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The metabolic syndrome (MetS) is a multiplex modifiable risk factor for cardiovascular disease, type 2 diabetes mellitus and other health outcomes, and is a major challenge to clinical practice and public health. The rising global prevalence of MetS, driven by urbanization, sedentary lifestyles and dietary changes, underlines the urgency of addressing this syndrome. We explore the complex underlying mechanisms, including genetic predisposition, insulin resistance, accumulation of dysfunctional adipose tissue and ectopic lipids in abdominal obesity, systemic inflammation and dyslipidaemia, and how they contribute to the clinical manifestations of MetS. Diagnostic approaches vary but commonly focus on abdominal obesity (assessed using waist circumference), hyperglycaemia, dyslipidaemia and hypertension, highlighting the need for population-specific and phenotype-specific diagnostic strategies. Management of MetS prioritizes lifestyle modifications, such as healthy dietary patterns, physical activity and management of excess visceral and ectopic adiposity, as foundational interventions. We also discuss emerging therapies, including new pharmacological treatments and surgical options, providing a forward-looking perspective on MetS research and care. This Primer aims to inform clinicians, researchers and policymakers about MetS complexities, advocating for a cohesive, patient-centred management and prevention strategy. Emphasizing the multifactorial nature of MetS, this Primer calls for integrated public health efforts, personalized care and innovative research to address this escalating health issue., (© 2024. Springer Nature Limited.)

Background: Maple syrup, a minimally transformed sweetener rich in polyphenols, can exert a action and improve metabolic parameters in animal models. However, no randomized clinical trial has investigated this., Objectives: This study aims to determine whether replacing refined sugars with an equivalent quantity of maple syrup could decrease key cardiometabolic risk factors in individuals with mild metabolic alterations., Methods: In a randomized, double-blind, controlled crossover trial with 42 overweight adults with mild cardiometabolic alterations, participants were instructed to substitute 5% of their total caloric intake from added sugars with either maple syrup or an artificially flavored sucrose syrup for 8 wk. The primary outcome included changes in glucose homeostasis, whereas secondary outcomes were changes in other cardiometabolic risk factors such as blood pressure, anthropometric indices, and blood lipid profiles. Exploratory outcomes involved analyzing changes in gut microbiota composition., Results: Replacing refined sugars with maple syrup over 8 wk decreased the glucose area under the curve when compared with substituting refined sugars with sucrose syrup, as determined during the oral glucose tolerance test, leading to a significant difference between the intervention arms (-50.59 ± 201.92 compared with 29.93 ± 154.90; P < 0.047). Substituting refined sugar with maple syrup also significantly decreased android fat mass (-7.83 ± 175.05 g compared with 67.61 ± 206.71 g; P = 0.02) and systolic blood pressure (-2.72 ± 8.73 mm Hg compared with 0.87 ± 8.99 mm Hg; P = 0.03). No changes in the blood lipid profile were observed. As an exploratory outcome, we further observed that substituting refined sugars with maple syrup promoted selective taxonomic changes in the gut microbiota such as a significant reduction in the abundance of Klebsiella species and decreased microbial functions associated with bacterial-induced cytokine response, when compared with substitution with sucrose syrup., Conclusions: Substituting refined sugars with maple syrup in individuals with mild metabolic alterations result in a significantly greater reduction of key cardiometabolic risk factors compared with substitution with sucrose syrup, in association with specific changes in gut microbiota. The role of the gut microbiota in these effects remains to be further explored. This trial was registered at clinicaltrials.gov as NCT04117802., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men., Methods and Results: We examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes., Conclusion: In women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT., Competing Interests: Declaration of competing interest Philippe Pibarot has received institutional funding from Edwards Lifesciences, Novartis, Medtronic and Pi-Cardia outside the submitted work and for which he has received no personal compensation. The other authors declared no conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat >5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations ( p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD., Competing Interests: Dr Philippe Pibarot reports grants from Novartis, during the conduct of the study. Dr Jean-Pierre Després reports personal fees from Inversago, outside the submitted work. Dr Frédéric Picard reports grants from the Canadian Institutes for Health Research and the IUCPQ Foundation, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2024 Rauzier et al.)

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, P < 0.0001) and lower subcutaneous (-56.2 mL, P < 0.05) and liver (-3.3%, P < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8 ± 0.9 kg, P < 0.05) and body mass index (-0.3 ± 0.3 kg/m 2 , P < 0.05). Loss of fat mass (-1.5 ± 1.0 kg, P < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, P < 0.07) were observed. Visceral adiposity (-14.1 ± 14.2 mL, P < 0.01) and waist circumference (-3.2 ± 1.7 cm, P < 0.0001) decreased, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss. NEW & NOTEWORTHY Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.

The worldwide prevalence of individuals with an elevated body weight has increased steadily over the past five decades. Billions of research dollars have been invested to improve our understanding of the causes and consequences of having an elevated body weight. All this knowledge has, however, failed to influence populational body weight trajectories of most countries around the world. Research on the definition of "obesity" has also evolved. Body mass index (BMI), the most commonly used tool to make its diagnosis, has major limitations. In this review article, we will highlight evidence from observational studies, genetic association studies and randomized clinical trials that have shown the remarkable inter-individual differences in the way humans store energy as body fat. Increasing evidence also suggests that, as opposed to weight inclusive, lifestyle-based approaches, weight-centric approaches advising people to simply eat less and move more are not sustainable for most people for long-term weight loss and maintenance. It is time to recognize that this outdated approach may have produced more harm than good. On the basis of pathophysiological, genetic and clinical evidence presented in this review, we propose that it may be time to shift away from the traditional clinical approach, which is BMI-centric. Rather, emphasis should be placed on actionable lifestyle-related risk factors aiming at improving overall diet quality and increasing physical activity level in the general population., Competing Interests: Declaration of competing interests BJA is a consultant for Novartis, Eli Lilly, Editas Medicine and Silence Therapeutics and has received research contracts from Pfizer, Eli Lilly, Ionis Pharmaceuticals and Silence Therapeutics. ACC received research funding by Eli Lilly (2019 - ongoing) and NovoNordisk (2021 - ongoing) and consultation fees by Eli Lilly, HLS Therapeutics, Janssen Inc., Novartis Pharmaceuticals Canada Inc., and Novo Nordisk Canada Inc. PP received continuous medical education/consultation fees from Abbott, Amgen, Astrazeneca, Bayer, Bausch Health, Boehringer Ingelheim, Eli Lilly, GSK, HLS Therapeutics Inc, Janssen Inc, Novartis Pharmaceuticals Canada Inc, Mantra Pharma, Novo Nordisk Canada Inc, Sanofi, Servier. JPD discloses having received consulting fees from Inversago., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health ( n = 88; mean age 49.0 ± 8.2 years) and fitness ( n = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF- vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR ( r = 0.27; p < 0.05 and r = 0.34; p < 0.005) and changes in CRF ( r = -0.31; p < 0.01 and r = -0.30; p < 0.05). IR improved in the CRF+ group ( p < 0.05) but remained stable in the CRF- group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF- group ( p < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.

Aims: To evaluate the clinical safety, tolerability, and pharmacokinetic and pharmacodynamic profile of the novel cannabinoid receptor-1 (CB1R) inverse agonist, INV-202, in adults with features of metabolic syndrome., Materials and Methods: This was a multicentre, randomized, double-blind, placebo-controlled, 28-day repeat-dose (INV-202 [25 mg] or placebo, once-daily oral tablet), parallel-group study in 37 participants aged 18 to 65 years (46% female, mean age 55 years, glycated haemoglobin 5.7% [39 mmol/mol], body mass index [BMI] 38.1 kg/m 2 ) with features of metabolic syndrome and glucose intolerance. An oral glucose tolerance test (OGTT) was performed at baseline and at the end of the study. Lipid profiles, weight, waist circumference and biomarkers were assessed weekly. Statistical comparisons were performed post hoc., Results: INV-202 was well tolerated with no serious or severe treatment-emergent adverse events; the most common events related to known effects of CB1R blockade in the gastrointestinal tract. INV-202 produced a significant mean weight loss of 3.5 kg (3.3% compared with placebo participants who gained a mean 0.6 kg [0.5%]). INV-202 also exhibited significant reductions in waist circumference and BMI (P ≤ 0.03). There was no significant difference in OGTT 0- to 3-hour area under the curve for INV-202 versus placebo: least squares mean 29.38 versus 30.25 h*mmol/L, with an INV-202: placebo ratio of 97.1% (95% confidence interval 90.2, 105.6; P = 0.43)., Conclusions: INV-202 was well tolerated, producing a signal for rapid weight loss with improvements in other metabolic syndrome markers in this population. These findings support further exploration and long-term assessment of cardiometabolic effects., (© 2023 Inversago Pharma. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Lay Summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms., Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes., Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL)., Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001)., Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity., 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 © 2023 Rauzier, Chartrand, Alméras, Lemieux, Larose, Mathieu, Pibarot, Lamarche, Rhéaume, Poirier, Després and Picard.)

Background The impact of an elevated body mass index (BMI) on atherosclerotic cardiovascular disease (ASCVD) risk in individuals who are metabolically healthy is debated. We investigated the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319 866 UK Biobank participants. Methods and Results We developed a cardiovascular health score (CVHS) based on 4 lifestyle and 6 cardiometabolic parameters. The impact of the CVHS on incident ASCVD (15 699 events) alone and in BMI and waist-to-hip ratio categories was assessed using Cox proportional hazards in women and men separately. In participants with a high CVHS (8-10), those with a BMI ≥35.0 kg/m 2 had a nonsignificantly higher ASCVD risk (hazard ratio [HR],  1.20 [95% CI, 0.84-1.70]; P =0.32) compared with those with a BMI of 18.5 to 24.9 kg/m 2 . In participants with a BMI of 18.5 to 24.9 kg/m 2 , those with a lower CVHS (0-2) had a higher ASCVD risk (HR, 4.06 [95% CI, 3.23-5.10]; P <0.001) compared with those with a higher CVHS (8-10). When we used the waist-to-hip ratio instead of the BMI, a dose-response relationship between the waist-to-hip ratio and ASCVD risk was obtained in healthier participants. Results were similar in women compared with men. Conclusions In women and men in the UK Biobank, the relationship between the BMI and ASCVD incidence in healthy individuals was inconsistent, whereas cardiovascular risk factors strongly predicted ASCVD incidence in all BMI categories. Assessing lifestyle and cardiometabolic risk factors as well as body fat distribution indices may help identify individuals at high ASCVD risk, regardless of body weight.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m 2 , cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass ( P < 0.0001), insulin resistance ( P < 0.0001), higher plasma triglyceride (TG) ( P < 0.0001), and lower HDL-cholesterol levels ( P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men ( r = -0.36, P < 0.0001) and women ( r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men ( R 2  = 0.23, P = 0.012) and women ( R 2  = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content. NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

Background: The number of people with metabolic syndrome (MetS) is increasing worldwide, and many socioeconomic and environmental factors contribute to this., Objectives: The authors investigated tangible trends in the prevalence of MetS using the 2001 to 2020 versions of the Korea National Health and Nutrition Examination Survey (KNHANES)., Methods: In these surveys, stratified multistage sampling designs were used to approximate the entire population. Blood pressure, waist circumference, and lifestyle variables were examined in a standardized fashion. Metabolic biomarkers were measured in a central laboratory operated by the Korean government., Results: The age-adjusted prevalence of MetS increased significantly from 27.1% in 2001 to 33.2% in 2020. It was more prevalent in men (25.8%→40.0%) but did not change in women (28.2%→26.2%). Among the 5 MetS components, the proportions of high glucose level and large waist circumference increased substantially by 17.9% and 12.2% over 20 years, while high-density lipoprotein cholesterol levels increased significantly, resulting in a decrease in low high-density lipoprotein cholesterol by 20.4%. Caloric intake derived from carbohydrates decreased from 68.1% to 61.3%, while fat consumption increased from 16.7% to 23.0%. Notably, sugar-sweetened beverage consumption showed an almost 4-fold increase from 2007 to 2020, while physical activity levels decreased by 12.2% from 2014 to 2020., Conclusions: Glycemic dysregulation and abdominal obesity were key features contributing to the increased prevalence of MetS observed in Korean men during the past 20 years. Rapid economic and socioenvironmental changes in this period may be involved in this phenomenon. Understanding these changes in MetS could be valuable for other countries undergoing such socioeconomic transformation., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Competing Interests: J-PD is the Scientific Director of the International Chair on Cardiometabolic Risk supported by the Fondation de l'Université Laval and is the co-chair holder of the Chaire de recherche en santé durable funded by Fonds de recherche du Québec—Santé. Research from J-PD is currently supported by the Canadian Institutes of Health Research (foundation grant FDN-167278). J-PD reports receiving consulting fees from Inversago and honoraria from Rockpointe for participation as a speaker at a Novo Nordisk sponsored symposium held at American Heart Association's annual meeting 2022.

Background: Regular physical activity (PA) plays a key role in the management and prevention of numerous chronic diseases. However, recent studies have suggested that occupational physical activity (OPA) may not always have health benefits. The aim of the present study was to examine the respective contributions of OPA vs. leisure-time physical activity (LTPA) to the variation in the cardiometabolic profile, including cardiorespiratory fitness (CRF), of employees involved in a workplace lifestyle modification program. Our study hypothesis was that LTPA would show a stronger association with indices of cardiometabolic health than OPA., Methods: A mobile health assessment unit was used to assess 5145 workers (3397 men and 1748 women) on site at their workplace. Assessments included lifestyle questionnaires (overall diet quality, type of OPA and level of LTPA), blood pressure measurements, blood tests, anthropometric measurements, and a submaximal treadmill exercise test to assess CRF. Results were adjusted for education, household income and age., Results: When workers were classified on the basis of their OPA (sedentary work, standing work, physical work, and heavy manual work), only a few significant differences in the cardiometabolic profile were observed in men, with those in the physical work category having more favorable values than sedentary workers. However, substantial and significant differences were observed among employees classified on the basis of their LTPA, these differences being observed in both men and women. For instance, waist circumference, the cholesterol/HDL cholesterol ratio, triglyceride concentrations and resting heart rate were lower in active individuals compared to inactive and moderately inactive individuals (p < 0.01). Furthermore, irrespective of whether or not employees were sedentary at work, a high level of LTPA was associated with a greater CRF (p < 0.001). Finally, we found that the lowest prevalence of hypertriglyceridemic waist (p < 0.01) and the highest score of overall diet quality (p < 0.001) were observed in active individuals, irrespective of their OPA category., Conclusion: Levels of LTPA were more strongly associated with cardiometabolic health than OPA in a cohort of blue- and white-collar employees. Furthermore, high levels of LTPA were found to counteract the potentially deleterious effects of a sedentary work on cardiometabolic health., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Observational studies have linked adiposity and especially abdominal adiposity to liver fat accumulation and non-alcoholic fatty liver disease. These traits are also associated with type 2 diabetes and coronary artery disease but the causal factor(s) underlying these associations remain unexplored., Methods: We used a multivariable Mendelian randomization study design to determine whether body mass index and waist circumference were causally associated with non-alcoholic fatty liver disease using publicly available genome-wide association study summary statistics of the UK Biobank ( n  = 461,460) and of non-alcoholic fatty liver disease (8434 cases and 770,180 control). A multivariable Mendelian randomization study design was also used to determine the respective causal contributions of waist circumference and liver fat ( n  = 32,858) to type 2 diabetes and coronary artery disease., Results: Using multivariable Mendelian randomization we show that waist circumference increase non-alcoholic fatty liver disease risk even when accounting for body mass index (odd ratio per 1-standard deviation increase = 2.35 95% CI = 1.31-4.22, p  = 4.2e-03), but body mass index does not increase non-alcoholic fatty liver disease risk when accounting for waist circumference (0.86 95% CI = 0.54-1.38, p  = 5.4e-01). In multivariable Mendelian randomization analyses accounting for liver fat, waist circumference remains strongly associated with both type 2 diabetes (3.27 95% CI = 2.89-3.69, p  = 3.8e-80) and coronary artery disease (1.66 95% CI = 1.54-1.8, p  = 3.4e-37)., Conclusions: These results identify waist circumference as a strong, independent, and causal contributor to non-alcoholic fatty liver disease, type 2 diabetes and coronary artery disease, thereby highlighting the importance of assessing body fat distribution for the prediction and prevention of cardiometabolic diseases., Competing Interests: Competing interestsThe authors declare the following competing interests: B.J.A. is a consultant for Novartis and Silence Therapeutics and has received research contracts from Pfizer, Ionis Pharmaceuticals and Silence Therapeutics. A.T. receives research funding from Johnson & Johnson Medical Companies, Medtronic, Bodynov, and GI Windows for studies on bariatric surgery and received consulting fees from Novo Nordisk and Bausch Health. All other authors declare no competing interests., (© The Author(s) 2022.)

Objective: Type 2 diabetes (T2D) is associated with significant end-organ damage and ectopic fat accumulation. Multiparametric magnetic resonance imaging (MRI) can provide a rapid, noninvasive assessment of multiorgan and body composition. The primary objective of this study was to investigate differences in visceral adiposity, ectopic fat accumulation, body composition, and relevant biomarkers between people with and without T2D., Methods: Participant demographics, routine biochemistry, and multiparametric MRI scans of the liver, pancreas, visceral and subcutaneous adipose tissue, and skeletal muscle were analyzed from 266 participants (131 with T2D and 135 without T2D) who were matched for age, gender, and BMI. Wilcoxon and χ 2 tests were performed to calculate differences between groups., Results: Participants with T2D had significantly elevated liver fat (7.4% vs. 5.3%, p = 0.011) and fibroinflammation (as assessed by corrected T1 [cT1]; 730 milliseconds vs. 709 milliseconds, p = 0.019), despite there being no differences in liver biochemistry, serum aspartate aminotransferase (p = 0.35), or alanine transaminase concentration (p = 0.11). Significantly lower measures of skeletal muscle index (45.2 cm 2 /m 2 vs. 50.6 cm 2 /m 2 , p = 0.003) and high-density lipoprotein cholesterol (1.1 mmol/L vs. 1.3 mmol/L, p < 0.0001) were observed in participants with T2D., Conclusions: Multiparametric MRI revealed significantly elevated liver fat and fibroinflammation in participants with T2D, despite normal liver biochemistry. This study corroborates findings of significantly lower measures of skeletal muscle and high-density lipoprotein cholesterol in participants with T2D versus those without T2D., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Purpose of Review: Despite its prevalence and well-documented impact on population health, obesity has not emerged as a strong independent risk factor for cardiovascular disease after control for intermediate risk factors. The purpose of this brief narrative review is to highlight results from imaging studies that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes., Recent Findings: Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity: waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts., Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable-adjusted regression and were replicated in the independent UK Biobank., Results: The Dallas Heart Study included 2064 participants (mean ± SD age, 44±9 years; 54% female; 47% black). High VAT-high LF and high VAT-low LF were associated with prevalent atherosclerosis, whereas low VAT-high LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VAT-high LF and high VAT-low LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VAT-high LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N=22,354; April 2014-May 2020), only high VAT-low LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9])., Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

At a population level, engagement in healthy lifestyle behaviors is suboptimal in the United States. Moreover, marked disparities exist in healthy lifestyle behaviors and cardiovascular risk factors as a result of social determinants of health. In addition, there are specific challenges to engaging in healthy lifestyle behaviors related to age, developmental stage, or major life circumstances. Key components of a healthy lifestyle are consuming a healthy dietary pattern, engaging in regular physical activity, avoiding use of tobacco products, habitually attaining adequate sleep, and managing stress. For these health behaviors, there are guidelines and recommendations; however, promotion in clinical settings can be challenging, particularly in certain population groups. These challenges must be overcome to facilitate greater promotion of healthy lifestyle practices in clinical settings. The 5A Model (assess, advise, agree, assist, and arrange) was developed to provide a framework for clinical counseling with consideration for the demands of clinical settings. In this science advisory, we summarize specific considerations for lifestyle-related behavior change counseling using the 5A Model for patients across the life span. In all life stages, social determinants of health and unmet social-related health needs, as well as overweight and obesity, are associated with increased risk of cardiovascular disease, and there is the potential to modify this risk with lifestyle-related behavior changes. In addition, specific considerations for lifestyle-related behavior change counseling in life stages in which lifestyle behaviors significantly affect cardiovascular disease risk are outlined. Greater attention to healthy lifestyle behaviors during every clinician visit will contribute to improved cardiovascular health.

Engagement in healthy lifestyle behaviors is suboptimal. The vast majority of the US population does not meet current recommendations. A healthy lifestyle is defined by consuming a healthy dietary pattern, engaging in regular physical activity, avoiding exposure to tobacco products, habitually attaining adequate amounts of sleep, and managing stress levels. For all these health behaviors there are well-established guidelines; however, promotion in clinical settings can be challenging. It is critical to overcome these challenges because greater promotion of heathy lifestyle practices in clinical settings effectively motivates and initiates patient behavior change. The 5A Model (assess, advise, agree, assist, and arrange) was developed to provide a framework for clinical counseling with requisite attention to the demands of clinical settings. In this science advisory, we present strategies, based on the 5A Model, that clinicians and other health care professionals can use for efficient lifestyle-related behavior change counseling in patients at all levels of cardiovascular disease risk at every visit. In addition, we discuss the underlying role of psychological health and well-being in lifestyle-related behavior change counseling, and how clinicians can leverage health technologies when providing brief patient-centered counseling. Greater attention to healthy lifestyle behaviors during routine clinician visits will contribute to promoting cardiovascular health.

Background: Adopting healthy lifestyle habits reduces the risk of type 2 diabetes (T2D) and its complications. The use of an activity tracker to monitor physical activity (PA) could favor behavior changes in patients with chronic diseases such as diabetes. The aims of this study were: (I) to evaluate the impact of an activity tracker on PA and cardiometabolic risk variables in patients with T2D; (II) to assess the feasibility of its implantation in a primary care setting., Methods: This 3-month study was a pilot randomized controlled trial of 30 patients with T2D followed at a university-affiliated Family Medicine Group. Patients were randomly assigned to either: (I) control group, including a PA promotion intervention supported by a kinesiologist or (II) intervention group, including a PA promotion intervention supported by a kinesiologist with the addition of an activity tracker (Fitbit). Cardiometabolic risk variables, PA and motivation were assessed at baseline and after three months. Satisfaction and acceptability of wearing the activity tracker were measured in the intervention group., Results: PA assessed by questionnaires increased in both groups, change being greater in the intervention group (P<0.05). Autonomous motivation in both groups was higher than controlled motivation (P<0.001). Eighty-six percent of the participants in the intervention group were satisfied with their activity tracker use and the compliance remained high. High-density lipoprotein cholesterol increased in the intervention group and decreased in the control group (P=0.014). Resting systolic and diastolic blood pressure decreased over time in both groups (P<0.05) whereas glycated hemoglobin tended to decrease in both groups (P=0.080). Significant correlations were observed between average steps per day and changes in waist circumference (pre: -0.721, P=0.044; post: -0.736, P=0.038), body mass index (pre: -0.764, P=0.010; post: -0.771, P=0.009) and fat percentage (pre: -0.654, P=0.040; post: -0.686, P=0.028) in the intervention group., Conclusions: Our pilot study shows that the use of an activity tracker improves cardiometabolic risk variables in patients with T2D and could potentially be a motivation tool to increase PA in primary care setting., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/mhealth-20-154). Dr. JPD reports grants from Canadian Institutes of Health Research, outside the submitted work. The other authors have no conflicts of interest to declare., (2021 mHealth. All rights reserved.)

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases., Competing Interests: Declaration of interests KK reports personal fees from Amgen, AstraZeneca, Bayer, NAPP, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Roche, Berlin-Chemie Menarini, Boehringer Ingelheim, Sanofi-Aventis, and Servier; other from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi-Aventis; and grants from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Servier, Pfizer, Boehringer Ingelheim, and Merck Sharp & Dohme, outside the submitted work. VJ reports grants and personal fees from Baxter Healthcare, grants from NephroPlus, and personal fees from AstraZeneca, outside the submitted work. RGG reports grants or research support in the past 2 years from Gilead Sciences; consultancy or adviser roles in the past 2 years for Abbott, AbbVie, Access Biologicals, Antios, Arrowhead, Bayer, Bristol Myers Squibb, Dova, Dynavax, Eiger, Eisai, Enyo, eStudySite, Forty-Seven, Genentech, Genlantis, Gerson Lehrman, Gilead Sciences, HepaTX, HepQuant, Intercept, Janssen, Helios, Eli Lilly, Merck Sharp & Dohme, Salix, Shionogi, and Viking Therapeutics; current activity with scientific or clinical advisory boards for Abbott, AbbVie, Merck Sharp & Dohme, Arrowhead, Bayer, Dova Pharmaceuticals, Eiger, Enyo, Gilead Sciences, HepQuant, Intercept, Janssen, and Prodigy, outside the submitted work. RGG is a member of Topography Health clinical trials alliance; chair of the Prodigy Clinical Advisory Board; an advisory consultant for Biocollections, Fibronostics, Fujifilm/Wako, and Quest; and member of the data safety monitoring board for ArrowHead and CymaBay Therapeutics. RGG currently has consulting confidentiality agreements with AbbVie, Abbott, Access Biologicals, ADMA Biologics, AEC Partners, Aligos Therapeutics, Arena Pharmaceuticals, ArrowHead, Arterys, Alexion, Altimmune, Antios Therapeutics, AprosTx, Bayer, Cirina, Consumer Health Products Association, CymaBay Therapeutics, DiaSorin, Dova Pharmaceuticals, DRG Abacus, DURECT, Dynavax, Echosens, Eiger, Enyp, Exelixis, Fibronostics, Forty-Seven, Fujifilm Wako Diagnostics, Gilead Sciences, HepQuant, HepaTx, IDLogiq, Intellia, Intercept, Inotek, Iqvia, Janssen/J&J, KannaLife, Laboratory for Advanced Medicine, Labyrinth, Life Line Screening, Eli Lilly, MedImmne, Merck Sharp & Dohme, New Enterprise Associates, Ogilvy CommonHealth, Organovo, Patient Connect, Prodigy Biotech, Prometheus Laboratories, Refuah Solutions, Regulus Therapeutics, Salix, Shionogi, Spring Bank, and Trimaran. RGG reports activities for Speakers Bureau, focusing on hepatitis B virus, hepatitis C virus, and liver cancer, specifically epidemiology, diagnosis, and treatment, and programme presentations on vaccination for hepatitis B virus and management of complications of cirrhosis. RGG has a speaker's contract to do promotional talks for AbbVie, BMS, Eisai, Gilead Sciences, and Intercept. RGG is a minor stock shareholder (only for projects in the liver space but not fatty liver disease-related) for RiboSciences and CoCrystal. RGG holds stock options in Eiger, Genlantis, HepQuant, and AngioCrine. MHN reports grants from Glycotest, Gilead Sciences, Pfizer, Enanta Pharmaceuticals, BK Kee Foundation, National Cancer Institute, and Vir Biotechnology; and personal fees from Spring Bank, Novartis, Janssen Pharmaceuticals, Eisai, Bayer, Intercept, Exact Sciences, Laboratory of Advanced Medicine, Helios, and Eli Lilly, outside the submitted work. J-PD reports grants from Canadian Institutes of Health Research, outside the submitted work. JCGH reports personal fees from Novo Nordisk, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Obesity contributes to reduced life expectancy because of its link with type 2 diabetes and cardiovascular disease. Yet, targeting this poorly diagnosed, ill-defined, and underaddressed modifiable risk factor remains a challenge. In this review, we emphasize that the tendency among health care professionals to amalgam all forms of obesity altogether as a single entity may contribute to such difficulties and discrepancies. Obesity is a heterogeneous condition both in terms of causes and health consequences. Attention should be given to 2 prevalent subgroups of individuals: 1) patients who are overweight or moderately obese with excess visceral adipose tissue; and 2) patients with severe obesity, the latter group having distinct additional health issues related to their large body fat mass. The challenge of tackling high-cardiovascular-risk forms of obesity through a combination of personalized clinical approaches and population-based solutions is compounded by the current obesogenic environment and economy., Competing Interests: Funding Support and Author Disclosures Dr Després is the Scientific Director of the International Chair on Cardiometabolic Risk supported by the Fondation de l’Université Laval. Research from Dr Després discussed in this paper has been and is currently supported by the Canadian Institutes of Health Research (Foundation grant: FDN-167278) as well as by the Fondation of the Québec Heart and Lung Institute. Dr Carpentier holds the Canada Research Chair in Molecular Imaging of Diabetes; and has received funding for consulting from Eli Lilly, HLS Therapeutics, Janssen, Novartis Pharmaceuticals Canada, and Novo Nordisk Canada. Dr Tchernof has received research funding from Johnson & Johnson Medical Companies, Medtronic, and Bodynov for studies unrelated to this work; and has received consulting fees from Bausch Health and Novo Nordisk. Dr Neeland has received a grant from National Institutes of Health/NIDDK (K23 DK106520); has received speaking and consultancy fees from Boehringer Ingelheim, Merck, and AMRA Medical; and has received a grant from Novo Nordisk. Dr Poirier has received honoraria for CME/consultant/expert events from Abbott, Amgen, AstraZeneca, Bayer, Bausch Health, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, and Servier., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The American Heart Association criteria for cardiovascular health include overall diet quality (DQ). The present study evaluated the effect of a workplace health promotion program targeting DQ and physical activity on features of cardiometabolic risk (CMR). Before and after the 3-month intervention, 2260 employees (1462 men and 798 women) completed a health and fitness evaluation including assessment of DQ using a validated food-based questionnaire. After the 3-month lifestyle modification program, DQ increased significantly in both sexes ( p < 0.0001) as well as physical activity level ( p < 0.0001). A reduction in waist circumference ( p < 0.0001) and improved lipid levels were also observed. Significant associations were found between changes in DQ index and changes in CMR variables in both men (standardized regression coefficients ranged from -0.19 (95% confidence interval: -0.26 to -0.12) to -0.29 (95% confidence interval: -0.34 to -0.25)) and women (standardized regression coefficients ranged from -0.18 (95% confidence interval: -0.25 to -0.11) to -0.27 (95% confidence interval: -0.41 to -0.13)). Multiple linear regression analyses showed a significant contribution of changes in the DQ index to the variation in some CMR variables, independent from changes in physical activity level and cardiorespiratory fitness. This study provides evidence that targeting DQ at the workplace is relevant to improve cardiometabolic health., Competing Interests: The authors declare no conflict of interest. The Grand Défi Entreprise Inc. was not involved in the analysis and interpretation of the data, nor in the writing of this paper.

The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.

Objectives: Second generation antipsychotics (SGAs) induce weight gain and dyslipidemia, albeit with important intervariability. Insulin-like growth factor binding protein (IGFBP)-2 is proposed as a circulating biomarker negatively associated with waist circumference and hypertriglyceridemia. Thus, we tested whether metabolic alterations developed upon the use of SGAs are associated with plasma IGFBP-2 levels., Methods: A cross-sectional study was performed in 87 men newly diagnosed with schizophrenia and administered for approximately 20 months with olanzapine or risperidone as their first antipsychotic treatment. Plasma IGFBP-2 concentration, anthropometric data, as well as glucose and lipid profiles were determined at the end of the treatments., Results: IGFBP-2 levels were similar between patients using olanzapine or risperidone and were negatively correlated with waist circumference, insulin sensitivity, and plasma triglycerides (TG). A higher proportion of men with a hypertriglyceridemic (hyperTG) waist phenotype was found in patients with IGFBP-2 levels lower than 220 ng/mL (43% for olanzapine and 13% for risperidone) compared to those with IGFBP-2 above this threshold (10% and 0%, respectively)., Conclusions: IGFBP-2 may have a role in altering metabolic risk in schizophrenic patients using SGAs. Longitudinal studies are required to evaluate whether IGFBP-2 can predict the development of a hyperTG waist phenotype in this population.

Background: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population., Method: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained., Results: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ± 3.0 kg/m 2 , 90 ± 8 cm, 194 ± 77 cm 2 , 85 ± 41 cm 2 , and 69.5 ± 9.1%, respectively, in men and 23.3 ± 3.1 kg/m 2 , 79 ± 8 cm, 120 ± 57 cm 2 , 123 ± 53 cm 2 , and 48.9 ± 9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm 2 (95% confidence interval [CI]: 41 cm 2 , 50 cm 2 ) higher in men and 43 cm 2 (95% CI: 37 cm 2 , 49 cm 2 ) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group., Conclusion: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

We assessed the reliability and validity of a Salty Food Frequency Questionnaire for Sodium (FFQ-Na) and a Discretionary Salt Questionnaire (DSQ) developed for the French-Canadian population. The reliability was evaluated according to temporal stability over a 7-15 day interval ( n = 36). Validity was evaluated by testing the tools against a 24-h urine sodium excretion (24 h Uri-Na) and a 3-day food record, and this at individual and group levels ( n = 164). The intra-class coefficients (ICC) values for the test-retest of the DSQ, the FFQ-Na and the two questionnaires combined were 0.73, 0.97 and 0.98 respectively. Correlations of the FFQ-Na with the 24 h Uri-Na and the 3-day food record were 0.3 ( p < 0.001) and 0.35 ( p < 0.001) respectively. The DSQ showed no significant correlation with the reference measures. The correlation between the two methods combined were 0.29 ( p < 0.001) with the 24 h Uri-Na and 0.31 ( p < 0.001) with the 3-day food record. The results of Bland-Altman indicated that for the combined questionnaires, there was a bias of measurement (underestimation of intake), but it was constant for every level of intake according to the reference measures. Finally, the cross-classification indicated an acceptable proportion of agreement, but a rate between 20% and 30% of classification in the opposite quartile. In conclusion, the developed tools are reliable and showed some facets of validity.

Physical inactivity is a well-established risk factor for cardiovascular disease (CVD) incidence and mortality. In the last decade, there is also emerging evidence of the role of sedentary behaviors (sitting) as a risk factor for CVD. Therefore, there is increasing interest in understanding the independent and joint effects of physical activity and sedentary behavior on CVD risk. Higher levels of moderate-to-vigorous physical activity and less time spent in sedentary behavior are associated with a decreased risk of CVD. There is also preliminary evidence that higher levels of light-intensity physical activity are associated with lower all-cause mortality rates; however, the cardio-protective effects of light-intensity physical activity are yet to be determined. The results from several studies have demonstrated that the effects of sedentary behavior on CVD risk is more pronounced among individuals who are physically inactive, compared to those who are more active. Further, high levels (60-75 min per day) of moderate-to-vigorous physical activity appear to eliminate the increased risk of CVD associated with excessive sedentary behavior. Replacing sedentary behavior with any intensity of physical activity will produce health benefits; however, the greatest benefits occur when replacing sedentary behavior with moderate-to-vigorous intensity physical activity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cardiorespiratory fitness (CRF) is positively associated with insulin sensitivity, whereas excessive levels of visceral adipose tissue (AT) and liver fat (LF) are both associated with insulin resistance and impaired plasma glucose-insulin homeostasis. To what extent levels of visceral AT and LF content contribute to the relationship between CRF and indices of plasma glucose-insulin homeostasis is uncertain. Our objective was to explore the interactions among CRF, visceral AT, and LF with glucose tolerance/insulin levels in asymptomatic and apparently healthy individuals. CRF was measured in 135 women and 177 men with a maximal treadmill graded exercise test. Indices of plasma glucose-insulin homeostasis were derived from a 3-h oral glucose tolerance test (OGTT) performed in the morning after a 12-h fast. Visceral AT levels and LF content were measured using magnetic resonance imaging and spectroscopy. For any given CRF level, women presented significantly lower visceral AT and LF than men as well as lower homeostasis model assessment of insulin resistance (HOMA-IR) and plasma glucose-insulin levels during the OGTT compared with men. In both sexes, there were significant negative correlations between CRF and HOMA-IR as well as glucose and insulin levels measured during the OGTT. Both glucose and insulin levels during the OGTT correlated positively with visceral AT and LF. In women and men, being in the top CRF tertile was associated with low levels of visceral AT and LF. Multivariable linear regression analyses suggested that visceral AT and LF were plausible mediators of the association between CRF and indices of plasma glucose-insulin homeostasis.

Aims: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI)., Methods and Results: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P < 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI., Conclusion: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m 2 ) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.

Objective: This study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS)., Methods: Immunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1-4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild-moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (V peak ), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a)., Results: Immunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised V peak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised V peak (p<0.001) and risk of AVR/cardiac death (p=0.03). Similar results were noted with OxPL-apoB and OxPL-apo(a). There was no association between autotaxin (ATX) on ApoB and ATX on Lp(a) with faster progression of AS. Proteomic analysis of purified Lp(a) showed that apoC-III was prominently present on Lp(a)., Conclusion: ApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death., Trial Registration: NCT00800800., Competing Interests: Competing interests: J-PD has served as a speaker for Abbott Laboratories, AstraZeneca, Solvay Pharma, GlaxoSmithKline, and Pfizer Canada, Inc.; has received research funding from Eli Lilly Canada; and has served on the advisory boards of Novartis, Theratechnologies, Torrent Pharmaceuticals Ltd., and Sanofi-Aventis. PM has a patent application on the use of Lp-PLA2 inhibitors in the treatment of AS. BA has received research funding from Ionis Pharmaceuticals, Merck and Pfizer. ST and JLW are co-inventors and receive royalties from patents owned by UCSD on oxidation-specific antibodies and of biomarkers related to oxidised lipoproteins and are co-founders of Oxitope, Inc. ST is a consultant to Boston Heart Diagnostics, a co-founder of Oxitope, Inc. and has a dual appointment at UCSD and Ionis Pharmaceuticals. JLW is a consultant to Ionis Pharmaceuticals and a co-founder of Oxitope, Inc., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations., Competing Interests: MM, CB, NA and VC have no conflicts of interest to declare. DV report grants from Astra Zeneca France outside the submitted work. MEP is research scholars from the Fonds de Recherche du Québec-Santé (FRQ-S) JPD reports personal fees from Abbott Laboratories, AstraZeneca, GSK, Merck and Pfizer Canada Inc. and personal fees from Abbott Laboratories, Sanofi and Torrent Pharmaceuticals Ltd. outside the submitted work. WCT reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. JB reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, NovartisPharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. JLP report grants from Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire outside the submitted work and personnal fees from Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed and Sefam outside the submitted work. FM reports grants and personal fees from Boehringer Ingelheim and GSK, grants from Nycomed and grants and personal fees from Novartis outside the submitted work. All fees are pooled with other revenues of the group of pulmonologists to which FM is a member and then shared among members of the group. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.

Although the first description of a syndrome defined by the co-existence of atherogenic and diabetogenic metabolic abnormalities is debated in the literature, it was Gerald Reaven who proposed, in his landmark 1988 Banting award lecture, that a significant proportion of individuals (with diabetes or not) were characterised by insulin resistance causing prejudice to cardiovascular health. However, Reaven was influenced by seminal observations made more than 50 years earlier by Himsworth who proposed that there were two forms of diabetes (insulin resistant v. insulin sensitive). Reaven went further in proposing the theory that insulin resistance was the most prevalent cause of CVD associated with metabolic abnormalities that he named syndrome X. Because there was a syndrome X documented in cardiology, the term evolved to insulin resistance syndrome. As Reaven could also find insulin-resistant individuals in non-obese subjects, he did not include obesity as a feature of syndrome X. Imaging studies then revealed that excess adipose tissue in the abdominal cavity, a condition described as visceral obesity, was the form of overweight/obesity associated with insulin resistance and its related abnormalities. As obesity risk assessment and management remain largely based on body weight (BMI) and weight loss, it is proposed that our clinical approaches and public health messages should be revisited. First, patients should be educated about the importance of monitoring their waistline as a crude index of abdominal adiposity. Secondly, public health approaches focussing on 'lifestyle vital signs' including achieving healthy waistlines rather than healthy body weights should be developed.

Background/objectives: Obesity has been associated with elevated leptinemia and vitamin D deficiency. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Our objective was to investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables, and changes in leptin levels produced by a 1-year lifestyle intervention program., Subjects/methods: Sedentary men (n = 113) with abdominal obesity, dyslipidemic, and non-vitamin D supplemented were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/exercise habits. Adiposity mapping by computed tomography and cardiometabolic biomarkers, as well as vitamin D measurements were performed at baseline and at the 1-year visit., Results: The 1-year intervention resulted in a 26% decrease in visceral adipose tissue volume (from 1951 ± 481 to 1463 ± 566 cm 3 ), a 27% decrease in leptin levels (from 12.0 ± 8.1 to 8.5 ± 7.8 ng/mL) and a 27% increase in plasma 25(OH) vitamin D concentrations (from 50 ± 18 to 60 ± 18 nmol/L, p < 0.0001). One-year increases in 25(OH) vitamin D levels were inversely correlated with 1-year changes in leptin levels (r = -0.41, p < 0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r = -0.30, p = 0.0019), subcutaneous adipose tissue (r = -0.35, p = 0.0004), total abdominal adipose tissue (r = -0.31, p = 0.0015), and fat mass (r = -0.31, p = 0.001)., Conclusions: In response to a 1-year lifestyle intervention, changes in 25(OH) vitamin D levels were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports a possible physiological link between leptinemia and 25(OH) vitamin D levels independent from adiposity and underscores the role of lifestyle modifications leading to lowered leptinemia in the clinical management of vitamin D deficiency.

Purpose: Fatty liver disease is associated with cardiometabolic disorders and represents a potential key comorbidity in Chronic Obstructive Pulmonary Disease (COPD). Some intermediary mechanisms of fatty liver disease (including its histological component steatosis) include tissue hypoxia, low-grade inflammation and oxidative stress that are key features of COPD. Despite these shared physiological pathways, the effect of COPD on the prevalence of hepatic steatosis, and the association between hepatic steatosis and comorbidities in this population remain unclear. Liver density measured by computed tomography (CT)-scan is a non-invasive surrogate of fat infiltration, with lower liver densities reflecting more fat infiltration and a liver density of 40 Hounsfield Units (HU) corresponding to a severe 30% fat infiltration., Patients and Methods: We took advantage of the international cohort ECLIPSE in which non-enhanced chest CT-scans were obtained in 1554 patients with COPD and 387 healthy controls to analyse the liver density at T12-L1., Results: The distribution of liver density was similar and the prevalence of severe steatosis (density<40 HU) was not different (4.7% vs 5.2%, p=0.7) between COPD and controls. In patients with COPD, the lowest liver density quartile was associated, after age and sex adjustment, with coronary artery disease (OR a =1.59, 95% CI 1.12 to 2.24) and stroke (OR a =2.20, 95% CI 1.07 to 4.50), in comparison with the highest liver density quartile., Conclusion: The present data indicate that a low liver density emerged as a predictor of cardiovascular comorbidities in the COPD population. However, the distribution of liver density and the prevalence of severe steatosis were similar in patients with COPD and control subjects., Competing Interests: MM, NA and IV have no conflicts of interest to declare. DV reports research grants from Astra Zeneca outside the submitted work. JPD reports personal fees from Abbott Laboratories, AstraZeneca, Sanofi, GSK, Torrent Pharmaceuticals Ltd., Merck and Pfizer Canada Inc., outside the submitted work. HOC reports personal fees and grants from GSK during the conduct of the original ECLIPSE study and no other conflicts during the present study. JLP reports a grant from a consortium of homecare providers (ADIR assistance, Agiradom, IPS, ISIS Medical, LINDE, LVL Medical, SOS Oxygen and Vitalaire) and CPAP companies (Bréas, Philips, Resmed and Sefam), grants from Air Liquide Foundation, Astra-Zeneca, Mutualia, Philips, RESMED, Fisher and Paykel, and personal fees from JAZZ, ITAMAR, Perimetre, Philips, Fisher and Paykel, RESMED, Astra-Zeneca, SEFAM, Agiradom, ELIA and Teva outside the submitted work. FM reports grants and personal fees from Boehringer Ingelheim and GSK, grants from Nycomed and AstraZeneca, and grants and personal fees from Novartis and Grifols outside the submitted work. All fees are pooled with other revenues of the group of pulmonologists to which FM is a member and then shared among members of the group. The authors report no other conflicts of interest in this work., (© 2019 Viglino et al.)