How Do Genetic and Environmental Factors Influence Cardiometabolic Risk Factors? Findings from the Isfahan Twins Study.

BACKGROUND: Disease-discordant twins are excellent subjects for matched case-control studies as they allow for the control of confounding factors such as age, gender, genetic background, and intrauterine and early environment factors. Study design: A cross-sectional study. METHODS: Past medical history documentation and physical examination were conducted for all participants. Fasting venous blood samples were taken to measure fasting blood glucose (FBG) and lipid levels. The ACE model, a structural equation model, was used to assess heritability. RESULTS: This study included 710 twin pairs (210 monozygotic and 500 dizygotic) ranging in age from 2 to 52 years (mean age: 11.67±10.71 years). The study was conducted using participants from the Isfahan Twin Registry (ITR) in 2017. Results showed that in early childhood (2-6 years), height, weight, and body mass index (BMI) were influenced by shared environmental factors (76%, 75%, and 73%, respectively). In late childhood (7-12 years), hip circumference, waist circumference (WC), and low-density lipoprotein (LDL) cholesterol were found to be highly heritable (90%, 76%, and 64%, respectively). In adolescents, height (94%), neck circumference (85%), LDL-cholesterol (81%), WC (70%), triglycerides (69%), weight (68%), and BMI (65%) were all found to be highly or moderately heritable. In adult twins, arm circumference (97%), weight (86%), BMI (82%), and neck circumference (81%) were highly heritable. CONCLUSION: This study demonstrates that both genetic and environmental factors play a role in influencing individuals at different stages of their lives. Notably, while certain traits such as obesity have a high heritability during childhood, their heritability tends to decrease as individuals transition into adulthood.

Unmasking the Risk Factors Associated with Undiagnosed Diabetes and Prediabetes in Ghana: Insights from Cardiometabolic Risk (CarMeR) Study-APTI Project.

INTRODUCTION: Undiagnosed diabetes poses significant public health challenges in Ghana. Numerous factors may influence the prevalence of undiagnosed diabetes among adults, and therefore, using a model that takes into account the intricate network of these relationships should be considered. Our goal was to evaluate fasting plasma levels, a critical indicator of diabetes, and the associated direct and indirect associated or protective factors. METHODS: This research employed a cross-sectional survey to sample 1200 adults aged 25-70 years who perceived themselves as healthy and had not been previously diagnosed with diabetes from 13 indigenous communities within the Cape Coast Metropolis, Ghana. Diabetes was diagnosed based on the American Diabetes Association (ADA) criteria for fasting plasma glucose, and lipid profiles were determined using Mindray equipment (August 2022, China). A stepwise WHO questionnaire was used to collect data on sociodemographic and lifestyle variables. We analyzed the associations among the exogenous, mediating, and endogenous variables using a generalized structural equation model (GSEM). RESULTS: Overall, the prevalence of prediabetes and diabetes in the Cape Coast Metropolis was found to be 14.2% and 3.84%, respectively. In the sex domain, females had a higher prevalence of prediabetes (15.33%) and diabetes (5.15%) than males (12.62% and 1.24%, respectively). Rural areas had the highest prevalence, followed by peri-urban areas, whereas urban areas had the lowest prevalence. In the GSEM results, we found that body mass index (BMI), triglycerides (TG), systolic blood pressure (SBP), gamma-glutamyl transferase (GGT), and female sex were direct predictive factors for prediabetes and diabetes, based on fasting plasma glucose (FPG) levels. Indirect factors influencing diabetes and prediabetes through waist circumference (WC) included childhood overweight status, family history, age 35-55 and 56-70, and moderate and high socioeconomic status. High density lipoprotein (HDL) cholesterol, childhood overweight, low physical activity, female sex, moderate and high socioeconomic status, and market trading were also associated with high BMI, indirectly influencing prediabetes and diabetes. Total cholesterol, increased TG levels, WC, age, low physical activity, and rural dwellers were identified as indirectly associated factors with prediabetes and diabetes through SBP. Religion, male sex, and alcohol consumption were identified as predictive factors for GGT, indirectly influencing prediabetes and diabetes. CONCLUSIONS: Diabetes in indigenous communities is directly influenced by blood lipid, BMI, SBP, and alcohol levels. Childhood obesity, physical inactivity, sex, socioeconomic status, and family history could indirectly influence diabetes development. These findings offer valuable insights for policymakers and health-sector stakeholders, enabling them to understand the factors associated with diabetes development and implement necessary public health interventions and personalized care strategies for prevention and management in Ghana.

Chrononutrition and Cardiometabolic Health: An Overview of Epidemiological Evidence and Key Future Research Directions.

Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is to summarize epidemiological evidence from observational and intervention studies regarding the role of chrononutrition metrics related to eating timing and regularity in cardiometabolic health preservation and cardiovascular disease prevention. Observational studies are limited due to the lack of time-stamped diet data in most population-based studies. Findings from cohort studies generally indicate that breakfast skipping or the later timing of the first eating occasion, a later lunch and dinner, and a greater proportion of caloric intake consumed in the evening are associated with adverse cardiometabolic outcomes, including higher risk for coronary heart disease, hypertension, type 2 diabetes, obesity, dyslipidemia, and systemic inflammation. Randomized controlled trials are also limited, as most in the field of chrononutrition focus on the cardiometabolic consequences of time-restricted feeding. Overall, interventions that shift eating timing patterns to earlier in the day and that restrict evening caloric intake tend to have protective effects on cardiometabolic health, but small sample sizes and short follow-up are notable limitations. Innovation in dietary assessment approaches, to develop low-cost validated tools with acceptable participant burden that reliably capture chrononutrition metrics, is needed for advancing observational evidence. Culturally responsive pragmatic intervention studies with sufficiently large and representative samples are needed to understand the impact of fixed and earlier eating timing schedules on cardiometabolic health. Additional research is warranted to understand the modifiable determinants of temporal eating patterns, to investigate the role of chrononutrition in the context of other dimensions of diet (quantity, quality, and food and nutrition security) in achieving cardiometabolic health equity, and to elucidate underlying physiological mechanisms.

[Predictive value of neck circumference for cardiometabolic risk in children].

Objective: To investigate the predictive value of neck circumference on cardiometabolic risk in children. Methods: This was a cross-sectional study of natural sources. As the prediction cohort, clinical data were collected from 3 443 children aged 5-14 years who underwent physical examination in the Department of Child Healthcare, Children's Hospital of Nanjing Medical University from July 2021 to September 2022. As the validation cohort for external validation, clinical data were collected from 604 children aged 5-14 years who underwent physical examination in the Department of Child Healthcare, Children's Hospital of Nanjing Medical University from October 2022 to March 2023. Height, weight, neck circumference, waist circumference and body composition were measured in both groups, and body mass index, neck circumference to height ratio (NHtR), waist circumference to height ratio, body fat percentage and skeletal muscle percentage were calculated. Systolic blood pressure, diastolic blood pressure, fasting blood glucose, blood lipid and uric acid and other cardiovascular and metabolic risk indicators were collected in both groups. The prediction cohort was further stratified into clustered and non-clustered groups based on the clustering of cardiometabolic risk factors (CCRF). Various variables between these 2 groups were compared using the Mann-Whitney U test. Pearson correlation and binary Logistic regression were conducted to investigate the correlations between neck circumference and cardiovascular metabolic risk factors. The accuracy of NHtR in predicting the CCRF was evaluated using the area under the curve (AUC) of receiver operating characteristic (ROC). The cutoff value was determined using the Youden index. The validation cohort was then divided into groups above and below the cutoff value, and the detection rate of CCRF between the 2 groups was compared using the χ2 test for validation. Results: In the prediction cohort of 3 443 children (2 316 boys and 1 127 girls), 1 395 (40.5%) children were overweight or obese, and 1 157 (33.6%) children had CCRF. Pearson correlation analysis revealed all significant positive correlations (all P<0.01) between neck circumference and systolic blood pressure (r=0.47, 0.39), diastolic blood pressure (r=0.27, 0.21), uric acid (r=0.36, 0.30), and triglycerides (r=0.20, 0.20) after adjusting for age in both males and females. Among both males and females, neck circumference both showed significant negative correlation (both P<0.01) with high-density lipoprotein cholesterol (r=-0.27, -0.28), and no correlation with fasting glucose levels (r=0.03, -0.03, both P>0.05). After adjusting for gender, age, and body fat percentage, increased body mass index, neck circumference, or waist circumference increased the risks of hypertension (OR=1.23, 1.39, 1.07, all P<0.001), hyperuricemia (OR=1.16, 1.23, 1.05, all P<0.001), hypertriglyceridemia (OR=1.08, 1.16, 1.02, all P<0.01), low high-density lipoprotein cholesterol (OR=1.10, 1.27, 1.03, all P<0.01), and the CCRF (OR=1.51, 1.73, 1.15, all P<0.01). The areas under the ROC curves of NHtR in predicting CCRF was 0.73, with sensitivity and specificity at 0.66 and 0.71, respectively. The corresponding optimal cut-off value was 0.21. Validation with 604 children confirmed that the detection of CCRF in the NHtR≥0.21 group was 3.29 times (60.5% (112/185) vs. 18.7% (79/422),χ2=107.82, P<0.01) higher compared to the NHtR <0.21 group. Conclusions: Neck circumference is associated with cardiovascular metabolic risks such as hypertension, hyperlipidemia, hyperglycemia, and hyperuricemia in children. When the NHtR is ≥0.21, there is an increased likelihood of CCRF.

A Study on Yoga-Based Lifestyle Intervention versus Dietary Intervention Alone on Cardiometabolic Risk Factors among People with Prediabetes.

BACKGROUND: Prediabetes is presented as a metabolic state that predisposes persons to a greater risk of diabetes progression in the future. Prediabetes is an intervening stage between normoglycemia and diabetes with impaired fasting glucose and impaired glucose tolerance. This study aimed to compare the effect of the yoga-based lifestyle intervention (including diet) versus dietary intervention (DI) alone on cardiometabolic parameters namely fasting blood glucose (FBG), glycated hemoglobin (HbA1C), lipid profile; triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), heart rate variability (HRV), and carotid intima-media thickness (CIMT) among people with prediabetes. METHODS: A randomized controlled study was conducted on 250 people with prediabetes who were randomly allocated by computer-generated methods to the yoga-based lifestyle intervention (including diet) (n = 125) and DI alone (n = 125) groups. Yoga sessions were approximately 45 min 6 days a week over a period of 6 months. Assessments were made at baseline and after 6 months of intervention. RESULTS: Post-intervention comparison of cardiometabolic parameters in yoga-based lifestyle intervention (including diet) versus DI alone showed a significant decline in body mass index (P = 0.0002), waist-hip ratio (P = 0.0001), systolic blood pressure (P = 0.0001), diastolic blood pressure (P = 0.0001), perceived stress score (P = 0.0001), FBG (P = 0.0001), HbA1C (P = 0.0001), lipid profile; TG (P = 0.008), LDL (P = 0.0001), VLDL (P = 0.0001), HRV (P = 0.0001), CIMT (P = 0.02) and a nonsignificant decline in, TC (P = 0.22), HDL (P = 0.211), FFQ (P = 0.164). CONCLUSION: The finding of this study suggests that a 24-week yoga-based lifestyle intervention which includes diet significantly decreased cardiometabolic parameters compared to DI alone among people with prediabetes.

Résumé Contexte:Le prédiabète est présenté comme un état métabolique qui prédispose les personnes à un risque plus élevé de progression du diabète dans le futur. Le prédiabète est une étape intermédiaire entre la normoglycémie et le diabète avec une altération de la glycémie à jeun et une altération de la tolérance au glucose. Cette étude visait à comparer l'effet d'une intervention sur le style de vie basée sur le yoga (y compris le régime) par rapport à une intervention diététique (DI) seule sur les effets cardiométaboliques. paramètres à savoir glycémie à jeun (FBG), hémoglobine glyquée (HbA1C), profil lipidique; triglycéride (TG), cholestérol total (TC), lipoprotéines de haute densité (HDL), lipoprotéines de basse densité (LDL), lipoprotéines de très basse densité (VLDL), variabilité de la fréquence cardiaque (VRC) et carotide épaisseur intima-média (CIMT) chez les personnes atteintes de prédiabète.Méthodes:Une étude contrôlée randomisée a été menée auprès de 250 personnes atteintes prédiabétiques qui ont été répartis au hasard, par des méthodes générées par ordinateur, dans l'intervention sur le style de vie basée sur le yoga (y compris le régime alimentaire) (n = 125) et groupes DI seul (n = 125). Les séances de yoga duraient environ 45 minutes 6 jours par semaine sur une période de 6 mois. Des évaluations ont été faites au départ et après 6 mois d'intervention.Résultats:Comparaison post-intervention des paramètres cardiométaboliques dans un mode de vie basé sur le yoga L'intervention (y compris le régime alimentaire) par rapport à l'ID seul a montré une baisse significative de l'indice de masse corporelle (P = 0,0002), du rapport taille-hanche (P = 0,0001), de la pression systolique. tension artérielle (P = 0,0001), tension artérielle diastolique (P = 0,0001), score de stress perçu (P = 0,0001), FBG (P = 0,0001), HbA1C (P = 0,0001), profile lipidique; TG (P = 0,008), LDL (P = 0,0001), VLDL (P = 0,0001), HRV (P = 0,0001), CIMT (P = 0,02) et une baisse non significative dans, TC (P = 0,22), HDL (P = 0,211), FFQ (P = 0,164).Conclusion:Les résultats de cette étude suggèrent qu'un mode de vie basé sur le yoga pendant 24 semaines une intervention qui comprend un régime a considérablement réduit les paramètres cardiométaboliques par rapport à l'ID seul chez les personnes atteintes de prédiabète.

Body Mass Index and Hypertension as Mediators of the Association Between Age at Menarche and Subclinical Atherosclerosis: A Sex-Specific Mendelian Randomization Analysis.

BACKGROUND: Early age at menarche (AAM) has been associated with a higher risk of carotid artery intima-media thickness (cIMT), an indicator of subclinical vascular disease, albeit the mechanisms underlying this association remain elusive. A better understanding of the relationship between AAM, modifiable cardiometabolic risk factors, and subclinical atherosclerosis may contribute to improved primary prevention and cardiovascular disease treatment. We aimed to investigate the putative causal role of AAM on cIMT, and to identify and quantify the potentially mediatory effects of cardiometabolic risk factors underlying this relationship. METHODS AND RESULTS: We conducted linkage disequilibrium score regression analyses between our exposure of interest, AAM, our outcome of interest, cIMT and potential mediators of the AAM-cIMT association to gauge cross-trait genetic overlap. We considered as mediators the modifiable anthropometric risk factors body mass index (BMI), systolic blood pressure (SBP), lipid traits (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), and glycemic traits (fasting glucose). We then leveraged the paradigm of Mendelian randomization to infer causality between AAM and cIMT, and to identify whether cardiometabolic risk factors served as potential mediators of this effect. Our analyses showed that genetically predicted AAM was inversely associated with cIMT, BMI, SBP, and triglycerides, and positively associated with high-density lipoprotein, low-density lipoprotein, and total cholesterol. We showed that the effect of genetically predicted AAM on cIMT may be partially mediated through BMI (20.1% [95% CI, 1.4% to 38.9%]) and SBP (13.5% [95% CI, 0.5%-26.6%]). Our cluster-specific Mendelian randomization revealed heterogeneous causal effect estimates of age at menarche on BMI and SBP. CONCLUSIONS: We highlight supporting evidence for a potential causal association between earlier AAM and cIMT, and almost one third of the effect of AAM on cIMT may be mediated by BMI and SBP. Early intervention aimed at lowering BMI and hypertension may be beneficial in reducing the risk of developing subclinical atherosclerosis due to earlier age at menarche.

Mediterranean Diet and Cardiometabolic Biomarkers in Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: No prior systematic review and meta-analysis has specifically verified the association of Mediterranean diet (MedDiet)-based interventions with biomarkers of cardiometabolic health in children and adolescents. Objective: To review and analyze the randomized clinical trials (RCTs) that assessed the effects of MedDiet-based interventions on biomarkers of cardiometabolic health among children and adolescents. Data Sources: Four electronic databases were searched (PubMed, Cochrane Library, Web of Science, and Scopus) from database inception to April 25, 2024. Study Selection: Only RCTs investigating the effect of interventions promoting the MedDiet on cardiometabolic biomarkers (ie, systolic blood pressure [SBP], diastolic blood pressure [DBP], triglycerides [TGs], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], glucose, insulin, and homeostatic model assessment for insulin resistance [HOMA-IR]) among children and adolescents (aged ≤18 years) were included. Data Extraction and Synthesis: A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were extracted from the studies by 2 independent reviewers. Results across studies were summarized using random-effects meta-analysis. Main Outcome and Measures: The effect size of each trial was computed by unstandardized mean differences (MDs) of changes in biomarker levels (ie, SBP, DBP, TGs, TC, HDL-C, LDL-C, glucose, insulin, HOMA-IR) between the intervention and the control groups. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Results: Nine RCTs were included (mean study duration, 17 weeks; range, 8-40 weeks). These studies involved 577 participants (mean age, 11 years [range, 3-18 years]; 344 girls [59.6%]). Compared with the control group, the MedDiet-based interventions showed a significant association with reductions in SBP (mean difference, -4.75 mm Hg; 95% CI, -8.97 to -0.52 mm Hg), TGs (mean difference, -16.42 mg/dL; 95% CI, -27.57 to -5.27 mg/dL), TC (mean difference, -9.06 mg/dL; 95% CI, -15.65 to -2.48 mg/dL), and LDL-C (mean difference, -10.48 mg/dL; 95% CI, -17.77 to -3.19 mg/dL) and increases in HDL-C (mean difference, 2.24 mg/dL; 95% CI, 0.34-4.14 mg/dL). No significant associations were observed with the other biomarkers studied (ie, DBP, glucose, insulin, and HOMA-IR). Conclusions and Relevance: These findings suggest that MedDiet-based interventions may be useful tools to optimize cardiometabolic health among children and adolescents.

The Impact of Cornelian Cherry (Cornus mas L.) on Cardiometabolic Risk Factors: A Meta-Analysis of Randomised Controlled Trials.

This meta-analysis aimed to summarise clinical evidence regarding the effect of supplementation with cornelian cherry (Cornus mas L.) on different cardiometabolic outcomes. An extensive literature survey was carried out until 10 April 2024. A total of 415 participants from six eligible studies were included. The overall results from the random-effects model indicated that cornelian cherry supplementation significantly reduced body weight (standardised mean difference [SMD] = -0.27, confidence interval [CI]: -0.52, -0.02, p = 0.03), body mass index (SMD = -0.42, CI: -0.73, -0.12, p = 0.007), fasting blood glucose (SMD = -0.46, CI: -0.74, -0.18, p = 0.001), glycated haemoglobin (SMD = -0.70, CI: -1.19, -0.22, p = 0.005), and HOMA-IR (SMD = -0.89, CI: -1.62, -0.16, p = 0.02), while high-density lipoprotein cholesterol significantly increased (SMD = 0.38, CI: 0.10, 0.65, p = 0.007). A sensitivity analysis showed that cornelian cherry supplementation significantly reduced total plasma triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Cornelian cherry supplementation did not significantly affect waist circumference and liver parameters among the participants. Considering these findings, this meta-analysis indicates that supplementation with cornelian cherry may impact diverse cardiometabolic risk factors among individuals considered to be at a high risk.

More Adult Women than Men at High Cardiometabolic Risk Reported Worse Lifestyles and Self-Reported Health Status in the COVID-19 Lockdown.

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Anthropometry for predicting cardiometabolic disease risk factors in adolescents.

OBJECTIVE: Early screening prevents chronic diseases by identifying at-risk adolescents through anthropometric measurements, but predictive value in diverse groups is uncertain. METHODS: A cross-sectional analysis of 12- to 19-year-old individuals from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) assessed the predictive ability of BMI percentile, total body fat percentage, waist circumference (WC), and waist-hip ratio (WHR) for four cardiometabolic risk factors across race and ethnicity groups using receiver operating characteristic curves. RESULTS: The unweighted sample (N = 1194; 51.2% male individuals; 23.7% Hispanic, 13.2% non-Hispanic Black [NHB], 51.1% non-Hispanic White [NHW], 12.0% other/multirace) had a weighted prevalence of elevated blood pressure of 2.7%, hyperglycemia of 36.8%, hypertriglyceridemia of 4.8%, and low high-density lipoprotein (HDL) cholesterol of 15%. WHR (area under the curve [AUC] = 0.77), WC (AUC = 0.77), and BMI percentile (AUC = 0.73) outperformed total body fat percentage (AUC = 0.56) in predicting elevated blood pressure (p < 0.001 for all). BMI percentile was more accurate than total body fat percentage in predicting hypertriglyceridemia (AUC = 0.70 vs. 0.59; p = 0.02) and low HDL cholesterol (AUC = 0.69 vs. 0.59; p < 0.001). Race and ethnicity-based predictions varied: NHW adolescents had the highest AUC (0.89; p < 0.01) for elevated blood pressure prediction compared with Hispanic and NHB adolescents (AUC = 0.77 for both). Total body fat percentage was more accurate in predicting low HDL cholesterol among Hispanic versus NHW adolescents (AUC = 0.73 vs. 0.58; p = 0.04). CONCLUSIONS: WHR, WC, and BMI percentile are better predictors of cardiometabolic risk factors in adolescents than total body fat percentage. Predictive abilities differed by race and ethnicity, highlighting the importance of tailored risk assessment strategies.

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country.

Background/aim: Type 2 diabetes mellitus (T2DM) is closely associated with atherosclerotic cardiovascular diseases (ASCVD). The objective of this study was to describe the degree of ASCVD risk factor control and their association with carotid intima-media thickness (CIMT) in T2DM patients followed up at a diabetes clinic in Southern, Sri Lanka. Materials and methods: A crosssectional study was conducted to examine the association between CIMT and nonalcoholic fatty liver disease (NAFLD)in 300 T2DM patients. Both CIMT and its associations with modifiable cardiometabolic risk factors were examined using ultrasonography. The recommended optimal targets for risk factors were defined as glycated hemoglobin (HbA1C) < 7 %, absence of NAFLD, albumin-to-creatinine ratio (ACR) < 30 mg, triglyceride (TG) < 150 mg/dL, low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) in men > 40 and in women > 50 mg/dL, systolic blood pressure (SBP) < 130 mmHg, and diastolic blood pressure (DBP) < 80 mmHg. Results: SBP, DBP, LDL-C, TG, HDL-C, HbA1C, and ACR were optimally controlled in 59.3%, 75.0%, 46.7%, 84.3%, 46.0%, 33.0%, and 18.7% of patients, respectively. Notably, nearly half of the study subjects did not have NAFLD. Only three patients (1%) had achieved all therapeutic targets. There were statistically significant differences in CIMT between optimally controlled TG and suboptimally controlled TG group (p = 0.027) and between the groups with and without NAFLD (p = 0.045) when adjusted for age and duration of diabetes. CIMT showed significant and positive associations with LDL-C (p = 0.024), TG (p = 0.026), and NAFLD (p = 0.005). Among these, the presence of NAFLD had the highest odds of having higher CIMT when compared to LDL-C and TG. Conclusion: The majority of patients have not achieved the recommended targets for ASCVD risk factors and are at high risk of ASCVD. It is therefore necessary to identify the reasons for not achieving the treatment targets in order to reduce the ASCVD burden by controlling LDL-C, TG, and NAFLD.

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

Longitudinal economic burden of incident complications among metabolic syndrome populations.

BACKGROUND: This study quantifies the longitudinal economic burden for a wide spectrum of incident complications, metabolic syndrome (MS)-related risk factors, and comorbidities in patients with MS. METHODS: This retrospective study utilized linked data from the 2013 National Health Interview Survey and the 2012-2021 National Health Insurance Research Database to identify MS individuals and their characteristics. The incidence rate of each complication was calculated as the number of complication events in the study period divided by the total person-years during follow-up. The healthcare costs of complications were analyzed using a generalized estimating equation model to determine the cost impact of complications after adjustment for patients' characteristics. Sensitivity analyses on variables with high missing rates (i.e., cause of death, body mass index) were performed. RESULTS: Among 837 identified MS individuals over 8.28 (± 1.35) years of follow-up, the most frequent complications were microvascular diseases (incidence rate for nephropathy/retinopathy/neuropathy: 6.49/2.64/2.08 events per 100 person-years), followed by cardiovascular diseases (2.47), peripheral vascular diseases (2.01), and cancers (1.53). Death was the costliest event (event-year cost per person: USD 16,429) and cancers were the most expensive complications (USD 9,127-11,083 for non-MS- and MS-related cancers). Developing non-MS/MS-related cancers, cardiovascular diseases, and obesity-related medical conditions increased annual costs by 273% (95% CI: 181-397%)/175% (105-269%), 159% (118-207%), and 140% (84-214%), respectively. Microvascular diseases had the lowest cost impact on annual costs (i.e., 27% [17-39%]/27% [11-46%]/24% [11-37%] increases for nephropathy/neuropathy/retinopathy, respectively). Having existing comorbidities increased annual costs by 20% (osteoarthritis) to 108% (depression). Having morbid obesity (i.e., body mass index ≥ 35 kg/m2) increased annual costs by 58% (30-91%). CONCLUSIONS: The economic burden from costly incident complications (i.e., cardiovascular diseases, peripheral vascular diseases, cancers), MS-related risk factors (i.e., morbid obesity), and comorbidities (i.e., depression) highlight the urgent need for early intervention to prevent MS and its progression. The comprehensive cost estimates reported in this study can facilitate the parameterization of economic analyses to identify cost-effective interventions for these patients.

Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS. METHODS: We conducted a systematic search of PubMed/Medline, Scopus, and the Cochrane Library for articles published in English from inception to March 2023. We included randomized controlled trials (RCTs) on the use of melatonin for patients with polycystic ovary syndrome (PCOS). We performed a meta-analysis using a random-effects model and calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Six studies met the inclusion criteria. The result of meta-analysis indicated that melatonin intake significantly increase TAC levels (SMD: 0.87, 95% CI: 0.46, 1.28, I2 = 00.00%) and has no effect on FBS, insulin, HOMA-IR, TC, TG, HDL, LDL, MDA, hs-CRP, mFG, SHBG, total testosterone, and pregnancy rate in patients with PCOS compare to controls. The included trials did not report any adverse events. CONCLUSION: Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS. However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs.

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

DNA Methylation Mediates the Association Between Cardiometabolic Risk Factors and Cognition: Findings From the Health and Retirement Study.

The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3 708 participants (mean [standard deviation {SD}] age: 67.3 [9.5], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014-2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016 and 2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% confidence interval [CI: -0.119, -0.004]) and diabetes (-0.134; 95% CI: [-0.198, -0.071]) were significantly associated with worse cognitive function while abnormal body weight and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (p = .002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: -0.033, -0.014), diabetes (-0.022; 95% CI: -0.032, -0.014), and obesity (-0.021; 95% CI: -0.033, -0.011) with cognitive function, whereas the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.

The impact of duration and severity of obesity exposure on cardiometabolic health.

PURPOSE: Duration and severity of exposure to excess adipose tissue are important risk factors for complications, but are generally not examined in conjunction. We developed a metric considering both factors to examine the relationship between obesity-related complications and parameters of cardiometabolic health in patients undergoing a metabolic bariatric procedure (MBS). MATERIALS & METHODS: Data from patients screened for primary MBS between 2017 and 2021 were analyzed. The Obesity Exposure score (OBES), based on self-reported years of life with a BMI ≥ 25 kg/m2, was calculated with increased weighting applied for higher BMI categories. Multivariate logistic regression analysis was performed, adjusting for multiple potential confounders. RESULTS: In total, 2441 patients were included (76% female, age 42.1 ± 11.9 years, BMI 42.0 ± 4.9 kg/m2). OBES was positively related to myocardial infarction, atrial fibrillation and renal function loss (per 10 OBES-units: OR 1.31, 95%CI [1.11-1.52], p = 0.002; OR 1.23, 95% CI [1.06-1.44], p = 0.008; and OR 1.26, 95% CI [1.04-1.51], p = 0.02). OBES was negatively associated with obstructive sleep apnea syndrome (OSAS) (OR 0.90, 95% CI [0.83-0.98], p = 0.02). In patients without obesity-related complications, OBES was related to lower HbA1c and higher HDL-cholesterol levels (ß -0.5 95% CI [-0.08-.0.02] p < 0.001 and ß 0.02 [0.00-0.04] p = 0.01). CONCLUSION: OBES was related to myocardial infarction, atrial fibrillation and renal function loss in patients applying for MBS. OBES was negatively related to OSAS, possibly because undiagnosed years were not taken into account. In the absence of obesity-related complications, OBES was not related to metabolic blood markers. Our data may aid in improving perioperative risk assessments.