Emmanuel S. Ganotakis

The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions

ABSTRACT Objective: The prevalence of metabolic syndrome (MetS), using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) definitions, was compared in 9669 subjects, representing the Greek population. Results: The age-adjusted prevalence of NCEP ATP III-defined MetS was 24.5% whereas that of IDF-defined MetS was 43.4% (+77%, p < 0.0001). The majority (up to 69%) of older age groups had IDF-defined MetS. The calculated vascular event risk was low (6.1% and 7.2% using the Framingham and PROCAM calculation, respectively) in those with IDF-defined MetS when compared with those with NCEP ATP III MetS (11.3% and 13.7%, respectively) ( p < 0.0001 for both comparisons). Conclusion: MetS could be considered as a ‘normal’ variant if it was present in the majority of the population. Moreover, the vascular risk associated with IDF-defined MetS could be low, raising cost-effectiveness issues. Alternatively, the new IDF definition may realistically reflect the current MetS epidemic. More studies are required to support or refute those interpretations.

Association of Drinking Pattern and Alcohol Beverage Type With the Prevalence of Metabolic Syndrome, Diabetes, Coronary Heart Disease, Stroke, and Peripheral Arterial Disease in a Mediterranean Cohort

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 = 4153) 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.

Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study

Objectives: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)—a major contributor to CVD—in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. Methods: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. Results: The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). Conclusion: A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.

Comparison of four definitions of the metabolic syndrome in a Greek (Mediterranean) population

Abstract 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.

Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study

SUMMARY Aims: To estimate the prevalence of vascular disease (coronary heart disease/stroke/peripheral arterial disease) in individuals with the metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) when compared with subjects without the MetSyn. Patients and methods: A cross-sectional analysis of a representative sample of Greek adults (n = 4153), men and women (49% and 51%, respectively), living in urban, semi-urban and rural areas (54%, 25% and 21%, respectively). The National Cholesterol Education Program – Adult Treatment Panel III definition of the MetSyn was used. Results: The age-adjusted prevalence of the MetSyn was 23.6% [95% confidence interval (CI) = 22.4%–25.1%]; this was similar in men and women. The fully adjusted prevalence of vascular disease in those with the MetSyn (n = 984) was 29.4%, significantly higher than in those without (n = 3169, 9.6%, p < 0.0001), while subjects without both the MetSyn and DM had the lowest vascular disease prevalence (n = 3035, 8.9%). Subjects with the MetSyn but no DM (n = 674) had a vascular disease prevalence of 24.1% ( p < 0.0001 vs. those without the MetSyn), which was similar to that in subjects with DM without the MetSyn (n = 134, 25.4%), but lower than in those with both the MetSyn and DM (n = 310, 40.7%, p < 0.0001 vs. all). In comparison to those without the MetSyn [odds ratio (OR) = 1], the ORs of prevalent vascular disease, after multivariate analysis for age, sex and components of the MetSyn, and antiatherosclerotic drugs were: all MetSyn = 1.94 (95% CI = 1.35–2.47), with both MetSyn and DM = 3.04 (95% CI = 1.98–4.11) and with MetSyn but no DM = 1.48 (95% CI = 1.12–1.92). Conclusions: The prevalence of vascular disease was markedly increased in the presence of the MetSyn. Those with both the MetSyn and DM had the highest prevalence of vascular disease, followed by those with the MetSyn without DM. Probably MetSyn without DM should be considered as a coronary heart disease-risk equivalent in future guidelines. This initiative would reset treatment targets and potentially provide additional benefit in patients with the MetSyn.

Early Effects of Simvastatin versus Atorvastatin on Oxidative Stress and Proinflammatory Cytokines in Hyperlipidemic Subjects

The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n=132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p=0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p=0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p=0.014 and p=0.001, respectively). TNF-a demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p=0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.

Liver Enzymes: Potential Cardiovascular Risk Markers?

Several cross-sectional studies have reported a relationship between elevated serum activity of liver enzymes [e.g. alanine aminotransferase (ALT) and gamma-glutamyltransferase (γGT)] and metabolic syndrome (MetS) and/or diabetes mellitus (DM). Raised serum activity of liver enzymes independently predicted the future development of MetS and DM as well as cardiovascular (CV) events and/or total/CV mortality in prospective studies. However, this association was not consistently demonstrated and it appears to be independent of alcohol intake. Even though these associations can be partly attributed to non-alcoholic fatty liver disease (NAFLD) and insulin resistance, there may be additional underlying mechanisms that contribute to the increased CV risk (e.g. inflammation and oxidative stress). The association of γGT with atherosclerotic plaque is of particular importance.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

The effect of apolipoprotein E polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate

Although the effect of apolipoprotein E gene polymorphism on the response to treatment with statins has been studied, the results are conflicting. Moreover, little is known about the possible effect of apolipoprotein E alleles on the response to treatment with fibrates. The purpose of this study was to evaluate the effect of apolipoprotein E polymorphism on lipid-lowering response to treatment with atorvastatin and fenofibrate in patients with different types of dyslipidemia. The study population included 136 patients with heterozygous familial hypercholesterolemia (type IIA dyslipidemia) treated with atorvastatin (20 mg/day) and 136 patients with either primary hypertriglyceridemia (type IV dyslipidemia) or mixed hyperlipidemia (type IIB dyslipidemia) treated with micronized fenofibrate (200 mg/day). Overall, no significant associations were detected between apolipoprotein E genotype and response to treatment with atorvastatin. In patients treated with fenofibrate, significant associations were noted between apolipoprotein E genotype and changes in apolipoprotein B, apolipoprotein E and triglyceride levels. Specifically, in apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 individuals, apolipoprotein B reductions were 22%, 17%, and 8%, respectively (P = .003); apolipoprotein E reductions were 45%, 20%, and 15%, respectively (P = .006); whereas triglyceride reductions reached 53%, 36%, and 33%, respectively (P = .033). In conclusion, apolipoprotein E genotype had no significant effect on the response to treatment with atorvastatin in patients with heterozygous familial hypercholesterolemia, but in patients with primary hypertriglyceridemia or mixed hyperlipidemia, there was a clear association between apolipoprotein E genotype and response to treatment with fenofibrate.

Ezetimibe; More Than a Low Density Lipoprotein Cholesterol Lowering Drug? An Update After 4 Years

Ezetimibe (EZE), a selective inhibitor of intestinal cholesterol absorption, is mostly used in combination with statins across various patient populations. Besides its low-density lipoprotein cholesterol (LDL-C) lowering, EZE exerts different effects on several other variables. In an earlier review, we discussed the effects of EZE on lipid parameters other than LDL-C [e.g. C-reactive protein (CRP) levels, insulin sensitivity and endothelial function]. In the present review, we consider recent evidence regarding these topics as well as data reporting novel EZE actions. EZE may protect from cholelithiasis and non-alcoholic fatty liver disease (NAFLD) and appears as an effective lipid-lowering treatment option for human-immunodeficiency virus (HIV)-positive patients, transplant recipients and children with familial hypercholesterolaemia (FH). Studies with EZE that raised concern about its effects on atherosclerosis are also discussed. The potential clinical benefit of these actions with respect to vascular events and overall mortality remains to be established in appropriately designed trials.