- Email: [email protected]
MS245 FTO POLYMORPHISM IS ASSOCIATED WITH MYOCARDIAL INFARCTION
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
was higher in patients with MH − 9 (37.5%) vs. 4 patients without MH (10%, p = 0.008). Multivariate regression analysis confirmed the correlation of MH with BMI and micro/macroalbuminuria but revealed also the association of MH with parameter of diastolic function E/E (r = 0.431, p < 0.05) and with intimomedial thickness (IMT) of carotid artery (r = 0.557, p < 0.05). Conclusion: Masked hypertension in treated type 2 diabetic patients is frequent and significantly associated with BMI, micro/macroalbuminuria, IMT of carotid artery and diastolic function parameter E/E . ˇ NR/9520−3 Supported by grant IGA MZ CR MS245 FTO POLYMORPHISM IS ASSOCIATED WITH MYOCARDIAL INFARCTION J. Hubacek1,2 , for the GENDEMIP Research Group. 1 Institute for Clinical and Experimental Medicine, 2 Centre for Cardiovascular Research, Prague, Czech Republic Introduction: Myocardial infarction (MI) is the most common cause of death in industrial countries. All general MI risk factors have some genetic components and the proportion of genetic predisposition is between 30−60%. FTO gene (“fat mass and obesity related gene”, DNA demethylase) and its variants have been described primarily like important determinant of body weight. Further, FTO gene variant increases general mortality independent of fatness in men. We have analysed the putative association between FTO SNP rs17817449 and risk of MI development on middle European Caucasians. Methods: FTO SNP rs17817449 (G → C) was analysed using PCR-RFLP in 1 191 representatively selected controls (age below 65) and 1 092 consecutive MI patients (age below 65). ANOVA and chi-square were used for statistical analysis. Results: FTO rs17817449 has significant effect on body mass index (kg/m2 ) both in controls (GG − 28.7±3.7; GT − 28.3±4.1; TT − 27.8±3.9; P = 0.014) and in patients (GG − 29.2±4.1; GT − 28.3±4.5; TT − 28.2±3.8; P = 0.006). Total cholesterol, HDL cholesterol, triglycerides, blood pressure were not associated with FTO variant. Further, the frequency of GG homozygotes is significantly higher in MI patients than between controls (21.4% vs 15.9%, P = 0.005; OR 1.38; 95% CI 1.10–1.73). Conclusion: FTO rs17817449 (G → C in first intron) SNP is newly recognized genetic risk factor for myocardial infarction development. Supported by project No. 1M0510 (MEYS, CR) MS246 LIPID PROFILE OF SPANISH PATIENTS WITH CORONARY HEART DISEASE TREATED WITH STATINS. THE DYSLIPIDEMIA INTERNATIONAL STUDY (DYSIS-SPAIN) J. Millan1 , J.R. Gonzalez-Juanatey2 , C. Guijarro3 , E. Alegria4 , J.V. Lozano5 , ˜ B. Gonzalez-Timon6 , G. Vitale6 . 1 Hospital Gregorio Maranon, Madrid, 2 Hopital Clinco Universitario, Santiago de Compostela, Santiago de Compostela, 3 Hospital de Alcorcon, Alcorcon, 4 Clinica Universitaria de Pamplona, Pamplona, 5 Primary Care Center La Serreria 2, Valencia, 6 Merck & Co., MSD, Madrid, Spain Introduction: LDL-C is the therapeutic target for cardiovascular (CV) prevention and main CV guidelines recommend statins to reduce LDL-C levels. Patients with coronary heart disease (CHD) are high CV risk patients and have a lower LDL-C target. Some studies have found that low HDL-C and high triglycerides (TG) may have a role in coronary risk but statins have limited action on them. In this analysis we describe the lipid profile of Spanish statin-treated patients with CHD. Methods: Analysis of 3710 Spanish statin-treated patients included in DYSIS (22,063 patients in Europe and Canada). We used the ATP-III recommendations to classify patient’s risk and define the LDL-C goal and normality or not of the HDL-C and TG levels. Results: In 3710 patients, 23.8% were diagnosed with CHD (68.0% men, 27.6% women, p < 0.001). In this subpopulation: 75.1% hypertensive, 44.8% diabetics, 16.8% smokers and 25.6% had a family history of premature CHD. LDL-C was not at goal in 46.9% of patients with CHD vs. 51.4% of patients without CHD (p < 0.05). The prevalence of low HDL-C was 34.9%, higher compared to patients without CHD (29.8%, p < 0.001) and TG were elevated in 35.1% comparing to 38.4% in patients without CHD. Conclusions: In this analysis of CHD patients, despite better control of LDL-C and TG than the total Spanish population studied, almost 50% of CHD patients do not reach LDL-C target. The prevalence of low HDL-C in these patients is significantly higher and 1/3 show high TG. A considerable number of CHD patients had an abnormal lipid profile. It is necessary to use new therapies focused on treating complete lipid profile (LDL-C, HDL-C and TG).
159
MS247 LEPTIN, ADIPONECTIN AND LEPTIN TO ADIPONECTIN RATIO IN DEPRESSIVE WOMEN M. Zeman1 , R. Jirak ´ 2 , M. Vecka1 , A. Zˇ ak ´ 1 , J. Macaˇ ´ sek1 , E. Tvrzicka´ 1 , T. Vaˇreka1 , L. Vavrov ´ a´ 1 , J. Kodydkova´ 1 , B. Stankov ˇ a´ 1 . 1 IVth Dept Int Med, 2 1st Psychiatric Dept, 1st Medical Faculty, Charles University, Prague, Czech Republic Background: Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistance (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated glycaemia, could stand behind the connection. Recent findings have shown that leptin and adiponectin might play a role in both depression and MetS. Materials and Methods: The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in group of 38 women with DD. The results were compared with those of 38 healthy women of control group, matched for age. Results: Women of DD group differed from those of control group in higher concentrations of plasma leptin (21.80±13.28 vs. 14.12±6.25) and the leptinto-adiponectin ratio (1.80±1.12 vs. 1.04±0.72), both P < 0.05. Concomitantly, they had higher plasma TG (1.60±1.06 vs. 1.19±0.28 mmol/l (P < 0.05), insulin (13.38±8.0 vs. 7.8±3.8, C-peptide (0.84±0.31 vs. 0.66±0.19), both P < 0.01), microalbuminuria (12.65±10.18 vs. 4.49±3.07, P < 0.05) and higher value of the HOMA-IR index (P < 0.01). Conclusions: In the presented pilot study, we found increased levels of plasma leptin in the group of depressive women and also the increased value of leptinto-adiponectin ratio plasma levels and certain features of MetS. This could be the factor connecting depression with an increased risk of either DM2 or CVD. Moreover, HAM-D score of DD cases correlated negatively with adiponectin concentrations (P < 0.01). Study was supported by the Research Project MSM 0021620820. MS248 WAIST CIRCUMFERENCE NEGATIVE CORRELATION WITH TESTOSTERONE AND SHBG IN YOUTH WITH PRE-METABOLIC AND METABOLIC SYNDROMES V. Dimitrijevic-Sreckovic1 , P. Djordjevic1 , S. Damjanovic1 , B. Sreckovic2 , V. Barac3 , I. Soldatovic4 , M. Cvetkovic1 . 1 Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 2 Bezanijska Kosa Clinical Center, 3 Institute of Medical Biochemistry, 4 Institute for Medical Statistics and Informatics, Clinical Center of Serbia, Belgrade, Serbia Background: Visceral obesity, in fact a metabolic syndrome (MS), is related to decreased testosterone and sex hormone-binding globulin (SHBG) in adults. Peripheral conversion of testosterone to estrogen in excess peripheral adipose tissue may lead to secondary hypogonadism through hypothalamic-pituitarygonadal axis inhibition. Aims of the study were to examine sex hormones in obese young males and correlations with visceral obesity, lipid status and blood pressure. Methods: The study included 44 obese male individuals aged 16−30. Three of the following five criteria were used for MS diagnosis: waist circumference >90Pct; triglycerides >1.7 mmol/l; HDL-cholesterol< 1.0 mmol/l; hypertension>90Pct; glycemia>6.0 mmol/L. Patients with less than three afore mentioned criteria were considered pre-MS. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and SHBG was determined by radioimmunoassay (RIA). Results: Decreased testosterone (< 12.0nmol/l) was found in 11.3% obese young males (8.1±3.1nmol/l), with low SHBG (10.6±4.5) and normal FSH, LH and estradiol. Patients with pre-MS had normal testosterone (17.3±4.3nmol/l), FSH (3.84±2.25mU/l), LH (3.4±1.79mU/l), estradiol (110.0±51.8pmol/l) and SHBG (42.5±9.4). Patients with MS had normal testosterone (17.0±6.4nmol/l), FSH (3.38±2.17mU/l), LH (3.0±1.6mU/l), estradiol (115.3±48.4pmol/l), and SHBG at lower limits (17.8±8.4). Correlations: WC negative with testosterone and SHBG (p < 0.05); SHBG negative with BMI (p < 0.05), systolic and diastolic blood pressure (p < 0.01); estradiol positive with total cholesterol (p < 0.01), LDL-cholesterol and diastolic blood pressure (p < 0.05). Conclusion: Negative correlation of waist circumference with testosterone and SHBG and of SHBG with BMI and blood pressure, proves the important effect of visceral obesity and insulin resistance on possible occurrence of secondary hypogonadism and infertility. MS249 ASSOCIATION OF THE Q223R POLYMORPHISM IN THE LEPTIN RECEPTOR GENE WITH AGE AT MENARCHE A. Garc´ıa Anguita, P. Riestra, C. Garces. ´ Lipid Metabolism Laboratory, ´ Jimenez Diaz, Madrid, Spain Fundacion Introduction: Energy regulating system plays an essential role in the pubertal development of females. Leptin, in addition to its role in body weight regulation, appears to be of critical importance on the onset of sexual maturation in children, in fact it is seems to be related to the age at menarche (AAM).
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
was higher in patients with MH − 9 (37.5%) vs. 4 patients without MH (10%, p = 0.008). Multivariate regression analysis confirmed the correlation of MH with BMI and micro/macroalbuminuria but revealed also the association of MH with parameter of diastolic function E/E (r = 0.431, p < 0.05) and with intimomedial thickness (IMT) of carotid artery (r = 0.557, p < 0.05). Conclusion: Masked hypertension in treated type 2 diabetic patients is frequent and significantly associated with BMI, micro/macroalbuminuria, IMT of carotid artery and diastolic function parameter E/E . ˇ NR/9520−3 Supported by grant IGA MZ CR MS245 FTO POLYMORPHISM IS ASSOCIATED WITH MYOCARDIAL INFARCTION J. Hubacek1,2 , for the GENDEMIP Research Group. 1 Institute for Clinical and Experimental Medicine, 2 Centre for Cardiovascular Research, Prague, Czech Republic Introduction: Myocardial infarction (MI) is the most common cause of death in industrial countries. All general MI risk factors have some genetic components and the proportion of genetic predisposition is between 30−60%. FTO gene (“fat mass and obesity related gene”, DNA demethylase) and its variants have been described primarily like important determinant of body weight. Further, FTO gene variant increases general mortality independent of fatness in men. We have analysed the putative association between FTO SNP rs17817449 and risk of MI development on middle European Caucasians. Methods: FTO SNP rs17817449 (G → C) was analysed using PCR-RFLP in 1 191 representatively selected controls (age below 65) and 1 092 consecutive MI patients (age below 65). ANOVA and chi-square were used for statistical analysis. Results: FTO rs17817449 has significant effect on body mass index (kg/m2 ) both in controls (GG − 28.7±3.7; GT − 28.3±4.1; TT − 27.8±3.9; P = 0.014) and in patients (GG − 29.2±4.1; GT − 28.3±4.5; TT − 28.2±3.8; P = 0.006). Total cholesterol, HDL cholesterol, triglycerides, blood pressure were not associated with FTO variant. Further, the frequency of GG homozygotes is significantly higher in MI patients than between controls (21.4% vs 15.9%, P = 0.005; OR 1.38; 95% CI 1.10–1.73). Conclusion: FTO rs17817449 (G → C in first intron) SNP is newly recognized genetic risk factor for myocardial infarction development. Supported by project No. 1M0510 (MEYS, CR) MS246 LIPID PROFILE OF SPANISH PATIENTS WITH CORONARY HEART DISEASE TREATED WITH STATINS. THE DYSLIPIDEMIA INTERNATIONAL STUDY (DYSIS-SPAIN) J. Millan1 , J.R. Gonzalez-Juanatey2 , C. Guijarro3 , E. Alegria4 , J.V. Lozano5 , ˜ B. Gonzalez-Timon6 , G. Vitale6 . 1 Hospital Gregorio Maranon, Madrid, 2 Hopital Clinco Universitario, Santiago de Compostela, Santiago de Compostela, 3 Hospital de Alcorcon, Alcorcon, 4 Clinica Universitaria de Pamplona, Pamplona, 5 Primary Care Center La Serreria 2, Valencia, 6 Merck & Co., MSD, Madrid, Spain Introduction: LDL-C is the therapeutic target for cardiovascular (CV) prevention and main CV guidelines recommend statins to reduce LDL-C levels. Patients with coronary heart disease (CHD) are high CV risk patients and have a lower LDL-C target. Some studies have found that low HDL-C and high triglycerides (TG) may have a role in coronary risk but statins have limited action on them. In this analysis we describe the lipid profile of Spanish statin-treated patients with CHD. Methods: Analysis of 3710 Spanish statin-treated patients included in DYSIS (22,063 patients in Europe and Canada). We used the ATP-III recommendations to classify patient’s risk and define the LDL-C goal and normality or not of the HDL-C and TG levels. Results: In 3710 patients, 23.8% were diagnosed with CHD (68.0% men, 27.6% women, p < 0.001). In this subpopulation: 75.1% hypertensive, 44.8% diabetics, 16.8% smokers and 25.6% had a family history of premature CHD. LDL-C was not at goal in 46.9% of patients with CHD vs. 51.4% of patients without CHD (p < 0.05). The prevalence of low HDL-C was 34.9%, higher compared to patients without CHD (29.8%, p < 0.001) and TG were elevated in 35.1% comparing to 38.4% in patients without CHD. Conclusions: In this analysis of CHD patients, despite better control of LDL-C and TG than the total Spanish population studied, almost 50% of CHD patients do not reach LDL-C target. The prevalence of low HDL-C in these patients is significantly higher and 1/3 show high TG. A considerable number of CHD patients had an abnormal lipid profile. It is necessary to use new therapies focused on treating complete lipid profile (LDL-C, HDL-C and TG).
159
MS247 LEPTIN, ADIPONECTIN AND LEPTIN TO ADIPONECTIN RATIO IN DEPRESSIVE WOMEN M. Zeman1 , R. Jirak ´ 2 , M. Vecka1 , A. Zˇ ak ´ 1 , J. Macaˇ ´ sek1 , E. Tvrzicka´ 1 , T. Vaˇreka1 , L. Vavrov ´ a´ 1 , J. Kodydkova´ 1 , B. Stankov ˇ a´ 1 . 1 IVth Dept Int Med, 2 1st Psychiatric Dept, 1st Medical Faculty, Charles University, Prague, Czech Republic Background: Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistance (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated glycaemia, could stand behind the connection. Recent findings have shown that leptin and adiponectin might play a role in both depression and MetS. Materials and Methods: The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in group of 38 women with DD. The results were compared with those of 38 healthy women of control group, matched for age. Results: Women of DD group differed from those of control group in higher concentrations of plasma leptin (21.80±13.28 vs. 14.12±6.25) and the leptinto-adiponectin ratio (1.80±1.12 vs. 1.04±0.72), both P < 0.05. Concomitantly, they had higher plasma TG (1.60±1.06 vs. 1.19±0.28 mmol/l (P < 0.05), insulin (13.38±8.0 vs. 7.8±3.8, C-peptide (0.84±0.31 vs. 0.66±0.19), both P < 0.01), microalbuminuria (12.65±10.18 vs. 4.49±3.07, P < 0.05) and higher value of the HOMA-IR index (P < 0.01). Conclusions: In the presented pilot study, we found increased levels of plasma leptin in the group of depressive women and also the increased value of leptinto-adiponectin ratio plasma levels and certain features of MetS. This could be the factor connecting depression with an increased risk of either DM2 or CVD. Moreover, HAM-D score of DD cases correlated negatively with adiponectin concentrations (P < 0.01). Study was supported by the Research Project MSM 0021620820. MS248 WAIST CIRCUMFERENCE NEGATIVE CORRELATION WITH TESTOSTERONE AND SHBG IN YOUTH WITH PRE-METABOLIC AND METABOLIC SYNDROMES V. Dimitrijevic-Sreckovic1 , P. Djordjevic1 , S. Damjanovic1 , B. Sreckovic2 , V. Barac3 , I. Soldatovic4 , M. Cvetkovic1 . 1 Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 2 Bezanijska Kosa Clinical Center, 3 Institute of Medical Biochemistry, 4 Institute for Medical Statistics and Informatics, Clinical Center of Serbia, Belgrade, Serbia Background: Visceral obesity, in fact a metabolic syndrome (MS), is related to decreased testosterone and sex hormone-binding globulin (SHBG) in adults. Peripheral conversion of testosterone to estrogen in excess peripheral adipose tissue may lead to secondary hypogonadism through hypothalamic-pituitarygonadal axis inhibition. Aims of the study were to examine sex hormones in obese young males and correlations with visceral obesity, lipid status and blood pressure. Methods: The study included 44 obese male individuals aged 16−30. Three of the following five criteria were used for MS diagnosis: waist circumference >90Pct; triglycerides >1.7 mmol/l; HDL-cholesterol< 1.0 mmol/l; hypertension>90Pct; glycemia>6.0 mmol/L. Patients with less than three afore mentioned criteria were considered pre-MS. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and SHBG was determined by radioimmunoassay (RIA). Results: Decreased testosterone (< 12.0nmol/l) was found in 11.3% obese young males (8.1±3.1nmol/l), with low SHBG (10.6±4.5) and normal FSH, LH and estradiol. Patients with pre-MS had normal testosterone (17.3±4.3nmol/l), FSH (3.84±2.25mU/l), LH (3.4±1.79mU/l), estradiol (110.0±51.8pmol/l) and SHBG (42.5±9.4). Patients with MS had normal testosterone (17.0±6.4nmol/l), FSH (3.38±2.17mU/l), LH (3.0±1.6mU/l), estradiol (115.3±48.4pmol/l), and SHBG at lower limits (17.8±8.4). Correlations: WC negative with testosterone and SHBG (p < 0.05); SHBG negative with BMI (p < 0.05), systolic and diastolic blood pressure (p < 0.01); estradiol positive with total cholesterol (p < 0.01), LDL-cholesterol and diastolic blood pressure (p < 0.05). Conclusion: Negative correlation of waist circumference with testosterone and SHBG and of SHBG with BMI and blood pressure, proves the important effect of visceral obesity and insulin resistance on possible occurrence of secondary hypogonadism and infertility. MS249 ASSOCIATION OF THE Q223R POLYMORPHISM IN THE LEPTIN RECEPTOR GENE WITH AGE AT MENARCHE A. Garc´ıa Anguita, P. Riestra, C. Garces. ´ Lipid Metabolism Laboratory, ´ Jimenez Diaz, Madrid, Spain Fundacion Introduction: Energy regulating system plays an essential role in the pubertal development of females. Leptin, in addition to its role in body weight regulation, appears to be of critical importance on the onset of sexual maturation in children, in fact it is seems to be related to the age at menarche (AAM).