Rheumatoid arthritis, cardiometabolic comorbidities, and related conditions: need to take action.

Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality, however, traditional cardiovascular risk factors do not fully explain this relationship. This high risk of cardiovascular morbidity and mortality in RA has been increasingly acknowledged in past decades, with accumulating evidence that RA is an independent cardiovascular risk factor; RA is also associated with metabolic syndrome, which correlates with disease activity, contributing to the increased prevalence of coronary heart disease in RA patients. Moreover, multimorbidity, including the presence of long-term conditions, impacts adverse clinical outcomes in RA patients, emphasizing the need for holistic management that requires an understanding of shared pathophysiological mechanisms, such as systemic inflammation and immune dysregulation. For all these reasons, the management of RA patients with cardiometabolic comorbidities is a complex endeavor that requires a patient-centered, multidisciplinary approach. In this sense, there is a need to re-evaluate the approach toward a proactive model of care, moving away from a reactive medical paradigm to a multidimensional integrated management model, including aggressive screening, preventive strategies, and tailored therapeutic interventions. The aim of this review was to thoroughly review the literature on cardiometabolic comorbidities and related conditions linked to RA to enable us to identify the necessary actions required to effectively tackle the increasing burden of illness from a fully comprehensive perspective.

Aging Reveals a Sex-Dependent Susceptibility of Sarcospan-Deficient Mice to Cardiometabolic Disease.

Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the SSPN locus have been linked with sex-dependent obesity-associated traits, however this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function we subjected young and aged global SSPN-deficient (SSPN-/-) male and female mice to obesogenic conditions (60% fat diet). We hypothesized that loss of SSPN combined with metabolic stress would increase susceptibility of mice to cardiometabolic disease. Baseline and endpoint assessments of several anthropometric parameters were performed including weight, glucose tolerance, and fat distribution of mice fed control (CD) and high fat diet (HFD). Doppler echocardiography was used to monitor cardiac function. White adipose and cardiac tissues were assessed for inflammation utilizing histological, gene expression and cytokine analysis. Overall, SSPN deficiency protected both sexes and ages from diet-induced obesity with a greater effect in females. While SSPN-/- HFD mice gained less weight than WT cohorts, SSPN-/- CD groups increased weight. Furthermore, aged SSPN-/- mice developed glucose intolerance regardless of diet. Echocardiography showed preserved systolic function for all groups, however aged SSPN-/- males (CD) exhibited significant increases in LVmass and (HFD) signs of diastolic dysfunction. Cytokine analysis revealed significantly increased IL-1α and IL-17A in white adipose tissue from young SSPN-/- male mice that may be protective from diet-induced obesity. Overall, these studies suggest several sex-dependent mechanisms influence the role SSPN plays in metabolic responses that become evident with age.

Cardiometabolic Risk Markers in Children With Obesity and Variants in MC4R Pathway-related Genes.

Context: Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective: We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods: A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results: Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion: Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels.

Engagement With Conversational Agent-Enabled Interventions in Cardiometabolic Disease Management: Protocol for a Systematic Review.

BACKGROUND: Cardiometabolic diseases (CMDs) are a group of interrelated conditions, including heart failure and diabetes, that increase the risk of cardiovascular and metabolic complications. The rising number of Australians with CMDs has necessitated new strategies for those managing these conditions, such as digital health interventions. The effectiveness of digital health interventions in supporting people with CMDs is dependent on the extent to which users engage with the tools. Augmenting digital health interventions with conversational agents, technologies that interact with people using natural language, may enhance engagement because of their human-like attributes. To date, no systematic review has compiled evidence on how design features influence the engagement of conversational agent-enabled interventions supporting people with CMDs. This review seeks to address this gap, thereby guiding developers in creating more engaging and effective tools for CMD management. OBJECTIVE: The aim of this systematic review is to synthesize evidence pertaining to conversational agent-enabled intervention design features and their impacts on the engagement of people managing CMD. METHODS: The review is conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Searches will be conducted in the Ovid (Medline), Web of Science, and Scopus databases, which will be run again prior to manuscript submission. Inclusion criteria will consist of primary research studies reporting on conversational agent-enabled interventions, including measures of engagement, in adults with CMD. Data extraction will seek to capture the perspectives of people with CMD on the use of conversational agent-enabled interventions. Joanna Briggs Institute critical appraisal tools will be used to evaluate the overall quality of evidence collected. RESULTS: This review was initiated in May 2023 and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in June 2023, prior to title and abstract screening. Full-text screening of articles was completed in July 2023 and data extraction began August 2023. Final searches were conducted in April 2024 prior to finalizing the review and the manuscript was submitted for peer review in July 2024. CONCLUSIONS: This review will synthesize diverse observations pertaining to conversational agent-enabled intervention design features and their impacts on engagement among people with CMDs. These observations can be used to guide the development of more engaging conversational agent-enabled interventions, thereby increasing the likelihood of regular intervention use and improved CMD health outcomes. Additionally, this review will identify gaps in the literature in terms of how engagement is reported, thereby highlighting areas for future exploration and supporting researchers in advancing the understanding of conversational agent-enabled interventions. TRIAL REGISTRATION: PROSPERO CRD42023431579; https://tinyurl.com/55cxkm26. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52973.

Simulating the impact of greenspace exposure on metabolic biomarkers in a diverse population living in San Diego, California: A g-computation application.

Introduction: Growing evidence exists that greenspace exposure can reduce metabolic syndrome risk, a growing public health concern with well-documented inequities across population subgroups. We capitalize on the use of g-computation to simulate the influence of multiple possible interventions on residential greenspace on nine metabolic biomarkers and metabolic syndrome in adults (N = 555) from the 2014-2017 Community of Mine Study living in San Diego County, California. Methods: Normalized difference vegetation index (NDVI) exposure from 2017 was averaged across a 400-m buffer around the participants' residential addresses. Participants' fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations, systolic and diastolic blood pressure, hemoglobin A1c (%), waist circumference, and metabolic syndrome were assessed as outcomes of interest. Using parametric g-computation, we calculated risk differences for participants being exposed to each decile of the participant NDVI distribution compared to minimum NDVI. Differential health impacts from NDVI exposure by sex, ethnicity, income, and age were examined. Results: We found that a hypothetical increase in NDVI exposure led to a decrease in hemoglobin A1c (%), glucose, and high-density lipoprotein cholesterol concentrations, an increase in fasting total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations, and minimal changes to systolic and diastolic blood pressure, waist circumference, and metabolic syndrome. The impact of NDVI changes was greater in women, Hispanic individuals, and those under 65 years old. Conclusions: G-computation helps to simulate the potential health benefits of differential NDVI exposure and identifies which subpopulations can benefit most from targeted interventions aimed at minimizing health disparities.

Prediction of visceral adipose tissue magnitude using a new model based on simple clinical measurements.

Aims: Waist circumference (WC) is a reliable obesity surrogate but may not distinguish between visceral and subcutaneous adipose tissue. Our aim was to develop a novel sex-specific model to estimate the magnitude of visceral adipose tissue measured by computed tomography (CT-VAT). Methods: The model was initially formulated through the integration of anthropometric measurements, laboratory data, and CT-VAT within a study group (n=185), utilizing the Multivariate Adaptive Regression Splines (MARS) methodology. Subsequently, its correlation with CT-VAT was examined in an external validation group (n=50). The accuracy of the new model in estimating increased CT-VAT (>130 cm2) was compared with WC, body mass index (BMI), waist-hip ratio (WHR), visceral adiposity index (VAI), a body shape index (ABSI), lipid accumulation product (LAP), body roundness index (BRI), and metabolic score for visceral fat (METS-VF) in the study group. Additionally, the new model's accuracy in identifying metabolic syndrome was evaluated in our Metabolic Healthiness Discovery Cohort (n=430). Results: The new model comprised WC, gender, BMI, and hip circumference, providing the highest predictive accuracy in estimating increased CT-VAT in men (AUC of 0.96 ± 0.02), outperforming other indices. In women, the AUC was 0.94 ± 0.03, which was significantly higher than that of VAI, WHR, and ABSI but similar to WC, BMI, LAP, BRI, and METS-VF. It's demonstrated high ability for identifying metabolic syndrome with an AUC of 0.76 ± 0.03 (p<0.001). Conclusion: The new model is a valuable indicator of CT-VAT, especially in men, and it exhibits a strong predictive capability for identifying metabolic syndrome.

Association of serum 25-hydroxy vitamin D status with cardiometabolic risk factors and total and regional obesity in southern Iran: evidence from the PoCOsteo study.

Cardiometabolic risk factors increase the chance of developing cardiovascular disease (CVD) and type 2 diabetes. Most CVD risk factors are influenced by total and regional obesity. A higher risk of developing CVD may be linked to vitamin D deficiency, which is more prevalent in the older population. With the goal of evaluating the association between vitamin D and cardiometabolic risk factors and total and regional obesity in older adults, this research included 25 (OH) vitamin D3 concentrations and biochemical markers associated with cardiometabolic diseases, as well as total and regional adiposity, which was measured by DXA. A total of 1991 older participants in the PoCOsteo study were included. Overall, 38.5% of participants had vitamin D deficiency. After adjusting for confounders, the results of multiple linear and logistic regression suggested an inverse association between vitamin D and body mass index (P = 0.04), waist circumference (P = 0.001), total fat (P = 0.02), android fat (P = 0.001), visceral fat (P < 0.001), subcutaneous fat (P = 0.01), trunk fat (P = 0.006), arm fat (P = 0.03), high systolic blood pressure (P = 0.004), high total cholesterol (P < 0.001), high LDL-cholesterol (P < 0.001), high serum triglycerides (P = 0.001), and high fasting glucose (P < 0.001). Additionally, higher vitamin D concentrations decreased the risk of dyslipidemia by 2%. Our results showed a significant association between serum vitamin D and a number of cardiometabolic risk factors, including total and regional obesity.

Assessing the prevalence of obesity in a Russian adult population by six indices and their associations with hypertension, diabetes mellitus and hypercholesterolaemia.

The anthropometric index that best predicts cardiometabolic risk remains inconclusive. This study therefore assessed the prevalence of obesity using six indices and compared their associations with obesity-related cardiometabolic disorders. We determined obesity prevalence according to body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio (WHtR), body fat percentage and fat mass index (FMI) using data from the Know Your Heart study (n = 4495, 35-69 years). The areas under the receiver operating characteristic curves (AUCs) provided predictive values of each index for detecting the presence of hypertension, hypercholesterolaemia and diabetes. Age-standardised obesity prevalence significantly varied according to anthropometric index: from 17.2% (FMI) to 75.8% (WHtR) among men and from 23.6% (FMI) to 65.0% (WHtR) among women. WHtR had the strongest association with hypertension (AUC = 0.784; p < 0.001) and with a combination of disorders (AUC = 0.779; p < 0.001) in women. In women, WHtR also had the largest AUCs for hypercholesterolaemia, in men - for hypertension, diabetes and a combination of disorders, although not all the differences from other obesity indices were significant. WHtR exhibited the closest association between hypertension and a combination of disorders in women and was non-inferior compared to other indices in men.

Sex and population differences in the cardiometabolic continuum: a machine learning study using the UK Biobank and ELSA-Brasil cohorts.

BACKGROUND: The temporal relationships across cardiometabolic diseases (CMDs) were recently conceptualized as the cardiometabolic continuum (CMC), sequence of cardiovascular events that stem from gene-environmental interactions, unhealthy lifestyle influences, and metabolic diseases such as diabetes, and hypertension. While the physiological pathways linking metabolic and cardiovascular diseases have been investigated, the study of the sex and population differences in the CMC have still not been described. METHODS: We present a machine learning approach to model the CMC and investigate sex and population differences in two distinct cohorts: the UK Biobank (17,700 participants) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (7162 participants). We consider the following CMDs: hypertension (Hyp), diabetes (DM), heart diseases (HD: angina, myocardial infarction, or heart failure), and stroke (STK). For the identification of the CMC patterns, individual trajectories with the time of disease occurrence were clustered using k-means. Based on clinical, sociodemographic, and lifestyle characteristics, we built multiclass random forest classifiers and used the SHAP methodology to evaluate feature importance. RESULTS: Five CMC patterns were identified across both sexes and cohorts: EarlyHyp, FirstDM, FirstHD, Healthy, and LateHyp, named according to prevalence and disease occurrence time that depicted around 95%, 78%, 75%, 88% and 99% of individuals, respectively. Within the UK Biobank, more women were classified in the Healthy cluster and more men in all others. In the EarlyHyp and LateHyp clusters, isolated hypertension occurred earlier among women. Smoking habits and education had high importance and clear directionality for both sexes. For ELSA-Brasil, more men were classified in the Healthy cluster and more women in the FirstDM. The diabetes occurrence time when followed by hypertension was lower among women. Education and ethnicity had high importance and clear directionality for women, while for men these features were smoking, alcohol, and coffee consumption. CONCLUSIONS: There are clear sex differences in the CMC that varied across the UK and Brazilian cohorts. In particular, disadvantages regarding incidence and the time to onset of diseases were more pronounced in Brazil, against woman. The results show the need to strengthen public health policies to prevent and control the time course of CMD, with an emphasis on women.

Type 2 Diabetes Mellitus and Cardiometabolic Prospects: A Rapid Narrative Review.

Cardiometabolic syndrome (CMS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases are among the major altruists to the international liability of disease. The lifestyle and dietary changes attributable to economic growth have resulted in an epidemiological transition towards non-communicable diseases (NCDs) as the leading causes of death. Low- and middle-income countries (LMICs) bear a more substantial disease burden due to limited healthcare sector capacities to address the rapidly growing number of chronic disease patients. The purpose of this narrative review paper was to explore the interrelationships between CMS, T2DM, and cardiovascular impairments in the context of NCDs, as well as major preventative and control interventions. The role of insulin resistance, hyperglycemia, and dyslipidemia in the pathogenesis of T2DM and the development of severe cardiovascular impairments was highlighted. This paper elaborated on the pivotal role of lifestyle modifications, such as healthy diets and physical activity, as cornerstones of addressing the epidemics of metabolic diseases. Foods high in calories, refined sugar, red meat, and processed and ready-to-eat meals were associated with an amplified risk of CMS and T2DM. In contrast, diets based on fruits, legumes, vegetables, and whole grain, home-cooked foods demonstrated protective effects against metabolic diseases. Additionally, the role of a psychological and behavioral approach in addressing metabolic diseases was highlighted, especially regarding its impact on patient empowerment and the patient-centered approach to preventative and therapeutic interventions.

Associations Between Sleep Duration and Cardiometabolic Diseases Among Residents in Southwest China.

Introduction: The burden of cardiometabolic diseases (CMDs), defined as stroke, coronary artery disease, and diabetes mellitus, continues to pose a global challenge. Sleep duration has been linked to cardiovascular health. However, there is a lack of focused investigations on CMDs in underdeveloped areas of China. Purpose: This study aimed to examine the relationship between sleep duration and CMDs among residents from southwest China. Patients and Methods: This large cross-sectional study screened data from the National Key Research and Development Program (2018YFC1311400). Based on sleep duration reported through a standardized questionnaire, encompassing the sleep patterns of the past five years, participants were classified into three groups: <6, 6-8, >8 hours. Baseline characteristics were compared, and Poisson regression models were used to assess the relationship between sleep duration and CMDs. Subgroup analysis was conducted based on age and gender. Results: This study included 28,908 participants with an average age of 65.6 ± 10.0 years, of whom 57.6% were female. The overall prevalence of CMDs was 22.6%. After multivariate adjustments, the prevalence ratios (PR) (95% CI) for CMDs across the three groups (6-8h, <6h and >8h) were: reference, 1.140 (1.068-1.218), 1.060 (0.961-1.169) (P for trend =0.003), respectively. The subgroup analysis revealed that among older females, a longer sleep duration (>8h) was also associated with an increased prevalence risk of CMDs, with PR 1.169 (1.001-1.365) (p=0.049). Conclusion: A shorter sleep duration (<6 hours) was associated with an increased risk of CMDs in the general population, while a longer sleep duration (>8 hours) also raised the prevalence risk among older females.

Association between single and multiple cardiometabolic diseases and all-cause mortality among Chinese older adults: A prospective, nationwide cohort study.

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

Longitudinal associations of DXA-measured visceral adipose tissue and cardiometabolic risk in middle-to-older aged adults.

BACKGROUND AND AIMS: DXA-measured visceral adipose tissue (VATDXA) is associated with adverse cardiometabolic risk profiles in cross-sectional studies, but longitudinal associations have not been investigated. We examined the longitudinal associations of baseline and change in VATDXA with future cardiometabolic risk in Australian participants of the Busselton Healthy Ageing study. METHODS AND RESULTS: We studied 3569 participants (54.7% female, aged 46-70 years) with data on VATDXA (GE Lunar Prodigy) and cardiometabolic risk factors at baseline and 6 years follow-up. The associations were examined using logistic and linear regression models, adjusting for baseline age and lifestyle factors. Mean baseline VATDXA mass was 1653 ± 880 g and 855 ± 580 g, and mean change in VATDXA +99 ± 500 g and +58 ± 312 g in males and females, respectively. Among all participants, 182 males (11.3%) and 197 females (10.1%) developed incident metabolic syndrome (MetS). Baseline VATDXA was associated with incident MetS with an adjusted odds ratio of 2.53 (95% CI: 2.03, 3.15) in males and 2.78 (2.30, 3.36) in females per SD increment. There was a graded positive association between longitudinal change in VATDXA and MetS severity z score in both sexes adjusted for baseline VAT (P < 0.001). All the above associations remained significant after further adjustment for baseline or change in BMI, waist circumference or waist-to-hip ratio in respective models (all P < 0.001). CONCLUSIONS: Higher baseline and greater longitudinal increase in VATDXA are independently associated with raised cardiometabolic risk over time, and may serve as useful markers for identifying middle-aged individuals at increased cardiometabolic risk.

A systematic review and meta-analysis of loss-of-control eating in relation to cardiometabolic health components and inflammatory markers.

INTRODUCTION: Loss-of-control (LOC) eating, or the subjective experience of being unable to stop eating, is a hallmark feature of binge-eating episodes, which are also characterized by consuming an unusually large amount of food. However, regardless of the size of eating episode, LOC-eating may be a risk factor for adverse health outcomes. This systematic review and meta-analysis comprehensively examine the relationship of LOC-eating with cardiometabolic health components and inflammatory markers. METHODS: Search procedures were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines in six electronic databases. Studies of adult or youth samples published in English from the year 2000 onward were included. Given heterogeneity in age groups and adjustment for body mass index across studies, these factors were included as meta-regression moderators. RESULTS: Fifty-eight studies were identified through the literature search. Among individuals with (versus without) LOC-eating, relative risk ratios provided evidence of a greater relative risk for metabolic syndrome, hypertension, and dyslipidemia; standardized mean differences also provided evidence of higher waist circumference and impaired levels of fasting plasma glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides, but not blood pressure. Age group did not impact cardiometabolic health components. Body mass index differences moderated the effect on waist circumference. A narrative review of inflammatory markers revealed mixed findings linking inflammatory markers to LOC-eating. DISCUSSION: Overall, evidence for the relationship between LOC-eating and impaired cardiometabolic health underscores LOC-eating as an important early intervention target for prevention of serious adverse health outcomes.

Identification of regulatory networks and crosstalk factors in brown adipose tissue and liver of a cold-exposed cardiometabolic mouse model.

BACKGROUND: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs). METHODS: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days. RESULTS: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans. DISCUSSION: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders.

Association of Non-High-Density Lipoprotein Cholesterol With Cardiometabolic Risk Factors in Patients With Hypothyroidism.

INTRODUCTION: Non-high-density lipoprotein cholesterol (non-HDL-C) levels can increase the cardiometabolic risk factors in patients with hypothyroidism, but the findings across studies have not been consistently conclusive. The aim of this study was to find the association between non-HDL-C and cardiometabolic risk factors in patients with hypothyroidism. MATERIAL AND METHODS: In this case-control study, a total of 120 subjects among which 60 diagnosed hypothyroidism patients and 60 age-matched healthy controls were enrolled, aged 30-65 years. Body mass index (BMI), waist circumference (WC), and systolic and diastolic blood pressures (SBP and DBP) were measured. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were estimated. Low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and non-HDL-C were calculated. A p-value of <0.05 was considered statistically significant. RESULTS: Mean of BMI, WC, FBS, TSH, TC, TG, non-HDL-C, LDL-C, VLDL-C, SBP, and DBP were significantly elevated in cases compared to controls (p<0.001). However, the mean of T3, T4, and HDL-C were significantly reduced in cases compared to controls (p<0.001). Non-HDL-C has shown a significant positive correlation with age (r=0.345, p<0.01), TC (r=0.451, p<0.01), TG (r=0.269, p<0.05), LDL-C (r=0.402, p<0.01), and VLDL-C (r=0.269, p<0.05) among cases. However, non-HDL-C has shown a significant negative correlation with HDL-C (r=-0.330, p<0.05) among cases. Non-HDL-C significantly predicted cardiometabolic risk in patients with hypothyroidism (F(13,46)=3.500, p<0.001). CONCLUSION: Non-HDL-C has shown a significant association with age and lipid abnormalities in patients with hypothyroidism. Non-HDL-C significantly predicts cardiometabolic risk factors in patients with hypothyroidism.

Epigenome-wide association study on the plasma metabolome suggests self-regulation of the glycine and serine pathway through DNA methylation.

BACKGROUND: The plasma metabolome reflects the physiological state of various biological processes and can serve as a proxy for disease risk. Plasma metabolite variation, influenced by genetic and epigenetic mechanisms, can also affect the cellular microenvironment and blood cell epigenetics. The interplay between the plasma metabolome and the blood cell epigenome remains elusive. In this study, we performed an epigenome-wide association study (EWAS) of 1183 plasma metabolites in 693 participants from the LifeLines-DEEP cohort and investigated the causal relationships in DNA methylation-metabolite associations using bidirectional Mendelian randomization and mediation analysis. RESULTS: After rigorously adjusting for potential confounders, including genetics, we identified five robust associations between two plasma metabolites (L-serine and glycine) and three CpG sites located in two independent genomic regions (cg14476101 and cg16246545 in PHGDH and cg02711608 in SLC1A5) at a false discovery rate of less than 0.05. Further analysis revealed a complex bidirectional relationship between plasma glycine/serine levels and DNA methylation. Moreover, we observed a strong mediating role of DNA methylation in the effect of glycine/serine on the expression of their metabolism/transport genes, with the proportion of the mediated effect ranging from 11.8 to 54.3%. This result was also replicated in an independent population-based cohort, the Rotterdam Study. To validate our findings, we conducted in vitro cell studies which confirmed the mediating role of DNA methylation in the regulation of PHGDH gene expression. CONCLUSIONS: Our findings reveal a potential feedback mechanism in which glycine and serine regulate gene expression through DNA methylation.

Perspectives on deprescribing in older people with type 2 diabetes and/or cardiovascular conditions: challenges from healthcare provider, patient and caregiver perspective, and interventions to support a proactive approach.

INTRODUCTION: For people with type 2 diabetes and/or cardiovascular conditions, deprescribing of glucose-lowering, blood pressure-lowering and/or lipid-lowering medication is recommended when they age, and their health status deteriorates. So far, deprescribing rates of these so-called cardiometabolic medications are low. A review of challenges and interventions addressing these challenges in this population is pertinent. AREAS COVERED: We first provide an overview of relevant deprescribing recommendations. Next, we review challenges for healthcare providers (HCPs) to deprescribe cardiometabolic medication and provide insight in the patient and caregiver perspective on deprescribing. We summarize findings from research on implementing deprescribing of cardiometabolic medication and reflect on strategies to enhance deprescribing. We have used a combination of methods to search for relevant articles. EXPERT OPINION: There is a need for rigorous development and evaluation of intervention strategies aimed at proactive deprescribing of cardiometabolic medication. To address challenges at different levels, these should be multifaceted interventions. All stakeholders must become aware of the relevance of deintensifying medication in this population. Education and training for HCPs and patients should support patient-centered communication and shared decision-making. Development of procedures and tools to select eligible patients and conduct targeted medication reviews are important for implementation of deprescribing in routine care.