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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.

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: 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.)

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.

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 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.

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.)

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.

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.)

Purpose: Low-attenuation muscle (LAM) area at mid-thigh, a computed tomography (CT)-derived index of intramuscular lipids, is associated with insulin resistance, obesity, and type 2 diabetes. The present study aimed at testing the hypothesis that changes in LAM area in trunk muscles from a single abdominal scan could provide relevant information to evaluate the effects of a lifestyle intervention without the use of a mid-thigh CT scan., Methods: Cardiometabolic risk variables, including waist circumference, lipoprotein-lipid profile, glucose tolerance, and cardiorespiratory fitness, were assessed in a sample of 102 dyslipidemic viscerally obese men at baseline and after a 1-yr lifestyle intervention. Abdominal (L4-L5) and mid-thigh CT scans were performed and abdominal muscles classified as psoas and core muscles. Scans were segmented to calculate muscle areas, LAM areas, and mean attenuation values., Results: All muscle groups showed a decrease in LAM areas (P < 0.0001) in response to the lifestyle intervention. Changes in LAM areas were significantly associated with changes in triglycerides, high-density lipoprotein (HDL) cholesterol, cholesterol/HDL cholesterol ratio and log triglycerides/HDL cholesterol ratio (mid-thigh, 0.20 ≤ |r| ≤ 0.29; psoas, 0.28 ≤ |r| ≤ 0.38; core, 0.29 ≤ |r| ≤ 0.34, P < 0.05). Changes in core LAM area were significantly associated with changes in 2-h glucose levels, glucose area measured during the oral glucose tolerance test and homeostasis model assessment of insulin resistance (0.21 ≤ r ≤ 0.34, P < 0.05). Stepwise regression analyses showed that changes in LAM psoas area were associated with changes in HDL cholesterol and the cholesterol/HDL cholesterol ratio independently from changes in visceral adiposity., Conclusions: Changes in trunk LAM areas are useful indices of changes in mid-thigh LAM area observed with a 1-yr lifestyle intervention. Thus, an additional mid-thigh scan is not necessary to evaluate muscle lipid content by CT when an abdominal CT scan is available.

High overall nutritional quality (NQ) is an important component of ideal cardiovascular health, a concept introduced in 2010 by the American Heart Association. However, data on the independent contribution of overall NQ to the variation in the cardiometabolic risk (CMR) profile are limited. This observational study aimed to investigate the association between overall NQ and the CMR profile in 4785 participants (65⋅4 % of men, age 43⋅3 (sd 10⋅8) years) who underwent a cardiometabolic health evaluation, including lifestyle habits, anthropometric measurements, blood pressure, lipid profile and HbA1c concentrations. In addition, a submaximal exercise test was conducted to assess cardiorespiratory fitness (CRF). Using a standardised NQ questionnaire (twenty-five items food-based questionnaire), participants were classified into three subgroups: (1) low, (2) moderate or (3) high NQ and variance and multiple linear regression analyses were performed. Results showed that less than 15 % of participants presented a high NQ. A high NQ was associated with a healthier lifestyle habits and a more favourable CMR profile (lower values of waist circumference and cholesterol:HDL-cholesterol ratio, lower concentrations of non-HDL-cholesterol, TAG and HbA1c). Some of these associations were independent of age, physical activity level (PAL) and CRF. A better NQ was also associated with a lower proportion of participants presenting the hypertriacylglycerolaemic waist phenotype independently of both PAL and CRF. The present study suggests that overall NQ can be assessed with a short food-based questionnaire and should be considered in clinical practice as a new 'vital sign' associated with other health behaviours and cardiometabolic health.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE)., Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism., Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018., Exposures: A panel of several established cardiovascular risk factors., Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI)., Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers., Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Obesity is recognized as a heterogeneous condition in which individuals with similar body mass index may have distinct metabolic and cardiovascular risk profiles. Susceptibility to obesity-related cardiometabolic complications is not solely mediated by overall body fat mass, but is largely dependent upon individual differences in regional body fat distribution and ability of subcutaneous adipose tissue to expand. The present review will discuss to what extent the individual variation in body fat distribution is one of the clinical key variables explaining the metabolic heterogeneity of obesity and its related cardiovascular risk. We will present the evidence for the complex nature of the relationship between obesity and cardiovascular disease, outline our current understanding of the mechanisms involved, and identify future direction of research pertinent to this interaction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases., (© 2018 American Heart Association, Inc.)

Although cardiovascular disease (CVD) and diabetes mellitus are largely lifestyle driven, lifestyle metrics are not used in clinical practice. This study examined the relevance of using a simple lifestyle risk score designed for primary care medicine by testing its ability to predict biological CVD risk factors in a cohort of 3,712 individuals involved in a workplace health evaluation or management program ("Grand Défi Entreprise" project). Using a lifestyle risk score based on waist circumference, fitness, nutritional quality, and physical activity level, employees were categorized into 3 distinct estimated lifestyle risk levels (low, intermediate, and high). A biological CVD risk score was also calculated, which included high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), cholesterol-to-HDL-C ratio, blood pressure, hemoglobin glycated levels, and medication use. Diastolic blood pressure, TG levels, and the cholesterol-to-HDL-C ratio increased across categories of lifestyle risk score, whereas HDL-C decreased (p <0.05). Calculated Framingham and diabetes risk scores as well as the prevalence of hypertriglyceridemic waist phenotype also increased across categories of lifestyle risk score (p <0.05). Finally, 1-way analysis of variance revealed that the biological risk score significantly increased across the lifestyle risk score categories (p <0.0001). Our study provides evidence that lifestyle variables can be measured and targeted in clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Chronic overconsumption of sugar-sweetened beverages (SSBs) is amongst the dietary factors most consistently found to be associated with obesity, type 2 diabetes (T2D) and cardiovascular disease (CVD) risk in large epidemiological studies. Intervention studies have shown that SSB overconsumption increases intra-abdominal obesity and ectopic lipid deposition in the liver, and also exacerbates cardiometabolic risk. Similar to the prevalence of obesity and T2D, national surveys of food consumption have shown that chronic overconsumption of SSBs is skyrocketing in many parts of the world, yet with marked heterogeneity across countries. SSB overconsumption is also particularly worrisome among children and adolescents. Although the relationships between SSB overconsumption and obesity, T2D, and CVD are rather consistent in epidemiological studies, it has also been shown that SSB overconsumption is part of an overall poor dietary pattern and is particularly prevalent among subgroups of the population with low socioeconomic status, thereby questioning the major focus on SSBs to target/prevent cardiometabolic diseases. Public health initiatives aimed specifically at decreasing SSB overconsumption will most likely be successful in influencing SSB consumption per se. However, comprehensive strategies targeting poor dietary patterns and aiming at improving global dietary quality are likely to have much more impact in addressing the unprecedented public health challenges that we are currently facing.

Our objective was to examine the respective contributions of changes in visceral adiposity, subcutaneous adiposity, liver fat, and cardiorespiratory fitness (CRF) to the improvements in cardiometabolic risk markers in response to a 3-yr healthy eating/physical activity lifestyle intervention. Ninety-four out of 144 viscerally obese healthy men completed a 3-yr lifestyle intervention. Body weight, body composition, and fat distribution were assessed by anthropometry and DEXA/computed tomography. CRF, adipokines, lipoprotein/lipid profile, and 75 g of oral glucose tolerance were assessed. CRF and visceral and subcutaneous adiposity significantly improved over the 3-yr intervention, with a nadir in year 1 and a partial regain in year 3 Liver fat (estimated by insulin hepatic extraction) stabilized from year 1 to year 3 , whereas HOMA-IR, ISI-Matsuda index, and adiponectin continued to improve. Multivariate analysis revealed that both visceral adiposity and estimated liver fat reductions contributed to the improved ISI-Matsuda index observed over 3 yr ( r 2 = 0.28, P < 0.001). Three-year changes in fat mass and CRF were independently associated with changes in visceral fat (adjusted r 2 = 0.40, P < 0.001), whereas only changes in CRF were associated with changes in estimated liver fat (adjusted r 2 = 0.18, P < 0.001). A long-term (3 yr) healthy eating/physical activity intervention in men improves several cardiometabolic risk markers over the long term (3 yr) despite a partial body weight regain observed between year 1 and year 3 The improvement in CRF contributes to visceral and estimated liver fat losses over the long term, which in turn explain the benefits of the lifestyle intervention on cardiometabolic risk profile., (Copyright © 2017 the American Physiological Society.)

Obesity is currently one of the greatest public health issues worldwide. However, despite its known deleterious effects on the cardiovascular system and its association with numerous cardiovascular diseases (CVD), recent findings leading to the development of concepts such as metabolically healthy obesity, the obesity paradox, and protective subcutaneous fat depots have raised a lively debate on the disparate effects of obesity on health outcomes. Regarding the concept of metabolically healthy obesity, by presumably labelling a subset of obese people as metabolically healthy, physicians may not feel pressed to curb the current obesity epidemic and prevent the next generation of people from becoming obese. Another issue is that the most commonly used anthropometric index to define obesity, the body mass index, is at the core of the controversy because of its limitations including its inability to discriminate between fat mass and muscle mass. Many recent epidemiological and metabolic studies have used other indices such as waist-hip ratio, waist circumference, and imaging (computed tomography or magnetic resonance imaging) measurements of visceral adiposity and of ectopic fat depots. In addition, emerging evidence supports the importance of cardiorespiratory fitness, skeletal muscle mass and strength in patients with obesity as useful variables to predict CVD risk beyond adiposity. In this review, we will discuss the complex and disparate effects of obesity on CVD, particularly focusing on whether, under given circumstances, it could be harmful, potentially harmless or neutral, or even possibly protective., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Mounting evidence has firmly established that low levels of cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease, all-cause mortality, and mortality rates attributable to various cancers. A growing body of epidemiological and clinical evidence demonstrates not only that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that the addition of CRF to traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The purpose of this statement is to review current knowledge related to the association between CRF and health outcomes, increase awareness of the added value of CRF to improve risk prediction, and suggest future directions in research. Although the statement is not intended to be a comprehensive review, critical references that address important advances in the field are highlighted. The underlying premise of this statement is that the addition of CRF for risk classification presents health professionals with unique opportunities to improve patient management and to encourage lifestyle-based strategies designed to reduce cardiovascular risk. These opportunities must be realized to optimize the prevention and treatment of cardiovascular disease and hence meet the American Heart Association's 2020 goals., (© 2016 American Heart Association, Inc.)

Background: The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes., Methods/design: Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition., Discussion: CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

Although it is generally agreed upon that a physically active lifestyle and regular exercise are good for heart health, it is much less appreciated by the public that the prolonged hours of sedentary time resulting from sitting at work or screen time are also risk factors for cardiovascular outcomes and other cardiometabolic diseases. In this short narrative review, evidence is discussed and prudent recommendations are made in the context of the sedentary, affluent lifestyle that characterizes a large proportion of our population. It has become overwhelmingly clear that a sedentary lifestyle is a powerful risk factor for cardiovascular and other chronic diseases. In addition, vigorous physical activity and exercise is also associated with metabolic and cardiovascular adaptations that are compatible with cardiovascular health. In that regard, cardiorespiratory fitness, a reliable metric to assess the ability of the cardiovascular system to sustain prolonged physical work, has been shown to be the most powerful predictor of mortality and morbidity, way beyond classical cardiovascular disease (CVD) risk factors such as smoking, cholesterol, hypertension, and diabetes. On the basis of the evidence available, it is proposed that both dimensions of overall physical activity level (reducing sedentary time and performing regular physical activity or endurance type exercise) should be targeted to reduce CVD risk. Finally, because of the robust evidence that poor cardiorespiratory fitness is an independent risk factor for CVD and related mortality, it is proposed that this simple physiological metric should be incorporated as a vital sign in CVD risk factor evaluation and management., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a "call to action" activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Although obesity is generally perceived as causing prejudice to heart health, there is considerable individual metabolic heterogeneity among equally overweight or obese individuals. Such heterogeneity suggests that several factors can modulate health risk at any given body weight. In the present article, the thesis that weight loss and achieving a healthy body weight through caloric restriction might not represent optimal clinical and public health messages to combat the current obesity epidemic is defended. Rather, it is proposed that reducing waist circumference and increasing cardiorespiratory fitness through improving nutritional quality, reducing sedentary behaviours, and increasing participation to physical activity/exercise might be associated with clinical benefits, sometimes even in the absence of weight loss., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

In 2013, the Global Congress theme at the American Heart Association (AHA) Annual Scientific Sessions was Physical Activity (PA). As a key component of the Congress, iHealth working in collaboration with AHA provided a Bluetooth-enabled wireless PA and sleep tracker to up to 2,000 Scientific Sessions attendees. Approximately 1850 Scientific Sessions attendees registered for, received a PA tracker and participated in the Walking Challenge. More than 10 million steps were walked by participants (10,703,504) during the 2.5 days of the Walking Challenge. This translates into almost 6000 miles walked (5976.3 miles) and 656,716 calories burned by participants during the Challenge. The Global Congress of PA held at Scientific Sessions 2013 not only extensively reviewed the science of PA as a powerful/independent and, most importantly, modifiable cardiovascular risk factor, but it also provided evidence from a fun and entertaining challenge that PA as a risk behavior can be assessed and targeted. We just took 10 million steps in the right direction. Join us and make your steps count!, (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Despite the key role played by lifestyle habits in the epidemic of type 2 diabetes (T2D), nutritional quality and physical activity are not systematically considered in clinical practice. The project was conducted to verify whether assessing/targeting lifestyle habits could reduce hemoglobin A1c (HbA1c) levels of employees., Methods: The intervention consisted of a 3-month competition among teams of five employees to favor peer-based support in the adoption of healthier lifestyle habits (Eat better, Move more, and Quit smoking) (n = 900). A comprehensive cardiometabolic/cardiorespiratory health assessment was conducted before and after the contest (nutrition/physical activity questionnaires, blood pressure, anthropometric measurements, lipid profile, HbA1c, fitness). HbA1c levels were used to identify individuals with prediabetes (5.7%-6.4%) or T2D (≥6.5%)., Results: At baseline, 51% of the employees had increased HbA1c levels (≥5.7%). The HbA1c levels were associated with waist circumference, independently of body mass index. Subjects with prediabetes showed a higher waist circumference as well as a more deteriorated cardiometabolic profile compared to workers with normal HbA1c levels. After the intervention, employees with elevated HbA1c significantly reduced their HbA1c levels., Conclusion: Results suggest that assessing/targeting key lifestyle correlates of the cardiometabolic profile represents a relevant approach to target abdominal obesity and fitness with a significant impact on HbA1c levels.

Health authorities worldwide recommend weight loss as a primary endpoint for effective obesity management. Despite a growing public awareness of the importance of weight loss and the spending of billions of dollars by Americans in attempts to lose weight, obesity prevalence continues to rise. In this report we argue that effective obesity management in today's environment will require a shift in focus from weight loss as the primary endpoint, to improvements in the causal behaviors; diet and exercise/physical activity (PA). We reason that increases in PA combined with a balanced diet are associated with improvement in many of the intermediate risk factors including cardiorespiratory fitness (CRF) associated with obesity despite minimal or no weight loss. Consistent with this notion, we suggest that a focus on healthy behaviors for the prevention of additional weight gain may be an effective way of managing obesity in the short term., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Worldwide, cardiovascular diseases (CVDs) are a leading cause of mortality. While in many westernized societies there has been a decrease prevalence of smoking and that a special emphasis has been put on the urgency to control the, so called, classical risk factors, it is more and more recognized that there remains a residual risk, which contributes to the development of CVDs. Imaging studies conducted over two decades have highlighted that the accumulation of ectopic visceral fat is associated with a plethora of metabolic dysfunctions, which have complex and intertwined interactions and participate to the development/progression/events of many cardiovascular disorders. The contribution of visceral ectopic fat to the development of coronary artery disease (CAD) is now well established, while in the last several years emerging evidence has pointed out that accumulation of harmful ectopic fat is associated with other cardiovascular disorders such as calcific aortic valve disease (CAVD), atrial fibrillation and left ventricular dysfunction. We review herein the key molecular processes linking the accumulation of ectopic fat to the development of CVDs. We have attempted, whenever possible, to use a translational approach whereby the pathobiology processes are linked to clinical observations.

Canada has experienced a substantial reduction in mortality related to cardiovascular disease (CVD). There is a general consensus that more effective and widespread health promotion interventions may lead to further reductions in CVD risk factors and actual disease states. In this paper, we briefly outline the prevalence of selected risk factors for CVD in Canada, describe characteristics of the Canadian labor market and workforce, and depict what is known about health and wellness program delivery systems in Canadian workplaces. Our review indicates that there have been numerous and diverse relevant legislative and policy initiatives to create a context conducive to improve the healthfulness of Canadian workplaces. However, there is still a dearth of evidence on the effectiveness of the delivery system and the actual impact of workplace health and wellness programs in reducing CVD risk in Canada. Thus, while a promising model, more research is needed in this area., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the 'obesity paradox', which associates better survival and fewer cardiovascular (CV) events in patients with elevated BMI afflicted with chronic diseases compared to non-obese patients. However, BMI cannot make the distinction between an elevated body weight due to high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently associated with metabolic abnormalities than a high level of lean body mass. Another explanation for the paradox is the absence of control for major individual differences in regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate of excess dietary lipids, which may determine whether or not body homeostasis will be maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity, also induces a variety of structural adaptations/alterations in CV structure/function. Adipose tissue can now be considered as an endocrine organ orchestrating crucial interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle, the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity., (© 2013.)

Cardiovascular complications (CVC) are the most common causes of death in patients with type 2 diabetes (T2D). However the pathophysiological determinants and molecular mechanisms involved in the progression of CVC in T2D are poorly understood. We have undertaken the challenging task of identifying some of the genetic and clinical determinants of CVC through a unique multidisciplinary approach involving Canadian and Finnish investigators. We are studying novel animal models combining atherosclerosis, diet-induced obesity and T2D to understand the molecular basis of CVC in obesity-linked T2D. We are also conducting clinical studies to identify key determinants of CVC in T2D patients and to determine whether a lifestyle modification program targeting loss of visceral adipose tissue/ectopic fat could be associated with clinical benefits in these patients. Together, we strongly believe that we can fill some gaps in our understanding of the CVC pathogenesis in T2D and identify novel therapeutic targets and hope that this new knowledge may be translated into the design of effective clinical interventions to optimally reduce cardiovascular risk in T2D subjects., (Copyright © 2013 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Adipose tissue, which has been considered mainly as a site of energy storage and mobilization, is found in many depots throughout the body. Adipose depots may have structural properties such as, for instance, the fat pads located in the hands and feet and the periorbital fat supporting the eyes. Adipose tissue also shows remarkable regional heterogeneity. For instance, substantial differences have been reported in the metabolic properties of visceral (intra-abdominal) vs. subcutaneous adipose depots. Visceral adipose tissue (VAT) has active endocrine and paracrine functions with the secretion of various pro-inflammatory chemokines potentially contributing to the progression of atherosclerosis related with obesity. In addition, adipose depots surrounding the heart, such as epicardial (EAT) and perivascular adipose tissues (PAT) may also exert important roles in the pathogenesis of cardiovascular disease beyond the contribution of VAT due to their close anatomic relationships with vascular structures and myocardium. The purpose of the present review is to outline the current understanding of the pathophysiological links between EAT, PAT and atherosclerotic cardiovascular disease. Also, we discuss the current investigative methods for PAT quantification and discuss the potential impact of PAT on cardiovascular risk prediction. Finally, potential clinical implications of these notions are discussed., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: We evaluated the risk assessment and management patterns employed by primary care physicians in patients at elevated cardiometabolic risk., Methods: Between April 2011 and March 2012, multiple physicians from 9 Primary Care Teams (PCTs) and 88 physicians from traditional nonteam (Solo) practices completed a practice assessment on the management of 2461 patients > 40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least 1 of the following: dyslipidemia, type 2 diabetes mellitus (T2DM), or hypertension., Results: Individuals with dyslipidemia, T2DM, or hypertension tended to have a body mass index ≥ 25 kg/m(2). Waist circumference measurements, obtained for only 392/829 (47.0%) Solo patients, revealed that 88.9% of these individuals were abdominally obese and that at least 52.2% of Solo patients had metabolic syndrome. Cardiovascular risk, determined by the physicians for 83.5% of all patients without T2DM and typically performed using traditional risk engines, was often miscalculated (43.2% PCTs, 58.8% Solo; P = 0.0007). Healthy behavioural modifications were infrequently recommended (< 50%). Pharmacotherapy was widely used (> 70%) but treatment targets were infrequently met. The composite outcome of guideline-recommended low-density lipoprotein cholesterol, glycemic, and blood pressure targets was met by 9.0% and 8.1% of patients managed by PCT and Solo physicians respectively., Conclusions: Obesity and cardiovascular risk were underassessed and the latter often underestimated. Patients were infrequently counselled on the benefits of healthy behavioural changes. A paradigm change in assessing and managing obesity and cardiovascular risk via aggressive lifestyle interventions is warranted in individuals at elevated cardiometabolic risk., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The Look AHEAD trial did not show that a lifestyle modification programme aimed at weight loss could reduce the incidence of cardiovascular disease events. We attempt to address why this trial was 'negative', and emphasize that further randomized trials of lifestyle modification focusing on the effects of physical activity and exercise are needed.

Background: Sedentary behaviour has recently emerged as a unique risk factor for chronic disease morbidity and mortality. One factor that may explain this relationship is visceral adiposity, which is prospectively associated with increased cardiometabolic risk and mortality. The objective of the present study was to determine whether sedentary behaviour was associated with increased accumulation of visceral fat or other deleterious changes in cardiometabolic risk over a 6-year follow-up period among adult participants in the Quebec Family Study., Methods: The current study included 123 men and 153 women between the ages of 18 and 65. Total sedentary time and physical activity were assessed by self-report questionnaire. Cross-sectional areas of visceral and subcutaneous abdominal adipose tissue were assessed using computed tomography. Cardiometabolic biomarkers including fasting insulin, glucose, blood lipids, HOMA-Insulin Resistance, and oral glucose tolerance were also measured. All variables of interest were collected at both baseline and follow-up., Results: After adjustment for age, sex, baseline BMI, physical activity, energy intake, smoking, education, income and menopausal status, baseline sedentary behaviour was not associated with changes in visceral adiposity or any other marker of cardiometabolic risk. In the longitudinal model which adjusted for all studied covariates, every 15-minute increase in sedentary behaviour from baseline to follow-up was associated with a 0.13 cm increase in waist circumference (95% CI = 0.02, 0.25). However, there was no association between changes in sedentary behaviour and changes in visceral adiposity or other markers of cardiometabolic risk., Conclusion: These results suggest that neither baseline sedentary behaviour nor changes in sedentary behaviour are associated with longitudinal changes in visceral adiposity in adult men and women. With the exception of waist circumference, the present study did not find evidence of a relationship between sedentary behaviour and any marker of cardiometabolic risk in this population.

Bariatric surgery has gained acceptance as the only treatment with long-term efficacy for severe obesity. Recent publications emphasize the usefulness of bariatric surgery in the reduction of long-term cardiometabolic risk, cardiovascular disease incidence and mortality, and the management of uncontrolled type 2 diabetes (T2DM), an important cardiovascular risk factor in individuals with severe obesity. The present review article offers a brief overview of the literature published over the past several months relevant to cardiometabolic outcomes in bariatric surgery patients. A recent report from the Swedish Obese Subjects (SOS) study specifically reported a reduced incidence of cardiovascular events on long-term prospective follow-up after bariatric surgery. In addition, abundant studies have been recently published on gastric bypass surgery showing high T2DM remission rates as well as improved blood lipids and inflammatory markers after surgery. Sleeve gastrectomy is increasingly performed as a stand-alone operation. Recent reports on this surgery pertaining to cardiometabolic risk showed variable T2DM remission rates that may possibly be explained by age of the patients and duration of T2DM. Available data suggest a possible favorable impact of the surgery on CRP levels and improvements in the blood lipid profile. How sleeve gastrectomy compares to other surgical approaches will require further study. Biliopancreatic diversion with duodenal switch has been reported to offer some of the best long-term weight loss for obese patients. Approximately 9 out of 10 patients treated with this surgical procedure show long-term remission rates of T2DM. Significant improvements in the cardiometabolic risk profile are also observed after BPD-DS; they are especially pronounced regarding dyslipidemia. In conclusion, bariatric procedures improve the cardiometabolic risk profile, a phenomenon that appears to be only partly explained by the magnitude of the weight loss. Significant variations are observed with respect to the type of surgery and patient characteristics. More research is clearly needed on the short and long-term cardiometabolic outcome of obesity surgeries.

Although excess body fat is a significant health hazard, estimation of body fat content with the body mass index may not adequately reflect the amount of atherogenic adipose tissue (AT), i.e. visceral and ectopic fat. As opposed to subcutaneous AT that supposedly acts as a metabolic sink buffering excess dietary energy, visceral or intra-abdominal AT depots respond to several external stimuli that trigger lipolysis and secretion of free fatty acids (FFAs). Reaching the liver, FFAs accumulate in the liver and, over time, promote a chronic condition known as non-alcoholic fatty liver disease (NAFLD). The liver of the typical NAFLD patient secretes large amounts of very-low-density lipoproteins, the lipid content of which may accumulate in additional organs (skeletal muscle, heart, and pancreas). Here, we review the evidence emerging from functional and population studies that point towards an important role of ectopic fat accumulation in the pathophysiology of type 2 diabetes and cardiovascular disease. We conclude that although patients with impaired glycemic control or type 2 diabetes are at increased cardiovascular disease (CVD) risk, estimating cardiovascular risk goes wellbeyond the assessment of glycemic control and traditional CVD risk factors, and the estimation of visceral/ectopic fat deposition via readily available imaging techniquesshould be considered.

It is well established that cardiovascular disease has an inflammatory component. The present narrative review explores the role of adipose tissue distribution, morphology, and function as potential mediators of the link between inflammation and cardiovascular disease. Evidence that abdominal obesity is a key driving force behind a constellation of atherothrombotic inflammatory abnormalities linked to insulin resistance and often referred to as the metabolic syndrome is also reviewed. It is also proposed that the amount of visceral adipose tissue and the liver fat content are important factors responsible for the link between abdominal obesity and features of the metabolic syndrome. It is suggested that the inflammatory profile associated with excess visceral adipose tissue/liver fat may be a consequence of the relative inability of subcutaneous adipose tissue to expand through hyperplasia and to act as a protective metabolic sink storing the chronic energy surplus resulting from a positive energy balance (overnutrition or lack of physical activity or both). In this model, the inflammatory profile often observed among sedentary overweight/obese individuals with an excess of visceral adipose tissue/liver fat may be a consequence of a more primary defect in subcutaneous adipose tissue. On that basis, it is proposed that therapeutic strategies relieving the stress for storage of a chronic energy surplus in the subcutaneous adipose tissue (reduced caloric intake, increase in energy expenditure, pharmacotherapy) should induce a substantial loss of visceral adipose tissue and of ectopic fat depots such as the liver, thereby substantially reducing inflammation., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The concept that raising HDL-cholesterol level will uniformly translate into cardiovascular risk reduction has been challenged by genetic epidemiology studies and large-scale, randomized clinical trials. Studies suggest that we should go beyond HDL cholesterol, and consider emerging biomarkers of HDL concentration, composition, and functionality as surrogates for cardiovascular risk reduction.

Heart rate variability (HRV) is affected by age, hyperglycemia and accumulation of body fat. This study compares the predictive value of four measurements of adiposity/obesity on HRV and investigates the specific role of age, metabolic contributors and degree/distribution of fat in HRV alterations. The sample consisted of 97 non-diabetic and non-medicated men with features of the metabolic syndrome (50±8 years of age, body mass index [BMI] 31±3 kg/m(2), waist circumference [WC] 107±9 cm, triglycerides 2.3±0.7 mmol/L, fasting glucose 6.0±0.5 mmol/L, insulin 156±71 pmol/L; mean±SD). WC, BMI, percent body fat (% fat, from dual energy X-ray absorptiometry) and visceral adipose tissue volume (VAT, from computed tomography) were used as measures of adiposity/obesity. HRV measures were obtained from 24-h, day- and night-time segments of Holter recordings. BMI presented no independent association with HRV. Percentage fat was the strongest obesity index to be associated with HRV: 24-h pNN50, rMSSD, HF and daytime pNN50, rMSSD, HF and LF (-0.27≤std β≤-0.20, P<.05). VAT was associated with 24-h SDNN, LF (std β=-0.25 and -0.20, P<.05, respectively) and daytime SDNN (std β=-0.24, P<.05) while WC was associated with nighttime SDNN and SDANN (std β=0.22 and 0.32, P<.05). In addition, age, fasting glucose, 2-h oral glucose tolerance test and triglycerides presented independent association with HRV. Adiposity/obesity measurements seem to be differently associated with HRV. An approach considering the combination of age, obesity and glucose metabolism factors could be helpful in the global cardiovascular risk management in abdominally obese men., (Copyright © 2012 Elsevier Inc. All rights reserved.)