HFE gene mutations in hyperferritinemia associated with one or more components of metabolic syndrome

Journal of the American Society of Hypertension 8(4S) (2014) e109–e111

METABOLIC SYNDROME (DIABETES/GLYCEMIC CONTROL; DYSGLYCEMIC DRUGS; INSULIN RESISTANCE) P-189 Dynamic homeostasis parameters in patients with atrial fibrillation and metabolic syndrome under the antiplatelet treatment Mariya A. Orynchak, Maryanna M. Vasylechko. Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine Purpose: To study the dynamics of the coagulation and platelet hemostasis parameters under the influens of complex treatment with including aspirin, omega-3 polyunsaturated fatty acids (omega-3) or aspirin with L-arginine in hypertensives with atrial fibrillation (AF) and metabolic syndrome (MS). Materials and methods: The study included 118 hypertensives (57 male, 61 female), mean age: 70
9 years with AF and MS by ATP III (2001). The paroxysmal form of AF was observed in 35 cases, persistent form - in 13 cases and permanent form - in 70 cases. Coagulation hemostasis parameters for prothrombin index, fibrinogen, soluble fibrin-monomer complexes (SFMC), D-dimers and platelet aggregative activity (PAA) such as the beginning of aggregation, the degree of aggregation rate, speed aggregation and platelet Villebrandt factor by standard procedures were measured. Investigation was performed before and after 2 months of complex treatment with including aspirin 100 mg/d at 44 patients (group 1), omega-3 in doses 1000 mg/d at 43 patients (group 2) and aspirin 100 mg plus Larginine 4.2 mg/d at 31 patients (group 3). The control group consisted of 20 healthy individuals. Results and discussion: All patients were diagnosed MS that’s why low risk of thromboembolism by CHADS2 and CHA2DS2-VASc indicators panel was not found. Basal blood activation aggregative function and fibrinolysis levels with increasing prothrombin index; fibrinogen and SFMC parameters by 20.39%; 64.14% and 61.05% vs. the control group 98.11
3.68%; 3.04
0.52 g/l and 3.80
0.85 mg/ml accordingly (p<0.05) were revealed. Hypercoagulable states with plasma positive Ddimers and higher PAA levels in 62 (52.54%) and in 56 (47.45%) cases (p<0.05) accordingly were found. Under the influence of treatment coagulation hemostasis parameters were achieved a decline in 12 (27.27%) cases (group 1) and 35 (81.39%) cases (group 2) and 17 (54.83%) cases (group 3) vs. basal states (p<0.05). Normalization of PAA levels with lengthening the start of aggregation and decreasing Villebrandt factor and reducing aggregation degree and speed were observed in 57% cases (group 1); 85% cases (group 2) and in 61% cases (group 3) vs. basal parameters (p<0.05). In all groups before and after the treatment the platelets number ranged 280.14
11.52109/l vs. 284.21
8.32109/l in the patients of control group (p>0.05). Conclusions: The patients with AF against the background of MS characterized by CHADS2 and CHA2DS2-VASc scales high risk degree and prothrombotic disorders of coagulation and platelet hemostasis parameters. Omega-3 promotes normalization of plasma fibrinogen, SFMC and D-dimers levels and improves the PAA a greater extent compared with aspirin or aspirin plus L-arginine at the patients with AF and MS. Keywords: metabolic syndrome; atrial fibrillation; hemostasis; treatment P-190 Effect of alogliptin on blood pressure in patients with type 2 diabetes mellitus Ryoko Mitsutake, Hidenori Urata, Keisuke Okamura. Fukuoka University Chikushi Hospital, Chikushino, Japan

Background: Alogliptin,a dipeptidyl peptidase-4 inhibitor, is used for the treatment of type 2 diabetes mellitus. Alogliptin increases the level of glucagon-like polypeptide1 that increases insulin secretion. In addition, GLP-1 decreases salt intakeand increases urinary salt excretion. We analyzed the relationship between the treatment with alogliptin and blood pressure lowering. Methods and results: A retrospective, observational study of 84 type 2 diabetes mellitus patients (59 male and 25 female, 66
1 years) was enrolled. We measured body mass index, blood pressure (BP), lipid profile, hemoglobin A1c (HbA1c), blood glucose, uric acid, and creatinine. Furthermore, we calculated estimated glomerular filtration rate at 0 and 12 months after alogliptin administration. There was significantly reduced in HbA1c from 7.5
0.1 % to 6.9
0.1 % (p<0.0001), while systolic and diastolic BP were also decreased (-8.1mmHg , p¼0.0002 and -5.4mmHg, p¼0.0001, respectively). Conclusion: Alogliptin therapy significantly reduced not only blood glucose, but also BP in patients with diabetes mellitus. Since alogliptin improve several cardiovascular risk factors, it might have cardioprotective clinical outcome. Keywords: DPP4 inhibitor; blood pressure

P-191 HFE gene mutations in hyperferritinemia associated with one or more components of metabolic syndrome Susana Tello-Blasco, Dolores Rey, Martın Fabregate, Rosa Fabregate, Andres Reyes, Borja Castejon, Daniel Herrera, Jose Saban-Ruiz. Ramon y Cajal Hospital, Madrid, Spain Aims: To evaluate the prevalence of hyperferritinemia (HF) in a population with mild-high cardiovascular risk. To assess the presence of mutations in patients with HF and its relationship with the hypertensive state, hyperglycemia and metabolic syndrome (MS). Methods: N¼ 884 patients with moderate-high cardiovascular risk (Framingham scale adapted for the Spanish population -REGICOR-), 499 men (56.4%), 385 women (43.6). 128 had HF (14.5%), 115 male (89.8 %) 13 female (10.2%), aged 52.7
12.1 and 65.1
11.8 respectively, p¼ 0.001. HF criteria: serum ferritin > or ¼ 180 mg/dl according to our laboratory normal range, twice in a minimum period of two months; measured by chimioluminiscense. DNA from blood samples, tested for C282Y and H63D DNA mutations and the gene HFE using real-timed CPR. 3 of the patients were excluded due to technical difficulties. Results: Prevalence of HF: 14.5 %. - Male: 37.4 % diabetes, 33.9 % type 2, 57.4 % hypertension, 54.8% primary form, 13.9 % liver fatty, 50.4 % had MS- Female: 38.5 % diabetes, all of them type 2, 84.6 % hypertension, all of them primary, 15.4 % liber fatty, 38.5 % MS. Mutations: 48.8% (61): Carriers (heterozygous): 41 (34.4 %), C282Y heterozygous : 8.0 % (10), H63D heterozygous: 26.4 % (33), C282Y Homozygous: 0, H63D Homozygous: 11.2% (14), Double heterozygous: 3.2 % (4). Discussion: The Insulin Resistance Syndrome (IRS) is a cluster of abnormalities associated with insulin resistance, including hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia and, lately, hyperferritinemia, either alone or related to a non-alcoholic steatohepatitis (NASH) due to ectopic fat storage. On the other hand, hyperferritinemia is a biomarker of hereditary hemochromatosis (HH) (primary hyperferritinemia), alcoholism and an acute-phase reactant (APR). IRS, alcoholism and APRs are secondary forms of hyperferritinemia. The HFE gene of HH has two common mutations, C282Y and H63D. Most people with two copies of C282Y or one copy each of C282Y/H63D do not manifest clinical

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Abstracts / Journal of the American Society of Hypertension 8(4S) (2014) e109–e111

hemochromatosis, it is known as low incomplete penetrance. It is not ruled out that many of the HF associated with metabolic pathology/hypertension have a genetic bases, and that is the main contribution of our study. Conclusions: The proportion of patients with HF in a population of mildhigh cardiovascular risk is low, but this diagnosis is critical for an appropiate patient management. Many of this patients with HF had MS, type 2 diabetes and/or were hypertensive, all of these in relation to insulin resistance. The most important gene mutation in our study was the heterozygous H63D. The genetic study is important not only for the patient but also for the family members. Keywords: Hyperferritinemia (HF); HFE gene mutations: C282Y, H63D; Insulin resistance; Metabolic-Syndrome P-192 Independent association between homocysteine plasma level and metabolic syndrome and synergistic effect on cardiovascular damage in essential hypertension Cristiana Catena, GianLuca Colussi, Flavia Martinis, Francesca Pezzutto, Leonardo A. Sechi. University of Udine, Udine, Italy Both metabolic syndrome and high plasma homocysteine levels are independent risk factors for the development of cardiovascular diseases. Experimental models have proposed that insulin influences homocysteine turnover. However, studies on the relationship between insulin resistance and homocysteine have given conflicting results and few studies have investigated this relationship in essential hypertension. The aim of this study was to evaluate the association between presence of metabolic syndrome and homocysteine levels in essential hypertensive patients and to verify whether plasma levels of homocysteine can predict the prevalence of cardiovascular events in presence of metabolic syndrome. In 562 hypertensive patients (53% males, age 56
13 years) we evaluated generic anthropometric variables, smoking status, severity and duration of hypertension, renal function, glucose, insulin, and lipids metabolism, plasma levels of homocysteine, vitamin B12, and folic acid, and the prevalence of diabetes, coronary artery disease and cerebrovascular disease. Patients in the higher quartiles of homocysteine levels had higher plasma triglycerides, HDL cholesterol, and uric acid levels, higher prevalence of metabolic syndrome, coronary artery and cerebrovascular diseases, and lower creatinine clearance, vitamin B12, and folic acid levels. Homocysteine levels were independently associated with age, male gender, presence of MS, and folic acid levels. Patients with MS in the higher homocysteine quartiles had greater prevalence of coronary artery disease than patients in lower quartiles. In conclusion, in essential hypertensive patients plasma homocysteine levels are independently associated to the presence of metabolic syndrome and high homocysteine levels might increase the risk of coronary artery disease in presence of metabolic syndrome. Keywords: homocysteine; metabolic syndrome; insulin; coronary artery disease

(HOMA) as index of insulin resistance, were evaluated at baseline and after 6 months of a diet characterized by 3 times weekly fish meals supplementation. The diet was designed to increase the polyunsaturated to saturated fatty acid (PUFA/SFA) ratio in RBC membranes and was followed by a dietician. At baseline hypertensive patients with MS had higher BMI, HOMA index, and triglycerides, glucose, insulin, and C-peptide levels, and lower HDL cholesterol, PUFA, PUFA/SFA ratio, and n-6 PUFA than patients without MS. Univariate analysis showed a strong and independent direct association between PUFA/SFA ratio in RBC membranes and HDL cholesterol levels (Figure). After 6 months of fish meals supplementation only 11 patients in both groups of patients, with and without MS, increased their PUFA/SFA ratio in RBC membranes (61% and 34%, respectively). The only predictor of such an increment was the lower baseline PUFA/SFA ratio (Odds Ratio 2.14e-20, 95% CI from 5.24e-40 to 0.87) in a model including also age, sex, and MS presence. HDL cholesterol increased in both groups of patients with and without MS (+12%, P<0.050, and +16%, P<0.001, respectively), whereas only patients with MS had an increment in insulin and C-peptide levels (+27% and +29%, respectively, both P<0.05). In conclusion, HDL cholesterol is strongly and independently associated to the baseline PUFA/SFA ratio in RBC membranes and also with the PUFA/SFA ratio increment after fish meals supplementation. Although these findings suggest a positive effect of the PUFA/SFA ratio in RBC membranes on HDL cholesterol independently of MS presence, the concomitant rise in insulin production in patients with MS could limit the overall beneficial effect of the intervention on the cardiovascular risk of these patients.

Keywords: polyunsaturated fatty acid; metabolic syndrome; HDL cholesterol; insulin resistance P-194

P-193 The beneficial effect of increased polyunsaturated to saturated fatty acid ratio in red blood cell membranes on HDL cholesterol is independent of metabolic syndrome presence in patient with primary hypertension GianLuca Colussi, Cristiana Catena, Leonardo A. Sechi. University of Udine, Udine, Italy In this study we evaluated the association between fatty acid composition of red blood cell (RBC) membranes as a marker of fatty acids intake and the metabolic profile of hypertensive patients with and without metabolic syndrome (MS). Fifty patients (age 63
8 yr, M/F¼24/26, BMI 28.0
3.8 Kg/m2) with primary hypertension were divided in those with and without MS (36% and 64%, respectively) according to the 2003 AACE criteria. In these patients, fatty acid composition of RBC membranes, variables of glucose and lipid metabolism, and the homeostasis model assessment

The effect of sitagliptin on blood pressure in hypertension with diabetes melitus Kazuo Takeda, Kazue Nakamura, Takakazu Yagi, Tetsuya Tatumi, Jiro Moriguchi, Masayuki Ikeda. Kyoto Industrial Health Association, Kyoto, Japan Aim: Hypertension with Diabetes Mellitus (DM) is very popular. For these patients, antidiabetic therapy is done concomitantly with antihypertensive therapy. Recently, DPP4 inhibitor is widly used to treat DM. However, the effect of DPP4 inhibitor on blood pressure is not known. In the present study, we used DPP4 inhibitor (Sitagliptine)with antihypertensive therapy for the hypertension patients with DM and cheched the blood pressure before and after using DPP4 inhibitor. Materials and method: 80 hypertensive patients with DM (male 72, female 8, mean age 63 years old) were used with DPP4 inhibitor: sitagliptine. Before sitagliptine administration and after one, two months, their