Panagiotis Anagnostis

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis

BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. METHODS GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. FINDINGS Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. FUNDING None.

Ectopic thyroid tissue: anatomical, clinical, and surgical implications of a rare entity

Ectopic thyroid tissue is a rare entity resulting from developmental defects at early stages of thyroid gland embryogenesis, during its passage from the floor of the primitive foregut to its final pre-tracheal position. It is frequently found around the course of the thyroglossal duct or laterally in the neck, as well as in distant places such as the mediastinum and the subdiaphragmatic organs. Although most cases are asymptomatic, symptoms related to tumor size and its relationship with surrounding tissues may also appear. Any disease affecting the thyroid gland may also involve the ectopic thyroid, including malignancy. The clinician must distinguish between ectopic thyroid and metastatic deposits emerging from an orthotopic gland, as well as other benign or malignant masses. Thyroid scintigraphy plays the most important role in diagnosing ectopy, but ultrasonography contributes as well. In cases of symptomatic disease, surgery is the treatment of choice, followed by radioiodine ablation and levothyroxine suppression therapy in more refractory cases. This review provides current understanding about the wide clinical spectrum of this rare condition, also referring to optimal diagnostic approach, differential diagnosis, and management strategies.

Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control

Type 2 diabetes mellitus is a well‐established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation‐resistant incretin mimetic exenatide and the glucagon‐like peptide‐1 (GLP‐1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)‐4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP‐1. GLP‐1 exerts its glucose‐regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose‐dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP‐1 receptors (GLP‐1Rs), although GLP‐1R‐independent pathways have been reported. Except for the pancreatic islets, GLP‐1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP‐1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP‐1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti‐inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP‐4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo‐controlled trials. This review discusses the role of GLP‐1 on the cardiovascular system and addresses the impact of GLP‐1‐based therapies on CVD outcomes.

Atherosclerosis and osteoporosis: age-dependent degenerative processes or related entities?

Osteoporosis and atherosclerosis, two multifactorial and degenerative entities, are major public health problems. These diseases accompany the aging process and share common risk factors. Furthermore, several common pathophysiological factors have been suggested. These include similar molecular pathways involving bone and vascular mineralization, estrogen deficiency, parathyroid hormone, homocysteine, lipid oxidation products, inflammatory process, as well as vitamin D and K. Moreover, the use of statins, biphosphonates, beta-blockers and experimental dual-purpose therapies based on the biological linkage of the above entities may simultaneously benefit bone loss and vascular disease. This review considers a potential link between osteoporosis and atherosclerosis beyond aging. These common factors may lead to appropriate treatment strategies.

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.

Vitamin D in human reproduction: a narrative review

Background:  Special attention has been given to the effect of vitamin D supplementation on fertility outcomes in both sexes.

11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?

OBJECTIVE Metabolic syndrome (MetS) and Cushings 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.

Health Benefits of the Mediterranean Diet An Update of Research Over the Last 5 Years

The Mediterranean Diet (MedDiet) has been reported to be protective against the occurrence of several diseases. Increasing evidence suggests that the MedDiet could counter diseases associated with chronic inflammation, including metabolic syndrome, atherosclerosis, cancer, diabetes, obesity, pulmonary diseases, and cognition disorders. Adoption of a MedDiet was associated with beneficial effects on the secretion of anti-inflammatory cytokines, antioxidant cellular and circulating biomarkers as well as with regulation of gene polymorphisms involved in the atherosclerotic process. The MedDiet has been considered for the prevention of cardiovascular and other chronic degenerative diseases focusing on the impact of a holistic dietary approach rather than on single nutrients. Epidemiological dietary scores measuring adherence to a MedDiet have been developed. This narrative review considers the results of up-to-date clinical studies (with a focus on the last 5 years) that evaluated the effectiveness of the MedDiet in reducing the prevalence of chronic and degenerative diseases.

Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome

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.

Ectopic parathyroid glands and their anatomical, clinical and surgical implications.

Ectopic parathyroid glands result from aberrant migration during early stages of development and lack of successful identification may lead to lack of success in parathyroid surgery. They constitute a common etiology of persistent or recurrent hyperparathyroidism, when they are missed at initial diagnosis. Their prevalence is about 2-43% in anatomical series and up to 16% and 14% in patients with primary and secondary hyperparathyroidism, respectively. Ectopic inferior parathyroids are most frequently found in the anterior mediastinum, in association with the thymus or the thyroid gland, while the most common position for ectopic superior parathyroids is the tracheoesophageal groove and retroesophageal region. Neck ultrasound and 99mTc Sestamibi scan are first-line imaging modalities, although with low sensitivity and specificity. However, their combination with modern techniques, such as single photon emission computed tomography (SPECT) alone or in combination with CT (SPECT/CT) increases their diagnostic accuracy. Fine needle-aspiration cytology of a lesion suspicious for parathyroid tissue and measurement of parathyroid hormone (PTH) in the aspired material further assist to the successful preoperative localization of ectopic glands. Common sites for surgical investigation are the upper thyroid pole and the upper vascular thyroid stalk behind the hypopharynx and cervical esophagus for the superior parathyroids, and the carotid artery bifurcation and the thymic tongue, for the inferior parathyroids. Radioguided minimally invasive parathyroidectomy after successful localization, assisted by rapid PTH measurement postoperatively, significantly improves surgical outcomes in patients with ectopic parathyroid adenomas.