Search

Background: The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact of sleep duration trajectory. This study aims to model the sleep duration trajectory as predictors for the subsequent development of cardio-metabolic disease., Methods: This study recruited a notably large population (n = 9883) of subjects aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS), who participated in sequential surveys conducted in 2011, 2013, 2015, and 2018. Sleep duration trajectories were plotted using data of night sleep duration recorded at intervals from 2011 to 2015 by latent class trajectory model. The onset of cardio-metabolic diseases from 2015 to 2018 were confirmed and then the risk of different sleep duration trajectories on incident cardio-metabolic disease was examined using cox proportional hazards regression model., Results: We identified four sleep duration trajectories. Compared to the normal-stable trajectory, the short-stable trajectory was significantly associated with higher risk of incident stroke (hazard ratio [HR], 1.32; 95 % confidence interval [CI], 1.02 to 1.70), dyslipidemia (HR, 1.22; 95%CI, 1.01 to 1.49), and diabetes (HR, 1.42; 95%CI, 1.13 to 1.78) within three years of follow-up, and the short-increasing trajectory predicted a higher risk of incident stroke (HR, 2.38; 95%CI, 1.25 to 4.55)., Conclusions: Short sleep trajectory could increase the risk of incident stroke, dyslipidemia, and diabetes, and an increasing sleep trajectory was associated with increased risk of incident stroke among middle-aged and older Chinese adults., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Microcirculatory dysfunction has been observed in the dermal white adipose tissue (dWAT) and subcutaneous white adipose tissue (scWAT) of obese humans and has been proposed as an early prediction marker for cardio-metabolic disease progression. In-vivo visualization and longitudinal monitoring of microvascular remodeling in these tissues remains challenging. We compare the performance of two optoacoustic imaging methods, i.e. multi-spectral optoacoustic tomography (MSOT) and raster-scanning optoacoustic mesoscopy (RSOM) in visualizing lipid and hemoglobin contrast in scWAT and dWAT in a mouse model of diet-induced obesity (DIO) undergoing voluntary wheel running intervention for 32 weeks. MSOT visualized lipid and hemoglobin contrast in murine fat depots in a quantitative manner even at early stages of DIO. We show for the first time to our knowledge that RSOM allows precise visualization of the dWAT microvasculature and provides quantitative readouts of skin layer thickness and vascular density in dWAT and dermis. Combination of MSOT and RSOM resolved exercise-induced morphological changes in microvasculature density, tissue oxygen saturation, lipid and blood volume content in dWAT and scWAT. The combination of MSOT and RSOM may allow precise monitoring of microcirculatory dysfunction and intervention response in dWAT and scWAT in a mouse model for DIO. Our findings have laid out the foundation for future clinical studies using optoacoustic-derived vascular readouts from adipose tissues as a biomarker for monitoring microcirculatory function in metabolic disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:V.N. is an equity owner and consultant for iThera Medical GmbH, Munich, Germany. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2024 The Authors.)

Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cardio-metabolic diseases, including a cluster of metabolic disorders and their secondary affections on cardiovascular physiology, are gradually brought to the forefront by researchers due to their high prevalence and mortality, as well as an unidentified pathogenesis. tRNA-derived small RNAs (tsRNAs), cleaved by several specific enzymes and once considered as some "metabolic junks" in the past, have been proved to possess numerous functions in human bodies. More interestingly, such a potential also seems to influence the progression of cardio-metabolic diseases to some extent. In this review, the biogenesis, classification and mechanisms of tsRNAs will be discussed based on some latest studies, and their relations with several cardio-metabolic diseases will be highlighted in sequence. Lastly, some future prospects, such as their clinical applications as biomarkers and therapeutic targets will also be mentioned, in order to provide researchers with a comprehensive understanding of the research status of tsRNAs as well as its association with cardio-metabolic diseases, thus presenting as a beacon to indicate directions for the next stage of study., Competing Interests: Declaration of competing interest All the authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In numerous brain structures, insulin signaling modulates the homeostatic processes, sensitivity to reward pathways, executive function, memory, and cognition. Through human studies and animal models, mounting evidence implicates central insulin signaling in the metabolic, physiological, and psychological consequences of early life adversity. In this review, we describe the consequences of early life adversity in the brain where insulin signaling is a key factor and how insulin may moderate the effects of adversity on psychiatric and cardio-metabolic health outcomes. Further understanding of how early life adversity and insulin signaling impact specific brain regions and mental and physical health outcomes will assist in prevention, diagnosis, and potential intervention following early life adversity., Competing Interests: Competing interests The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Cardio-metabolic diseases has been shown to be strongly associated with obesity. The aim of this study was to compare the predictive value of traditional and novel anthropometric measurement indices for cardio-metabolic diseases risk and evaluate whether new indicators can provide important information in addition to traditional indicators., Methods and Results: China Health and Nutrition Survey (CHNS) data were obtained for this study. Baseline information for healthy participants was gathered from 1997 to 2004. The incidence of cardio-metabolic diseases was collected from 2009 to 2015 for cohort analysis. The predictive ability of each index for the risk of cardio-metabolic diseases was evaluated with time-dependent ROC analysis. Body mass index (BMI) showed the greatest predictive ability for cardio-metabolic disease incidence among all traditional and novel indices (Harrell's C statistic (95% CI): 0.7386 (0.7266-0.7507) for hypertension, 0.7496 (0.7285-0.7706) for diabetes, 0.7895 (0.7593-0.8196) for stroke and 0.7581 (0.7193-0.7969) for myocardial infarction). The addition of novel indices separately into the BMI model did not improve the predictive ability. Novel anthropometric measurement indices such as a body shape index (ABSI), abdominal volume index (AVI) and triponderal mass index (TMI), had a certain prediction ability for adults with BMI <24 kg/m 2 compared to those with BMI ≥24 kg/m 2 ., Conclusion: No strong evidence supports novel anthropometric measurement indices were better than BMI in the prediction of cardio-metabolic diseases incidence among Chinese adults. Novel anthropometric measurement indices, mainly for abdominal obesity, may have a high predictive effect for adults with BMI <24 kg/m 2 ., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background Diabetes and hypertension have been associated with adverse left ventricular (LV) remodeling. While they often occur concurrently, their individual effects are understudied. We aimed to assess the independent effects of diabetes and hypertension on LV remodeling in Black adults. Methods and Results The JHS (Jackson Heart Study) participants (n=4143 Black adults) with echocardiographic measures from baseline exam were stratified into 4 groups: neither diabetes nor hypertension (n=1643), only diabetes (n=152), only hypertension (n=1669), or both diabetes and hypertension (n=679). Echocardiographic measures of LV structure and function among these groups were evaluated by multivariable regression adjusting for covariates. Mean age of the participants was 52±1 years, and 63.7% were women. LV mass index was not different in participants with only diabetes compared with participants with neither diabetes nor hypertension ( P =0.8). LV mass index was 7.9% (6.0 g/m 2 ) higher in participants with only hypertension and 10.8% (8.1 g/m 2 ) higher in participants with both diabetes and hypertension compared with those with neither ( P <0.001). LV wall thickness (relative, posterior, and septal) and brain natriuretic peptide levels in participants with only diabetes were not significantly higher than participants with neither ( P >0.05). However, participants with both diabetes and hypertension demonstrated higher LV wall thickness and brain natriuretic peptide levels than participants with neither ( P <0.05). Conclusions In this cross-sectional analysis, diabetes was not associated with altered LV structure or function in Black adults unless participants also had hypertension. Our findings suggest hypertension is the main contributor to cardiac structural and functional changes in Black adults with diabetes.

Resolution of inflammation is a complex, dynamic process consisting of several distinct processes, including inhibition of endothelial activation and leukocyte trafficking; promotion of inflammatory cell apoptosis and subsequent non-phlogistic scavenging and degradation; augmentation of pathogen phagocytosis; modulation of stromal cell phenotype coupled to the promotion of tissue regeneration and repair. Among these tightly regulated processes, the clearance and degradation of apoptotic cells without eliciting an inflammatory response is a crucial allostatic mechanism vital to developmental processes, host defence, and the effective resolution of inflammation. These efferocytic and subsequent effero-metabolism processes can be carried out by professional and non-professional phagocytes. Defective removal or inadequate processing of apoptotic cells leads to persistent unresolved inflammation, which may promote insidious pathologies including scarring, fibrosis, and eventual organ failure. In this manuscript, the well-established role of endothelial activation and leukocyte extravasation, as classical vascular targets of the 'inflammation pharmacology', will be briefly reviewed. The main focus of this work is to bring attention to a less explored aspect of the 'resolution pharmacology', aimed at tackling defective efferocytosis and inefficient effero-metabolism, as key targeted mechanisms to prevent or pre-empt vascular complications in cardio-metabolic diseases. Despite the use of gold standard lipid-lowering drugs or glucose-lowering drugs, none of them are able to tackle the so called residual inflammatory risk and/or the metabolic memory. In this review, the development of synthetic mimetics of endogenous mediators of inflammation is highlighted. Such molecules finely tune key components across the whole inflammatory process, amongst various other novel therapeutic paradigms that have emerged over the past decade, including anti-inflammatory therapy. More specifically, FPR2-agonists in general, and Lipoxin analogues in particular, greatly enhance the reprogramming and cross-talk between classical and non-classical innate immune cells, thus inducing both termination of the pro-inflammatory state as well as promoting the subsequent resolving phase, which represent pivotal mechanisms in inflammatory cardio-metabolic diseases., (Copyright © 2022. Published by Elsevier Ltd.)

Cardio-metabolic diseases are the leading causes of premature death worldwide. The conditions are together some of the most prevalent and severe multimorbidities and include conditions such as diabetes, hypertension, coronary heart disease and stroke. People with these conditions are at a higher risk of all-cause death and have a reduction in life expectancy when compared to patients without cardio-metabolic disorders. As a result of the increasing prevalence and impact of cardio-metabolic multimorbidity on disability, no healthcare system can 'treat' its way out of this pandemic. 'Treating our way out' requires the use of multiple medications which can lead to improper prescribing, insufficient compliance, overdosing or underdosing, improper drug choice, insufficient monitoring, unfavourable drug effects, and drug interactions and inappropriate wastes and costs. Therefore, individuals living with these conditions should be empowered to adopt lifestyle changes that foster independent living with their conditions. Adopting these healthy lifestyles such as smoking cessation, improving dietary habits, sleep hygiene and physical activity is a suitable adjunctive measure if not an alternative to polypharmacy in cardio-metabolic multimorbidity.

Background: Paraoxonases (PON) 1-3 are lactonases with antioxidant and atheroprotective properties. The best known single nucleotide polymorphisms (SNPs) within the PON family, include: Q192R (rs662), L55M (rs854560) in the PON1 gene and C311S (rs7493) in the PON2 gene. Their influence on the occurrence and course of coronary artery disease (CAD) is unclear. The aim of this study was to assess the association between the most common PON1 and PON2 genetic variants with the presence of CAD, as well as their relation to coronary lesion complexity in accordance with the ACC/AHA standard., Methods: We included 1027 individuals: 367 CAD patients qualified for coronary angiography and 660 healthy volunteers as controls. We extracted DNA from circulating blood leukocytes, amplified the PON1 and PON2 genetic sequence and used restriction enzymes to identify the SNPs. Patients with CAD underwent coronary angiography and were assigned to two groups based on lesion severity: patients with at least one type C lesion and without a type C lesion. The former where categorized into those with a significant narrowing (≥50% diameter stenosis) and those without one., Results: We found no association between the analyzed SNPs and symptomatic CAD. However, in patients with diagnosed CAD, the PON311S allele was independently associated with the risk of the most complex type C coronary lesion occurrence., Conclusions: Our study is the first report of an association between PON2 311S SNP and the type of coronary atherosclerotic lesions in humans., (Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Metabolic syndrome (MetS) refers to a cluster of co-existing cardio-metabolic risk factors, including visceral obesity, dyslipidemia, hyperglycemia with insulin resistance, and hypertension. As there is a close link between MetS and cardiovascular diseases, we aimed to investigate the sex-based differences in MetS-associated heart failure (HF) and cardiovascular response to regular exercise training (ET)., Methods: High-fat diet-fed male and female APOB-100 transgenic (HFD/APOB-100, 3 months) mice were used as MetS models, and age- and sex-matched C57BL/6 wild-type mice on standard diet served as healthy controls (SD/WT). Both the SD/WT and HFD/APOB-100 mice were divided into sedentary and ET groups, the latter running on a treadmill (0.9 km/h) for 45 min 5 times per week for 7 months. At month 9, transthoracic echocardiography was performed to monitor cardiac function and morphology. At the termination of the experiment at month 10, blood was collected for serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol measurements and homeostatic assessment model for insulin resistance (HOMA-IR) calculation. Cardiomyocyte hypertrophy and fibrosis were assessed by histology. Left ventricular expressions of selected genes associated with metabolism, inflammation, and stress response were investigated by qPCR., Results: Both HFD/APOB-100 males and females developed obesity and hypercholesterolemia; however, only males showed insulin resistance. ET did not change these metabolic parameters. HFD/APOB-100 males showed echocardiographic signs of mild HF with dilated ventricles and thinner walls, whereas females presented the beginning of left ventricular hypertrophy. In response to ET, SD/WT males developed increased left ventricular volumes, whereas females responded with physiologic hypertrophy. Exercise-trained HFD/APOB-100 males presented worsening HF with reduced ejection fraction; however, ET did not change the ejection fraction and reversed the echocardiographic signs of left ventricular hypertrophy in HFD/APOB-100 females. The left ventricular expression of the leptin receptor was higher in females than males in the SD/WT groups. Left ventricular expression levels of stress response-related genes were higher in the exercise-trained HFD/APOB-100 males and exercise-trained SD/WT females than exercise-trained SD/WT males., Conclusions: HFD/APOB-100 mice showed sex-specific cardiovascular responses to MetS and ET; however, left ventricular gene expressions were similar between the groups except for leptin receptor and several stress response-related genes., (© 2022. The Author(s).)

Background: Nurse-led health and lifestyle modification programmes can prevent cardio-metabolic diseases and be advantageous where health disparities exist., Aims: To assess the effectiveness of a nurse-driven health and lifestyle modification programme in improving cardio-metabolic risk parameters for higher-risk regional residing adults., Methods: We conducted an open, parallel-group randomized controlled trial in two sites. Participants were aged 40-70 years with no prior cardiovascular disease who had any three or more of; central obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure (BP) and dysglycaemia. Intervention participants received individual face-to-face and telephone coaching for improving cardio-metabolic risk. Control group participants received standard care and general information about risk factor management. The primary endpoint was the percentage of participants who achieved the target risk factor thresholds or clinically significant minimum changes for any three or more cardio-metabolic risk factors during 24 months of follow-up., Results: Participant average age was 57.6 (SD 7.6) years, 61% were female and 71% were employed. The primary endpoint was achieved by 76% intervention (97 of 127) and 71% usual care (92 of 129) participants [adjusted risk ratio (RR): 1.08; 95% CI 0.94, 1.24; P = 0.298]. Improved BP in the intervention group was more likely than in the control group (84% vs. 65%) (adj. RR: 1.28; 95% CI 1.11, 1.48; P = 0.001) but no other cardio-metabolic component., Conclusion: Nurse intervention to modify cardio-metabolic risk parameters had no enhanced effectiveness compared with usual care. However, participation was associated with improvements in cardio-metabolic abnormalities, with particular emphasis on BP., Trial Registration: Registered with the Australian New Zealand Clinical Trial Registry (ACTRN12616000229471)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are endogenously produced signalling molecules from cholesterol, can affect CMD risk and progression and directly affect the gut microbiome (GM). Moreover, studies focusing on the GM and CMD risk have dramatically increased in the past decade. It has also become clear that the GM can function as a "new" endocrine organ. BA and GM have a complex and interdependent relationship with several CMD pathways. This review aims to provide a comprehensive overview of the interplay between BA metabolism, the GM, and CMD risk and progression.

Background: The health impacts of dietary fat-to-energy ratio (FER) compared to carbohydrate-to-energy ratio (CER) are widely discussed topics in public health. This study aimed to assess the health impacts of FER and CER by establishing trajectory-patterns of FER and CER over the course of adult life. Methods: This study used the weighted longitudinal data of the China Health and Nutrition Survey, including eight surveys from 1991 to 2011. The trajectories of FER and CER were determined via latent class trajectory modeling. The trajectories were then cross-grouped into different trajectory-patterns. Multivariate Cox regression models were used to assess the relationship between these trajectory-patterns and cardio-metabolic diseases and all-cause mortality. Ten thousand nine hundred and twenty-six adults with a total of 50,693 observations across eight surveys were included. Results: Compared to the trajectory-pattern of persistently low-FER (increased from 10 to 20%) and moderate-CER (stable and ranging from 55 to 65%) over the adult life-course, the two trajectory-patterns that showed changing to high-FER and low-CER were significantly associated with obesity [HR 1.83 [95% CI, 1.10-3.04]; HR 1.46 [95% CI, 1.02-2.17]], diabetes [HR 1.80 [95% CI, 1.03-3.16]; HR 1.49 [95% CI, 1.01-2.25]], and all-cause mortality [HR 2.29 [95% CI, 1.35-3.87]; HR 1.62 [95% CI, 1.18-2.22]]. In contrast, the trajectory-pattern of a persistently low-FER and high-CER diet was not associated with obesity [HR 1.19 [95% CI, 0.82-1.17]], diabetes [HR 1.41 [95% CI, 0.98-2.02]], cardiovascular-disease [HR 1.48 [95% CI, 0.91-2.39]], and all-cause mortality [HR 1.23 [95% CI, 0.94-1.61]]. Conclusions: This study indicates that changing to a high-FER and low-CER diet over the course of adult life was significantly associated with obesity, diabetes, and all-cause mortality in the Chinese adult population. In addition, low-FER and high-CER were not associated with cardio-metabolic disease and all-cause mortality. These observations may provide insights into nutritional policy and dietary guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Xu, Gao, Wang, Hou, Wu, Sun, Li and Han.)

Background Although chronic cardio-metabolic disease is a common comorbidity among patients with COVID-19, its effects on the clinical characteristics and outcome are not well known. Methods and Results This study aimed to explore the association between underlying cardio-metabolic disease and mortality with COVID-19 among hospitalized patients. This multicenter, retrospective, and real-world study was conducted from January 22, 2020 to March 25, 2020 in China. Data between patients with and without 5 main cardio-metabolic diseases including hypertension, diabetes mellitus, coronary heart disease, cerebrovascular disease, and hyperlipidemia were compared. A total of 1303 hospitalized patients were included in the final analysis. Of them, 520 patients (39.9%) had cardio-metabolic disease. Compared with patients without cardio-metabolic disease, more patients with cardio-metabolic disease had COVID-related complications including acute respiratory distress syndrome (9.81% versus 3.32%; P <0.001), acute kidney injury (4.23% versus 1.40%; P= 0.001), secondary infection (13.9% versus 9.8%; P= 0.026), hypoproteinemia (12.1% versus 5.75%; P <0.001), and coagulopathy (19.4% versus 10.3%; P <0.001), had higher incidences of the severe type of COVID-19 (32.9% versus 16.7%; P <0.001), more were admitted to the intensive care unit (11.7% versus 7.92%; P= 0.021), and required mechanical ventilation (9.8% versus 4.3%; P <0.001). When the number of the patients' cardio-metabolic diseases was 0, 1, and >2, the mortality was 4.2%, 11.1%, and 19.8%, respectively. The multivariable-adjusted hazard ratio of mortality among patients with cardio-metabolic disease was 1.80 (95% CI, 1.17-2.77). Conclusions Cardio-metabolic disease was a common condition among hospitalized patients with COVID-19, and it was associated with higher risks of in-hospital mortality.

Background: Rapid eye movement sleep -predominant sleep-disordered breathing (REM-SDB) is a condition in which sleep apneas or hypopneas predominantly occur during REM sleep. This study aimed to investigate the prevalence, clinical findings including daytime sleepiness or comorbid cardio-metabolic diseases, and detailed polysomnographic features of REM-SDB in Japanese population., Methods: Total of 1458 patients diagnosed as SDB were selected for this study. Prevalence of REM-SDB was estimated in the groups of mild, moderate and severe SDB. Polysomnographic findings, daytime sleepiness self-measured with Epworth Sleepiness Scale (ESS) and history of comorbid cardio-metabolic diseases were obtained and compared between the groups with REM-SDB and non-stage specific SDB., Results: Prevalence of REM-SDB according to the criteria #2 was 22.1% in total SDB subjects, 46,1% in mild SDB and 18.9% in moderate SDB. None was found in severe SDB. Patients with REM-SDB showed milder SDB, higher BMI and higher female predominance than those with non-stage specific SDB. They also showed lower arousal index, respiratory arousal index per total AHI, percentage of N1 sleep, total AHI, ODI, and higher sleep efficiency. Meanwhile, maximum event durations of obstructive apnea and hypopnea were significantly longer, and the nadir SpO 2 was lower in REM-SDB. The ESS score and percentages of comorbid cardio-metabolic diseases were roughly equivalent between REM-SDB and non-stage specific SDB., Conclusion: REM-SDB was associated with high obesity, female gender, and mild severity of SDB. They showed daytime sleepiness and comorbid cardio-metabolic diseases quite equally to patients with non-stage specific SDB in spite of their lower AHI and better sleep quality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Efficient delivery of specific cargos in vivo poses a major challenge to the secretory pathway, which shuttles products encoded by ∼30% of the genome. Newly synthesized protein and lipid cargos embark on the secretory pathway via COPII-coated vesicles, assembled by the GTPase SAR1 on the endoplasmic reticulum (ER), but how lipid-carrying lipoproteins are distinguished from the general protein cargos in the ER and selectively secreted has not been clear. Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. While both genes are implicated in lipid regulation in humans, hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. These findings show that the pairing between SURF4 and SAR1B synergistically operates a specialized, dosage-sensitive transport program for circulating lipids, while further suggesting a potential translation to treat atherosclerosis and related cardio-metabolic diseases., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Globally, cardiometabolic multimorbidity pattern (CMP) is a complex chronic health status that negatively effects the life expectancy of adults globally, even more than single diseases. We aimed to identify multimorbidity patterns in Korean adults to clarify the associations between dietary factors and CMP. Nationally representative data of 9011 Korean adults aged 19-64 years were obtained from the Korean National Health and Nutrition Examination Survey (KNHANES) from the period 2013 to 2015. Multimorbidity patterns for CMP, inflammatory disease, cancer and other disease patterns were identified by exploratory factor analysis. Dietary factors including food and nutrient intake and dietary habits were evaluated. Multivariable-adjusted logistic regression models examined the associations between dietary factors and CMP. More than half of the multimorbidity patterns were CMP ( n = 4907, 54.5%); CMP subjects were more likely to be older, male, less educated, lower income, laborers, smokers, and high-risk consumers of alcohol than those of non-CMP subjects. A higher intake of calcium (OR = 0.809, 95% CI = 0.691-0.945), potassium (OR = 0.838, 95% CI = 0.704-0.998), and fruits (OR = 0.841, 95% CI = 0.736-0.960) were inversely associated with the prevalence of CMP, while the consumption of irregular meals (OR = 1.164, 95% CI = 1.034-1.312) and skipping breakfast (OR = 1.279, 95% CI = 1.078-1.518) was positively related to a 16% and 28% higher likelihood of CMP, respectively. CMP accounts for more than half of the multimorbidity patterns in the Korean population, and lower intake of calcium, potassium, fruits, and skipping meals have strong associations with CMP.

It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents., (© 2020 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

In the absence of therapeutic interventions, and a possible vaccine candidate, the spread of COVID-19 disease and associated fatalities are on the rise. The high mutation frequency in the genomic material of these viruses supports their ability to adapt to new environments, resulting in an efficient alteration in tissue tropism and host range. Therefore, the coronavirus' health threats could be relevant for the long-term. The epidemiological data indicate that age, sex, and cardio-metabolic disease have a significant impact on the spread and severity of COVID-19. In this review, we highlight recent updates on the pathogenesis of SARS-CoV-2 among men and women, including children. We also discuss the role of the cellular receptors and coreceptors used by the virus to enter host cells on differential infection among men, women, and cardio-metabolic patients.

(1) Background: Cardio-metabolic diseases (CMD), including cardiovascular disease, stroke, and diabetes, have numerous common individual and environmental risk factors. Yet, few studies to date have considered how these multiple risk factors together affect CMD disparities between Blacks and Whites. (2) Methods: We linked daily fine particulate matter (PM 2.5 ) measures with survey responses of participants in the Southern Community Cohort Study (SCCS). Generalized linear mixed modeling (GLMM) was used to estimate the relationship between CMD risk and social-demographic characteristics, behavioral and personal risk factors, and exposure levels of PM 2.5 . (3) Results: The study resulted in four key findings: (1) PM 2.5 concentration level was significantly associated with reported CMD, with risk rising by 2.6% for each µg/m 3 increase in PM 2.5 ; (2) race did not predict CMD risk when clinical, lifestyle, and environmental risk factors were accounted for; (3) a significant variation of CMD risk was found among participants across states; and (4) multiple personal, clinical, and social-demographic and environmental risk factors played a role in predicting CMD occurrence. (4) Conclusions: Disparities in CMD risk among low social status populations reflect the complex interactions of exposures and cumulative risks for CMD contributed by different personal and environmental factors from natural, built, and social environments., Competing Interests: The authors declare no conflict of interest.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF.

The role of physical activity in determining the metabolic health of adolescents is poorly understood, particularly concerning the effect on low-grade chronic inflammation (chronic elevation of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and acute phase protein CRP, which is implicated in the etiology of atherosclerosis) and anti-inflammatory mediators such as IL-10. Furthermore, there is limited information on the mediating effects of performance on the multi-stage fitness test (MSFT), V ˙ O 2 peak and adiposity on risk factors for cardio-metabolic disease in adolescents. Purpose: To examine the effect of performance on the MSFT, V ˙ O 2 peak and adiposity on risk factors for cardio-metabolic diseases in adolescents. Methods: Following ethical approval, 121 adolescents (11.3 ± 0.8 year) completed the study. Risk factors for cardio-metabolic disease (circulating inflammatory cytokines, blood glucose and plasma insulin concentrations) was assessed using a fasted capillary blood sample. Participants were separated into quartiles based upon distance ran during the MSFT, the blood lactate response to submaximal exercise, V ˙ O 2 peak (determined during an uphill graded treadmill test), and adiposity (determined as the sum of four skinfolds). The blood lactate response to submaximal exercise and V0 2 peak were measured in a sub-group of participants. Data were analyzed using two-way between-subjects ANCOVA and multiple linear regression. Results: Participants with the lowest performance on the MSFT had higher blood concentrations of IL-6 (3.25 ± 0.25 pg mL -1 ) and IL-1β (4.78 ± 0.54 pg mL -1 ) and lower concentrations of IL-10 (1.80 ± 0.27 pg mL -1 ) when compared with all other quartiles (all p < 0.05). Yet, when categorized into V ˙ O 2 peak quartiles, no differences existed in any of the inflammatory mediators (all p > 0.05). Performance on the MSFT was the only predictor of IL-6 (β = -0.291, p = 0.031), IL-1β (β = -0.405, p = 0.005), IL-10 (β = 0.325, p = 0.021) and fasted blood glucose (β = -0.545, p < 0.001) concentrations. Adiposity was the only predictor of plasma insulin concentration (β = 0.515, p < 0.001) and blood pressure (diastolic: β = 0.259, p = 0.042; mean arterial pressure: β = 0.322, p = 0.011). Conclusion: Enhanced performance on the MSFT, but not V ˙ O 2 peak, was associated with a favorable inflammatory profile in adolescents; whilst adiposity adversely affected plasma insulin, diastolic and mean arterial blood pressure. These findings demonstrate that enhancing performance on the MSFT and maintaining a healthy body composition are a potential therapeutic intervention for the attenuation of risk factors for cardio-metabolic diseases in adolescents.

Aims: Duration of endogenous estrogen exposure is apparently associated with risk of cardiovascular disease, the longer durations being more cardiovascular disease protective in women. We aimed to investigate the association of cumulative duration of endogenous estrogen exposure over women's reproductive lifespans with cardiovascular disease outcomes., Main Methods: For the purpose of the present study, of 10,192 female participants, after excluding those using HRT (n = 84), 3656 women, aged ≥30 years, who met eligibility criteria were selected and divided into three groups based on tertiles (T1, T2, T3) of exposure durations to endogenous estrogen. Cox proportional hazards regression model was used to estimate associations between exposure durations and cardiovascular disease outcomes., Key Findings: Cardiovascular events occurred in 352 participants over a median follow-up of 14.2 (13.5, 14.6) years (7.7 per 1000 person years; 95% CI: 6.9-8.5). Incidence of outcome was 10.9 per 1000 person years (CI, 9.4-12.8) in T 1 , 7.2 per 1000 person years (CI, 6.0-8.7) in T 2 , and 5.1 per 1000 person years (CI, 4.1-6.4) in T 3 . The hazard ratio of cardiovascular events in T 1 was significantly higher than that inT 3 , before and after adjustment for confounding variables. Before adjustment, women in T 2 had a 40% higher risk of CVD, compared to T 3 ; after adjustment however the risk was similar to that of women in T 3 ., Significance: Shorter durations of exposure to endogenous estrogen may increase the risk of cardiovascular diseases among these women later in life. Future studies should target women with short duration of exposure for timely screening and implementation of preventative interventions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose of Review: This review summarizes our current understanding of factors associated with childhood obesity, including latest prevalence rates, effectiveness of intervention strategies, and risk for concomitant disease later in life., Recent Findings: Obesity has reached global dimensions, and prevalence of childhood obesity has increased eightfold since 1975. Interventions for obesity prevention have mainly focused on behavioral settings to date, i.e., interventions that have focused on behavioral changes of the individuum such as increasing daily physical exercise or optimizing diet. However, effects have been very limited worldwide and could not stop the increase of obesity prevalence so fare. Thus, community-based/environment-oriented measures are urgently needed, such as promotion of healthy food choices by taxing unhealthy foods, mandatory standards for meals in kindergarten and schools, increase of daily physical activity at kindergartens, and schools as well as ban on unhealthy food advertisement for children. Restructuring obesity interventions towards community-based/environment-oriented measures to counteract an obesogenic environment is mandatory for sustainable success and to stop the obesity epidemy. There is need to move fast, as already moderate overweight before the start of puberty is associated with significantly increased risk for type 2 diabetes and cardiovascular disease in midlife.

Marine omega-3 polyunsaturated fatty acids (n-3 PUFA) are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and randomized trials have suggested a potential association of maternal intake of marine n-3 PUFAs during pregnancy with pregnancy and birth outcomes. However, there is inconsistency in the literature on whether marine n-3 PUFA supplementation during pregnancy can prevent maternal complications of pregnancy. This narrative literature review summarizes recent evidence on observational and clinical trials of marine n-3 PUFA intake on maternal risk factors and effects on offspring cardio-metabolic health. The current evidence generally does not support a role of maternal n-3 PUFA supplementation in altering the incidence of gestational diabetes, pregnancy-induced hypertension, or pre-eclampsia. It may be that benefits from marine n-3 PUFA supplementation are more pronounced in high-risk populations, such as women with a history of complications of pregnancy, or women with low marine n-3 PUFA intake. Discrepancies between studies may be related to differences in study design, dosage, fatty acid interplay, and length of treatment. Further prospective double-blind studies are needed to clarify the impact of long-chain marine n-3 PUFAs on risk factors for cardio-metabolic disease in the offspring.

Aims: The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP's individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN))., Methods: Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study. During this visit, we collected mothers' history of GDM and HDP in all live births in a chronicle sequence and assessed the cardio-metabolic risks based on blood pressure, anthropometry and a panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN according to Adult Treatment Panel III 2000 and World Health Organization guidelines., Results: Of 276 mothers, 157 (56.9%) had histories of GDM while 23 (8.3%) had histories of HDP. After full adjustment, we found associations of GDM episodes with postpartum abnormal glucose metabolism (single episode: relative risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (≥2): RR = 3.8 (2.1-6.8)). Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5, 8.6)). Having either (RR 2.6 (1.7-3.9)) or both gestational complications (RR 2.7 (1.6-4.9)) was associated with similar risk of postpartum cardio-metabolic disease., Conclusions: Mothers with GDM or HDP had a threefold increased risk of postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and HDP during past pregnancies was not associated with additional risk of postpartum cardio-metabolic diseases beyond that associated with either complication alone., (© 2018 The authors.)

Background: There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new onset T2DM, hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and markers of cardio-renal disease) in participants aged 5-40 years with risk factors for T2DM., Methods: This was a randomised controlled trial performed at the National Diabetes Centre, Sri-Lanka. We individually randomised 4672 participants at risk of T2DM, of whom 3539 (mean age 22.5 (range 6-40 years, 48% males) received either trimonthly (P-LSM n = 1726) or 12-monthly (C-LSM n = 1813) peer educator advice aimed at reducing weight, improving diet, reducing psychological stress and increasing physical activity., Results: During a median follow-up of 3 years, the cumulative incidence of the primary endpoint was n = 479 in P-LSM (74 per 1000 person years) vs. 561 in C-LSM (96 per 1000 person years), with an incident rate ratio (IRR) of 0.89 (95% CI 0.83-0.96, P = 0.02). In post hoc analyses, new onset dysglycaemia (T2DM, IFG and IGT), was the major contributor to the composite and was significantly reduced by P-LSM (IRR 0.9, 95% CI 0.83-0.97, P = 0.01). A significant impact of P-LSM on the incidence of the composite endpoint was noted in 1725 participants (P-LSM n = 850, C-LSM n = 875) aged below 18; P-LSM n = 140 (48 per 1000 person years) versus C-LSM n = 174 (55.4 per 1000 person years), with an IRR of 0.83 (95% CI 0.73-0.94, P = 0.004)., Conclusions: In a young at-risk South-Asian population, a pragmatic LSM programme significantly reduces the incidence of predictors of cardio-metabolic disease. Our results highlight the importance of early intervention in young at-risk subjects., Trial Registration: World Health Organization international clinical trial registry platform ( SLCTR/2008/003 ). Registration Date: March 28, 2008. Retrospectively registered.

Background: Latin America is facing an increasing burden of nutrition-related non-communicable disease. Little is known about dietary patterns in Guatemalan adults and how dietary patterns are associated with cardio-metabolic disease (CMD) risk., Methods: This analysis is based on data from a 2002-04 follow-up study of the INCAP Nutrition Supplementation Trial Longitudinal Cohort. Diet data were collected using a validated, semi-quantitative food frequency questionnaire. We derived dietary patterns using principal components analysis. CMD risk was assessed by anthropometry (body mass index, waist circumference), biochemistry (fasting blood glucose and lipids), and clinical (blood pressure) measures. We used sex-stratified multivariable log binomial models to test associations between dietary pattern tertile and CMD risk factors. The sample included 1,428 participants (681 men and 747 women) ages 25-43 years., Results: We derived 3 dietary patterns (traditional, meat-based modern, and starch-based modern), collectively explaining 24.2% of variance in the diet. Dietary patterns were not associated with most CMD risk factors; however, higher starch-based modern tertiles were associated with increased prevalence of low high density lipoprotein cholesterol (HDL-c) in men (Prevalence Ratio (PR) 1.17, 95% Confidence Interval (CI) 1.01, 1.20 for tertile 2; PR 1.20, 95% CI 1.00, 1.44 for tertile 3; p trend 0.04). Higher traditional tertile was associated with increased prevalence of abdominal obesity in women (PR 1.24, 95% CI 1.07, 1.43 for tertile 2; PR 1.19, 95% CI 1.02, 1.39 for tertile 3; p trend 0.02) but marginally significant reduced prevalence of low HDL-c in men (PR 0.88, 95% CI 0.76, 1.00 for tertile 2; PR 0.85, 95% CI 0.72, 1.00 for tertile 3; p trend 0.05)., Conclusion: Our findings suggest the presence of two 'modern diet' patterns in Guatemala - one of which was associated with increased prevalence of low HDL-c in men. The association between the traditional dietary pattern and some CMD risk factors may vary by sex., Competing Interests: Competing interests: None of the authors have any competing interests to disclose.

Obesity causes insulin resistance via a chronic low-grade inflammation. This inflammation is characterized by elevated pro-inflammatory markers and macrophage accumulation in the adipose tissue (AT). AT inflammation is a key factor causing insulin resistance and thus type 2 diabetes, both linked to atherosclerotic cardiovascular disease. Osteopontin (OPN), a well-known inflammatory cytokine, is involved in obesity-linked complications including AT inflammation, insulin resistance, atherosclerosis and CVD. During inflammation, OPN is proteolytically cleaved by matrix metalloproteinases or thrombin leading to increased OPN activity. Therefore, OPN provides a new interesting target for immunological prevention and treatment of obesity-associated diseases. The aim of our study was to evaluate peptide-based vaccines against integrin binding sites of OPN and to examine whether these active immunotherapies are functional in reducing metabolic tissue inflammation, insulin resistance, and atherosclerosis in a cardio-metabolic (Ldlr -/- mice) and a diet-induced obesity model (WT mice). However, atherosclerosis, insulin resistance and AT inflammation were not diminished after treatment with OPN-derived peptides in murine models. Lack of efficacy was based on a failure to induce antibodies capable to bind epitopes in the context of functional OPN protein. In conclusion, our data point to unexpected challenges in the immunotherapeutic targeting of adhesive motives, such as RGD containing sequences, on endogenous proteins., (Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Aim: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) has identified increased cardio-metabolic risk and outcome in European populations. The goal of this study was to see if this ratio would also have clinical utility in identifying cardio-metabolic risk in an East Asian population., Methods: Measurements of various cardio-metabolic risk factors, including coronary calcium scores, were available on 12,166 apparently healthy Korean adults. Approximately 25% of men and women with the highest TG/HDL-C ratios were classified as being at high cardio-metabolic risk, and their risk factor profiles compared to the remainder of the population, as well as to individuals with the metabolic syndrome (MetS)., Results: High cardio-metabolic risk (upper 25%) was defined as a TG/HDL-C ratio ≥3.5 (men) or ≥2.0 (women), and all cardio-metabolic risk factors measured, including coronary calcium scores, were significantly more adverse when compared to individuals beneath these cut-points. Although cardio-metabolic risk profiles appeared reasonably comparable in subjects identified by either a high TG/HDL-C or a diagnosis of MetS, use of the TG/HDL-C increased the numbers at high risk., Conclusion: Evidence that determination of the plasma TG/HDL-C concentration ratio provides a simple way to identify individual at increased cardio-metabolic risk has been extended to an East Asian population. The ability of an elevated TG/HDL-C ratio to accomplish this goal is comparable to that achieved using the more complicated MetS criteria., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)