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1.  Statins and cardiovascular outcomes in elderly and younger patients with coronary artery disease: a post hoc analysis of the GREACE study 
The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly.
Material and methods
The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on “structured care” with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on “usual care” (n = 800) followed up by specialists or general practitioners of the patient's choice outside the hospital.
In the elderly (mean age 69 ±4 and 70 ±3 years in the “structured” and “usual care”, respectively) the absolute CVD event reduction between “structured” and “usual care” was 16.5% (p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the “structured” and “usual care”, respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients.
All age groups benefited from statin treatment, but the elderly on “structured care” had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to “usual care”. These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement.
PMCID: PMC3701988  PMID: 23847661
cardiovascular disease; age; statin; chronic kidney disease; GREek Atorvastatin and Coronary-heart-disease Evaluation
5.  IMproving the imPlemEntation of cuRrent guidelines for the mAnagement of major coronary hearT disease rIsk factors by multifactorial interVEntion. The IMPERATIVE renal analysis 
The short-term effects of multifactorial intervention for cardiovascular disease (CVD) prevention on renal function and serum uric acid (SUA) levels in patients with stage 3 chronic kidney disease (CKD) and multiple CVD risk factors are unclear. The aim of the study was to prospectively assess these effects.
Material and methods
This post hoc analysis of 5 "best practice" studies involved patients with multiple CVD risk factors. Estimated glomerular filtration rate (eGFR) was assessed using the Modification of Diet in Renal Disease (MDRD) formula. Among the 4,153 patients, 1,235 (29.7%) had stage 3 CKD (eGFR between 30 and 59 ml/min/1.73 m2). A baseline visit was followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment, including a statin, for all vascular risk factors. After 6 months eGFR and SUA levels were re-evaluated.
The intervention improved compliance to lifestyle measures and increased the use of evidence-based medication, including a statin. There was also a 5.6% increase in eGFR (p < 0.001) in patients with stage 3 CKD and a 6.1% reduction in SUA levels (p < 0.001). Among patients with stage 3 CKD, 127 (10.3%) improved to stage 2 CKD and 9 (0.7%) advanced to stage 4 CKD by the end of the 6-month study period. There were no major side-effects.
Multitargeted intervention, including a statin, may improve renal function and reduce SUA levels within 6 months, thus offsetting 2 potential CVD risk factors in high-risk patients.
PMCID: PMC3264990  PMID: 22328881
renal function; uric acid; dyslipidaemia; diabetes mellitus; hypertension; metabolic syndrome; multifactorial intervention; statin
6.  Is there an additional benefit from coronary revascularization in diabetic patients with acute coronary syndromes or stable angina who are already on optimal medical treatment? 
Archives of Medical Science : AMS  2011;7(6):1067-1075.
Cardiovascular disease (CVD) is common in patients with diabetes mellitus (DM) and related clinical outcomes are worse compared with non-diabetics. The optimal treatment in diabetic patients with coronary heart disease (CHD) is currently not established. We searched MEDLINE (1975-2010) using the key terms diabetes mellitus, coronary heart disease, revascularization, coronary artery bypass, angioplasty, coronary intervention and medical treatment. Most studies comparing different revascularization procedures in patients with CHD favoured coronary artery bypass graft (CABG) surgery in patients with DM. However, most of this evidence comes from subgroup analyses. Recent evidence suggests that advanced percutaneous coronary intervention (PCI) techniques along with best medical treatment may be non-inferior and more cost-effective compared with CABG. Treatment of vascular risk factors is a key option in terms of improving CVD outcomes in diabetic patients with CHD. The choice between medical therapy and revascularization warrants further assessment.
PMCID: PMC3265001  PMID: 22328892
diabetes; coronary heart disease; acute coronary syndrome; coronary artery bypass graft; percutaneous coronary intervention; statin
7.  Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: a post hoc analysis of the randomised ATTEMPT study 
Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS), is common and accounts for 80% of cases of elevated liver function tests (LFTs). We assessed the long-term effects of multifactorial intervention on LFTs and their association with cardiovascular disease (CVD) events in patients with MetS without diabetes mellitus or CVD.
Material and methods
This prospective, randomized, open label study included 1,123 patients (aged 45-65 years). Patients received intensive lifestyle intervention and pharmacotherapy: atorvastatin in all patients (low density lipoprotein cholesterol [LDL-C] targets of<100 mg/dl [group A] or<130 mg/dl [group B]), inhibitors of the renin-angiotensin-aldosterone axis for hypertension, metformin for dysglycaemia and orlistat for obesity.
Among participants, 326 had modestly elevated LFTs and ultrasonographic (US) evidence of NAFLD (165 patients in group A2 and 161 patients in group B2). The NAFLD resolved during the 42-month treatment period in 86% of patients in group A2 and in 74% of patients in group B2 (p<0.001). In both groups nearly 90% of patients attained lipid goals. Mean LDL-C and TG levels were higher in group B2 than in group A2 (p<0.001). There were no CVD events in group A2 whereas 5 non-fatal events occurred in group B2 (log-rank-p = 0.024). There were no major side-effects.
Attaining multiple treatment targets is safe and beneficial in primary prevention patients with MetS and NAFLD. Lipid levels and LFTs normalized, US findings associated with NAFLD resolved and no CVD events occurred in patients with LDL-C levels<100 mg/dl (group A2). Resolution of NAFLD might have contributed to the prevention of CVD events.
PMCID: PMC3258797  PMID: 22291824
non-alcoholic fatty liver disease; metabolic syndrome; multifactorial treatment; atorvastatin; cardiovascular disease
10.  Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study 
The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100–125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110–125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG.
Material and methods
Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study.
Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100–109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100–109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102–186) vs. 186 mg/dl (IQR = 115–242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9–7.3) vs. 4.1% (IQR = 0.7–5.8), p = 0.002).
The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.
PMCID: PMC3832824  PMID: 24273558
prediabetes; impaired fasting glucose; American Diabetes Association; World Health Organization; cardiovascular risk; triglycerides
11.  Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy 
Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1.
Materials and methods
Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied.
NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.
PMCID: PMC3602235  PMID: 23497378
Curcumin; Diabetes type I; Heme-oxygenase-I; Diabetic cardiomyopathy; p300
12.  Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches 
Nutrients  2013;5(3):928-948.
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.
PMCID: PMC3705327  PMID: 23507795
lipoproteins; small dense low density lipoprotein; obesity; metabolic syndrome; obesity treatment; anti-obesity drugs; lipid-lowering drugs
16.  Gender and Socio-economic Differences in Daily Smoking and Smoking Cessation Among Adult Residents in a Greek Rural Area 
Despite the well-known health risks, smoking is still highly prevalent worldwide. Greece has the highest level of adult smoking rate (40%) across the European Union. We investigated gender and socio-economic differences in daily smoking and smoking cessation among Greek adults. We conducted a cross-sectional survey between October and November 2009 in 434 adults residing in a Greek rural area. Data were collected with the use of the World Health Organization Global Adult Tobacco Survey (WHO GATS) Core Questionnaire. Respondents were classified into smokers (if they had smoked at least 100 cigarettes in their lifetime and continued to smoke) or non-smokers. Overall, 58.1% (n=252) were smokers (58.5% male, n=127 and 57.8% female, n=125); 51.2% (n=222) were younger than 18 years-old when they started smoking. Men tended to start smoking at a younger age, to smoke more cigarettes/day and to have smoked a greater average of cigarettes during the last 5 days. Overall, 82.5% of smokers attempted to stop smoking a year prior to the study, with women having a greater difficulty in quitting smoking. The main source of information on smoking was the mass media (73.5%) and books (53.7%), whereas doctors and other health professionals were the least listed source of relative information (27.7 and 8.1%, respectively). Smoking rates among Greek adults were high, but a considerable number of individuals who smoked, wished to quit and had attempted to do so. Smoking cessation clinics are not perceived as a valuable support in quitting effort.
PMCID: PMC3308319  PMID: 22435078
Adults; gender; rural; smoking; smoking cessation; socio-economic.
17.  Water Soluble Vitamin E Administration in Wistar Rats with Non-alcoholic Fatty Liver Disease 
A diet rich in fat is associated with hepatic fat deposition [steatosis; non-alcoholic fatty liver disease (NAFLD)]. The exact cause of NAFLD however, is still unknown. The aim of this study was to assess the effect of a water-soluble formulation of vitamin E on a dietary-induced-NAFLD animal model.
Adult male Wistar rats (n=20) were allocated to 2 groups: Controls (Group A, n=6), which received a standard chow diet for 24 weeks and a High Cholesterol group (HC: n=14), which received a standard chow diet enriched with cholesterol for the first 14 weeks of the experiment (t1). At t1, the HC group was divided into: Group HC(B), which received a high-saturated-fat/high-cholesterol (HSF/HCH) diet and Group HC(C), which followed the same HSF/HCH diet but was also administered water soluble vitamin E (10 IU/kg body weight/day), for 10 more weeks.
At the end of the study, group HC(C) exhibited significantly lower mean total cholesterol (T-CHOL) than group HC(B) (p<0.001). No significant differences were observed between HC(C) and Control groups in blood glucose and serum lipid concentrations. Liver Function Tests did not vary between all groups at the end of the study. Animals in group HC(B) exhibited higher SGOT at the end of the study compared with the beginning of the study (p<0.05). Group HC(B) exhibited the highest scores in steatosis, and grading (according to the NAFLD scoring system) in the histopathological analysis (p≤0.001 in all cases).
Vitamin E seems to exert a hypolipidemic and hepatoprotective role in the presence of a HSF/HCH atherogenic diet in a rat model.
PMCID: PMC3428633  PMID: 22930662
Cholesterol; High saturated fat diet; Non-alcoholic fatty liver disease; Steatosis; Vitamin E; Wistar rats.
18.  Weekend Versus Weekday, Morning Versus Evening Admission in Relationship to Mortality in Acute Coronary Syndrome Patients in 6 Middle Eastern Countries: Results from Gulf Race 2 Registry 
We used prospective cohort data of patients with acute coronary syndrome (ACS) to compare their management on weekdays/mornings with weekends/nights, and the possible impact of this on 1-month and 1-year mortality. Analyses were evaluated using univariate and multivariate statistics. Of the 4,616 patients admitted to hospitals with ACS, 76% were on weekdays. There were no significant differences in 1-month (odds ratio (OR), 0.88; 95% CI: 0.68-1.14) and 1-year mortality (OR, 0.88; 95% CI: 0.70-1.10), respectively, between weekday and weekend admissions. Similarly, there were no significant differences in 1-month (OR, 0.92; 95% CI: 0.73-1.15) and 1-year mortality (OR, 0.98; 95% CI: 0.80-1.20), respectively, between nights and day admissions. In conclusion, apart from lower utilization of angiography (P < .001) at weekends, there were largely no significant discrepancies in the management and care of patients admitted with ACS on weekdays and during morning hours compared with patients admitted on weekends and night hours, and the overall 30-day and 1-year mortality was similar between both the cohorts.
PMCID: PMC3447162  PMID: 23002404
Acute coronary syndrome; Weekend; Weekday; Mortality; Admission.
19.  Patient with Hypertriglyceridemia, Type 2 Diabetes, and Chronic Kidney Disease Treated with Atorvastatin and Omega-3 Fatty Acid Ethyl Esters 
This is a case report that describes a 67-year-old woman with mixed hyperlipidemia and diabetic nephropathy. She was initially prescribed a combination of simvastatin plus gemfibrozil by her general practitioner (GP). When referred to our cardiovascular unit, we further diagnosed the patient to have mixed hyperlipidemia and rhabdomyolysis. Because of concerns with her chronic kidney disease (CKD), we temporarily stopped all her drug treatments and started insulin treatment for her type 2 diabetes (T2D). A month later when her T2D was stabilised, we prescribed atorvastatin and an omega-3 fatty acid ethyl ester supplement to treat her hypertriglyceridemia. Within two months her blood lipids were within the recommended range. In patients with stage 3–5 CKD, it is not advisable to prescribe the fibrate gemfibrozil, particularly in combination with a statin that is metabolised predominantly in the kidneys. To minimise adverse events without compromise on efficacy, we used a combination of omega-3 fatty acid ethyl esters, which are not metabolised in the kidneys, with a statin that is minimally metabolised in the kidneys for the treatment of her hyperlipidemia.
PMCID: PMC3468870  PMID: 23066433
Hypertriglyceridemia; statin; omega-3 fatty acid ethyl esters; type 2 diabetes.
20.  The Role of Psychobiological and Neuroendocrine Mechanisms in Appetite Regulation and Obesity 
Obesity is a multifactorial disease. Among its causes are physical inactivity and overeating. In addition, other factors may play an important role in the development of overweight/obesity. For example, certain hormones including leptin, insulin and ghrelin, may influence appetite and consequently body weight. Obesity frequently co-exists with metabolic disorders including dyslipidemia, hypertension and insulin resistance, thus constituting the metabolic syndrome which is characterized by increased cardiovascular risk.
Lack of comprehensive knowledge on obesity-related issues makes both prevention and treatment difficult. This review considers the psychobiological and neuroendocrine mechanisms of appetite and food intake. Whether these factors, in terms of obesity prevention and treatment, will prove to be relevant in clinical practice (including reducing the cardiovas-cular risk associated with obesity) remains to be established.
PMCID: PMC3549543  PMID: 23346258
Obesity; appetite; psychobiology; neuroendocrine mechanisms; leptin; insulin; ghrelin; cardiovascular risk.
21.  Erythropoietin update 2011 
Traditionally, erythropoietin (EPO) is described as a hematopoietic cytokine, regulating proliferation and differentiation and survival of the erythroid progenitors. The recent finding of new sites of EPO production and the wide spread distribution of EPO receptors (EPO-R) on endothelial cells, cardiomyocytes, renal cells as well as the central and peripheral nervous system raised the possibility that EPO may exert pleiotropic actions on several targets. Indeed studies (mainly preclinical) have documented protective, non-hematopoietic, abilities of EPO in a variety of tissue. However, the data obtained from clinical studies are more skeptical about these properties. This article provides a comprehensive overview of EPO and its derivatives.
PMCID: PMC3539497  PMID: 22037755
erythropoietin; erythropoietin-receptor; erythropoiesis-stimulating agents; anemia
23.  Dyslipidaemia of Obesity, Metabolic Syndrome and Type 2 Diabetes Mellitus: the Case for Residual Risk Reduction After Statin Treatment 
Dyslipidaemia is frequently present in obesity, metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). The predominant features of dyslipidaemia in these disorders include increased flux of free fatty acids (FFA), raised triglyceride (TG) and low high density lipoprotein cholesterol (HDL-C) levels, a predominance of small, dense (atherogenic) low density lipoprotein cholesterol (LDL) particles and raised apolipoprotein (apo) B values Posprandial hyperlipidaemia may also be present. Insulin resistance (IR) appears to play an important role in the pathogenesis of dyslipidaemia in obesity, MetS and T2DM. The cornerstone of treatment of this IR-related dyslipidaemia is lifestyle changes and in diabetic patients, tight glycaemic control. In addition to these measures, recent clinical trials showed benefit with statin treatment. Nevertheless, a substantial percentage of patients treated with statins still experience vascular events. This residual vascular risk needs to be addressed. This review summarizes the effects of hypolipidaemic drug combinations (including statins with cholesterol ester protein inhibitors, niacin, fibrates or fish oil, as well as fibrate-ezetimibe combination) on the residual vascular risk in patients with obesity, MetS or T2DM.
PMCID: PMC3109607  PMID: 21660248
Dyslipidaemia; obesity; metabolic syndrome; type 2 diabetes mellitus; residual vascular risk.
24.  Rectus Sheath Hematoma: A Simplified Emergency Surgical Approach 
Rectus sheath hematoma (RSH) is an uncommon clinical event usually associated with trauma or coagulation disorders. It can also occur spontaneously. RSH usually runs a benign course but it can present with hypovolemic shock. When conservative management fails, surgical exploration becomes mandatory. We propose a technique of emergency ligation of the inferior epigastric artery. This is a simple approach as this artery originates at the posterior rectus sheath above the inguinal ligament. This safe technique provides immediate hemodynamic stabilization.
PMCID: PMC3109664  PMID: 21660196
Rectus sheath; hematoma; inferior epigastric artery.
25.  Nutrition During Pregnancy and the Effect of Carbohydrates on the Offspring’s Metabolic Profile: In Search of the “Perfect Maternal Diet” 
Fetal growth and development is primarily dependent upon the nutritional, hormonal and metabolic environment provided by the mother. A wartime famine study in Holland first showed that a low food intake reduces the glucose offered to the fetus and thus produces smaller size infants at birth. Maternal glucose regulation is however affected by numerous factors including physiological changes of pregnancy (e.g. insulin resistance [IR]), pathological conditions (e.g. gestational diabetes mellitus) and maternal nutrition. Maternal glucose is substantially influenced by the type of carbohydrates in the diet through its direct effect on glycemia. The rate at which each carbohydrate raises blood glucose levels after ingestion, can be measured via the dietary glycemic index (GI). Carbohydrate type and the GI of the diet enhance or inhibit abnormal hyperglycemia during pregnancy caused by either pathological conditions or the inability of the mother to cope with the physiological IR of pregnancy. In turn, maternal gestational hyperglycemia may be involved in the pathogenesis of IR, impaired glucose tolerance, type 2 diabetes mellitus, the Metabolic Syndrome and subsequent cardiovascular diseases in adult offspring. A low GI maternal diet has been associated with measurable benefits to the offspring. These include a positive effect on altering maternal blood glucose production, insulinemia and reduced adiposity as well as fetal and placental insulin and glucose regulation, fetal growth, birth weight and offspring adiposity. We review the possible links between dietary carbohydrate in health during pregnancy and the effect of maternal carbohydrate ingestion on programming the offspring’s metabolic profile.
PMCID: PMC3111740  PMID: 21673843
Pregnancy; nutrition; carbohydrates; metabolic profile; glycemic index.

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