Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form. Four thousand thirty-two patients were eligible for inclusion; more than half of them had thalassaemia major. Compared to the previous report, a reduction in the total number of all hemoglobinopathies except for hemoglobinopathy "Η" was evident. The total number of affected births was also reduced; most of them were attributable to diagnostic errors and lack of awareness. Importantly, data on iron overload are reported for the first time; although most patients had low or moderate liver iron concentration (LIC) values, a non-negligible proportion of patients had high LIC. The burden due to heart iron overload was less prominent. Cardiac- and liver-related complications are the major causes of morbidity and mortality. From 2000 to 2015, a decrease in heart-related deaths along with an increase in liver-associated fatalities was observed. The Hellenic Prevention Program along with advances in chelation regimens and iron status monitoring have resulted in improved patient outcomes. The NRHG gives insight into the effectiveness of prevention programs, the therapeutic management of hemoglobinopathies and associated outcomes. NRHG may contribute to the formulation of a roadmap for hemoglobinopathies in Europe and promote the implementation of effective public health policies.

Background/Aim: The adipocytokines leptin and adiponectin represent a critical link between metabolism, immunity and chronic inflammation. A chronic vascular inflammatory state plays an important role in the pathophysiology of thalassaemia. We aimed to analyze the levels of these adipocytokines and determine any possible correlations with disease severity or vascular inflammation markers in beta-thalassaemia. Methods: Serum leptin, adiponectin, high-sensitivity C-reactive protein, endothelins, vascular adhesion molecule-1, intracellular adhesion molecule-1 and L- and E-selectin were measured in 28 beta-thalassaemia patients and compared with levels in healthy controls. Results: Leptin was significantly lower in patients compared to controls (2.23 ± 1.8 vs. 10.24 ± 5.78 µg/l; p = 0.0018), whereas adiponectin was elevated (11.75 ± 5.67 vs. 6.83 ± 2.75 µg/l; p = 0.009). For both adipocytokines, no correlations were found with characteristics such as age, gender, type of chelation, body mass index z score or haemoglobin. Leptin, but not adiponectin, was negatively correlated with ferritin (p = 0.032, r = –0.61). No correlations were found between leptin and the inflammation markers. However, adiponectin was positively correlated with endothelin-1 (p = 0.022, r = 0.63). Conclusions: Serum leptin is low in beta-thalassaemia, perhaps due to the toxic effect of iron overload on adipose tissue. Paradoxically, adiponectin levels are high and positively correlated with endothelin-1, raising questions about the pro- or anti-inflammatory role of this adipocytokine in beta-thalassaemia.

Summmary Background Although the relationship of elevated serum uric acid levels and cardiovascular disease has been established in a great number of studies, the causal relevance of this finding remains ambiguous. An approach to evaluate the causal relevance of biomarkers is to exploit the natural randomised allocation of allelic variation in genes affecting their level, also known as Mendelian randomisation. Aim The aim of this paper is to review the current literature regarding serum uric acid levels and cardiovascular and renal disease risk in Mendelian randomisation studies. Methods PubMed and Scopus databases were searched to retrieve Mendelian studies regarding uric acid, hyperuricaemia and cardiovascular risk. Conclusions Genetic evidence based on conventional and novel Mendelian randomisation approaches suggest a modest, if any, causal effect of serum uric acid concentration on the development of cardiovascular disease, suggesting that further study of uric acid genes is needed in order to elucidate the relationship of serum uric acid levels and cardiovascular disease.

1012 Background. Vascular endothelial cell activation and chronic inflammatory processes along with concomitant chronic energy deficiency characterize the steady state of sickle cell disease (SCD). Adipose tissue besides its lipid storage has also an endocrine function producing adipokines most important of which are leptin and adiponectin. These two hormones regulate food intake and energy expenditure but they are also involved in the regulation of inflammatory responses, hematopoiesis and angiogenesis. We evaluated leptin and adiponectin blood levels and determined any possible correlations with disease severity and inflammation markers in steady state SCD patients. Methods. We measured leptin and adiponectin using ELISA as well as high sensitivity C-reactive protein (hs-CRP) using nephelometry, in blood serum of 42 patients (24 male-18 female, median age 34 years, range 29–52 years) with steady state sickle cell/beta thalassemia and 40 healthy individuals matched for age, sex and body mass index (BMI) z-score who served as controls. Steady state was defined as a crisis-free period for at least 4 weeks after the previous clinical event and 3 or more months since the last blood transfusion. After natural logarithmic transformation, the measured values were investigated for correlations against hemoglobin, white blood cells, bilirubin, lactate dehydrogenase (LDH), ferritin, insulin levels, fetal hemoglobin (HbF), number of events/year (severe painful crises, transfusions, severe infections or other complications) and treatment with iron-removing agents or hydroxurea. Results. Leptin was found significantly lower in patients compared to controls (median±SD, 2.9±1.9 vs 8.5±4.9 ng/ml, p=0.006), whereas adiponectin and hs-CRP were found significantly elevated (median±SD 11.3±6.1 vs 7.5±3.1 μg/ml, p=0.003 and 2.8±1.1 mg/L vs 1.4±0.9; p=0.018, respectively). No correlations were found between adipokines and age, gender, chelation or hydroxurea treatment, ferritin, insulin, HbF, hemoglobin or clinical events. Leptin, but not adiponectin, levels were positively correlated with BMI z-score (r= 0.71, p=0.018) and negatively correlated with LDH levels (r=0.69, p=0.012). Concerning adiponectin, significant positive correlation was noted with hs-CRP levels and white blood cell number (r=0.644, p=0.015 and r=0.68, p=0.028). Conclusions. Adipokine blood levels are altered in steady state SCD possibly reflecting the effect of chronic hemolytic and inflammatory state on adipose tissue dysfunction. This could be considered as another endocrinopathy that affects SCD patients. Disclosures: No relevant conflicts of interest to declare.