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Aims: We aimed to evaluate the association between metabolic syndrome (MetS) and long-term all-cause mortality., Methods and Results: The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006, and 2015. MetS was diagnosed based on the National Cholesterol Education Program, Adult Treatment Panel III (NCEP/ATP III), and Joint Interim Statement (JIS) criteria. The cohort was divided into four groups: non-obese patients without MetS, obese patients without MetS, non-obese patients with MetS, and obese patients with MetS. Differences in all-cause mortality were analysed using Kaplan-Meier and Cox regression analyses. A total of 45 615 participants were enrolled (mean age 56.3, standard deviation: 11.8 years; 61.7% female). MetS was diagnosed in 14 202 (31%) by NCEP/ATP III criteria and 17 216 (37.7%) by JIS criteria. Follow-up was available for 44 620 (97.8%, median duration 15.3 years) patients. MetS was associated with increased mortality risk among the obese {hazard ratio, HR: 1.88 [95% confidence interval (CI) 1.79-1.99] and HR: 1.93 [95% CI 1.82-2.04], according to NCEP/ATP III and JIS criteria, respectively} and non-obese individuals [HR: 2.11 (95% CI 1.85-2.40) and 1.7 (95% CI 1.56-1.85) according to NCEP/ATP III and JIS criteria, respectively]. Obese patients without MetS had a higher mortality risk than non-obese patients without MetS [HR: 1.16 (95% CI 1.10-1.23) and HR: 1.22 (95% CI 1.15-1.30), respectively in subgroups with NCEP/ATP III and JIS criteria applied]., Conclusions: MetS is associated with increased all-cause mortality risk in non-obese and obese patients. In patients without MetS, obesity remains significantly associated with mortality. The concept of metabolically healthy obesity should be revised., Competing Interests: Conflict of interest: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.J. and M.B. have received an unrestricted educational grant from Valeant and have served as consultants or speakers for Valeant. P.P. owns four shares in AstraZeneca PLC and has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Mylan, Napp, and Sanofi. All other authors declare no conflicts of interest concerning the results of this analysis. All authors revised the article critically for important intellectual content. All authors gave final approval of the work, have participated sufficiently in the work, and take public responsibility for appropriate portions of the content., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the " cardiometabolic continuum " and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm.

The prevalence of non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is rising. About 25% of adults worldwide are probably affected by NAFLD. Insulin resistance (IR) and fat accumulation in the liver are strongly related. The association between NAFLD, metabolic syndrome (MetS) and IR is established, but an independent impact of NAFLD on vascular risk and progression of cardiovascular (CV) disease (CVD) still needs to be confirmed. This narrative review considers the evidence regarding the link between NAFLD, IR and CVD risk. There is strong evidence for a "concomitantly rising incidence" of NAFLD, IR, MetS and CVD but there is no definitive evidence regarding whether NAFLD is, or is not, an independent and significant risk factor the development of CVD. There are also considerations that type 2 diabetes mellitus (T2DM) may be a common link between NAFLD/non-alcoholic steatohepatitis (NASH) and CVD. NAFLD may be associated with widespread abnormal peri-organ or intra-organ fat (APIFat) deposition (e.g. epicardial adipose tissue) which may further contribute to CV risk. It is clear that NAFLD patients have a greater CV risk (independent or not) which needs to be addressed in clinical practice., Competing Interests: Declaration of competing interest EM has given talks or attended conferences sponsored by Novo Nordisk, SANOFI, AstraZeneca, SERVIER and Merck. DPM has given talks, acted as a consultant or attended conferences sponsored by Amgen, Novo Nordisk and Libytec. The article is based on a lecture given by DPM as part of the 18th Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease meeting, Los Angeles, USA, December 3–5, 2020. DPM received a fee from the organizers of the meeting; there was no specific pharmaceutical industry funding or any involvement in the content of the lecture or present review. CM reports grants, personal fees and other from Coherus Inc., grants, personal fees and other from Novo Nordisk, personal fees and non-financial support from Ansh, personal fees and non-financial support from Aegerion, personal fees and non-financial support from PES, personal fees and non-financial support from California Walnut Commission, personal fees from Genfit, personal fees from Intercept, personal fees from Regeneron, personal fees from CardioMetabolic Health Conference - The Metabolic Institute of America, personal fees from Amgen, outside the submitted work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Obesity frequently co-exists with type 2 diabetes mellitus (T2DM), leading to the socalled "diabesity epidemic". The metabolic syndrome (MetS), a cluster of central obesity, hypertension, dysglycemia, insulin resistance and/or atherogenic dyslipidemia, as well as non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of MetS, has been associated with increased cardiovascular disease (CVD), T2DM and chronic kidney disease (CKD) incidence. However, the association between obesity, MetS (including NAFLD) and diabetic microvascular complications is less evident., Methods: The present narrative review discusses the associations of obesity, MetS and NAFLD with diabetic kidney disease (DKD), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN) as well as cardiac autonomic neuropathy (CAN). The available data on the effects of lifestyle measures and bariatric surgery on these diabetic complications are also briefly discussed., Results: Overall, both obesity and MetS have been related to DKD, DR and DPN, although conflicting results exist. Links between NAFLD and diabetic microvascular complications have also been reported but data are still limited. Lifestyle intervention and bariatric surgery may prevent the development and/or progression of these microvascular complications but more evidence is needed., Conclusion: Clinicians should be aware of the frequent co-existence of MetS and/or NAFLD in T2DM patients to prevent or treat these metabolic disorders, thus potentially minimizing the risk for both CVD and diabetic microvascular complications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: We investigated the association between Dietary Inflammatory Index (DII ® ) scores and cardio-metabolic risk factors singly and in combination as metabolic syndrome (MetS)., Methods: We used data from participants selected from the US National Health and Nutrition Examination Survey (NHANES). Analyses were restricted to participants with data available on dietary intake, biochemical data, and anthropometric measurements from 2005 to 2012. Statistical analyses used the SPSS ® Complex Samples v22.0 (IBM Corp, Armonk, NY) and accounted for the survey design and sample weights. Energy-adjusted-DII (E-DII ® ) expressed per 1000 kcal was calculated from 24-h dietary recalls. Of the 17,689 participants with evaluable data, 8607 (48.3%) were men. The mean age was 45.8 years in the overall sample, with men being slightly younger than women (44.9 vs. 46.5 years, p = 0.05)., Results: In multivariable-adjusted regression models, the odds of MetS, its components, as well as obesity, and elevated high-sensitivity C-reactive protein (hsCRP) increased across increasing quartiles of E-DII (p < 0.001). In age, sex, race, income-to-poverty ratio-adjusted models, these and other cardiovascular disease risk factors (triglycerides/high density lipoprotein cholesterol (HDL-C) ratio, apolipoprotein (B) and HbA1C) increased across quartiles of the E-DII (all p < 0.001), while HDL-C levels decreased (p < 0.001)., Conclusions: This study suggests associations between MetS, its components, subclinical inflammation, and the DII. These results reinforce the view that diet plays an important role in the occurrence of cardiovascular diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Metabolic syndrome (MetS) is a cluster of central obesity, dyslipidaemia, insulin resistance and hypertension. MetS frequently co-exists with non-alcoholic fatty liver disease (NAFLD), which is characterized by fat accumulation in the liver in the absence of alcohol abuse, viral hepatitis and other causes of chronic liver diseases. Both MetS and NAFLD are associated with an increased risk for cardiovascular disease and type 2 diabetes mellitus. There are also other associations between MetS and NAFLD. In the present narrative review, we discuss the links between MetS and NAFLD in terms of prevalence, risk factors and treatment (both lifestyle interventions and drug therapy). Such associations highlight the common pathophysiological pathways of these metabolic disorders, although data for an independent association are not robust. Nevertheless, NAFLD may be regarded as a hepatic manifestation of MetS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Metabolic syndrome (MetS) represents a constellation of risk factors, including central obesity, elevated fasting blood glucose, high blood pressure and atherogenic dyslipidemia. This prospective observational study aimed to assess the impact of MetS on perioperative outcomes of patients undergoing elective abdominal surgery with laparotomy., Methods: We included 105 consecutive non-diabetic patients undergoing elective abdominal surgery with laparotomy. Patients were divided into two groups based on MetS diagnosis. Perioperative adverse events were recorded according to the definitions of the European Perioperative Clinical Outcome guidelines., Results: The prevalence of MetS was 57.1%. The presence of MetS was associated with a 2.64 higher odds (95% CI 1.18-5.95, P = 0.019) for respiratory events and a 3.42 higher odds (95% CI 1.05-11.13, P = 0.041) for superficial surgical site infections. Furthermore, regarding MetS patients, all individual components of MetS were associated with worse outcomes in an independent manner., Conclusions: MetS as an entity along with its individual components are associated with an increased risk of perioperative events in patients undergoing elective abdominal surgery with laparotomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health., (© The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Aim: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH., Methods: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values., Results: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20(th), which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group., Conclusion: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.

Background: There is no widely accepted treatment for non-alcoholic fatty liver disease (NAFLD) or its advanced form, non-alcoholic steatohepatitis (NASH)., Methods: We administered rosuvastatin (10 mg/day) for 1 year in patients with metabolic syndrome (MetS), NASH on liver biopsy and dyslipidaemia (but without diabetes or arterial hypertension). Patients also received lifestyle advice., Results: We report preliminary results for 6 patients. The second biopsy (at the end of the study) showed complete resolution of NASH in 5 patients, while the 6(th), which had no improvement, developed arterial hypertension and substantial rise in triglyceride levels during the study. We suspect alcohol abuse despite advice to abstain. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were reduced by 76 and 61%, respectively (p < 0.001 for both), during treatment, while γ-glutamyl transpeptidase (γ-GT), and alkaline phosphatase (AP) showed smaller non significant reductions. Fasting plasma glucose and glycated haemoglobin (HbA1c) were significantly reduced (p<0.05). Lipid values were totally normalised and liver ultrasonography showed a complete resolution of NASH in 5 patients. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed to treatment with rosuvastatin. A substantial limitation of the study is the small number of patients., Conclusions: These preliminary findings suggest that rosuvastatin could ameliorate NASH within a year of treatment in MetS patients with dyslipidaemia.

Metabolic syndrome (MetS), a cluster of dyslipidaemia, central obesity, hypertension and/or insulin resistance, is associated with increased cardiovascular disease (CVD) type 2 diabetes risk. Different diagnostic criteria for MetS have been proposed but in 2009 a joint statement by several scientific societies was released. Apart from the diagnostic criteria, MetS has also been associated with other risk factors including waist to hip ratio, high density lipoprotein dysfunction, small dense low density lipoprotein, postprandial hypertriglyceridaemia, lipoprotein (a), uric acid, liver function tests, prothrombotic factors, cytokines, adipokines, vitamin D, arterial stiffness, renal dysfunction, nephrolithiasis, polycystic ovary syndrome, obstructive sleep apnea. We discuss the extensive list of MetS-associated factors that may influence vascular risk. Furthermore, we discuss the impact of frequently prescribed drugs (e.g. hypolipidaemic agents) on these variables. These effects may need to be taken into consideration when treating MetS patients.

In humans uric acid (UA) is the end product of degradation of purines. The handling of UA by the renal system is a complex process which is not fully understood. To date, several urate transporters in the renal proximal tubule have been identified. Among them, urate transporter 1 (URAT1) and a glucose transporter 9 (GLUT9) are considered of greater importance, as potential targets for treatment of hyperuricemia and the potential associated cardio-metabolic risk. Therefore, the recognition of the metabolic pathway of UA and elucidation of occurrence of hyperuricemia may provide important insights about the relationship between UA, pre-hypertension (preHT) and the metabolic syndrome (MetS). We also review the available clinical studies in this field, including experimental studies dealing with the mechanisms of UA transport via different transporters, as well as current treatment options for hyperuricemia in patients with MetS, preHT or cardiovascular risk factors.

The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Several international organizations have defined MetS using different diagnostic criteria that produced discrepancies in the results of previous studies, thus leading to the latest Joint Interim Societies (JIS) MetS definition. Other risk factors than the diagnostic criteria that have been associated with MetS include lipid abnormalities, uric acid, liver function, prothrombotic factors, cytokines, adipokines, vitamin D, arterial stiffness, polycystic ovary syndrome and obstructive sleep apnea. Apart from CVD and T2DM, MetS has been related to non-cardiac vascular diseases and in particular to stroke, carotid artery disease, peripheral artery disease, chronic kidney disease, atherosclerotic renal artery stenosis and abdominal aortic aneurysms. In this narrative review, the associations of these diseases with MetS and its components will be discussed. These associations may further increase CVD risk in MetS patients, highlighting the importance of treating such high-risk individuals early and "to target". In this context, multifactorial treatment including a statin has been proven beneficial, and thus should be considered, in MetS patients.

Metabolic syndrome (MetS) is associated with increased risk of both atherothrombotic cardiovascular events and venous thromboembolism. The pro-thrombotic potential of MetS, may explain this association. In this review we discuss the relationship of MetS with hemostasis focusing on endothelial function, platelet activity, coagulation, fibrinolysis and hemorheologic markers. Endothelial-dependent vasodilatation is impaired in MetS. This is mostly mediated by a reduced expression of vasodilators (nitric oxide and prostacyclin) with a concomitant increase of vasoconstrictors (endothelin- 1, angiotensin II and thromboxane A2). Platelet activity is enhanced in MetS. A cross-talk between activated endothelium and platelets results in a pro-thrombotic vicious cycle. Enhanced coagulation together with impaired fibrinolysis is also present in MetS. This is mirrored by high fibrinogen and plasminogen activator inhibitor-1 levels. Endothelial dysfunction, expressed by high von Willebrand factor and tissue plasminogen factor levels, also contributes to this abnormality. Whole blood and plasma viscosity is increased in MetS. Lifestyle intervention can improve the MetS-related pro-thrombotic state. These measures include weight reduction and improved composition of the diet. A Mediterranean-style diet rich in olive oil, as a source of monounsaturated fat, and low saturated fat consumption may also be beneficial.

The metabolic syndrome (MetS) is a cluster of risk factors including insulin resistance, dyslipidemia and hypertension which are also relevant for the development of chronic kidney disease (CKD). It has proven difficult to elucidate whether the renal dysfunction in MetS is due to the MetS itself or the individual risk factors. For example, obesity - which is also part of the MetS - may enhance the risk of renal dysfunction development probably through mechanisms associated with renal hyperfiltration, hyperperfusion and focal glomerulosclerosis. Insulin resistance also promotes kidney disease by worsening renal hemodynamics. In patients with MetS, tubular atrophy, interstitial fibrosis, and arteriolar sclerosis indicating the presence of vascular damage, have also been described. As yet, there has been little evidence that preventing or treating symptoms of the MetS protects patients from renal impairment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.

Objective: Metabolic syndrome (MetS) and Cushing's syndrome share common features. It has been proposed that increased glucocorticoid activity at peripheral tissues may play a role in the pathogenesis of MetS and obesity-related disorders. It is well-known that intracellular cortisol concentrations are determined not only by plasma levels but also by the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyzes the conversion of inactive cortisone to active cortisol, especially in the liver and adipose tissue. Another isoenzyme exists, the 11β-hydroxysteroid dehydrogenase type 2, which acts in the opposite direction inactivating cortisol to cortisone in the kidney. This review considers the significance of the 11β-HSD1 inhibition in the treatment of several features of MetS and provides current data about the development of 11β-HSD1 inhibitors, as new agents for this purpose., Materials/methods: Using PubMed, we searched for publications during the last 20years regarding the development of 11β-HSD1 inhibitors., Results: Emerging data from animal and human studies indicate an association of 11β-HSD1 over-expression with obesity and disorders in glucose and lipid metabolism. This has led to the hypothesis that selective inhibition of 11β-HSD1 could be used to treat MetS and diabetes. Indeed, natural products and older agents such as thiazolidinediones and fibrates seem to exert an inhibitory effect on 11β-HSD1, ameliorating the cardiometabolic profile. In view of this concept, novel compounds, such as adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones, BVT2733, INCB-13739, MK-0916 and MK-0736, are currently under investigation and the preliminary findings from both experimental and human studies show a favourable effect on glucose and lipid metabolism, weight reduction and adipokine levels., Conclusions: Many compounds inhibiting 11β-ΗSD1 are under development and preliminary data about their impact on glucose metabolism and obesity-related disorders are encouraging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3½ year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.

Aims: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Several definitions of MetS have been proposed. The aim of the present study was to estimate and compare the prevalence of MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association-National Heart Lung and Blood Institute (AHA-NHLBI), International Diabetes Federation (IDF) and the more recent Joint Interim Statement (JIS) definitions in patients attending a hypertension clinic., Methods: The records of patients referred to the hypertension clinic at the University Hospital (Heraklion, Crete) from January 2001 to June 2009 were screened retrospectively. A total 384 patients (146 men) were included in the study., Results: The prevalence of MetS according to the IDF and JIS definitions was significantly higher compared with that of the NCEP ATP III in both genders (IDF: P = .009 and P = .002, JIS: P = .002 and P = 0.001 for men and women, respectively); this was the case for the AHA-NHLBI definition only among women (P = .03). All MetS components differed significantly (P from < .0001 to .02) between patients with and without MetS for all definitions., Conclusions: The prevalence of MetS varies considerably depending on the definition used in a hypertensive population in a Mediterranean country. These differences will influence risk assessment.

Aim: To assess the reduction in estimated cardiovascular disease (e-CVD) risk after multifactorial treatment for 6 months and follow this change during the next 3-years., Patients-Methods: This prospective, randomized, target driven study included 1,123 subjects (512/611 men/women, aged 45-65 years) with metabolic syndrome (MetS) without diabetes or CVD referred to specialist outpatient clinics. Patients were randomized to two treatment groups: group A with low density lipoprotein cholesterol (LDL-C) target of < 100 mg/dl and group B with a target of < 130 mg/dl. Atorvastatin was used in both groups on top of optimal multifactorial treatment, (quinapril, amlodipine, hydrochlorothiazide for hypertension, metformin for impaired fasting glucose, and orlistat for obesity). The e-CVD risk was calculated using the Framingham, the PROCAM and Reynold's equations., Results: Reductions in e-CVD risk at 6 months were > 50%in all patients, but were superior in group A and in women. Reductions were even greater during the next 3-years and were mainly attributed to changes in lipid profile. Actual CVD events were 1 in group A and 13 in group B; p=0.0012., Conclusions: Attaining the treatment target of LDL-C < 100 mg/dl within multifactorial treatment of MetS by expert clinics, is achievable and beneficial even in patients without diabetes or known CVD. This induces a considerable e-CVD risk reduction in MetS patients. Actual CVD events were negligible, suggesting that e-CVD risk overestimates actual CVD risk in MetS, at least in patients achieving LDL-C < 100 mg/dl [ClinicalTrials.gov ID: NCT00416741].

The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field.

Aim: To assess the effects of long-term multifactorial intervention on renal function and serum uric acid (SUA) levels and their association with estimated cardiovascular disease (eCVD) risk and actual CVD events., Methods: This prospective, randomized, target-driven study included 1123 subjects (45.6% men, age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD. Patients were randomized to multifactorial treatment. Atorvastatin was titrated from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30-59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same group, unpaired Student t-test to compare results between groups at specific time points, and log-rank test to compare event free survival., Results: The eCVD-risk reduction was greater in group A. In the overall study population, eGFR increased by 3.5% (p < 0.001) and SUA levels fell by 5.6% (p < 0.001). In patients from group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p < 0.001) from baseline and by 7.5% (p < 0.001) in group B1 (n = 177; p < 0.001 vs. the change in group A1). The corresponding fall in SUA levels was 10.7% in group A1 (p < 0.001 vs. baseline) and 8.3% in group B1 (p < 0.001 vs. baseline and group A1). These changes were mainly attributed to atorvastatin treatment. Among the CKD stage 3 patients there were no CVD events in group A1, while 6 events occurred in group B1 (p = 0.014)., Conclusions: Multifactorial intervention in patients with MetS without established CVD improved renal function and reduced SUA levels. These changes were more prominent in stage 3 CKD patients and might have contributed to the reduction in eCVD risk and clinical events. Original study registration number [ClinicalTrials.gov ID: NCT00416741].

Introduction: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy., Patients and Methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%., Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86-0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85., Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis., (© 2011 John Wiley & Sons A/S.)

Background and Aim: The treatment-of-choice for the optimal management of the dyslipidemia of the metabolic syndrome (MetS) is not clearly defined. We compared the efficacy of 4 drug regimes for the management of this dyslipidemia in a mouse model., Materials and Methods: A total of 60 C57Bl6 mice comprised the study group. The first 10 received standard mouse food for the whole experiment (control group). The remaining 50 mice received atherogenic diet for 14 weeks until the development of the MetS. The mice were then divided into 5 groups: the 1st group continued receiving atherogenic diet, while the other 4 groups received atherogenic diet plus ezetimibe (10 mg/kg per day), fenofibrate (100 mg/kg per day), low-dose atorvastatin (10 mg/kg per day), or high-dose (40 mg/kg per day) atorvastatin, respectively, for another 8 weeks., Results: High-dose atorvastatin treatment achieved the best lipid profile compared with low-dose atorvastatin, ezetimibe, and fibrate therapy. The lipid profile of mice receiving atherogenic diet plus high-dose atorvastatin treatment was similar with mice on regular chow., Conclusions: High-dose atorvastatin treatment resulted in optimization of the lipid profile in the presence of a high-fat atherogenic diet in a mouse model. Our results suggest that high-dose atorvastatin treatment may be the optimal treatment option for the dyslipidemia associated with MetS. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.

In addition to bone homeostasis, vitamin D is involved in the physiological functions of several tissues and its insufficiency may contribute to various disorders. Vitamin D status seems to be associated with each of the components of metabolic syndrome (MetS), as well as MetS overall. We review these associations as well as the effects of vitamin D supplementation on MetS.

Background: There is a need to evaluate the prevalence of metabolic syndrome (MetS) diagnosed by the new Joint Interim Societies (JIS) MetS definition. The JIS definition was compared with three previous definitions to assess their ability to predict cardiovascular disease (CVD) risk., Methods: A cross-sectional analysis of a representative sample of Greek adults (n = 9669) was performed to estimate the prevalence of MetS and CVD using the JIS vs. the three older definitions of MetS: the National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP-III), the International Diabetes Federation (IDF) and the American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) definitions., Results: The age-adjusted MetS prevalence was 45.7%, 43.4%, 24.5% and 26.3% (ANOVA p < 0.001) with the JIS, IDF, NCEP and AHA/NHLBI definitions. The prevalence of CVD was 11.4% in the whole study population and 17.6%, 18.3%, 23.3%, 22.6% and in subjects with MetS according to the JIS, IDF, NCEP and AHA/NHLBI definitions (ANOVA p < 0.001). The prevalence of CVD was only 10.4% (i.e., lower than in the whole study population) in subjects with MetS according to the JIS but not according to the NCEP-ATP-III and AHA/NHLBI definitions (p < 0.001 vs. subjects with MetS as defined by NCEP-ATP-III or AHA/NHLBI)., Conclusions: When diagnosed according to the new JIS definition, the prevalence of MetS was high in a Greek Mediterranean cohort (nearly half of the adult population). The NCEP-ATP-III and AHA/NHLBI definitions were more predictive of CVD risk than the new JIS definition. These findings, though limited by the cross sectional analysis, may have implications regarding the choice of the definition to diagnose MetS.

We investigated cardiovascular disease (CVD) risk factors in 1501 Greeks (613 men and 888 women, aged 40-65 years) referred to outpatients with metabolic syndrome (MetS) and without diabetes mellitus or CVD. The 10-year risk of fatal CVD events was calculated using European Society of Cardiology Systematic Coronary Risk Estimation (ESC SCORE), Hellenic-SCORE, and Framingham equations. Raised blood pressure (BP) and hypertriglyceridemia were more common in men (89.6% vs 84.2% and 86.8% vs 74.2%, respectively; P < .001). Low high-density lipoprotein cholesterol (HDL-C) and abdominal obesity were more common in women (58.2% vs 66.2% and 85.8% vs 97.1%, respectively; P < .001). The 10-year risk of fatal CVD events using HellenicSCORE was higher in men (6.3% +/- 4.3% vs 2.7% +/- 2.1%; P < .001). European Society of Cardiology Systematic Coronary Risk Estimation and Framingham yielded similar results. The risk equations gave similar assessments in a European Mediterranean population except for HellenicSCORE that calculated more MetS women requiring risk modification. This might justify local risk engine evaluation in event-based studies. (Clinical-Trials.gov ID: NCT00416741).

Context: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities that increase the risk for type 2 diabetes mellitus and vascular disease. The common characteristics of MetS and hypercortisolemic conditions such as Cushing's syndrome (CS) suggest that the pathogenesis of MetS and central obesity might involve prolonged and excessive exposure to glucocorticoids. The present review summarizes the evidence on the potential role of cortisol in the pathogenesis of MetS and discusses new therapeutic approaches for these patients., Evidence Acquisition: Using PubMed, we searched for publications during the last 20 yr regarding the possible pathogenetic role of cortisol in the development of MetS., Evidence Synthesis: Emerging data suggest that patients with MetS show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a state of "functional hypercortisolism." The cause for this activation of the HPA axis remains uncertain but may be partly associated with chronic stress and/or low birth weight, which are both associated with increased circulating cortisol levels and greater responsiveness of the HPA axis. Increased exposure to cortisol contributes to increased fat accumulation in visceral depots. However, cortisol metabolism is not only centrally regulated. The action of 11beta-hydroxysteroid dehydrogenase-1 at the tissue level also modulates cortisol metabolism. Increased 11beta-hydroxysteroid dehydrogenase-1 activity in adipose tissue and liver might contribute to the development of several features of the MetS., Conclusions: MetS shares many characteristics of CS, and cortisol might play a role in the development of MetS at both a central and a peripheral level.

Type 2 diabetes is usually associated with a number of metabolic and cardiovascular (or cardiometabolic) risk factors that contribute to a high rate of vascular events in these patients. Adipose tissue is now known to secrete a number of pro-inflammatory adipokines that are thought to mediate the link between obesity, insulin resistance and atherosclerosis. Therefore, not only is abdominal obesity a major cardiometabolic risk factor per se, it has the potential to give rise to other emerging risk factors. Plasma concentrations of inflammatory markers, such as C-reactive protein, may provide additional information to guide management and may even represent therapeutic targets. Reducing the risk of cardiovascular events in patients with Type 2 diabetes will involve targeting traditional risk factors and probably novel cardiometabolic factors.

The purpose of this study was to investigate the relationship between alcohol consumption and the prevalence of the metabolic syndrome (MetS), type 2 diabetes mellitus (DM), coronary heart disease (CHD), stroke, peripheral arterial disease (PAD), and overall cardiovascular disease (CVD) in a Mediterranean cohort. It consisted of a cross-sectional analysis of a representative sample of Greek adults (n = 4,153) classified as never, occasional, mild, moderate, or heavy drinkers. Cases with overt CHD, stroke, or PAD were recorded. In our population, 17% were never, 23% occasional, 27% mild, 24% moderate, and 9% heavy drinkers. Moderate alcohol consumption was associated with a lower trend for the prevalence of the MetS (P = .0001), DM (P < .0001), CHD (P = .0002), PAD (P = .005), and overall CVD (P = .001) but not stroke compared with no alcohol use. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Wine consumption was associated with a slightly better effect than beer or spirits consumption on the prevalence of total CVD, and beer consumption was associated with a better effect than spirits consumption. Alcohol intake was positively related with body weight, high-density lipoprotein cholesterol levels, and hypertension. Moderate alcohol consumption is associated with a lower prevalence of the MetS, DM, PAD, CHD, and overall CVD but not stroke compared with no alcohol use in a Mediterranean population. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Advice on alcohol consumption should probably mainly aim at reducing heavy drinking.

The insulin resistance/metabolic syndrome is characterized by the variable co-existence of hyperinsulinemia, obesity, dyslipidemia (small dense low-density lipoprotein, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol), and hypertension. The pathogenesis of the syndrome has multiple origins. However, obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. This multifactorial and complex trait of metabolic syndrome leads to increased risk of cardiovascular disease. The scope of this review is to examine the differences in prevalence of the metabolic syndrome in various groups (eg, according to age, sex, ethnicity, social status, or presence of obesity) that could help with the better understanding of the pathogenesis of this syndrome. This review also considers the impact of metabolic syndrome on cardiovascular disease.

This review considers the use of the first selective blocker of the cannabinoid receptor type 1, rimonabant, to reduce weight and improve cardiovascular disease risk factors in obese patients with metabolic syndrome or multiple cardiovascular disease risk factors. In 4 large trials-Rimonabant in Obesity (RIO)-Lipids, RIO-Europe, RIO-North America, and RIO-Diabetes-after 1 to 2 years of treatment, rimonabant (20 mg/day) led to a significantly greater weight loss and reduction in waist circumference compared with placebo. Treatment with rimonabant was also associated with other favorable changes, including better glycemic control in type 2 diabetes mellitus, improved lipid profile, reduced blood pressure, increased adiponectin levels, fall in high-sensitivity C-reactive protein concentrations, and an overall decrease in the prevalence of the metabolic syndrome. Initial experience with rimonabant shows that it is generally well tolerated with the most common side effect of mild nausea. Rimonabant may be a useful adjunct to lifestyle and behavior modification in the treatment of obese subjects with metabolic syndrome or multiple cardiometabolic risk factors.

The metabolic syndrome (MetS) is a strong predictor of cardiovascular morbidity and mortality, as well as new Type 2 diabetes. MetS consists of visceral obesity, elevated blood pressure, impaired glucose metabolism, atherogenic dyslipidaemia (elevated triglycerides and low levels of high-density lipoprotein cholesterol), as well as other metabolic abnormalities. The underlying pathophysiology seems to be largely, but not uniquely, attributable to insulin resistance. Existing antihypertensive drugs were designed to lower blood pressure rather than to modify the metabolic abnormalities associated with hypertension. This review considers the role of renin-angiotensin system inhibition and especially the use of angiotensin receptor blockers (ARBs) in the treatment of hypertension in MetS. There are differences among ARBs. Among them is the uricosuric effect of losartan. Furthermore, telmisartan may function as a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

Background: Metabolic syndrome (MetS) is associated with increased risk for both vascular and chronic kidney disease. Whether statins ameliorate these risks is not established., Methods: This post hoc analysis of the GREek Atorvastatin and Coronary heart disease (CHD). Evaluation (GREACE) examines the effect of statins on estimated glomerular filtration rate (e-GFR) and serum uric acid (SUA) levels and their relation to vascular events in CHD patients with MetS. MetS patients were divided into two groups: Group A (n = 365) received lifestyle advice, target-driven treatment with statins (mainly atorvastatin) and treatment for hypertension and elevated glucose. Group B (n = 347) received the same except for statins. Patients without MetS were divided into those who received treatment similar to Group A and Group B [Groups C (n = 504) and D (n = 384), respectively]. All patients were followed for 3 years., Results: A total of 12.1% of patients in Group A experienced a vascular event vs 28% in Group B; risk ratio (RR) 0.43, 95% confidence interval (CI) 0.20-0.64, P < 0.0001, while in those without MetS (Group C vs Group D), the respective RR was 0.59, 95% CI 0.41-0.79, P < 0.0001. In Group A, e-GFR increased by 13.7% and SUA levels fell by 8.9%, while in Group B e-GFR was reduced by 5.8% and SUA increased by 4.3% (P < 0.005). Stepwise regression analysis showed that these changes were independently related to vascular events., Conclusion: Among CHD patients, those with MetS benefited more from statin treatment than those without MetS. This benefit could be partially attributed to favourable changes in e-GFR and SUA levels probably induced by statin treatment.

Elevated serum uric acid (SUA) levels are commonly seen in patients with the metabolic syndrome (MetS). Several mechanisms, both direct and indirect, connect the increased SUA levels with the established diagnostic criteria of MetS. It is possible that the increased cardiovascular disease risk associated with the MetS is partially attributed to elevated circulating SUA concentration. Several drugs used in the treatment of MetS may alter SUA levels. Thus, lifestyle measures together with the judicious selection of drugs for the treatment of hypertension, dyslipidemia, and insulin resistance associated with MetS may result in a reduction of SUA levels and possibly cardiovascular disease risk. This review summarizes the pathophysiologic association between SUA and MetS and focuses on the prevention of hyperuricemia and its cardiovascular consequences.

Background: Postprandial hyperlipidaemia may be a predictor of vascular risk., Design: We evaluated postprandial lipaemia after an oral fat tolerance test (OFTT) in men (n=41) and women (n=21) with metabolic syndrome (MetS)., Methods: Triglyceride (TG) levels were measured before and 2, 4, 6 and 8 h after the fat load., Results: Men showed a greater plasma TG response 8 h after the fat load (284+/-117 versus 224+/-126 mg/dl, P=0.029). Only fasting TG levels significantly predicted the TG area under the curve (AUC) and incremental AUC., Conclusions: Men had a more pronounced postprandial hypertriglyceridaemia and seem to have delayed TG clearance.

The hypertriglyceridemic waist (HTGW) phenotype (hypertriglyceridemia and increased waist circumference) has been proposed as an inexpensive tool to monitor individuals with the atherogenic metabolic triad, hyperinsulinemia, hyperapobetalipoproteinemia, and increased levels of small, dense LDL (sdLDL) particles. We assessed the association of the HTGW phenotype with the metabolic syndrome (MetSyn) and the atherogenic metabolic triad in inhabitants (n = 260) of northwestern Greece attending the Outpatient Lipid Clinic of the University Hospital of Ioannina. The LDL subfractions were assessed using the Lipoprint LDL System. HTGW (+) individuals had a more adverse lipid and lipoprotein profile compared with HTGW (-) individuals. Moreover, HTGW (+) subjects had elevated levels of sdLDL-C, as well as decreased mean and peak LDL particle size compared with HTGW (-) subjects. To our knowledge, this is the first report documenting the sdLDL-C abnormality in HTGW (+) subjects. Among men (n = 105), 52.3% of the MetSyn (+) individuals and 66.7% of the HTGW (+) individuals had the metabolic triad. Among women (n = 155), the corresponding percentages were 42.3% and 50.0%. Only 22.2% and 10.6% of the MetSyn (-) subjects (men and women, respectively) and 19.6% and 15.2% of the HTGW (-) subjects (men and women, respectively) had the atherogenic metabolic triad. In conclusion, the HTGW (+) phenotype is associated with a hostile lipid profile that includes higher levels of sdLDL-C and decreased LDL particle size. The HTGW phenotype, compared with the MetSyn criteria, can provide an easy and inexpensive tool to monitor patients characterized by an adverse lipid and lipoprotein profile.

The metabolic syndrome is a clustering of risk factors including central obesity, insulin resistance, dyslipidaemia and hypertension. This syndrome is associated with increased risk of cardiovascular disease and is a common early abnormality in the development of type 2 diabetes. The pathogenesis of the syndrome has multiple origins. Obesity and sedentary lifestyle coupled with genetic factors interact to produce the syndrome. Here, we consider two components of the metabolic syndrome, dyslipidaemia and hypercoagulability.

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidaemia and is associated with an increased risk of vascular events. Since the initial description of the MetS, several expert groups produced different definitions. This variability led to confusion and absence of comparability between studies. Although there is agreement that the MetS is a major public health challenge worldwide and consistent evidence stresses the need for intervention, the definition of the syndrome remains a matter of debate. This review considers the different definitions of the MetS. These include those proposed by the World Health Organisation, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program Adult Treatment Panel III, the American College of Endocrinology and American Association of Clinical Endocrinologists and the latest International Diabetes Federation definition which includes ethnic-specific waist circumference cut-off points. These definitions share several features but also include important differences; all have limitations. Selected (after a Medline search) studies comparing the different definitions are also considered. There is a need for a standardised definition of the MetS. Furthermore, a definition tailored for children and adolescents is essential. Prospective long-term studies are needed to validate the prognostic power of these definitions. As new information becomes available the definition of the MetS might be further modified.

Background: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD., Aim: To evaluate a multifactorial intervention in the treatment of NAFLD., Methods: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study., Results: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects., Conclusions: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).