Markers Of Cardiometabolic Disease Research Articles

Menopause Predisposes Women to Increased Risk of Cardiovascular Disease.

(1) Background: Menopause is an important event in women's lives, possibly contributing to the development of CVD, which is associated with changes in the cardiovascular risk profile, markers of metabolic health, and subclinical atherosclerosis. The aim of this study was to assess the association of menopause with CVD risk factors and subclinical markers of cardiometabolic disease. (2) Methods: The study involved 235 women from the general population at different stages of menopause. The methods used in this study were: diagnostic survey, anthropometric measurement (WC, height, BMI, WHtR), blood pressure measurement, biochemical analysis of venous blood (lipid profile, glucose, insulin, HbA1c), and CVD risk assessment (ASCVD Risk Calculator, POL-SCORE, SCORE-2). (3) Results: The vast majority of respondents had low cardiovascular risk, irrespective of the scale used for measuring the risk of CVD. The age at menopause was not an independent risk factor for CVD. In Model 1, the age at menopause and the time since menopause were found to be factors that increased CVD risk (OR = 1.186 and 1.267, respectively). In Models 2 and 3, the severity of menopausal symptoms was not a risk factor for CVD. Models 3 and 4 demonstrated that women with metabolic syndrome (MetS) were at a significantly higher risk of CVD. In model 5, the odds ratio of CVD with MetS as a standalone factor was 13.812. (4) Conclusions: Menopause predisposes women to an increased risk and MetS to a significantly higher risk of CVD.

Abstract 16132: Cardiometabolic Risk Factors and Non-Culprit Plaque Characteristics in Patients With STEMI in REAL-TIMI 63B

Introduction: Greater non-calcified plaque volume (NCPV) measured by coronary CT angiography (CCTA) is associated with higher risk of future myocardial infarction in stable patients. However, NCPV and associations with clinical characteristics in patients presenting with a first acute STEMI are not well described. Methods: The REAL-TIMI 63B trial randomized 593 patients with no prior MI presenting with acute STEMI to intravenous recombinant human lecithin-cholesterol acyltransferase (MEDI6012) or placebo; a subset were to undergo CCTA 48-72h after STEMI. Global NCPV, low-attenuation PV (LAPV), and calcified PV (CPV) were measured by a centralized core laboratory blinded to treatment arm. Revascularized segments were excluded from coronary plaque quantification. Results: 188 patients had a CCTA performed at baseline. Of these, 80.3% had NCPV and 77.4% had LAPV outside of the revascularized segments. Median NCPV was 28.4mm 3 [IQR 1.4-92.1], LAPV 3.8mm 3 [0.1-14.9], and CPV 92.4mm 3 [22.6-201.8]. Among the characteristics examined, male vs. female sex (51.3 mm 3 [3.47-100.3] vs 5.6 mm 3 [0.0-17.3]; p=0.0003), BMI >25 kg/m 2 (overweight or obese) (41.20 mm 3 [2.01-104.50] vs 10.98 mm 3 (0.0-61.5); p=0.01) and diabetes (82.6 mm 3 [59.0-123.4] vs 24.2 mm 3 [1.21-85.2]; p=0.038) were associated with greater NCPV (Figure). Conclusions: Among patients with no prior MI undergoing primary PCI for STEMI, we found that most patients had NCPV and LAPV outside the culprit lesion. Male sex and markers of cardiometabolic disease including higher BMI and diabetes were associated with a greater burden of NCPV. These observations underscore the need for intensive medical therapies that may stabilize vulnerable plaque in patients presenting with acute myocardial infarction.

The relationships between the plasma metabolome and orthostatic blood pressure responses

Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and 818 plasma metabolites in middle-aged subjects from the general population. We included 3803 out of 6251 subjects (mean age, 57 years; 52% women) from the Malmö sub-cohort of The Swedish CardioPulmonary bioImage Study with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses were determined using multivariable linear regression analysis and p values were corrected using the Bonferroni method. Six amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics were associated with orthostatic blood pressure after adjusting for age, gender and systolic blood pressure. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic. Twenty-two out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.

The relationships between the plasma metabolome and orthostatic blood pressure responses

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the Swedish Heart-Lung Foundation Objective Impaired orthostatic blood pressure responses may be an indicator of cardiovascular autonomic dysfunction, which can be seen in the metabolic syndrome. Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and over 800 plasma metabolites in middle-aged subjects from the general population. Methods We included 3,803 subjects (mean age, 57 years; 52 % women) with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses as well as orthostatic hypotension were determined using multivariable linear regression analysis. The Bonferroni corrected p-value was used in this study (p value < 6.11×10-5 (0.05/818) and 2.273×10-3 (0.05/22) respectively). Results We identified five amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics that were associated with orthostatic blood pressure responses. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic, with the most significant relationships for lipids in the dihydrosphingomyelin and sphingosine pathways. Conclusions In this exploratory study, we found that 22 out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.

New metrics of dietary carbohydrate quality.

The aim of this study was to introduce novel metrics of dietary carbohydrates quality relevant for products and diets. Carbohydrate quality has long been associated with a low glycemic index. More recently, novel metrics of carbohydrate quality featuring variations of total carbohydrates-fibers-free sugars ratios have been applied to carbohydrate-rich foods, including grains, beans, vegetables, and fruit. High scoring products had higher levels of health-promoting nutrients (protein, dietary fiber, iron, magnesium, zinc, potassium, selenium, and various B-vitamins) and lower levels of nutrients of public health concern (total sugar, added/free sugars, and fat profile). Cross-sectional studies also found variants of carbohydrate quality metrics to be associated with better markers of cardiometabolic disease, including lower levels of blood triglycerides:high-density lipoprotein cholesterol ratio, homeostatic model assessment of insulin resistance, and SBP. New ratio-based carbohydrate quality metrics are built around high fiber and whole grain content, combined with a low free sugar content. Such metrics allow the identification of food products of higher overall nutritional quality, and are associated with improved diet quality and certain health outcomes.

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.

Associations between cardiometabolic disease severity, social determinants of health (SDoH), and poor COVID-19 outcomes.

ObjectiveThis study aimed to determine the ability of retrospective cardiometabolic disease staging (CMDS) and social determinants of health (SDoH) to predict COVID‐19 outcomes.MethodsIndividual and neighborhood SDoH and CMDS clinical parameters (BMI, glucose, blood pressure, high‐density lipoprotein, triglycerides), collected up to 3 years prior to a positive COVID‐19 test, were extracted from the electronic medical record. Bayesian logistic regression was used to model CMDS and SDoH to predict subsequent hospitalization, intensive care unit (ICU) admission, and mortality, and whether adding SDoH to the CMDS model improved prediction was investigated. Models were cross validated, and areas under the curve (AUC) were compared.ResultsA total of 2,873 patients were identified (mean age: 58 years [SD 13.2], 59% were female, 45% were Black). CMDS, insurance status, male sex, and higher glucose values were associated with increased odds of all outcomes; area‐level social vulnerability was associated with increased odds of hospitalization (odds ratio: 1.84, 95% CI: 1.38‐2.45) and ICU admission (odds ratio 1.98, 95% CI: 1.45‐2.85). The AUCs improved when SDoH were added to CMDS (p < 0.001): hospitalization (AUC 0.78 vs. 0.82), ICU admission (AUC 0.77 vs. 0.81), and mortality (AUC 0.77 vs. 0.83).ConclusionsRetrospective clinical markers of cardiometabolic disease and SDoH were independently predictive of COVID‐19 outcomes in the population.

Associations of total urinary arsenic with total cholesterol and high-density lipoprotein among 12-17-year-old participants from the 2009-2016 NHANES cycles: A cross-sectional study.

Hypertension and diabetes are highly prevalent among US adults. Arsenic exposure is associated with these cardiometabolic morbidities but the relationship between arsenic exposure and cholesterol markers of cardiometabolic disease has not been elucidated, especially at younger ages, when many chronic diseases may initiate. This study examined the association of total urinary arsenic with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL) and explored effect modification by weight status. The study sample consisted of 12-17-year-old participants with complete data from the 2009-2016 National Health and Nutrition Examination Survey cycles. The cross-sectional associations of creatinine-adjusted total urinary arsenic with TC and HDL were assessed using multivariable linear regression models with survey weights. Three models were built, adjusting for varying combinations of age, gender, race/ethnicity, weight status, survey cycle, family income to poverty ratio, reference person education level, arsenobetaine, and dimethylarsinic acid (DMA). Model adjustments for arsenobetaine approximated inorganic arsenic exposure, and further adjustment for DMA approximated unmethylated inorganic arsenic exposure. We also explored weight status (underweight/healthy, overweight, and obese) as a potential effect modifier of these relationships using stratified analyses and interaction tests. The final analytical sample consisted of 1,177 12-17-year-old participants. After adjusting for covariates and arsenobetaine, creatinine-adjusted arsenic was positively associated with HDL levels (β=0.063; 95% CI: 0.007, 0.119). Upon further adjustment for DMA, creatinine-adjusted arsenic was positively associated with HDL levels (β=0.079; 95% CI: 0.015, 0.143) and TC levels (β=0.258; 95% CI: 0.002, 0.515). No effect modification by weight status was observed. We found a positive association of approximated unmethylated inorganic arsenic exposure with TC, and contrary to our expectation, with HDL. There was no effect modification by weight status. Our findings should be confirmed by conducting longitudinal studies among adolescents exposed to low-level arsenic and focusing specifically on urinary inorganic arsenic concentrations.

Relation of Menopause With Cardiovascular Risk Factors in South Asian American Women (from the MASALA Study)

The menopausal transition is a time of accelerating risk of cardiovascular disease (CVD), and promoting cardiovascular health during midlife is an important period of time to prevent CVD in women. The association of menopause with cardiovascular risk factors or subclinical atherosclerosis has not previously been evaluated in South Asian American women, a population with a disproportionately higher CVD burden compared with other race/ethnic groups. The objective of this study was to evaluate the association of menopause with CVD risk factors and subclinical cardiometabolic disease markers. We studied women aged 40 to 84 years from the Mediators of Atherosclerosis in South Asians Living in America study. The association of self-reported menopausal status with multiple demographic and clinical variables was assessed with linear and logistic regression adjusted for age and cardiovascular health behaviors. In a secondary ("age-restricted") analysis, postmenopausal participants outside the age range of premenopausal participants were excluded. In the age-restricted sample, menopause was associated with a higher adjusted odds of hypertension (odds ratio=1.19, 95% confidence interval [CI] 1.02 to 1.41), and higher systolic blood pressure (β=6.34, 95% CI 0.82 to 11.87), and significantly higher subcutaneous fat area (β=42.8, 95% CI 5.8 to 91.4). No significant associations between menopause and ectopic fat deposition, coronary artery calcium, or carotid intima-media thickness were observed. In South Asian American women in the Mediators of Atherosclerosis in South Asians Living in America study, menopause was associated with cardiovascular risk factors and higher subcutaneous fat deposition. Menopausal status is an important factor to examine and address CVD risk factors.

Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9).

To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. UK free-living population. Totally, 5015 adults aged 19-64 years. Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices.

Effect of an office-based intervention on visceral adipose tissue: the WorkACTIVE-P randomized controlled trial.

Office-based activity reduces sedentariness, yet no randomized controlled trials (RCTs) have assessed how such activity influences visceral adipose tissue (VAT). This study examined the effect of an office-based, multicomponent activity intervention on VAT. The WorkACTIVE-P RCT enrolled sedentary office workers (body mass index: 31.4 (standard deviation (SD) 4.4) kg/m2) to an intervention (n = 20) or control (n = 20) group. For 3 months, the intervention group received an office-based pedal desk, further to an intervention promoting its use and increased walking. The control group maintained habitual activity. At baseline and follow-up, VAT, cardiometabolic disease risk markers, physical activity, and food intake were measured. Steps/day were not altered relative to control (P ≥ 0.51), but the pedal desk was utilized for 127 (SD 61) min/day. The intervention reduced VAT relative to control (-0.15 kg; 95% confidence interval (CI) = -0.29 to -0.01; P = 0.04). Moreover, the intervention decreased fasting glucose compared with control (-0.29 mmol/L; 95% CI = -0.51 to -0.06; P = 0.01), but no differences in other cardiometabolic disease markers or food intake were revealed (P ≥ 0.11). A multicomponent intervention decreased VAT in office workers who were overweight or obese. Though longer-term studies are needed, office-based, multicomponent activity regimens may lower cardiometabolic disease risk. Trial registered at ClinicalTrials.gov (NCT02561611). Novelty: In WorkACTIVE-P, a multicomponent activity intervention decreased visceral adipose tissue relative to control in office workers. The intervention also reduced glucose compared with control, though other metabolic risk markers and food intake were not altered. Such multicomponent interventions could help reduce cardiometabolic disease risk, but longer studies are needed.

Abstract 14300: The Relationship Between the American Heart Association’s Life Simple 7, Ectopic Fat and Insulin Resistance Among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Introduction: The inverse association between ideal cardiovascular health (CVH) as measured by AHA’s Life simple 7, and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and surrogate markers of cardiometabolic disease, including ectopic fat depots, insulin resistance, and β-cell dysfunction is sparse. Methods: Among 906 South Asian participants (mean age 55 y, SD=9.4, 46% women) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we assigned each LS7 component a score of 0, 1, and 2, and summed these scores to derive an overall CVH score. Visceral, subcutaneous, pericardial, and intermuscular fat and hepatic fat attenuation were measured using computed tomography. We used a homeostasis model assessment for insulin resistance (HOMA-IR) for insulin resistance and HOMA-β for β-cell function. We used multiple linear regression to model the associations between CVH score and natural log-transformed ectopic fat measures, HOMA-IR, and HOMA-β. Results: In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 53.9% (95% CI, 39.7 - 69.4) higher visceral fat area, 66.5% (50.5 - 84.2) higher pericardial fat volume, and 35.1% (23.0 - 48.4) higher subcutaneous fat area, but only 8% (3.1 - 13.0) higher intermuscular fat area and 15.9% (11.2 - 20.4) higher intrahepatic fat (all p&lt;0.001). Also, poor CVH was associated with 154% (117.5 - 198) higher HOMA-IR. Similarly, participants with intermediate CVH demonstrated significantly larger measures of ectopic fat and HOMA-IR. There was no significant association between CVH and HOMA-β. Conclusion: We found that poor and intermediate CVH, as defined by LS7 metrics, was associated with significantly higher measures of ectopic fat and insulin resistance among South Asians. Long-term follow-up of the MASALA cohort will examine the association of LS7 metrics with the incident CVD events.

Association Between a Physical Activity Vital Sign and Cardiometabolic Disease in High-Risk Patients.

To determine the association between the physical activity vital sign (PAVS) and markers of cardiometabolic disease. Patients were assessed through the PAVS, a validated tool self-reporting the frequency and duration of physical activity. Patients were categorized into 3 groups: inactive (0 minutes per week), underactive (1-149 minutes per week), and active (>150 minutes per week). Associations were tested between the PAVS and the cardiometabolic disease biomarkers of body mass index, hemoglobin A1c (A1c), blood pressure, and low-density lipoprotein (LDL) using one-way analyses of variance. High-risk family medicine residency clinic. Two thousand three hundred twenty-one adult patients (age ≥ 18 years). Participants reported a mean of 97.87 (SD = 149.35) minutes per week of exercise. Overall, 50.1% reported physical inactivity, 25.7% were underactive, and 24.3% were active. Younger individuals (P < 0.001) and men (P < 0.05) reported more physical activity than older individuals and women. Patients who reported being active were significantly less likely to be overweight (P < 0.05), obese (P < 0.05), or hypertensive (P < 0.05), but there was no association with A1c or LDL levels. This is the first investigation to examine the PAVS in a high-risk population. In these patients, reported levels of physical inactivity are 150% higher than other clinical settings, and the PAVS is only associated with improvements in 2 of 4 major cardiometabolic risk factors. For this group, self-reported levels of physical activity may need to be higher for cardiovascular benefits to be realized in all 4 cardiometabolic domains. The PAVS offers health professionals an opportunity to encourage lifestyle-based interventions to reduce cardiovascular risk, but refinements may be necessary to address this population.

Postprandial Insulin and Triglyceride Concentrations Are Suppressed in Response to Breaking Up Prolonged Sitting in Qatari Females.

Background: Cultural, environmental and logistical factors challenge the Qatari population, particularly females, to engage in physical activity, and there is a high prevalence of diabetes in this population. Sedentary behavior is associated with increased cardiometabolic disease risk and early mortality and breaking up sitting can attenuate postprandial cardiometabolic risk markers. However, no studies have evaluated the cardiometabolic response to breaking up sitting in a Qatari population.Purpose: To examine the effects of breaking up sitting with moderate-intensity walking breaks on cardiometabolic disease markers in Qatari females.Methods: Eleven sedentary (sitting ≥ 7 h/day) females completed two experimental conditions in a cross-over randomized design. The two conditions were identical, except participants either remained seated for 5-h (SIT), or interrupted their sitting every 30-min with a 3-min walk (WALK) on a motorized treadmill (rating of perceived exertion 12–14). A fasting venous blood sample was obtained at baseline (-10-min) followed by samples at 0.5-, 1-, 2-, 3-, 3.5-, 4-, and 5-h. Postprandial cardiometabolic variables (insulin, glucose, triglycerides) were calculated as derivatives of total area under the curve [AUC; total (tAUC), net incremental (iAUC) and positive AUC].Results: Data is reported as effect size; ±90% confidence limit. There was a most likely “moderate” lower tAUC (-0.92 ± 0.26), iAUC (-0.96 ± 0.33), and positive AUC (-0.96 ± 0.33) for insulin in WALK compared to SIT. Additionally, there was a most likely “moderate” lower tAUC (-0.63 ± 0.37), iAUC (-0.91 ± 0.49), and positive AUC (-0.91 ± 0.49) for triglycerides in WALK compared to SIT. Glucose did not differ between conditions.Conclusion: Breaking up prolonged sitting with moderate-intensity walking offers a culturally compatible intervention to acutely improve cardiometabolic risk markers in sedentary Qatari females. Whilst the data offers promise, the long-term chronic effects of breaking up sitting in Qatari adults requires investigation before population level and/or policy recommendations can be made.

Metformin and Dipeptidyl Peptidase-4 Inhibitor Differentially Modulate the Intestinal Microbiota and Plasma Metabolome of Metabolically Dysfunctional Mice

ObjectivesRecent evidence indicates that gut microbiota is altered considerably by a variety of commonly prescribed medications. This study assessed the impact of 2 antidiabetic therapeutics on gut microbiota and markers of cardiometabolic disease in metabolically dysfunctional mice. MethodsC57BL/6 mice were fed a high-fat diet for 24 weeks while receiving 1 of 2 antidiabetic therapeutics—metformin or dipeptidyl peptidase-4 (DPP-4) inhibitor, PKF-275-055—for the final 12 weeks. Mice were assessed for weight gain, glucose and cholesterol metabolism, and adiposity. In addition, cecal microbiota was analyzed by 16S compositional sequencing, and plasma metabolome was analyzed by liquid chromatography with tandem mass spectrometry. ResultsBoth therapeutics had similar metabolic effects, attenuating mesenteric adiposity and improving cholesterol metabolism and insulin sensitivity. However, multivariate analyses of microbiota and metabolomics data revealed clear divergence of the therapeutic groups. Although both metformin and PKF-275-055 mice displayed significantly decreased Firmicutes/Bacteroidetes ratios, only metformin harboured metabolic health-associated Akkermansia, Parabacteroides and Christensenella. Paradoxically, metformin also reduced α diversity, a metric frequently associated with host metabolic fitness. PKF-275-055 mice displayed elevated levels of butyrate-producing Ruminococcus and acetogen Dorea, with reduced levels of certain plasma sphingomyelin, phosphatidylcholine and lysophosphatidylcholine entities. In turn, metformin reduced levels of acylcarnitines, a functional group associated with systemic metabolic dysfunction. Finally, several associations were identified between metabolites and altered taxa. ConclusionsThis study represents the first direct comparison of the microbiota-modifying effects of metformin and a DPP-4 inhibitor, and proposes several putative microbial targets both in terms of novel therapeutic development and adverse effect prevention.

Effects of Gender-Affirming Hormones on Lipid, Metabolic, and Cardiac Surrogate Blood Markers in Transgender Persons.

Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised. A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles. Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.

Percentile curves for cardiometabolic disease markers in Canadian children and youth: a cross-sectional study

BackgroundThe objective of this study to develop percentile curves for cardiometabolic disease markers in a population-based sample of Canadian children and youth.MethodsThe analysis used data from 6116 children and adolescents between 6 and 19 years of age who participated in the Canadian Health Measures Survey cycles 1 (2007/2009), 2 (2009/2011), and 3 (2012/2013). Total cholesterol, HDL cholesterol, and hemoglobin A1c levels as well as fasting levels of triglycerides, insulin, and homeostasis model assessment insulin resistance were measured using standardized procedures. Age- and sex-specific centiles for all markers were calculated using Cole and Green’s LMS method.ResultsWith the exception of hemoglobin A1c, all markers showed age- and sex-related differences during childhood and adolescence.ConclusionsWe have developed centile curves for cardiometabolic disease markers in Canadian children and adolescents and demonstrated age and sex differences that should be considered when evaluating these markers in this age group.

Abdominal adiposity distribution in elite rugby union athletes using magnetic resonance imaging

This study aimed to assess visceral adipose tissue (VAT), an established marker for cardiometabolic complications, in elite rugby union athletes, with specific consideration given to ethnicity. The ability of dual-energy X-ray absorptiometry (DXA) to estimate VAT in athletic populations compared to the criterion magnetic resonance imaging (MRI) was also explored. Thirty elite male rugby union athletes (age 23.9 ± 4.0 years; stature 186.7 ± 7.0 cm; mass 101.9 ± 11.2 kg) underwent assessment via DXA for body composition, and MRI for abdominal adiposity, at the start of the pre-season training period. Participants were ascribed a specific ethnicity when three or more of their grandparents were of either Caucasian or Polynesian descent. MRI VAT did not differ between ethnicities (Caucasian 92.7 ± 26.7 cm2; Polynesian 86 ± 27.3 cm2; p = 0.52); however, there was a trend for forwards (96.7 ± 25.0 cm2) to have higher VAT than backs (81.7 ± 27.3 cm2; p = 0.13) which provides an area of interest for researchers. Thirty-seven percent of athletes (eight forwards, three backs) were found to have VAT > 100 cm2, a threshold for increased cardiometabolic risk within the general population. Bland–Altman analysis indicated that DXA VAT underestimated MRI VAT by ~ 25 cm2, with relatively wide limits of agreement (− 24.0 to 75.6 cm2). Given the size of rugby union athletes, and the association between elevated VAT and cardiometabolic complications in “supersized” athletes from other sports, further investigation into VAT and other markers of cardiometabolic disease in rugby union populations is warranted. Further, DXA was found to underestimate VAT compared to the criterion MRI in this athletic population.

Insulin Resistance and Hypertension in Obese Youth With Sleep-Disordered Breathing Treated With Positive Airway Pressure: A Prospective Multicenter Study.

There is evidence that cardiometabolic disease associated with obesity and sleep-disordered breathing (SDB) in adults is present in youth. SDB is often treated with positive airway pressure (PAP) in youth with obesity. Our aims were to determine: (1) the prevalence of cardiometabolic disease and (2) whether PAP improves markers of cardiometabolic disease, in youth with obesity and newly diagnosed moderate-severe SDB. A prospective multicenter cohort study was conducted in youth (8 to 16 years old) with obesity, prescribed PAP therapy for newly diagnosed moderate-severe SDB. Assessments occurred at baseline and at 6 and 12 months. Outcomes included markers of insulin resistance (change in homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months = primary outcome), hypertension (24-hour ambulatory/blood pressure) and inflammation (high-sensitivity C-reactive protein: hs-CRP). Twenty-seven participants were enrolled. Of those with baseline testing available, 10/25 (40%) had HOMA-IR above the 97th percentile, 10/23 (44%) were hypertensive, 16/23 (70%) had loss of nocturnal blood pressure dip and hs-CRP was elevated in 16/27 (64%). There were no significant changes over time in markers of metabolic dysfunction or blood pressure, nor between PAP-adherent and non-adherent subgroups. In youth with obesity and SDB, metabolic dysfunction and hypertension were highly prevalent. There were no statistically significant improvements in cardiometabolic markers 1 year after the prescription of PAP therapy, although clinically relevant improvements were seen in insulin resistance and systolic blood pressure load, important predictors of future risk of cardiovascular disease. Larger, longer-term studies are needed to determine whether PAP improves cardiometabolic outcomes in obese youth. A commentary on this article appears in this issue on page 1025.

Investigating the links between habitual diet, the gastrointestinal microbiota, and cardiovascular disease risk factors in healthy weight, overweight, and obese men and women

BackgroundThe connection between diet and the gastrointestinal (GI) microbiota is an area of intense interest as the microbiota is increasingly linked to a growing list of not only gastrointestinal, but also metabolic diseases. Dietary factors including saturated fat, added sugars, and dietary fiber are all related to cardiometabolic health. However, the relationship between the human GI microbiota, blood lipids, and habitual diet remains under‐investigated.ObjectiveWe aimed to determine the relationships among bacterial taxa, blood lipids, and dietary intake patterns in healthy weight, overweight, and obese men and women.MethodsBlood and fecal samples were collected from adults (n=68, 31 males; 25–45 years of age) without physician diagnosed metabolic or gastrointestinal diseases. Dietary intake patterns were assessed using the Diet History Questionnaires (DHQII, Past Year and Past Month with Portion Size) and Healthy Eating Index (HEI‐2010) scores were calculated to assess diet quality. Following DNA isolation, bacterial (V4 region of 16S rRNA), fungal (ITS1‐4), and archaeal amplicons were generated using a Fluidigm Access Array followed by high‐throughput sequencing on an Illumina MiSeq. Sequences were quality filtered, then operational taxonomic units (OTUs) were picked against the Greengenes 13‐8 reference database using QIIME versions 1.8 and 1.9. Total cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high density lipoprotein (HDL) cholesterol, non‐HDL‐cholesterol (nHDLc), and triglycerides were measured using a chemical analyzer. Body composition was assessed using dual energy x‐ray absorptometry. Data were analyzed using SAS 9.4.ResultsBivariate correlations revealed positive associations between Phascolarctobacterium and nHDLc (r=0.28, p=0.03) and refined grains (r=0.34, p=0.01). However, these relationships were mitigated by age and whole body percent fat. Dorea spp were positively related to nHDLc (r=0.38, p=0.003), total cholesterol (r=0.40, P=0.001), LDL‐cholesterol (r=0.34, p=0.007), and total dairy intake (p=0.35, p=0.01). The positive association between Dorea spp. and total cholesterol remained significant after controlling for whole body percent fat, age, total HEI‐2010 score and dietary intake of saturated fat/kcal and total dairy. Total dairy intake tended to positively relate to nHDLc (r=0.26, p=0.07).ConclusionsThese results suggest potential relationships between microbial, metabolic, and dietary factors. Specifically, Dorea is independently related to increased cardiometabolic disease markers and dietary components such as total dairy intake in US adults. Future directions include assessments of additional dietary factors including types of fat, bile acids, and inflammatory markers to better define the interconnections between the gut microbiota composition, habitual diet, and human health.Support or Funding InformationSupported in part by the USDA National Institute of Food and Agriculture, Hatch project ILLU‐668‐902 and Haas Avocado Board.