Cardiometabolic Risk Biomarkers Research Articles

Effect of Including Lean Red Meat in a Plant-Based Dietary Pattern on Biomarkers of Cardiometabolic Disease Risk

The objective of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on clinical biomarkers of cardiometabolic disease risk in women with overweight. We hypothesized that there would be no differences in markers of acute inflammation, glycemic control or expression of miRNAs associated with metabolic disease risks detected after consumption of a diet containing 2 servings of lean red meat/day compared to a diet void of lean red meat. Secondary analyses were performed using plasma samples collected within a randomized, crossover design study in 17 women (mean ± SEM, age: 33±1y; BMI: 27.8±0.1kg/m2) who consumed a plant-based diet containing either 0 or 2 servings of red meat/d for 1 wk/pattern. A 3-wk washout period occurred between patterns. Participants were provided with eucaloric, isonitrogenous plant-based diets containing 3 daily meals (28% of daily calories/meal) and an evening snack (16% of daily calories) that differed only in protein source. The protein sources in the plant-based diet without red meat (MEATLESS) were 100% plant-based, whereas the plant-based diet with red meat (RED MEAT) replaced a portion of plant protein with 2 servings/d of lean beef. Fasting blood samples were collected at the end of each dietary pattern for the assessment of plasma glucose, insulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), adiponectin, and branch chain amino acids (BCAA) via colorimetric (glucose), enzyme-linked immunoassays, and high-performance liquid chromatography (BCAA). Homeostatic Model Assessment (HOMA) was used to evaluate insulin resistance (IR) and sensitivity (%S) and beta cell function (%B). Paired sample t-tests were utilized to compare the main effect of protein source (RED MEAT vs. MEATLESS) on fasting plasma biomarkers of cardiometabolic disease risk. p<0.05 was considered significant. Additional ongoing analyses include querying expression of a microRNA (miRNA) panel associated with metabolic disease risks via qPCR. No differences in plasma fasting glucose (76.67±2.08 vs. 76.48±1.98mg/dL); insulin (45.89±5.47 vs. 46.31±5.49pmol/L); IL-6 (1.18±0.27 vs. 1.13±0.30pg/mL); TNF-α (4.11±0.30 vs. 4.13±0.24pg/mL); CRP (0.37±0.07 vs. 0.41±0.09mg/dL); adiponectin (10.53±1.52 vs. 10.35±1.36ug/mL); or BCAA (118.49±9.09 vs. 121.94±9.39mg/mL) concentrations or differences in HOMA -IR (1.46±0.18 vs. 1.47±0.19), -%S (115.83±11.92 vs. 117.67±14.38), or -%B (135.64±11.30 vs. 137.56±10.41) were detected when comparing RED MEAT vs. MEATLESS dietary patterns. The consumption of as much as 2 servings of lean red meat/d does not negatively influence inflammatory or metabolic signals related to cardiometabolic disease risk. These findings suggest that lean red meat can serve as a nutrient-dense protein source within a healthy dietary pattern. The Beef Checkoff; not offcial Army/DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Background: Childhood obesity is a globally increasing pathological condition leading to long-term health issues such as cardiovascular diseases and metabolic syndrome (MetS). This study aimed to determine the clinical value of the Complete Blood Count-derived inflammation indexes Monocyte/HDL-C ratio (MHR), Lymphocyte/HDL-C ratio (LHR), Neutrophil/HDL-C ratio (NHR), and System Inflammation Response Index (SIRI) to predict the presence of metabolic syndrome and its association with cardiovascular risk markers (HOMA-IR, TG/HDL-C, and non-HDL-C) in children and adolescents with obesity. Methods: The study included a total of 552 children/adolescents with severe obesity (BMI: 36.4 [32.7-40.7] kg/m2; 219 males, 333 females; age: 14.8 [12.9-16.3] years), who were further subdivided based on the presence or absence of metabolic syndrome (MetS+ and MetS respectively). Results: The MHR, LHR, and NHR indexes (p < 0.0001), but not SIRI (p = 0.524), were significantly higher in the MetS+ compared to the MetS- subgroup, showing a positive correlation with the degree of MetS severity (p < 0.0001). Furthermore, MHR, LHR, and NHR were positively associated with cardiometabolic risk biomarkers (HOMA-IR: MHR p = 0.000, LHR p = 0.001, NHR p < 0.0001; TG/HDL-C: MHR, LHR, NHR p < 0.000; non-HDL-C: MHR, LHR p < 0.0001, NHR p = 0.000). Finally, the ROC curve analysis demonstrated that among the analyzed indexes, only MHR, LHR, and NHR had diagnostic value in distinguishing MetS patients among children and adolescents with obesity (MHR: AUC = 0.7045; LHR: AUC = 0.7205; NHR: AUC = 0.6934; p < 0.0001). Conclusions: In conclusion, the MHR, LHR, and NHR indexes, but not the SIRI index, can be considered useful tools for pediatricians to assess the risk of MetS and cardiometabolic diseases in children and adolescents with obesity and to develop multidisciplinary intervention strategies to counteract the widespread disease.

Abstract P104: Geospatially Varying Relationships of Green and Blue Spaces With Biomarkers of Stress and Cardiometabolic Risk in Racially and Ethnically Diverse Children

Introduction: Neighborhood green (e.g., parks) and blue (e.g., lakes) spaces have been associated with reduced stress and cardiometabolic risk (CMR), but research is limited in socially vulnerable urban communities affected by structural racism and redlining. This study explored the spatial correlation between green and blue spaces and cortisol levels, BMI percentile, waist circumference (WC), pulse, and systolic (SBP) and diastolic blood (DBP) pressure in a sample of racially/ethnically diverse children. Methods: We used cross-sectional data from the Family Matters cohort study, consisting of 1307 racially/ethnically diverse families with children (age 7±1.5 yrs). Participant addresses were matched to the US 2010 Census tract attributes. We used 246 sample locations across 149 census tracts in the 7-county Twin Cities, MN, metro area. Green and blue spaces were retrieved from the Twin Cities Metropolitan Council. Hair cortisol (chronic stress biomarker), BMI, WC, pulse, SBP and DBP were objectively measured in a subsample of 246 children. We used Decision Tree and Geographically Weighted Regression (GWR) to examine the spatially varying associations of CDC’s Social Vulnerability Index (SVI) and green and blue spaces (independent variables) with biomarkers of stress and CMR (dependent variables). SVI reflects four themes: socioeconomic status, household composition and disability, racial and ethnic minority status and language, and housing type and transportation. Results: Northwest Minneapolis was identified as a hotspot for elevated cortisol, BMI, and WC, while east St. Paul was a hotspot for elevated BMI and WC. Decision trees indicated that green and blue spaces explain variation in accumulated cortisol after tract socioeconomic status and racial and ethnic minority status. GWR revealed nonuniform relationships with the highest explanatory power in high social vulnerability hotspots. GWR’s R 2 for cortisol (0.07), BMI (0.14), and WC (0.14) were driven by hotspots where local R 2 was 2-5 times stronger than areas not identified as hotspots indicating robust geographical variations in the northern areas (areas of high social vulnerability) and distance from green and blue spaces. Patterns were inconsistent for pulse, SBP, and DBP. Conclusions: The spatially varying relationships of green and blue spaces with biomarkers of stress and CMR in children were heterogeneous, possibly indicating different mechanisms across biomarkers and geographical areas. Higher cortisol levels, BMI percentile, and WC in northern Twin Cities areas may reflect the legacy of structural racism and redlining, which have resulted in inequitable use of green and blue spaces for minoritized communities. Future interventions co-developed with local communities to improve green and blue spaces’ access and use, as well as to reduce disparities in stress and CMR, are needed to advance health equity.

Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

Background: Metabolic syndrome (MetS) is a globally increasing pathological condition. Recent research highlighted the utility of complete blood count-derived (CBC) inflammation indexes to predict MetS in adults with obesity. Methods: This study examined CBC-derived inflammation indexes (NHR, LHR, MHR, PHR, SIRI, AISI, and SII) in 231 adults with severe obesity (88 males, 143 females; age: 52.3 [36.4-63.3] years), divided based on the presence (MetS+) or absence (MetS-) of MetS. The relationships between the indexes and the cardiometabolic risk biomarkers HOMA-IR, TG/HDL-C, and non-HDL-C were also evaluated. Results: Individuals with metabolic syndrome (MetS+) had significantly higher values of MHR, LHR, NHR, PHR, and SIRI than those without (MetS-) (MHR and NHR: p < 0.0001; LHR: p = 0.001; PHR: p = 0.011; SIRI: p = 0.021). These values were positively correlated with the degree of MetS severity. Logistic regression (MHR and NHR: p = 0.000; LHR: p = 0.002; PHR: p = 0.022; SIRI: p = 0.040) and ROC analysis (MHR: AUC = 0.6604; LHR: AUC = 0.6343; NHR: AUC = 0.6741; PHR: AUC = 0.6054; SIRI: AUC = 0.5955) confirmed the predictive potential of CBC-derived inflammation indexes for MetS in individuals with severe obesity. CBC-derived inflammation indexes also correlated with HOMA-IR (MHR, LHR, and NHR: p < 0.0001; PHR: p < 0.001; SIRI: p = 0.000) and TG/HDL-C (MHR, LHR, NHR and PHR: p < 0.0001; SIRI: p = 0.006). Conclusions: In conclusion, this study validates CBC-derived inflammation indexes for predicting MetS in individuals with severe obesity. The relationships between these indexes and cardiometabolic risk factors can enable clinicians to better grade MetS associated with obesity.

Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

Diverse impacts of red palm olein, extra virgin coconut oil and extra virgin olive oil on cardiometabolic risk markers in individuals with central obesity: a randomised trial.

Dietary fats with an abundance of phytonutrients have garnered public attention beyond fatty acids per se. This study was set to investigate the impact of consuming diets with red palm olein (RPOO), extra virgin coconut oil (EVCO) and extra virgin olive oil (EVOO, as a control) on cardiometabolic risk biomarkers and lipid profile. We recruited a total of 156 individuals with central obesity, aged 25-45years, with waist circumference ≥ 90cm for men and ≥ 80cm for women in a parallel single-blind 3-arm randomised controlled trial. The participants consumed isocaloric diets (~ 2400kcal) enriched with respective test fats (RPOO, EVCO or EVOO) for a 12-week duration. The mean of the primary outcome plasma high sensitivity C-reactive protein was statistically similar between the three diets after a 12-week intervention. EVOO resulted in significantly lower mean LDL cholesterol compared with RPOO and EVCO, despite similar effects on LDL and HDL cholesterol subfractions. The RPOO diet group showed elevated mean and -carotenes levels compared with EVCO and EVOO diet groups (P < 0.05), corresponding with the rich carotenoid content in RPOO. The three oils, each of which has unique phytonutrient and fatty acid compositions, manifested statistically similar cardiometabolic effects in individuals with central obesity at risk of developing cardiovascular diseases with distinct circulating antioxidant properties. ClinicalTrials.gov (NCT05791370).

The effect of observing religious or faith-based fasting on cardiovascular disease risk factors: A systematic review and meta-analysis

AimsCardiovascular diseases (CVD) are the leading cause of death worldwide. Fasting is common in many religions and is associated with health benefits. This systematic review to compares the impact of different religious fasting practices, on risk of cardiometabolic diseases. Data synthesisThe search covered five databases following PRISMA guidelines to identify papers published in English from inception to March 2023 (updated January 2024). Inclusion criteria were healthy adults in observational studies, who engaged in religious fasting practices, studies were included where data on matched non-fasting individuals was available. Outcomes were systolic and diastolic blood pressure, body mass index (BMI), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and fasting plasma glucose levels. A meta-analysis was conducted, and the review was registered (CRD42022352197). Fourteen studies were met the inclusion criteria with ten studies data being suitable for meta-analysis, reporting on 755 adults participating in fasting practices and 661 non-fasting controls. Religious fasting was associated with a reduction in BMI (−0.40 kg/m2, 95% CI [-0.70, −0.10], p < 0.01). Observance of Ramadan fasting was associated with decreased systolic blood pressure (−3.83 mmHg, 95% CI [-7.44, −0.23], p = 0.04). The observance of Orthodox Christian fasting was associated with a reduction in TC (−0.52 mmoL/l, 95%CI [–0.64, −0.39], p < 0.01). No difference was found for the other outcomes. ConclusionThis review found religious fasting practices which were associated with a reduction in some biomarkers of cardiometabolic diseases risk. Further research on other fasting practices is needed due to limited data.

Dynamic Changes in Adiponectin and Resistin Drive Remission of Cardiometabolic Risk Biomarkers in Individuals with Obesity Following Bariatric Surgery.

The remission of obesity-related diseases following bariatric surgery appears to result from the reorganization of metabolic and hormonal pathways involving adipokines. This study aimed to investigate the relationship between changes in body adiposity and serum adipokine levels, as well as the association between variations in adiponectin or resistin levels and cardiometabolic risk blood biomarkers before and after Roux-en-Y gastric bypass. A longitudinal and prospective study was conducted with bariatric surgery patients. Anthropometric, body composition and blood biochemical parameters were measured before and at 2 and 6 months post-surgery. The data were analyzed using ANOVA, Pearson or Spearman correlation, and simple linear regression with a significance level of p < 0.05. Among 36 mostly female patients aged 30 to 39 years, significant reductions in body weight (-26.8%), fat mass (-50%), waist circumference (-18%) and waist-to-height ratio (-22%) were observed post-surgery. Serum adiponectin levels increased (+107%), while resistin (-12.2%), TNF-α (-35%), and PAI-1 (-11.1%) decreased. Glucose, insulin, CRP, cholesterol, LDL-c, triglycerides, and vitamin D also decreased. Waist circumference variation showed a positive correlation with PAI-1 and TNF-α and a negative correlation with adiponectin. The total fat mass showed a positive correlation with PAI-1. Adiponectin variation correlated negatively with glucose, resistin, and CRP but positively with HDL-c. Resistin showed a positive correlation with insulin and CRP. In conclusion, 6 months post-bariatric surgery, reducing abdominal adiposity had a more significant impact on serum adipokine levels than total fat mass. Adiponectin increase and resistin decrease acted as endocrine mediators driving the remission of cardiometabolic risk biomarkers in individuals with obesity following Roux-en-Y gastric bypass.

Increasing Access to Medical Care for Hispanic Women Without Insurance: A Mobile Clinic Approach.

The purpose of this study was to describe the health status and barriersof people who sought care on a freemobile health clinic for women without insurance in California.Participants were 221 women who attended the Salud para Mujeres (Women's Health) mobile medical clinic between 2019 and 2021. Medical chart abstractions provided data on sociodemographic factors, medical history, barriers to care, depressive symptoms, anddietary factors. Anthropometric measure, blood pressure, and biomarkers of cardiometabolic disease risk were also abstracted.Participants were young adult (29.1 [SD 9.3] years), Hispanic (97.6%), farm-working (62.2%) women from Mexico (87.0%). Prevalent barriers to accessing (non-mobile) medical care included high cost (74.5%), language (47.6%), hours of operation (36.2%), and transportation (31.4%). The majority (89.5%) of patientshad overweight (34.0%) or obesity (55.5%), and 27% had hypertension. Among those (n = 127) receiving a lipid panel, 60.3% had higher than recommended levels of low-density lipoprotein and 89% had lower than recommended levels of high-density lipoprotein. Point-of-care HbA1c tests (n = 133) indicated that 9.0% had diabetes and 24.8% had prediabetes. Over half (53.1%) of patients reported prevalent occupational exposure to pesticides and 19% had moderate to severe depressive symptoms. Weekly or more frequent consumption of sugar sweetened beverages (70.9%) and fast food (43.5%) were alsoprevalent.Mobile health units have potential for reaching women who face several barriers to care and experience major risk factors for cardometabolic disease. Findings suggest a compelling need to assure that Hispanic and Indigenous women and farmworkers have access to healthcare.

A red-fleshed apple rich in anthocyanins improves endothelial function, reduces inflammation, and modulates the immune system in hypercholesterolemic subjects: the AppleCOR study.

The study determines the sustained and acute effects of a red-fleshed apple (RFA), rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an infusion from Aronia melanocarpa (AI) with an equivalent content of ACNs as RFA, on different cardiometabolic risk biomarkers in hypercholesterolemic subjects. A randomized, parallel study was performed for 6 weeks and two dose-response studies were performed at the baseline and after intervention. At 6 weeks, RFA consumption improved ischemic reactive hyperemia and decreased C-reactive protein and interleukine-6 compared to WFA consumption. Moreover, at 6 weeks, AI decreased P-selectin compared to WFA and improved the lipid profile. Three products reduced C1q, C4 and Factor B, and RFA and AI reduced C3. Although both RFA and AI have a similar ACN content, RFA, by a matrix effect, induced more improvements in inflammation, whereas AI improved the lipid profile. Anti-inflammatory protein modulation by proteomic reduction of the complement system and immunoglobulins were verified after WFA, AI and RFA consumption.

Chronic consumption of a bergamot-based beverage does not affect glucose, lipid and inflammatory biomarkers of cardiometabolic risk in healthy subjects: a randomised controlled intervention study.

Background: Pure bergamot juice exerts lipid lowering effects in dyslipidemic subjects. It is unknown whether bergamot-based beverages exert similar effects in healthy subjects. Aim: To assess the effects, if any, of a bergamot-based beverage (BBB, bergamot juice ≤25%) on lipid, metabolic and inflammatory biomarkers. Methods: Forty-five healthy subjects were randomised 1 : 1 to BBB intake (400 mL day-1) (55.5%) or control (44.5%) for 12 weeks. Anthropometric (waist circumference, body mass index (BMI)) and clinical (blood pressure) parameters, blood samples (glucose, glycated haemoglobin, insulinemia, lipid profile, liver and renal function, inflammatory biomarkers) and 24-h urine for the analysis of (poly)phenol metabolites were collected at the baseline and at 12 weeks. Intakes of energy, nutrients and food groups were assessed by a 7-day dietary record. Results: Both groups exhibited a time-related significant decrease in total cholesterol (p = 0.02), fasting plasma glucose (p = 0.016), insulin (p = 0.034), BMI (p < 0.001) and waist circumference (p = 0.04), but with no significant between-arm difference. The urinary profile of metabolites from the BBB-derived (poly)phenols well discriminated the two study groups, documenting good compliance in the intervention arm. Notably, urinary bergamot 3-hydroxy-3-methylglutaryl (HMG) -containing flavanones or derived HMG-containing metabolites were not detectable. BBB was well tolerated and no adverse events were recorded. Conclusion: This first randomized controlled trial of BBB consumption in healthy subjects showed no effects of BBB on the cardiometabolic risk profile. BBB consumption is a safe nutritional adjunct in the context of a well balanced diet.

Clonal Hematopoiesis, Inflammation, Hemostasis, and Cardiometabolic Biomarkers: The Reasons for Geographic and Racial Differences in Stroke Study

CONCLUSIONS Clonal hematopoiesis (CH) is implicated in the pathogenesis of multiple age-associated disorders including malignancy, cardiovascular disease (CVD), chronic kidney disease, and mortality. Some of these adverse outcomes may be mediated by CH-driven inflammatory dysregulation, but the association of CH with biomarkers in other pathways related to these outcomes has not been studied. We studied the association between CH and biomarkers of inflammation, hemostasis and cardiometabolic risk in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. REGARDS is a prospective study that enrolled 30,239 Black and White individuals ≥45 years across United States between 2003 and 2007, and collected extensive health data by telephone and in-person exams. Biomarkers listed in Table 2, and CH were measured in baseline blood samples in an age-, sex-, and race-stratified cohort random sample (CRS). We excluded participants with prior history of CVD. Sequencing was performed at &amp;gt;500x depth to identify somatic mutations in 24 of the most common CH genes, capturing &amp;gt;95% of CH observed in the general population. CH was categorized based on variant allele frequency (VAF) of the dominant mutation as 0%, &amp;gt;0-&amp;lt;2%, 2-10% and &amp;gt;10%. Linear regression was used to calculate the age-, sex-, and race-adjusted difference in mean biomarker level for those with versus those without CH. The study included 781 participants (mean age at enrollment: 66 years [SD 12.1], 46% male, 50% Black individuals). The prevalence of CH at varying VAF was: VAF 0% - 43.3%; VAF &amp;gt;0 to &amp;lt;2% - 32.5%; 2 to 10% - 18.4%; &amp;gt;10% - 5.8%. Mutations were most prevalent in DNMT3A (60.3%), then TET2 (13.8%) and ASXL1 (10.1%). The mean age was higher in participants with CH (73 years, SD 10) than in those without CH (61 years, SD 11). Distributions of the most common CH mutations at VAF ≥2% by age, sex and race are shown in Table 1. Mutations in DNMT3A were overrepresented in Black participants and women, whereas mutations in TET2 and ASXL1 were more common in White participants. Associations of CH with inflammation, hemostasis and cardiometabolic biomarkers were presented in Table 2. Mean Log IL-8 was 0.23 (95% CI 0.05-0.41) units higher in those with high VAF CH (&amp;gt;10%) versus those without CH, with no association among other inflammation biomarkers.Among hemostasis biomarkers, mean log D-dimer was 0.26 (95% CI 0.01-0.52) units higher in those with high VAF CH versus those without CH. There was a non-significant trend towards an association between CH and lower Factor VIII and higher fibrinogen (Table 2). Among cardiometabolic biomarkers, mean log Adiponectin was 0.32 (95% CI 0.04-0.61) units higher in those with high VAF CH versus no CH. We did not identify a statistically significant association between CH and other cardiometabolic markers. CH is prevalent in the general population, especially at low VAF. In addition to inflammatory dysregulation, findings here suggest possible other pathways for deleterious effects of CH on health via hemostasis and cardiometabolic pathways. Since our study was cross-sectional, we could not ascertain if CH leads to abnormal biomarker levels or if pathways represented by the above biomarkers predispose to CH. Studying associations of CH with serial biomarkers in a larger population, by specific mutations, and by sex and race will provide mechanistic insights on CH associated adverse outcomes.

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association.

Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated "omic" fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.

Association between circulating micro-ribonucleic acids and metabolic syndrome in older adults from a population-based study

Aging is a major factor in development of chronic non-communicable diseases (NCD). Epigenetic causes are risk factors in NCD development since studies indicate that the expression of micro-ribonucleic acids (miRs) is altered under different clinical conditions. This study aimed to analyze the expression profile of circulating miRs and investigate their association with biomarkers of cardiometabolic risk in older adults living in São Paulo municipality, Brazil. A cross-sectional study was conducted based on the analysis of data from 200 older adults, with a mean age of 69.1 (0.5) years old participating in the ISA-Nutrition. The expression profiles of 21 plasma miRs related to glycemic and lipid metabolism, adiposity, and inflammation were evaluated in relation to cardiometabolic risk. Individuals were distributed into groups according to diagnosis of metabolic syndrome (MetS). The Stata Somersd module was used to calculate confidence intervals for Kendall's tau-a to estimate the correlations among variables. Differences in the plasma expression were observed in two of the 21 miRs evaluated according to the MetS presence in participants. Individuals with MetS showed higher expression of miR-30a and miR-122 than individuals without MetS. Considering that miR-30, and miR-122 were altered due to MetS, these miRs may be potential biomarkers for MetS in older adults.

Association between biomarkers of iron status and cardiometabolic risk in Spanish children aged 9–10 years. The ELOIN study

The relationship between iron metabolism and cardiometabolic risk factors has been scarcely studied in children, and the results are controversial. The objective of this study was to evaluate the association between iron parameters and lipid, glycemic and blood pressure alterations in the pediatric population. This was a cross-sectional study of 1954 children between 9 and 10 years of age in Madrid (Spain), participants in a longitudinal study of childhood obesity. Iron metabolism parameters, i.e., serum iron (Is), ferritin (Fs), transferrin (Tf) and transferrin saturation (STf) and lipid, glycemic and blood pressure profiles were evaluated. Odds ratios (ORs) were estimated using logistic regression models adjusted for sociodemographic characteristics, diet, physical activity, C-reactive protein and body mass index. Compared with the participants in the low Is and STf tertiles, those in the upper tertiles had a lower risk of low HDL-Chol (OR: 0.34; 95%CI: 0.17; 0.67) and OR: 0.44 (95%CI: 0.23; 0.84), respectively, and children in the upper Fs tertile had an OR of 2.07 (95%CI: 1.16; 3.68) for low HDL-Chol. Children in the highest Is and STf tertiles had a lower risk of prediabetes [OR: 0.63 (95%CI: 0.41; 0.97) and OR: 0.53 (95%CI: 0.34; 0.82)] and insulin resistance (IR) (OR: 0.37; 95%CI: 0.22; 0.64), and those in the upper Tf tertile had a higher risk of IR (OR: 1.90; 95%CI: 1.16; 3.12). An increased risk of hypertension was found only in children in the upper Fs tertile (OR: 1.46; 95%CI: 1.01; 2.13). Conclusions: Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population, with a variable direction and magnitude depending on the indicators used.What is Known:• Iron metabolism is related to important cardiometabolic alterations such as metabolic syndrome and its components.• Association between biomarkers of iron status and cardiometabolic risk have been less explored in children.What is New:• Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population.• Iron parameters in the pediatric population could be of great help to detect and prevent cardiometabolic abnormalities early.

O.3.2-2 Substituting device-measured sedentary time with alternative 24-hour movement behaviours: compositional associations with adiposity, cardiometabolic risk and arterial stiffness in the ORISCAV-LUX 2 study

Abstract Purpose There is a considerable burden of sedentary time in European adults. We aimed to quantify the differences in adiposity, cardiometabolic risk biomarkers, and arterial stiffness associated with exchanging sedentary time for alternative 24-hour movement behaviours. Methods This observational cross-sectional study included Luxembourg residents aged 18-79y who each provided ≥4 valid days of triaxial accelerometry (n=1046). Covariable adjusted compositional isotemporal substitution models were used to examine if replacing device-measured sedentary time with more time in the sleep period, light physical activity (PA), or moderate-to-vigorous PA (MVPA) was associated with waist circumference, numerous biomarkers of cardiometabolic health (fasting plasma glucose and insulin, triglycerides, high-density lipoprotein cholesterol (HDL-c), the ratio of apolipoprotein B/A1), and arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)). We further investigated the cardiometabolic properties of replacing sedentary time accumulated in prolonged (≥30 minute) with non-prolonged (&amp;lt;30 minute) bouts. The results are presented as 30 minute time exchanges (β (95% confidence interval)). Results Replacing 30 minutes of sedentary time with MVPA was favourably associated with waist circumference (-1.09 (-1.68 to -0.51) cm), HDL-c (1.30 (0.68 to 1.93) mg/dL), fasting glucose (-1.02 (-1.64 to -0.39) mg/dL), insulin (-4.71 (-7.12 to -2.24) %), and cfPWV (-1.70 (-2.76 to -0.62) %). Substituting sedentary time with light PA was associated with fasting insulin (-3.29 (-5.71 to -0.81) %), and was the only time-exchange to predict lower triglycerides (-2.32 (-4.38 to -0.21) %) and a lower apolipoprotein B/A1 ratio (-0.01 (-0.02 to -0.00)). Exchanging sedentary time with more time in the sleep period was associated with lower fasting insulin (-2.56 (-3.99 to -1.11)), and also with lower waist circumference (-1.39 (-2.30 to -0.48) cm) and cfPWV (-1.96 (-3.74 to -0.15) %) in short sleepers (&amp;lt;7h per night (n=349)). There was no evidence that replacing prolonged with non-prolonged sedentary time was related to outcomes. Conclusions Replacing sedentary time with MVPA is beneficially associated with the widest range of cardiometabolic risk factors, but light PA confers additional and unique benefit. Extending sleep, by redistributing sedentary time, may be an appropriate strategy to lower obesity risk and improve arterial health in short-sleeping individuals. Funding Luxembourg Institute of Health.

Ethnic differences in multimorbidity after accounting for social-economic factors, findings from The Health Survey for England.

Social-economic factors and health behaviours may be driving variation in ethnic health inequalities in multimorbidity including among distinct ethnic groups. Using the cross-sectional nationally representative Health Surveys for England 2011-18 (N = 54438, aged 16+), we performed multivariable logistic regression on the odds of having general multimorbidity (≥2 longstanding conditions) by ethnicity [British White (reference group), White Irish, Other White, Indian, Pakistani, Bangladeshi, Chinese, African, Caribbean, White mixed, Other Mixed], adjusting for age, sex, education, area deprivation, obesity, smoking status and survey year. This was repeated for cardiovascular multimorbidity (N = 37148, aged 40+: having ≥2 of the following: self-reported diabetes, hypertension, heart attack or stroke) and multiple cardiometabolic risk biomarkers (HbA1c ≥6.5%, raised blood pressure, total cholesterol ≥5mmol/L). Twenty percent of adults had general multimorbidity. In fully adjusted models, compared with the White British majority, Other White [odds ratio (OR) = 0.63; 95% confidence interval (CI) 0.53-0.74], Chinese (OR = 0.58, 95% CI 0.36-0.93) and African adults (OR = 0.54, 95% CI 0.42-0.69), had lower odds of general multimorbidity. Among adults aged 40+, Pakistani (OR = 1.27, 95% CI 0.97-1.66; P = 0.080) and Bangladeshi (OR = 1.75, 95% CI 1.16-2.65) had increased odds, and African adults had decreased odds (OR = 0.63, 95% CI 0.47-0.83) of general multimorbidity. Risk of cardiovascular multimorbidity was higher among Indian (OR = 3.31, 95% CI 2.56-4.28), Pakistani (OR = 3.48, 95% CI 2.52-4.80), Bangladeshi (OR = 3.67, 95% CI 1.98-6.78), African (OR = 1.61, 95% CI 1.05-2.47), Caribbean (OR = 2.18, 95% CI 1.59-2.99) and White mixed (OR = 1.98, 95% CI 1.14-3.44) adults. Indian adults were also at risk of having multiple cardiometabolic risk biomarkers. Ethnic inequalities in multimorbidity are independent of social-economic factors. Ethnic minority groups are particularly at risk of cardiovascular multimorbidity, which may be exacerbated by poorer management of cardiometabolic risk requiring further investigation.

Impact of upper-body ergometer rowing exercise on aerobic fitness and cardiometabolic disease risk in individuals with spinal cord injury: A 6-month follow-up study

Objective We recently demonstrated that upper-body rowing exercise (UBROW) improved aerobic fitness in individuals with spinal cord injury (SCI), with no effect on traditional cardiometabolic risk factors. Here, we tested the hypothesis that the exercise-induced increase in aerobic fitness was maintained at 6-month (6M) follow-up. Design Six-month follow-up. Setting University/hospital. Participants Seventeen wheelchair-dependent participants with SCI. Interventions 12-week of exercise training (UBROW) or control (CON). Outcome Measures Aerobic fitness (POpeak and V̇O2peak), body composition, blood pressure, and blood biomarkers of cardiometabolic risk were assessed at 6M follow-up and compared to baseline (BL) and immediately post-intervention (12-week). Minutes of mild, moderate, and heavy intensity leisure time physical activity (LTPA) were assessed by self-report. Results Fourteen participants returned at 6M follow-up (CON, n = 6; UBROW, n = 8). In UBROW, POpeak (median (Q1-Q3)) increased from BL (70 W (37–84)) to 12-week (77 W (58–109), P = 0.01) and 6M follow-up (81 W (51–96), P = 0.01), with no difference between 12-week and 6M follow-up (P = 0.21). Similarly, V̇O2peak increased from BL (15.4 ml/kg/min (10.5–19.4)) to 12-week (16.6 ml/kg/min (12.8–21.3), P = 0.01) with no difference between 12-week and 6M follow-up (16.3 ml/kg/min (12.9–19.7), P = 0.74). No differences were found in CON for either POpeak (P = 0.22) or V̇O2peak (P = 0.27). There were no changes over time in traditional cardiometabolic risk factors or for minutes of different LTPA intensities. Conclusion We demonstrate that improvements in aerobic fitness are maintained for at least six months after completion of a 12-week exercise intervention, supporting the use of periodic exercise interventions to boost aerobic fitness level in individuals with SCI. Trial registration: ClinicalTrials.gov identifier: NCT04390087..

Association of Apolipoprotein B /Apolipoprotein A-I Ratio with Cardio Metabolic Risk Biomarkers in Type 2 Diabetes Mellitus

Background: Individuals diagnosed with Type 2 Diabetes Mellitus and metabolic syndrome are at a heightened risk for cardiovascular disease. Apolipoprotein B (Apo B) is a reliable measure for assessing atherogenic particles, while Apolipoprotein A-I (ApoA-I) plays a key role in antiatherogenic high-density lipoproteins. Timely identification and evaluation of cardio metabolic risk factors can decrease the likelihood of developing CVD. Objectives: This study aimed to evaluate the association of Apo B/Apo A-I ratio with cardiometabolic risk biomarkers in T2DM. Materials and Methods: This cross-sectional study conducted at Tribhuvan University Teaching Hospital and involved 120 individuals diagnosed with Type 2 Diabetes Mellitus who visited the Medicine Outpatient Department, as well as 120 apparently healthy controls. Clinical and anthropometric characteristics were documented using a clinical proforma, and fasting blood samples were collected for the estimation of plasma glucose, Apolipoprotein B (ApoB), Apolipoprotein A-I (ApoA-I), traditional lipid profile analysis, and calculation of the Apolipoprotein B/Apolipoprotein A-I ratio. Results: The mean values of cardiometabolic risk biomarkers and Apo B/Apo A-I ratio in patients with T2DM were significantly higher, whereas HDL-C was significantly lower than that of a control group (p≤0.001). The Apo B/Apo A-I ratio was strongly positively correlated with LDL-C, TC, Non-HDL-C, and Apo B (r=0.68-0.89, p&lt;0.001) and modestly positively correlated with BMI, WC, TG, and VLDL-C (r=0.55-0.67, p&lt;0.001). Additionally, there was a weak but significant positive correlation (r=0.18-0.35, p&lt;0.05) with weight, systolic blood pressure, and fasting blood glucose. On the other hand, the Apo B/Apo A-I ratio showed a negative correlation with HDL-C and Apo A-I (r = -0.58, p&lt;0.001). Conclusion: The present study demonstrated that an elevated Apo B/Apo A-I ratio constituted a good association with several cardiometabolic biomarkers and supports that the Apo B/Apo A-I ratio as a potentially useful risk marker for predicting future cardiovascular disease in patients with type 2 diabetes mellitus

Plasma Carnitine, Choline, -Butyrobetaine, and Trimethylamine N-oxide, but not Zonulin, are reduced in overweight/obese Patients with Pre/diabetes or Impaired Glycemia

Background and Aims: Zonulin, carnitine, choline, g-butyrobetaine (g-BB), and trimethylamine N-oxide (TMAO) are intricately involved in metabolic anomalies and type 2 diabetes mellitus (T2D). This study aimed to compare and correlate the plasma levels of zonulin, carnitine, choline, g-butyrobetaine, and TMAO, along with the adiposity, atherogenicity, surrogate insulin resistance (sIR), and proinflammatory hematological indices of newly diagnosed drug-naive pre-diabetic and diabetic patients vs. apparently healthy normoglycemic controls.&#x0D; Methods: In a cross-sectional study, 30 normoglycemic subjects (controls) and 16 pre-diabetic (PreDM) and 14 type 2 diabetes (T2D) cases, that were gender and age-matched, were enrolled. Zonulin, carnitine, choline, g-BB, and TMAO plasma levels were appraised using colorimetric assays. A comparison between the study groups was conducted by ANOVA while Spearman rank correlations between the metabolic risk biomarkers and between the risk markers and adiposity, sIR, atherogenicity, and proinflammatory hematological indices were also examined.&#x0D; Results: Significant intergroup discrepancies in plasma carnitine, choline, g-BB, and TMAO (but not zonulin) could be recognized in the cases vs. controls. Fasting blood glucose (FPG), glycated hemoglobin (A1C), triglycerides (TG), body mass index (BMI), lipid accumulation product (LAP), visceral adiposity index (VAI), atherogenic index of plasma (AIP), and all sIR were outstandingly higher in the cases vs. controls. Blood indices lacked a scoring value to discriminate cases from controls. Inadvertently, no relation was found between plasma carnitine, choline, g-BB, TMAO, or zonulin in cases. Among the rest of the markers and sIR indices; The triglyceride-glucose-body mass index (TyG*BMI) related reciprocally to zonulin. Noticeably, among adiposity indices, TyG*BMI, triglyceride glucose-waist circumference (TyG*WC), and metabolic score for insulin resistance (MetS-IR) positively associated with waist circumference (WC), hip circumference (HC), BMI, body adiposity index (BAI), and waist-to-height ratio (WHtR). Exceptionally LAP proportionally correlated with all sIR. TyG*WC and MetS-IR correlated directly with the conicity index (CI). WHR directly associated with triglyceride-glucose (TyG) index and TyG*WC. Remarkably, the TyG index (but not TyG*BMI, TyG*WC, or MetS-IR) positively associated with all atherogenicity indices and RDW (but none of other blood indices). TMAO correlated inversely (P &lt; 0.05) and moderately with choline. Distinctively, carnitine associated negatively with TC (P &lt; 0.05). Both choline and carnitine related similarly and directly with PLR but inversely with lymphocytes (p &lt;0.05). Effectively, gButyrobetaine associated with both WC and the TyG-WC index equally negatively (P &lt; 0.05). Substantially, gButyrobetaine correlated inversely with both atherogenic LDL-C/HDL-C ratio and MPV (P &lt; 0.05). No pronounced relations were detected between the five microbiome signature determinants and glycemic control parameters (FBG and A1C %), sIR (TyG, TyG-BMI or MetS-IR), adiposity (WHR, WHtR, CI, BAI, LAP, or VAI), atherogenicity indices (TC/HDL-C ratio, non‑HDL‑C/HDL-C ratio, or AIP), or blood indices (NLR or MLR).Conclusion: Given the intergroup discrepancies in sIR, plasma zonulin, carnitine, choline, g-BB, and TMAO along with their elective correlations with indices and clinical parameters of metabolic dysregulations, our study cannot rule out any possible molecular crosstalk and interplay of the biomarkers studied with the pathophysiology of prediabetes/diabetes. All in all, plasma zonulin, carnitine, choline, g-BB, and TMAO with sIR can be putative surrogates for molecular cardiometabolic risk biomarkers to use as prognostic/predictive tools for the diagnosis/prevention and potential targets for prediabetes/diabetes management modalities.