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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.

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: Early identification of individuals at increased cardiometabolic risk is an essential step to improve primary preventive interventions. Excessive maximal exercise blood pressure (EBP) has been associated with several adverse outcomes. We examined how submaximal EBP could help us to identify individuals with a deteriorated cardiometabolic risk profile., Methods: Data from an observational study of 3,913 participants from a convenience sample were used. Subjects included in the analyses completed a comprehensive cardiometabolic health assessment (resting blood pressure [BP]; waist circumference; lipid profile; HbA1c; submaximal treadmill exercise test including a standardized stage [3.5 mph and 2% slope] with BP and heart rate measurements). Participants were classified on BP response at the standardized stage (Normal or Excessive Response). Excessive response was defined as systolic BP ≥ 80th percentile or diastolic BP ≥ 90 mmHg. Subjects were also classified into five resting BP subgroups according to current guidelines., Results: The Excessive Response group had more deteriorated cardiometabolic and cardiorespiratory profiles than the Normal Response group (P ≤ 0.01). The Excessive Response group also showed a greater proportion of carriers of the hypertriglyceridemic waist phenotype in most resting BP subgroups (P ≤ 0.05). Finally, excessive BP response to submaximal exercise showed an independent contribution on cardiometabolic and cardiorespiratory factors beyond age, sex, and resting BP., Conclusions: This study demonstrates that an excessive BP response to a submaximal exercise is associated with a deteriorated cardiometabolic risk profile beyond resting BP profile. Therefore, submaximal EBP represents a simple screening tool to better identify at-risk individuals requiring aggressive preventive lifestyle interventions., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Diastolic dysfunction (DD) is increasingly common. However, its metabolic determinants are poorly known. This study aims to determine which metabolic and inflammatory features predict DD in initially healthy adults., Methods: We prospectively analyzed the association between metabolic features and DD in 728 initially healthy adults aged 30-60 from Eastern France enrolled in the STANISLAS population-based cohort. Clinical and biological cardiovascular features were collected at baseline (1994-1995). DD was assessed twenty years later (2011-2016) by echocardiography using current international guidelines. For replication purposes, 1463 subjects from the Malmö Preventive Project cohort were analyzed., Results: In the STANISLAS cohort, 191 subjects (26.2%) developed DD. In age-sex-adjusted logistic models, significant predictors of DD were body mass index (BMI, odds ratio for 1-standard-deviation increase (OR) 1.28, 95% CI 1.08-1.52), waist circumference (WC, OR 1.48, 95% CI 1.18-1.84), waist-hip ratio (OR 1.53, 95% CI 1.16-2.02), systolic blood pressure (OR 1.19, 95% CI 1.00-1.43) and triglycerides (TG, OR 1.18, 95% CI 1.00-1.40). Subjects with elevated WC (> 80th percentile) and TG (> 50th percentile) had a twofold higher DD risk (age-sex-adjusted odds ratio 2.00, 95% CI 1.20-3.31, P = 0.008), whereas no such interplay was observed for BMI. In the Malmö cohort, BMI was similarly associated with DD; participants with both elevated BMI and TG were at higher DD risk (age-sex-adjusted odds ratio 1.61, 95% CI 1.18-2.20, P = 0.002)., Conclusions: Subjects with elevated WC and TG may have a higher long-term DD risk. Prevention targeting visceral obesity may help reduce the incidence of DD.

The translation of the growing increase of findings emerging from basic nutritional science into meaningful and clinically relevant dietary advices represents nowadays one of the main challenges of clinical nutrition. From nutrigenomics to deep phenotyping, many factors need to be taken into account in designing personalized and unbiased nutritional solutions for individuals or population sub-groups. Likewise, a concerted effort among basic, clinical scientists and health professionals will be needed to establish a comprehensive framework allowing the implementation of these new findings at the population level. In a world characterized by an overwhelming increase in the prevalence of obesity and associated metabolic disturbances, such as type 2 diabetes and cardiovascular diseases, tailored nutrition prescription represents a promising approach for both the prevention and management of metabolic syndrome. This review aims to discuss recent works in the field of precision nutrition analyzing most relevant aspects affecting an individual response to lifestyle/nutritional interventions. Latest advances in the analysis and monitoring of dietary habits, food behaviors, physical activity/exercise and deep phenotyping will be discussed, as well as the relevance of novel applications of nutrigenomics, metabolomics and microbiota profiling. Recent findings in the development of precision nutrition are highlighted. Finally, results from published studies providing examples of new avenues to successfully implement innovative precision nutrition approaches will be reviewed., Competing Interests: The authors declare no conflict of interest.

Background: Abdominal obesity and presence of the metabolic syndrome (MetS) are associated with cardiac abnormalities. Among those, left ventricular diastolic dysfunction (LVDD) is the most frequently encountered in clinical practice. Few studies evaluated the reversibility of LVDD by an approach promoting lifestyle modifications in abdominally obese subjects with MetS., Methods: We assessed the impact of a 1-year lifestyle modification program combining nutritional and physical activity counseling on LVDD and metabolic profile of abdominally obese men with MetS. Echocardiograms, oral glucose tolerance test, lipids profile, dual energy X-ray absorptiometry, computed tomography scans (visceral obesity assessment), heart rate variability (HRV), as well as maximal and submaximal exercise tests were performed in participants before and after a 1-year program combining healthy eating and a physical activity/exercise program., Results: Fifty-one abdominally obese men participated in this study. At baseline, 86% of the participants had LVDD (n = 44). After the 1-year program, LVDD improved in 57% of participants (n = 29, P < 0.0001). All metabolic, adiposity, and exercise tolerance measures improved from baseline (P < 0.0001), but were not associated with improvement in LVDD. Participants who improved LVDD had better exercise performance at baseline. Exercise tolerance during the submaximal exercise test, parasympathetic cardiac autonomic activity, and fasting insulin predicted 50% of LVDD improvements., Conclusions: There was a significant improvement in LVDD after a 1-year lifestyle intervention program in abdominally obese men with MetS, such an improvement being associated with increased exercise tolerance, enhanced HRV, and reduced insulin levels.

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.)

Despite its well-documented relation with visceral adiposity (VAT) and cardiometabolic risk (CMR), whether waist circumference (WC) should be measured in addition to body mass index (BMI) remains debated. This study tested the relevance of adding WC to BMI for the estimation of VAT and CMR. In the International Study of Prediction of Intra-abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-abdominal Adiposity, 297 physicians recruited 4,504 patients (29 countries). Both BMI and WC were measured, whereas VAT and liver fat were assessed by computed tomography. A composite CMR score was calculated. From the 4,109 patients included in the present analyses (20 ≤ BMI < 40 kg/m(2), 47% women), about 30% displayed discordant values for WC and BMI quintiles, despite a strong correlation between the 2 anthropometric variables (r = 0.87 and r = 0.84 for men and women, respectively, p <0.001). Within each single BMI unit, VAT and WC showed substantial variability between subjects (mean difference between 90th and 10th percentiles: 175 cm(2)/16 cm and 137 cm(2)/18 cm for VAT/WC in men and women, respectively). Within each BMI category, increasing gender-specific WC tertiles were associated with significantly higher VAT, liver fat, and with a more adverse CMR profile. In conclusion, this large international cardiometabolic study highlights the frequent discordance between BMI and WC, driven by the substantial variability in VAT for a given BMI. Within each BMI category, WC was cross-sectionally associated with VAT, liver fat, and CMR factors. Thus, WC allows a further refinement of the CMR related to any given BMI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess whether plasma IGFBP-2 is independently associated with components of the lipoprotein-lipid profile and to suggest a cutoff value that could identify subjects with the features of the metabolic syndrome., Methods: In this cross-sectional study, 379 Caucasian men from the general population and covering a wide range of BMI were recruited through the media. Subjects with type 2 diabetes, BMI values > 40 kg/m(2), or taking medication targeting glucose or lipid metabolism or blood pressure were excluded. Anthropometric data were collected and plasma IGFBP-2 concentrations, glucose tolerance and an extensive plasma lipid profile were determined after an overnight fast., Results: Subjects with low IGFBP-2 levels were characterized by increased fat mass (p < 0.0001), impaired insulin sensitivity (p < 0.0001) and higher plasma triglyceride (TG) levels (p < 0.0001). When divided into 6 quantiles, only subjects with the highest IGFBP-2 levels (>221.5 ng/mL) did not meet the NCEP ATP III criteria for the clinical diagnosis of the metabolic syndrome. In addition, circulating IGFBP-2 levels were significantly associated with VLDL-TG (r = -0.51, p < 0.0001) and HDL-C (r = -0.27, p < 0.0001) levels. After adjustments, plasma IGFBP-2 was found to be independently associated with VLDL-TG levels but not with HDL-C concentrations., Conclusions: In our cohort, IGFBP-2 levels <221.5 ng/mL are incrementally associated with a detrimental plasma lipoprotein-lipid profile. After adjustment for covariates, IGFBP-2 remained independently associated with VLDL-TG but not HDL-C levels. This study supports further investigations in other populations and validation of IGFBP-2 as a biomarker of early dyslipidemia., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. 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.

Objective: The objective of this study was to investigate the association between self-reported sleep duration and the incidence of features of the metabolic syndrome in adults., Methods: A longitudinal analysis from the Quebec Family Study (Canada) was conducted on 293 participants, aged 18 to 65 years, followed for a mean of 6 years (until 2001). Participants were categorized as short (≤6 h), adequate (7-8 h) or long (≥9 h) sleepers. The metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute's criteria. The hypertriglyceridemic waist phenotype was defined as high waist circumference (≥90 cm in men and ≥85 cm in women) combined with high fasting triglyceride level (≥2.0 mmol/L in men and ≥1.5 mmol/L in women)., Results: The incidence rates of metabolic syndrome and hypertriglyceridemic waist phenotype were 9.9% and 7.5%, respectively. Short sleepers were significantly more at risk of developing the metabolic syndrome (relative risk (RR): 1.74; 95% confidence interval (CI): 1.05-2.72) and the hypertriglyceridemic waist phenotype (RR: 1.82; 95% CI: 1.16-2.79), compared to those sleeping 7 to 8h per night after adjusting for covariates. However, long sleep duration was not associated with an increased risk of developing the metabolic syndrome or the hypertriglyceridemic waist phenotype (either unadjusted or adjusted models)., Conclusion: Short sleep duration is associated with an increased risk of developing features of the metabolic syndrome in adults., (© 2013.)

Introduction: Abnormalities in the autonomic nervous system in the presence of insulin resistance may be involved in the pathophysiology of obesity-associated hypertension. We evaluated the association between exercise-induced exaggerated blood pressure (BP) response [exercise-induced hypertension (EIH)] and heart rate variability (HRV) and insulin resistance in men with metabolic syndrome (MetS)., Materials and Methods: Ninety-eight resting normotensive men with MetS underwent a maximal symptom-limited treadmill test. BP was measured after a 5-min rest (anticipatory BP) every 3 min during exercise and during the recovery period. EIH was defined as maximum systolic BP of 220 mmHg or higher and/or maximum diastolic BP of 100 mmHg or higher. Insulin resistance was estimated using HOMA-IR. Each participant underwent a 3-h oral glucose tolerance test (OGTT). HRV was derived from a 24-h Holter., Results: About half of the participants (52%) presented EIH. Resting BPs at baseline were 125 ± 10/83 ± 7 mmHg in participants with EIH and 120 ± 9/80 ± 6 mmHg (P = 0.01) in the group with normal BP response to exercise. OGTT glucose levels were higher in the group with EIH (all P < 0.04) as well as HOMA-IR compared with participants with normal BP response to exercise (P = 0.03). In terms of HRV, 24-h standard deviation of the RR intervals (SDNN) was lower in participants with EIH (P = 0.04) as well as 24-h daytime and night-time high frequency and low frequency (P < 0.05)., Conclusion: Normotensive men with MetS but with EIH have greater insulin resistance as well as lower HRV parasympathetic and sympathetic indices. These features may be involved in the pathophysiology of EIH.

Background: Previous studies looking at the relationship between sleep duration and the metabolic syndrome have only used a dichotomous approach (presence/absence) and failed to adjust for important confounding factors. The objective of the present study was to examine the association between self-reported sleep duration and features of the metabolic syndrome in adults., Methods: A cross-sectional analysis from the Quebec Family Study (Canada) was conducted on 810 participants aged 18 to 65 years. Participants were categorized as short (≤6 h), adequate (7-8 h) or long (≥9 h) sleepers. The metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute's criteria., Results: Overall, 24.6% of the sample had the metabolic syndrome. A U-shaped relationship between sleep duration and the prevalence of metabolic syndrome (33.3%, 22.0% and 28.8% in short, adequate and long sleepers, respectively) was observed (P<0.01). Only short sleepers had a significant increase in the odds of having the metabolic syndrome (OR = 1.76, 95% CI = 1.08-2.84) compared to adequate sleepers after adjustment for age, sex, smoking habits, highest education level, total annual family income, alcohol consumption, coffee intake, menopausal status, daily caloric intake, and moderate-to-vigorous physical activity. Likewise, the clustered cardiometabolic risk score (i.e. continuous risk score based on the metabolic syndrome components) was significantly higher in short sleepers compared to adequate sleepers after adjustment for covariates (P<0.05)., Conclusion: Sleeping ≤6 h per night is associated with an elevated cardiometabolic risk score and an increase in the odds of having the metabolic syndrome after adjusting for possible confounders. These results strongly suggest that short sleep duration is a risk factor for the metabolic syndrome.

With regard to the beneficial impact of lifestyle interventions on weight and abdominal obesity management, our objective was to identify which components of a lifestyle-intervention program [physical activity (PA), energy and macronutrient intake, diet quality] had an influence on visceral adipose tissue (VAT) loss. The present lifestyle intervention targeted a daily energy deficit (500 kcal), coupled with a PA program (160 min/wk). From the 144 participants initially recruited, 93 viscerally obese men (age: 49 ± 1 y; waist circumference: 108 ± 9 cm; plasma triglyceride concentration: 2.46 ± 0.09 mmol/L) who completed a 3-d dietary journal both at baseline and after 1 y of intervention and a daily PA journal for 1 y were considered in the present analyses. Body composition and fat distribution were assessed by using dual-energy X-ray absorptiometry and computed tomography. After 1 y, abdominally obese men significantly improved their diet quality, as assessed by the Dietary Approaches to Stop Hypertension (DASH)-derived diet quality (DQ) score (P < 0.0001). Improved DQ and higher levels of PA were both independently and significantly associated with reductions in body weight, fat mass, VAT, and thigh muscle fat content, beyond reported energy intake or diet macronutrient composition. When stratified according to the level of PA and DQ [PA- (low PA), DQ- (low DQ), PA+ (high PA), DQ+ (high DQ)], the PA+/DQ+ group showed reductions in VAT that were 20% greater than in the PA-/DQ+ group, 28% greater than in the PA+/DQ- group, and 50% (P < 0.05) greater than in the PA-/DQ- group. Our results highlight the strong contribution of DQ beyond macronutrient and energy content to changes in body composition and suggest that synergistic changes in both DQ and PA levels optimally reduce VAT in men with features of metabolic syndrome.

Objective: The aim of this study was to examine the effect of brisk walking on cardiometabolic risk profile and on the gene expression (ie, messenger RNA [mRNA] levels) of inflammatory and thrombotic markers in abdominal and femoral subcutaneous adipose tissues (SATs) among sedentary overweight to obese women with different menopause statuses., Methods: Sixteen late premenopausal (mean [SD] age, 49 [3] y; mean [SD] body mass index, 31.9 [3.0] kg/m) and 14 early postmenopausal (53 [2] y; 30.8 [1.9] kg/m) women were involved in a 16-week walking program (three sessions of 45 min/wk at 60% of heart rate reserve). Glucose-insulin homeostasis, lipid-lipoprotein profile, and inflammatory (tumor necrosis factor-α, interleukin-6 [IL-6], and adiponectin) and thrombotic (plasminogen activator inhibitor-1) SAT mRNA and plasma levels were measured before and after the intervention., Results: Glucose area under the curve was reduced in all participants (P = 0.03) after the walking program. Increases in plasma tumor necrosis factor-α were observed in both groups (P = 0.001), whereas increases in plasminogen activator inhibitor-1 levels were found in postmenopausal women only (P = 0.014). However, plasma IL-6 and adiponectin levels remained unchanged after the intervention (0.07 < P < 0.98). Although femoral SAT adiponectin mRNA levels decreased in postmenopausal women only (P = 0.008), abdominal SAT IL-6 mRNA levels were reduced in both groups (P = 0.01)., Conclusions: Taken together, our results show that, despite a reduced abdominal SAT IL-6 expression, brisk walking does not seem to exert a favorable impact on the cardiometabolic risk profile of overweight to obese women, irrespective of their menopause status.

Objective: Metabolic syndrome is associated with increased cardiac morbidity. The aim of this study was to evaluate exercise-induced hypertension (EIH) in men with metabolic syndrome and to explore potential associations with anthropometric and metabolic variables., Methods: A total of 179 normotensive men with metabolic syndrome underwent a maximal symptom-limited treadmill test. Blood pressure was measured at 5-min rest prior to exercise testing (anticipatory blood pressure), at every 3 min during the exercise, and during the recovery period. EIH was defined as maximum systolic blood pressure (SBP) ≥220 mmHg and/or maximum diastolic blood pressure (DBP) ≥100 mmHg., Results: Of the 179 men, 87 (47%) presented EIH. Resting blood pressure values at baseline were 127±10/83±6 mmHg in EIH and 119±9/80±6 mmHg (P=0.01 for both) in normal blood pressure responders to exercise. Anticipatory SBP and DPS were higher in the group with EIH (P=0.001). Subjects with EIH presented higher waist circumference (WC) (P<0.01), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) levels as well as insulin resistance (all P<0.05). Abdominal subcutaneous adipose tissue and total body fat mass were comparable between groups. Subjects with EIH had higher abdominal visceral adipose tissue (P<0.001). The best predictors of EIH were resting SBP and abdominal obesity. Each increment of 5 cm in WC was associated with an odds ratio of 1.30 (1.20-1.68) for EIH., Conclusion: About half of our subjects with metabolic syndrome showed EIH. These men are characterized by a worsened metabolic profile. Our data suggest that a treadmill exercise test may be helpful to identify a potentially higher risk metabolic syndrome subset of subjects.

Background: Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution., Objective: We aimed to identify differences across ethnic groups in interrelations between BMI, abdominal adiposity, liver fat, and CMR profile., Design: In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured., Results: Higher ranges of BMI were associated with higher levels of visceral [visceral adipose tissue (VAT)] and deep subcutaneous [deep subcutaneous adipose tissue (DSAT)] adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration., Conclusions: Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.

Objectives: The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS., Background: Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression., Methods: This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography., Results: Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not., Conclusions: MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Visceral adiposity is an important correlate of cardiometabolic risk, yet its association after the diagnosis of type 2 diabetes remains unclear., Methods: Our objective was to assess the independent and combined associations of visceral adiposity and type 2 diabetes to cardiometabolic risk. The INternational Study of Prediction of Intra-abdominal adiposity and its RElationships with cardioMEtabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) is a cross-sectional computed tomography imaging study with data collected from June 2006 to May 2008. General physicians, cardiologists, and diabetologists (n = 297) in 29 countries recruited 4144 (51.8% men) men (39-71 yr) and women (44-71 yr). Patients were categorized according to visceral adiposity tertiles, type 2 diabetes status, and sex. All results were adjusted for age, body mass index, region, and physician's specialty., Results: Markers of insulin resistance, lipid/lipoproteins, inflammatory markers, and liver fat increased with visceral adiposity in men and women with and without type 2 diabetes. Prevalent cardiovascular disease increased with visceral adiposity tertiles, regardless of type 2 diabetes status. Visceral adiposity [odds ratio = 1.25 (1.09-1.44) for men and 1.78 (1.50-2.12) for women] was positively associated with type 2 diabetes, whereas liver attenuation (inversely related to liver fat) was negatively associated with type 2 diabetes [odds ratio = 0.66 (0.59-0.75) for men and 0.63 (0.55-0.72) for women]. Subcutaneous adipose tissue was inversely related to type 2 diabetes in women [0.76 (0.0.66-0.88)] and not associated with type 2 diabetes in men [0.97 (0.85-1.11)]., Conclusions: Visceral, but not sc, abdominal adiposity is strongly related to cardiometabolic risk factors and to the prevalence of cardiovascular disease and may be an important driver of cardiometabolic risk in patients regardless of type 2 diabetes status.

Objective: The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese., Design, Setting, Patients, Interventions and Results: A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima-media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima-media thickness from baseline to month 30 was 0.010 ± 0.095 mm in the rimonabant group and 0.012 ± 0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005 ± 0.042 mm for the rimonabant-treated group and 0.007 ± 0.043 mm for the placebo-treated group (p=0.45)., Conclusions: There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima-media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome. Clinical trial registration information clinicaltrials.gov Identifier: NCT00228176.

Context: Both excess visceral adipose tissue (VAT) and low cardiorespiratory fitness (CRF) levels are associated with a deteriorated cardiometabolic risk profile., Objective: The aim of the study was to examine the respective contributions of changes in VAT accumulation vs. changes in CRF to 6-yr longitudinal changes in cardiometabolic risk markers., Design, Settings, and Participants: We conducted a prospective, population-based study with an average follow-up of 5.9 ± 0.8 yr. We followed 132 middle-aged participants from the Quebec Family Study (mean age, 35.3 ± 13.9 yr). VAT was measured by computed tomography, whereas the level of CRF was assessed by a submaximal physical working capacity test at baseline and at follow-up. A complete cardiometabolic risk profile, including systolic and diastolic blood pressure, fasting glucose and insulin levels, C-reactive protein (n = 72), as well as a standard lipoprotein-lipid profile, was obtained at baseline and at follow-up., Main Outcome Measures: We measured changes in CRF, VAT, and cardiometabolic risk profile over 6 yr., Results: After adjusting for age and sex, 6-yr changes in VAT were negatively correlated with changes in CRF (r = -0.38; P < 0.001). In a multivariate model that included age, sex, changes in VAT, changes in CRF, as well as baseline levels of the above cardiometabolic risk factors, 6-yr changes in VAT were the most important predictor of the change in the metabolic syndrome score (R(2) = 13.2%; P < 0.001). Adding 6-yr changes in CRF levels significantly improved the predictability of the model (R(2) = 19.7%; P = 0.002)., Conclusions: Changes in both VAT and CRF levels observed over 6 yr are associated with changes in parameters of the lipoprotein-lipid profile, glucose-insulin homeostasis, and inflammatory markers. Thus, maintaining a low level of VAT and a high level of CRF are important targets for maintenance of cardiometabolic health.

The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although the total to high-density lipoprotein cholesterol ratio (TC/HDL-C) has been used for decades to identify individuals at risk for coronary heart disease (CHD), apolipoprotein-based (apolipoprotein B/apolipoprotein A-I [apoB/apoA-I]) and nuclear magnetic resonance spectroscopy (NMR)-based lipoprotein concentrations (low-density lipoprotein(NMR) /high-density lipoprotein(NMR) [LDL(NMR) /HDL(NMR)]) may also be useful for CHD risk stratification., Materials and Methods: In a case-control study conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study population, 870 individuals who developed CHD during a 6-year follow-up were matched to 1659 controls on the basis of gender, age and enrollment time. LDL(NMR) and HDL(NMR) were measured by proton NMR spectroscopy., Results: After adjusting for traditional CHD risk factors, men in the top quintile of the various lipoprotein ratios proved to be at increased CHD risk (OR = 2·59 [95% IC, 1·76-3·83] for TC/HDL-C ratio, 2·59 [1·75-3·83] for apoB/apoA-I ratio and 2·78 [1·86-4·17] for LDL(NMR) /HDL(NMR) ratio) compared with men in the bottom quintile. Similar associations were observed in women (OR = 2·86 [1·71-4·80] for TC/HDL-C ratio, 2·94 [1·74-4·97] for apoB/apoA-I ratio and 2·03 [1·21-3·43] for LDL(NMR)/HDL(NMR) ratio). Compared with participants with only one component of the metabolic syndrome, those who had five had an increased TC/HDL-C ratio (73·0% and 80·4% in men and women respectively), apoB/apoA-I ratio (58·0% and 62·9% in men and women respectively) and for LDL(NMR)/HDL(NMR) ratio (52·6% and 54·1% in men and women respectively)., Conclusion: In this European study population, the TC/HDL-C, apoB/apoA-I and LDL(NMR) /HDL(NMR) ratios were similarly associated with components of the metabolic syndrome and CHD risk., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed., Research Design and Methods: We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes., Results: Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1-2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or <1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12-1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02-1.42]., Conclusions: In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.

Background: The association of metabolic syndrome and risk of CHD is now well established. The association between 'metabolic dyslipidemia' as defined by high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels and the risk of coronary heart disease (CHD) risk is not known. The aim of this study was to investigate the association between metabolic dyslipidemia, and risk of coronary heart disease (CHD) in apparently healthy men and women., Methods: Metabolic dyslipidemia was defined by combination of increased triglyceride (TG) levels (≥150 mg/dl) and low high-density lipoprotein cholesterol (HDL-C) levels (≤50 mg/dl for women and ≤40 mg/dl for men). In the EPIC-Norfolk prospective population study, 21,340 participants without diabetes (9326 men and 12,014 women) were followed for a mean of 11.4 years during which 2075 CHD events occurred. Three multivariate models were used adjusting for other metabolic risk factors including low-density lipoprotein cholesterol (LDL-C)., Results: Compared to men with normal HDL and normal TG, men with metabolic dyslipidemia had an increased risk for CHD (HR 1.61, 95% CI 1.40-1.86). The increased risk remained significant after adjustment for LDL-C and other metabolic risk factors. Among women, metabolic dyslipidemia was associated with increased CHD risk (HR 1.78, 95% CI 1.47-2.15). This association was lost when the model was additionally adjusted for other metabolic syndrome risk factors. In men and women Kaplan-Meier survival curves according to HDL and TG levels revealed that participants with metabolic dyslipidemia had poorer survival compared to people without metabolic dyslipidemia (logrank p<0.001 for each)., Conclusions: Metabolic dyslipidemia is associated with an increased risk of CHD. This relationship was independent from LDL-C and other risk factors of the metabolic syndrome in men, but not in women. A better management of this phenotype via lifestyle modification or pharmacotherapy may be warranted., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to examine the relationship between metabolic syndrome (MetS) and left ventricular (LV) geometry and function in patients with asymptomatic aortic stenosis (AS)., Background: Recent experimental studies reveal that, among animals with sustained pressure overload, those with insulin resistance induced by a high-carbohydrate/high-fat diet have more severe LV hypertrophy and dysfunction compared to animals fed with standard diet., Methods: Among the 272 patients who were recruited in the ASTRONOMER (Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin) study, none had hypercholesterolemia, diabetes mellitus, or coronary artery disease (exclusion criteria) at baseline. However, 33% had systemic hypertension and 27% had MetS as identified by the National Cholesterol Education Program, Adult Treatment Panel III, clinical criteria., Results: Patients with MetS had higher LV mass index (53 +/- 14 g/m(2.7) vs. 47 +/- 15 g/m(2.7); p = 0.002), relative wall thickness ratio (0.47 +/- 0.09 vs. 0.42 +/- 0.09; p = 0.001), and prevalence of LV concentric hypertrophy (42% vs. 23%) and lower peak early diastolic (8.2 +/- 2.4 cm/s vs. 9.6 +/- 3.1 cm/s, p = 0.001) and peak systolic (7.9 +/- 1.7 cm/s vs. 8.7 +/- 2.2 cm/s, p = 0.009) mitral annular myocardial velocities compared to patients without MetS. After adjustment for age, sex, low-density lipoprotein cholesterol, hypertension, and valvuloarterial impedance (i.e., global LV hemodynamic load), MetS was independently associated with higher relative wall thickness ratio (p = 0.01), higher prevalence of concentric hypertrophy (p = 0.03), and reduced diastolic (p = 0.01) and systolic (p = 0.03) myocardial velocities., Conclusions: Notwithstanding AS severity and increase in hemodynamic load, MetS is independently associated with more pronounced LV concentric hypertrophy and worse myocardial function in patients with AS, which may, in turn, predispose them to the occurrence of adverse events. (Effects of Rosuvastatin on Aortic Stenosis Progression [ASTRONOMER]; NCT00800800)., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The metabolic syndrome, a constellation of metabolic abnormalities, which include abdominal obesity, insulin resistance, an atherogenic dyslipidemia, elevated blood pressure, a prothrombotic profile, and inflammation is associated with an increased risk of type 2 diabetes (1), cardiovascular disease (2), and mortality (3). The prevalence of individuals with these clustering abnormalities has been steadily increasing over the past two decades, is now estimated to affect at least a quarter of the US population, and is particularly prevalent among older adults (4). Similarly, abdominal obesity, as crudely estimated by an elevated waist circumference, is the most prevalent manifestation of the metabolic syndrome and affects 36% of men and 52% of women, according to the 1999-2000 US National Health and Nutrition Examination Study (5).

Background: The ratio of limb fat to trunk fat (LF/TF) is associated with markers of cardiometabolic risk in elderly men and women. It is unknown if LF/TF is associated with cardiometabolic risk beyond that explained by LF and TF independently., Methods: Participants included abdominally obese men (n = 58) and women (n = 78) between 60 and 80 years of age. Regional adiposity was quantified using magnetic resonance imaging. Insulin resistance, fasting glucose, high-density lipoprotein (HDL) cholesterol, plasma triglycerides, and adiponectin were determined using standard procedures., Results: After control for potential confounders, TF was positively associated with fasting glucose, insulin resistance, and plasma triglycerides and negatively associated with HDL cholesterol and adiponectin (p < or = .05). These associations were strengthened after further control for LF (p < .05), with the exception of adiponectin in men (p > .05). After control for potential confounders, LF was negatively associated with adiponectin in men (p < .05) but not with any other marker of cardiometabolic risk (p > .05). After further control for TF, LF was negatively associated with plasma triglycerides and positively associated with HDL cholesterol in both genders combined (p < .05) and with adiponectin in women (p < .05) but not in men (p > .05). LF/TF was not associated with any marker of cardiometabolic risk after control for LF and TF., Conclusion: These results suggest that it is the absolute, rather than relative, amounts of LF and TF that have the greatest influence on cardiometabolic risk in elderly men and women.

Objective: To assess the impact of a weight management program on metabolic health of second-generation antipsychotic (SGA)-treated patients., Methods: A prospective 12-week intervention program including individual exercise training and nutritional group sessions was performed as a pilot study. An intervention group of 6 SGA-treated patients (5 men and 1 woman; mean 15.0, SD 11.8 months) was compared with 10 reference patients under SGAs (8 men and 2 women; mean 14.0, SD 14.2 months), presenting similar age and baseline weekly levels of physical activity. For patients of both groups, anthropometric measurements and basic fasting lipid profile were assessed. For patients in the intervention group, an adapted Rockport Test was performed to evaluate their aerobic fitness and compliance to training sessions, and was recorded., Results: After the 12-week period, reference patients significantly gained weight (P = 0.001), whereas intervention patients showed significant weight loss and decreased body mass index (P = 0.02); interaction between groups: P < 0.01. This weight loss was accompanied by a decreased cholesterol-high-density lipoprotein cholesterol ratio (P = 0.04). Overall, the intervention patients' adherence to exercise prescription was 95.1 %, and this adherence induced a significant improvement of their aerobic fitness (P = 0.05)., Conclusion: This pilot study suggests that patients under SGAs may benefit from a weight management program and improve their metabolic health, as well as their aerobic fitness.

Global risk calculators such as the Framingham risk score generally take into account traditional risk factors such as age, sex, blood pressure, smoking status, total cholesterol and high-density lipoprotein cholesterol levels, and the presence of diabetes which are recommended to be used in clinical practice to estimate patients' cardiovascular disease (CVD) risk. Over the last decades, the prevalence of obesity has dramatically increased all over the world. The deleterious form of obesity, visceral obesity, is the most prevalent form of the so-called metabolic syndrome, a constellation of risk factors associated with perturbations of the lipoprotein-lipid profile and of the plasma glucose-insulin homeostasis also likely to be associated with increased blood pressure and a proinflammatory and prothrombotic state. To this date, metabolic syndrome is still in need of a place in global CVD risk prediction. As the metabolic syndrome is not likely to replace currently used global risk scoring algorithms, both traditional risk factors and emerging metabolic markers associated with the metabolic syndrome should be incorporated in future risk scoring systems to be developed in order to adapt CVD risk prediction tools to the epidemic of obesity which has direct consequences on the daily life of health professionals., (Copyright 2008 S. Karger AG, Basel.)

There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.

Context: Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease., Objective: To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome., Design, Setting, and Patients: Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia., Interventions: Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676)., Main Outcome Measures: The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV)., Results: In the rimonabant vs placebo groups, PAV (95% confidence interval [CI]) increased 0.25% (-0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm3 (-4.09 to -0.24) vs an increase of 0.88 mm3 (-1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (-0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm3 (-3.8 to -0.10) vs an increase of 1.19 mm3 (-0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg [-5.1 to -3.5] vs 0.5 kg [-1.3 to 0.3]) and greater decrease in waist circumference (4.5 cm [-5.4 to -3.7] vs 1.0 cm [-1.9 to -0.2]) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (-35.4 to -17.3) (20.5%) vs 8.9 mg/dL (-14.2 to -1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL [-1.7 to -1.2] [50.3%] vs 0.9 mg/dL [-1.4 to -0.5] [30.9%]) and less increase in glycated hemoglobin levels (0.11% [0.02% to 0.20%] vs 0.40% [0.31% to 0.49%]) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001)., Conclusions: After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way., Trial Registration: clinicaltrials.gov Identifier: NCT00124332.

The lack of physical activity and the adoption of poor nutritional habits is the major cause of the obesity epidemic that is currently sweeping the world. The expansion of adipose tissue mass, especially of the visceral adipose tissue depot, is observed in the vast majority of individuals carrying the clinical features of the metabolic syndrome, an important (and reversible) risk factor of type 2 diabetes and cardiovascular disease. As waist circumference can be used as a crude estimate of visceral fat accumulation, its measurement provides further information on cardiovascular and type 2 diabetes risk, at any given body mass index value. However, an elevated waist circumference might also be the result of an increased 'cardioprotective' subcutaneous adipose tissue mass. We have proposed that the measurement of plasma triglycerides along with waist circumference, the so-called 'hypertriglyceridemic waist' might better quantify visceral obesity and its health hazards than waist circumference alone. "Hypertriglyceridemic waist" is thought to represent an altered, dysfunctional, and highly lipolytic adipose tissue that is a major culprit abnormality behind the metabolic syndrome and associated cardiometabolic risk, independently from classical cardiovascular disease risk factors such as age, sex, and plasma low density lipoprotein (LDL) cholesterol levels.

Background: Postoperative atrial fibrillation (POAF) is a highly prevalent complication after cardiac surgery with substantial effects on outcomes. Previous studies have reported that obesity is a risk factor for POAF after cardiac surgery. However, it is unknown whether the metabolic syndrome (MS) also increases the risk of postoperative atrial fibrillation., Methods and Results: We retrospectively analyzed the association between obesity and MS and the incidence of new-onset POAF in a total of 5085 patients who underwent isolated coronary artery bypass grafting surgery with no concomitant valvular surgery. Of these patients, 1468 (29%) were obese (body mass index > or = 30 kg/m2) and 2320 (46%) had a MS as defined by the NCEP-ATPIII. POAF occurred in 1374 (27%) of the patients. Obesity was associated (P<0.001) with increased incidence of POAF in the whole cohort as well as in patients > 50 years old but not in patients < or = 50 years old. In these patients, MS was the only metabolic factor to be significantly associated with higher incidence of POAF (12% versus 6%, P=0.01). In > 50-year-old patients, mild (30 < or = body mass index < 35 kg/m2) and moderate-severe (body mass index > or = 35 kg/m2) obesity were independently associated with a 1.4-fold (95% CI: 1.10 to 1.71; P=0.004) and 2.3-fold (95% CI: 1.71 to 3.13; P<0.0001) increase in the risk of POAF, respectively. In < or = 50-year-old patients, MS (relative risk [RR]: 2.36; 95% CI: 1.10 to 5.12; P=0.02) but not obesity was independently associated with POAF., Conclusions: This study demonstrates that obesity is a powerful risk factor for the occurrence of POAF after isolated coronary artery bypass grafting surgery in patients older than 50 years. However, in the younger population, this association is not observed and MS is the only metabolic risk factor to be independently associated with POAF.

Objectives: The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG)., Background: Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a significant impact on operative mortality after this procedure. We hypothesized that the metabolic abnormalities associated with MS could negatively influence the operative outcome of CABG surgery., Methods: We retrospectively analyzed the data of 5,304 consecutive patients who underwent an isolated CABG procedure between 2000 and 2004. Of these 5,304 patients, 2,411 (46%) patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS. The primary end point was operative mortality., Results: The operative mortality after CABG surgery was 2.4% in patients with MS and 0.9% in patients without MS (p < 0.0001). The MS was a strong independent predictor of operative mortality (relative risk 3.04 [95% confidence interval (CI) 1.73 to 5.32], p = 0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69-fold (95% CI 1.43 to 5.06; p = 0.002) in patients with MS and diabetes and 2.36-fold (95% CI 1.26 to 4.41; p = 0.007) in patients with MS and no diabetes, whereas it was not significantly increased in the patients with diabetes and no MS., Conclusions: This is the first study to report that MS is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a CABG surgery. Thus, interventions that could contribute to reduce the prevalence of MS in patients with coronary artery disease or that could acutely modify the metabolic perturbations of MS at the time of CABG might substantially improve survival in these patients.

Background: It has been suggested that overweight and obese individuals with an adequate level of cardiorespiratory fitness (CRF), the so-called fat and fit, are at reduced risk of coronary heart disease and type 2 diabetes mellitus., Methods: To determine whether individuals with low CRF have more visceral adipose tissue (AT) accumulation compared with individuals with high CRF and to verify whether low CRF is associated with a poorer metabolic profile, we performed a cross-sectional study of 169 asymptomatic men without diabetes mellitus (mean +/- SD body mass index [calculated as weight in kilograms divided by height in meters squared], 25.9 +/- 4.4; and mean +/- SD age, 37.1 +/- 14.0 years). Abdominal AT accumulation, CRF, and indexes of plasma glucose-insulin homeostasis and of the lipoprotein-lipid profile were measured., Results: More visceral AT accumulation was observed among men in the lowest tertile of CRF compared with men in the highest tertile of CRF (mean +/- SD, 139.6 +/- 70.2 cm2 vs 74.7 +/- 41.6 cm2; P < .001). Overall, the plasma lipoprotein-lipid profiles were more favorable in men with a high CRF compared with individuals with a low CRF, as men with a low CRF had higher triglyceride (mean +/- SD, 161 +/- 73 mg/dL vs 99 +/-45 mg/dL; P < .001) and apolipoprotein B (mean +/- SD, 106 +/- 23 mg/dL vs 89 +/- 24 mg/dL; P < .009) levels and an increased total cholesterol-high-density lipoprotein cholesterol ratio (mean +/- SD, 5.27 +/- 1.00 vs 3.96 +/- 1.17; P = .002) than men with high CRF. After matching individuals with similar body mass index values but with high or low CRF, men with low CRF were characterized by more visceral AT accumulation than men with high CRF (mean +/- SD, 114.4 +/- 59.9 cm2 vs 87.8 +/- 49.1 cm2; P < .007) and by a poorer metabolic profile. However, when matched for visceral AT accumulation, such differences were no longer statistically significant., Conclusion: This study underlines the importance of visceral AT accumulation in the previously reported association between CRF and metabolic complications predictive of coronary heart disease and type 2 diabetes mellitus.

Diabetes and cardiovascular disease have emerged as major threats to human health, and the risk of developing these chronic conditions is increased in individuals with abdominal obesity and the metabolic syndrome. Excess visceral abdominal tissue (VAT) accumulation appears to be a key feature of abdominal obesity contributing to the development of the metabolic syndrome. For instance, excess VAT is accompanied by elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and/or elevated fasting plasma glucose. In addition, the rather normal or only marginally elevated low-density lipoprotein (LDL) cholesterol concentrations in patients with excess VAT could provide misleading information as viscerally obese patients have an increased plasma concentration of small, dense LDL particles. Prospective studies have suggested that even among patients with LDL cholesterol concentrations within normal limits, an increased concentration of small LDL particles is associated with higher risk of cardiovascular disease. With the treatment of abdominal obesity and excess VAT, an increase in patients' LDL particle size and improvements in other cardiovascular risk factors (eg, insulin levels, glucose tolerance, HDL, C-reactive protein [CRP], and adiponectin levels) can be achieved. Waist circumference can be used in clinical practice as a first approach and as a crude index to identify patients who have excess VAT, particularly when the elevated waistline is accompanied by the clinical features of the metabolic syndrome, among which an elevated fasting triglyceride concentration appears to be predictive of a reduced LDL particle size and of further metabolic abnormalities frequently referred to as the metabolic syndrome. Lifestyle changes, including more physical activity and healthier nutritional habits, are the cornerstone of therapy for high-risk abdominally obese patients with an excess of VAT. In addition, results from the RIO-Lipids study, which was conducted in high-risk obese, dyslipidemic patients, have provided evidence that CB1 receptor blockade with rimonabant can induce significant weight loss, and, more importantly, improve the cardiometabolic risk profile beyond what could be explained by the weight loss effects of the drug.

The metabolic syndrome represents a cluster of cardiovascular risk factors co-occurring in the same individual. The aim of this study was to identify chromosomal regions encoding genes predisposing to the metabolic syndrome using composite factors derived from maximum likelihood-based factor analysis. Genetic data were obtained from the Quebec Family Study and included 707 subjects from 264 nuclear families. Factor analyses were performed on eight metabolic syndrome-related phenotypes including waist circumference; BMI; systolic and diastolic blood pressure; and plasma insulin, glucose, triglyceride, and high-density lipoprotein-cholesterol levels. Three factors were identified and interpreted as general metabolic syndrome, blood pressure, and blood lipids, respectively. The general metabolic syndrome factor had high factor loadings (>0.4) for all phenotypes and explained 42% of the total variance, and family membership accounted for 45.6% of the factor variance. A genome-wide linkage scan performed with this first factor revealed the existence of a quantitative trait locus on chromosome 15 (86 cM) with a logarithm of odds score of 3.15. Suggestive evidence of linkage (logarithm of odds > 1.75) was also observed on chromosomes 1p, 3p, 3q, 6q, 7p, 19q, and 21q. These quantitative trait loci may harbor genes contributing to the clustering of the metabolic syndrome-related phenotypes.

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

The aim of the present study was to evaluate the relation among alcohol consumption, the metabolic syndrome, and the risk of ischemic heart disease (IHD). The study was conducted in a cohort of 1966 men from the Quebec Cardiovascular Study. All men were initially free of IHD and, during the follow-up period of 13 y, 219 first cases of IHD were diagnosed. Alcohol consumption was determined by calculating the g/d intake based on standard portions of beer, wine, and spirits. Metabolic syndrome was diagnosed according to a modification of the National Cholesterol Education Program Adult Treatment Panel III definition. Men who consumed >or=15.2 g of alcohol/d (4th quartile of the distribution) were younger (P < 0.001), had elevated plasma HDL-C concentrations (P < 0.001), and lower plasma concentrations of insulin (P = 0.01), CRP (P = 0.01), and fibrinogen (P < 0.001) than men in the 1st quartile (<1.3 g of alcohol/d). After adjustment for a series of coronary risk factors, alcohol consumption >or=15.2 g/d was associated with a 39% reduction in the 13-y risk of IHD [relative risk (RR) of IHD = 0.61, P = 0.02]. Finally, an alcohol consumption <15.2 g/d was associated with an increase of the risk of IHD in men with the metabolic syndrome (RR = 2.24, P < 0.001) but not in men without the metabolic syndrome (RR = 1.31, P = 0.22). These results confirm that moderate daily alcohol consumption has cardioprotective properties and suggest that the effects may be more important in subjects with a deteriorated risk profile, such as those with the metabolic syndrome.

Background: Several studies have reported similarities between calcification of the native aortic valve and atherosclerosis. Recent studies also suggested that hypercholesterolemia may be a risk factor for calcific degeneration of bioprosthetic valves. The metabolic syndrome (MS) is associated with a higher risk of vascular atherosclerosis. We thus hypothesized that the atherogenic features of MS could accelerate bioprosthetic valve degeneration., Methods and Results: We included 217 patients who underwent aortic valve replacement with a bioprosthetic valve in the study. Of these patients, 71 patients (33%) had MS defined according to the modified criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III. The annualized increase in mean transprosthetic gradient and the worsening of transprosthetic regurgitation measured by Doppler echocardiography were used to assess the deterioration of valve hemodynamic function. Patients with MS had higher progression of gradient (+4+/-5 mm Hg/year versus +2+/-2 mm Hg/year, P<0.001), higher proportion of > or = 1/3 degree worsening of regurgitation (25% versus 12%, P=0.02), and higher proportion of valve function deterioration defined as regurgitation worsening and/or > or = 3 mm Hg/year increase in gradient (41% versus 25%, P=0.02) when compared with patients without MS. On multivariate analysis, MS was an independent predictor of gradient progression (P=0.01), regurgitation worsening (P=0.02), and valve function deterioration (P=0.02). The other independent predictors were diabetes, renal insufficiency, and higher mean gradient at baseline., Conclusions: This is the first study to report that the MS is independently associated with faster bioprosthetic valve degeneration. This study could pave the way for the development of a new medical therapy able to significantly reduce the structural valve deterioration of bioprostheses.

Objectives: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS)., Background: It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS., Methods: We retrospectively analyzed the data of 105 consecutive patients (age 69 +/- 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 +/- 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up., Results: The hemodynamic progression of the stenosis was twice as fast (-0.14 +/- 0.13 cm2/year vs. -0.08 +/- 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 +/- 8% vs. 69 +/- 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001)., Conclusions: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.