fetal life, childhood, and adolescence can have a profound impact on health and disease in adulthood. In this volume of The Journal, Andrade et al report on an assessment of adverse childhood experiences and increased cardiometabolic risk in Hispanic adolescents. The authors included 10 adverse experiences that are commonly evaluated and added bullying as an additional adverse experience. They found that those adolescents who experience 4 or greater adverse childhood experiences were more likely to have obesity and markers of cardiometabolic risk than those with fewer adverse experiences (Figure). Research is needed to better understand the mechanisms by which adverse experiences in childhood result in increased cardiometabolic risk. Such research may lead to interventions that could prevent atherosclerotic cardiovascular disease. In the meantime, efforts should be made to reduce the number and severity of adverse experiences for children. Article page 267 ▸ Adverse Childhood Experiences Are Associated with Cardiometabolic Risk among Hispanic American AdolescentsThe Journal of PediatricsVol. 237PreviewTo assess the relationship between adverse childhood experiences (ACEs) and cardiometabolic risk among Hispanic adolescents. Full-Text PDF

Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

BackgroundFetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood.MethodsIn a population-based prospective cohort study among 225 mother–child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC–MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood.ResultsNo associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics.DiscussionHigher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.

Adverse childhood experiences and adult cardiometabolic risk factors and disease outcomes: Cross-sectional, population-based study of adults in rural Uganda

BackgroundCardiovascular diseases (CVD) pose a major threat to public health in sub-Saharan African communities, where the burden of these classes of illnesses is expected to double by 2030. Growing research suggests that past developmental experiences and early life conditions may also elevate CVD risk throughout the life course. Greater childhood stress and adversity are consistently associated with a range of adult CVDs and associated risk factors, yet little research exists on the long-term effects of early life stress on adult physical health outcomes, especially CVD risk, in sub-Saharan African contexts. This study aims to evaluate the associations between adverse childhood experiences and adult cardiometabolic risk factors and health outcomes in a population-based study of adults living in Mbarara, a rural region of southwestern Uganda.MethodsData come from an ongoing, whole-population social network cohort study of adults living in the eight villages of Nyakabare Parish, Mbarara. A modified version of the Adverse Childhood Experiences-International Questionnaire (ACEs) assessed past exposure to physical, emotional, and sexual adversity. Participants also took part in a health fair where medical histories on cardiometabolic risk factors and cardiovascular diseases were gathered. Multiple logistic regression models estimated the associations between ACEs and cardiometabolic risk factors and health outcomes.ResultsData were available on 545 adults. The average number of ACEs was 4.9 out of a possible 16. The cumulative number of ACEs were associated with having a history of heart attack and/or heart failure (adjusted odds ratio (AOR) = 1.11, 95% confidence interval (CI) = 0.999-1.234, P = 0.051), but the estimated association was not statistically significant. ACEs did not have statistically significant associations with any others measures of adult cardiometabolic risk and CVD.ConclusionsAdverse childhood experiences are not associated with a range of adult cardiometabolic risk factors and health outcomes in this sample of rural Ugandan adults. Further research in this sample is necessary to identify the pathways that may motivate these null relationship and possibly protect against adverse cardiometabolic and cardiovascular health outcomes.

Adverse Childhood Experiences Are Associated with Cardiometabolic Risk among Hispanic American Adolescents

To assess the relationship between adverse childhood experiences (ACEs) and cardiometabolic risk among Hispanic adolescents. This cross-sectional study was conducted at an academic research center in Gainesville, Florida. Participants were locally recruited, and data were collected from June 2016 to July 2018. Participants (n=133, 60.2% female) were healthy adolescents aged 15-21years who self-identified as Hispanic, were born in the US, and had a body mass index (BMI) between ≥18.5 and≤40kg/m2. Primary outcomes were BMI, body fat percentage, waist circumference, and resting blood pressure. Associations between ACEs and cardiometabolic measures were assessed by multivariable logistic regression models, which controlled for sex, age, parental education, and food insecurity. Results were sex-stratified to assess potential variations. Reporting ≥4 ACEs (28.6%) was significantly associated with a greater BMI (P=.004), body fat percentage (P=.02), and diastolic blood pressure (P=.05) compared with reporting <4 ACEs. Female participants reporting ≥4 ACEs were significantly more likely to have a greater BMI (P=.04) and body fat percentage (P=.03) whereas male participants reporting ≥4 ACEs were significantly more likely to have a greater BMI (P=.04), systolic blood pressure (P=.03), and diastolic blood pressure (P=.03). Hispanic adolescent participants who experienced ≥4 ACEs were more likely to have elevated risk markers of obesity and cardiometabolic disease. Further research is needed to elucidate the physiological mechanisms driving these relationships.

Biological changes in the pregnancy-postpartum period and subsequent cardiometabolic risk-UPSIDE MOMS: A research protocol.

Multiple physiological changes occur in pregnancy as a woman's body adapts to support the growing fetus. These pregnancy-induced changes are essential for fetal growth, but the extent to which they reverse after pregnancy remains in question. For some women, physiological changes persist after pregnancy and may increase long-term cardiometabolic disease risk. The National Institutes of Health-funded study described in this protocol addresses a scientific gap by characterizing weight and biological changes during pregnancy and an extended postpartum period in relation to cardiometabolic risk. We use a longitudinal repeated measures design to prospectively examine maternal health from early pregnancy until 3 years postpartum. The aims are: (1) identify maternal weight profiles in the pregnancy-postpartum period that predict adverse cardiometabolic risk profiles three years postpartum; (2) describe immune, endocrine, and metabolic biomarker profiles in the pregnancy-postpartum period, and determine their associations with cardiometabolic risk; and (3) determine how modifiable postpartum health behaviors (diet, physical activity, breastfeeding, sleep, stress) (a) predict weight and cardiometabolic risk in the postpartum period; and (b) moderate associations between postpartum weight retention and downstream cardiometabolic risk. The proposed sample is 250 women. This study of mothers is conducted in conjunction with the Understanding Pregnancy Signals and Infant Development study, which examines child health outcomes. Biological and behavioral data are collected in each trimester and at 6, 12, 24, and 36 months postpartum. Findings will inform targeted health strategies that promote health and reduce cardiometabolic risk in childbearing women.

An Epigenomic Signature in Children Born Small for Gestational Age (SGA) With “Catch-up” Growth Is Present From Birth and Predicts Early Adulthood Pre-Hypertension

Abstract Background: Cardiometabolic conditions in adulthood are more common in children born SGA1. The relationship of the transcriptome (gene expression) and epigenome (DNA methylation) to birth size and the future development of cardiometabolic disease has not been characterized. Aims: To identify I) the relationship between epigenome at age 0, 7 and 17 years, transcriptome at age 9 years and birth size in a normal population; II) links between the transcriptome and epigenome in childhood and adult cardiometabolic risk. Study Design: Normal children (n=6487) from the Avon Longitudinal Study of Parents and Children were assigned to groups based on birth size using bodyweight (BW) and gestation and divided into groups using the population 10th centile. Adverse cardiometabolic risk at age 17 years was defined by the National Heart Lung and Blood Institute criteria of prehypertension using systolic and diastolic blood pressure as well as HDL and LDL2. Blood transcriptome at age 9 and blood epigenome at age 0, 7, and 17 years and were available from 980 and 947 children, respectively. Hypernetworks were used to integrate differentially expressed genes in the transcriptome (DEGs) and differentially methylated points (DMPs) in the epigenome, identifying functional links. Random Forest, a machine learning approach, was used to determine the predictive value of ‘omic data presented as the area under the curve (AUC) of the receiver operating characteristic. Results: Pre-hypertensive participants at age 17 years were distinguished from normotensive participants and this group was enriched for children born small who caught up by age 7 years (155/611 unhealthy/healthy SGA compared to 1979/12746 in all other BW groups; 1.6-fold, p&amp;lt;1x10-5). This group had a greater height velocity during their catch-up period than the normotensive participants (1.2-fold, p=0.027). Hypernetwork integration of ‘omic data identified a functional relationship between 55 DEGs at age 9 years and DMPs at age 7 years. Random forest analysis was able to accurately predict the presence of pre-hypertensive young adults from the age 9 transcriptome (AUC: 0.973). Using a gene-level contraction of DMPs which map to the 55 DEGs (i.e. cis-DMPs), we demonstrated accurate classification of pre-hypertensive young adults from their blood methylome at age 0 (AUC [95% CI]: 0.92 [0.89-0.95]), 7 (0.90 [0.87-0.93]), and 17 (0.91 [0.88-0.94]) years. Conclusions: Through the integration of transcriptome and epigenome, we have identified a set of genes with an epigenomic and transcriptomic signature which predict pre-hypertension in children born SGA who catch up. Specifically, we have shown that the associated epigenomic signature tracks from birth to early adulthood, indicating the possibility of early detection of risk and primordial prevention. 1 Barker etal. (1988) BMJ 297(6641):134-135. 2 Chobanian etal. (2003) JAMA 289(19):2560-2571.

Black Women Have a Worse Cardio-Metabolic Risk Profile Compared to White Women with Polycystic Ovary Syndrome in the United States: A Systematic Review and Meta-Analysis

Health disparities may influence cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The magnitude and direction of differences in cardio-metabolic risk between Black and White women with PCOS remain uncertain due to inconsistent reports. We conducted a systematic review and meta-analysis to evaluate evidence on cardio-metabolic health disparities between Black and White women with PCOS in the US in response to the call for further delineation of these disparities by the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Web of Science, and Scopus were searched (January 1990 to September 2020) to identify observational studies documenting cardio-metabolic risk profile (glucoregulatory, lipid profile, anthropometric, blood pressure status) in Black and White women with PCOS. The primary outcome was fasting glucose. Further, cardiovascular events (stroke, coronary heart disease, heart failure) and mortality rate (cardiovascular death, total mortality) data were evaluated between groups. Studies on children (< 17 yrs.), pregnant or menopausal-aged (> 50 yrs.) women were excluded. Data were pooled by random-effects models and expressed as weighted mean differences and 95% confidence intervals. Eleven studies (n = 2,821; [626 Black; 2,195 White women]) evaluated cardio-metabolic risk profile, yet none reported on cardiovascular events/mortality rate. Black women had comparable fasting glucose (-0.61 [-1.69, 2.92] mg/dL; I2 = 62.5%), yet exhibited increased fasting insulin (6.76 [4.97, 8.56] µIU/mL; I2 = 59.0%); homeostatic model assessment of insulin resistance (HOMA-IR; 1.47 [0.86, 2.08]; I2 = 83.2%); systolic blood pressure (SBP, 3.32 [0.34, 6.30] mmHg; I2 = 52.0%) and decreased triglyceride (-32.56 [-54.69, -10.42] mg/dL; I2 = 68.0%) when compared to White women with PCOS (All: P ≤ 0.03). Groups were comparable in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and diastolic blood pressure (All: P ≥ 0.06). Paucity in the number of studies that evaluated cardiovascular events or mortality limits any conclusions about potential disparities. Overall, Black women with PCOS have a greater tendency for an adverse cardio-metabolic risk profile (increased insulin, HOMA-IR, SBP), despite lower triglyceride levels than White women. Our observations support consideration of these disparities for diagnostic, monitoring, management, and public health practices, and for future guideline recommendations. Heterogeneity among studies warrants future research to address the relative contributions of biological, environmental, socioeconomic, and healthcare factors to the observed disparities. Longitudinal research should address cardiovascular events and mortality rate in Black women with PCOS (www.crd.york.ac.uk/PROSPERO ID, CRD42020183485).

Association of serum 25-Hydroxy vitamin D with total and regional adiposity and cardiometabolic traits.

Lower serum 25-hydroxyvitamin D [25(OH)D] is associated with greater adiposity and adverse cardiometabolic risk profile. The evidence is inconsistent among South Asian Indians. We aimed to examine associations between 25(OH)D and cardiovascular (CVD) risk markers in a rural and urban cohort from South India. In this cross sectional study, 373 individuals (men, n = 205) underwent detailed CVD risk marker assessment including anthropometry [body mass index (BMI), waist, (WC) and hip circumferences (HC)], body composition analysis using dual energy x-ray absorptiometry (DXA), blood pressure and biochemical analysis (glucose, insulin and lipids). The distribution of CVD risk factors were compared across serum 25(OH)D levels, stratified as deficiency (<20 ng/ml), insufficiency (20 to 29 ng/ml) and normal (≥30 ng/ml) levels. Multiple regression analysis, adjusting for potential confounders, was used to study associations of 25(OH)D with adiposity and cardiometabolic traits. The mean and standard deviation (SD) of age, BMI and 25(OH)D levels were 41.4 (1.1) years, 25.5 (4.8) kg/m2 and 23.4 (10.4) ng/ml respectively. The prevalence of 25(OH)D deficiency was 39.9% in this cohort. Individuals in the 25(OH)D deficiency category had significantly higher mean (SD) BMI [26.6 (5.1) kg/m2], waist circumference [89.9 (12.5) cm] and total fat mass [20.6 (7.9) kg] compared with the Vitamin D sufficient group [BMI: 24.0 (4.4); WC 84.7 (12.0); total fat mass: 15.2 (6.8)]. Significantly inverse associations were observed with DXA measured total and regional fat depots with 25(OH)D levels, while anthropometric indices of adiposity showed significant inverse association only in women. After adjusting for total fat mass, no significant associations were observed between 25(OH)D and the cardiometabolic traits. Our results confirm that lower 25(OH)D is independently associated with both total and regional adiposity, but not with cardiometabolic traits, in this population.