- Email: [email protected]
INFLAMMATORY RESPONSE TO LYPOPOLYSACCHARIDE IN MONONUCLEAR CELLS FROM POLYCYSTIC OVARY SYNDROME INSULIN RESISTANT ADOLESCENTS
Poster Sessions PO26 Insulin resistance mg/dL at entry. Atorvastatin (A, 10 mg), fenofibrate (F, 200 mg), both drugs (A+F) or placebo (P) were initiated up to the third day after hospital discharge. Hypertensive patients stage 1 or 2 (n=92) were used for IgG titer comparisons. Human LDL was obtained from a healthy donor, oxidized by copper, anti-oxLDL measured by ELISA in oxLDL sensitized plates. TBARS (MDA, nM), hs-CRP (nephelometry, mg/L), and oxLDL were obtained at baseline (B), 3 and 6-wk. We used GLM-repeated measures and p<0.05. Results: The groups with ACS were comparable at baseline regarding TBARS, hs-CRP and titers of anti-oxLDL. There was a significant decrease in anti-oxLDL, TBARs and hs-CRP at 6-wk w/o differences regarding treatment regimens. Hypertensive patients presented anti-oxLDL titers higher than those with ACS (1.87±0.95 vs. 0.85±0.43 OD; p<0.0001). Conclusions: Adaptive immune responses may play a role in plaque instabilization. Short-term treatment with statins or fibrates did not modify antibody titers. Low titers of serum anti-oxLDL can be markers of unstable coronary disease. PO25-415
ASSOCIATION OF N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE WITH CARDIOVASCULAR RISK FACTORS: RESULTS FROM THE DETECT STUDY
H. Scharnagl 1 , T. Stojakovic 1 , D. Pittrow 2 , L. Pieber 2 , S. Boehler 3 , G. Ruf 3 , W. Maerz 4 , H. Wittchen 2 . 1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; 2 Clinical Psychology and Psychotherapy, Technical University, Dresden, Germany; 3 Pfizer GmbH, Karlsruhe, Germany; 4 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany Background and aims: Brain-type natriueretic peptide (BNP) and the amino terminal fragment of BNP (NT-proBNP) are prognostic markers used for the diagnosis of heart failure and have been shown to predict mortality in patients with acute coronary syndrome. The aim of our study was to investigate the association of NT-proBNP with cardiovascular risk factors in a general population. Methods: The epidemiological study DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment) was launched to assess physicians’ awareness, attitudes, and
PO26 INSULIN RESISTANCE PO26-417
INFLAMMATORY RESPONSE TO LYPOPOLYSACCHARIDE IN MONONUCLEAR CELLS FROM POLYCYSTIC OVARY SYNDROME INSULIN RESISTANT ADOLESCENTS
A. Fulghesu 1 , F. Sanna 2 , S. Uda 2 , E. Portoghese 1 , R. Magnini 1 , A. Saddi 2 , B. Batetta 1 . 1 Dipartimento chirurgico,materno-infantile e di Scienze delle immagini, University of Cagliari, Italy; 2 Dipartimento di Scienze e Tecnologie Biomediche, Sez.Patologia Sperimentale, University of Cagliari, Italy Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterised by excessive androgen secretion or activity, and health complications including obesity, insulin-resistance and type 2 diabetes. Although hyperglycemia, dyslipidaemia and high levels of inflammatory markers are often present in middle-aged PCOS women, evidence of a cardiovascular risk in PCOS adolescents is less defined. To investigate the latter inflammatory response was evaluated in peripheral lympho-mononuclear cells from 5 PCOS insulin-resistant girls (evaluated by OGTT and by HOMA test) aged 17-20 years, and results compared with those of five matched healthy girls. Pro-inflammatory (TNF-α, IL-6 and IL-1β) and anti-inflammatory (TGF-β and Il-10) cytokine secretion was determined (Elisa) in monocytes incubated for 48 hours with lypopolysaccharide (100 ng/ml) and in 48 hour PHA activated lymphocytes. The results obtained demonstrated a similar proliferative response and cytokine secretion in lymphocytes from both groups. Cytokine secretion was moreover similar in LPS activated monocytes, but IL-6 secreted from PCOS was significantly higher (as evaluated by Mann-Whitney U and Kolmogorov-Smirnov tests, p=0.01 and p<0.05, respectively) in all experiments performed. Although markers of inflammation (CRP, leucocytes, fibrinogen) were all within normal range and a comparable basal secretion cytokine was observed in both groups, activation with LPS invariably produced an increased secretion of IL-6 in PCOS adolescents. Since Il-6 is an acknowledged cause on inflammation to the arterial wall and a stimulator of CRP, we suggest that in a life-long time, an excessive IL-6 response to numerous microbial and metabolic stimuli may constitute a hazard for the arterial wall. PO26-418
ASSOCIATION OF ADIPONECTIN WITH INSULIN RESISTANCE AND LIVER ENZYMES IN DYSLIPIDEMIC SUBJECTS: RELATIONSHIP TO NONALCOHOLIC FATTY LIVER DISEASE?
H. Vaverkova 1 , D. Jackuliakova 1 , D. Karasek 1 , D. Novotny 2 , J. Lukes 2 . Department of Internal Medicine, Medical Faculty and University Hospital Olomouc, Olomouc, Czech Republic; 2 Department of Clinical Biochemistry, University Hospital Olomouc, Olomouc, Czech Republic 1 3rd
The aim of our study was to evaluate the interrelationship of adiponectin, parameters of insulin resistance and liver enzymes ALT and GMT as markers of fatty liver disease in dyslipidemic subjects. Material: We examined 371 dyslipidemic subjects, their first degree relatives and spouses, until now not treated with hypolipidemic drugs.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background: Gonadotropin releasing hormone (GnRH) agonists are the cornerstone of metastatic prostate cancer treatment. Fibrinolytic system components play a central role in cardiovascular risk and atherosclerosis. In this study, we investigated the short term effects of GnRH agonists on plasma fibrinolytic parameters in patients with metastatic prostate cancer. Methods: Eleven patients (mean age 69.3±6.5) with metastatic prostate cancer and a clinical indication for GnRH agonist therapy were selected. Plasma plasminogen activator inhibitor (PAI-1) antigen (Ag), tissue plasminogen activator (t-PA) Ag and trombin-activatable fibrinolysis inhibitor (TAFI) Ag levels were measured. All patients received the first dose of GnRH agonist, Goserelin Acetate (Zoladex ® , s.c administration, 10.8 mg). Plasma PAI-1 Ag, t-PA Ag and TAFI levels were measured at 4 weeks after Goserelin Acetate administration. Results: Serum Prostate Spesific Antigen (PSA) levels significantly decreased from 36,6±19.3 ng/ml to 1.1±0.3 ng/ml after Goserelin acetate treatment (p=0.005). Significant changes in these fibrinolytic parameters were noted at 4 weeks after treatment with GnRH agonists. Plasma t-PA levels decreased (16.3±4.9 vs. 12.2±2.8 p=0.047) after the treatment. In contrast, plasma PAI-1 Ag (59.0±48.5 vs. 56.4±30.5, p=0.8), and TAFI Ag levels (130.6±9.5 vs. 124.2±26.5, p=0.3) did not change significantly. After GnRH agonists, PAI-1/t-PA molar ratio (4.8±3.6 vs. 6.6±3.4, p=0.16) increased without reaching statistical significance. Conclusion: This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels, and increasing PAI-1/t-PA Ag ratio. PO25-416
practice patterns concerning coronary heart disease, arterial hypertension, diabetes mellitus, and lipid disorders. DETECT is a large multistage cross-sectional and prospective study of 60000 consecutive patients in over 3000 primary care offices, nationwide. A subset of 6336 patients was characterized by an extensive standardized laboratory program. Results: NT-proBNP was associated with New York Heart Association functional class, left ventricular hypertrophy, peripheral vascular disease, and cerebrovascular disease. NT-proBNP was positively related to age, female sex, hypertension, and C-reactive protein and negatively related to body mass index and glomerular filtration rate. Dyslipidemia, type 2 diabetes mellitus, and coronary artery disease were more frequent in patients with high concentrations of NT-proBNP (>400 ng/L) compared to patients with normal NT-proBNP (<100 ng/L). Conclusions: NT-proBNP was associated with cardiovascular risk factors and related to cardiovascular and cerebrovascular disease. The measurement of NT-proBNP may contribute to the risk assessment of cardiovascular diseases in the general population.
SHORT TERM EFFECTS OF GNRH AGONISTS ON PLASMA FIBRINOLYTIC SYSTEM IN METASTATIC PROSTATE CANCER
O. Baykan 1 , A. Cincin 1 , A. Tekin 2 , F. Sengor 2 , M. Demir 3 , M. Agirbasli 1 . 1 Department of Cardiology, Marmara University School of Medicine, Istanbul, Turkey; 2 Department of Urology, Haydarpasa Numune Hospital, Istanbul, Turkey; 3 Department of Internal Medicine, Division of Hematology, Trakya University School of Medicine, Edirne, Turkey
119
ASSOCIATION OF N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE WITH CARDIOVASCULAR RISK FACTORS: RESULTS FROM THE DETECT STUDY
H. Scharnagl 1 , T. Stojakovic 1 , D. Pittrow 2 , L. Pieber 2 , S. Boehler 3 , G. Ruf 3 , W. Maerz 4 , H. Wittchen 2 . 1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; 2 Clinical Psychology and Psychotherapy, Technical University, Dresden, Germany; 3 Pfizer GmbH, Karlsruhe, Germany; 4 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany Background and aims: Brain-type natriueretic peptide (BNP) and the amino terminal fragment of BNP (NT-proBNP) are prognostic markers used for the diagnosis of heart failure and have been shown to predict mortality in patients with acute coronary syndrome. The aim of our study was to investigate the association of NT-proBNP with cardiovascular risk factors in a general population. Methods: The epidemiological study DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment) was launched to assess physicians’ awareness, attitudes, and
PO26 INSULIN RESISTANCE PO26-417
INFLAMMATORY RESPONSE TO LYPOPOLYSACCHARIDE IN MONONUCLEAR CELLS FROM POLYCYSTIC OVARY SYNDROME INSULIN RESISTANT ADOLESCENTS
A. Fulghesu 1 , F. Sanna 2 , S. Uda 2 , E. Portoghese 1 , R. Magnini 1 , A. Saddi 2 , B. Batetta 1 . 1 Dipartimento chirurgico,materno-infantile e di Scienze delle immagini, University of Cagliari, Italy; 2 Dipartimento di Scienze e Tecnologie Biomediche, Sez.Patologia Sperimentale, University of Cagliari, Italy Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterised by excessive androgen secretion or activity, and health complications including obesity, insulin-resistance and type 2 diabetes. Although hyperglycemia, dyslipidaemia and high levels of inflammatory markers are often present in middle-aged PCOS women, evidence of a cardiovascular risk in PCOS adolescents is less defined. To investigate the latter inflammatory response was evaluated in peripheral lympho-mononuclear cells from 5 PCOS insulin-resistant girls (evaluated by OGTT and by HOMA test) aged 17-20 years, and results compared with those of five matched healthy girls. Pro-inflammatory (TNF-α, IL-6 and IL-1β) and anti-inflammatory (TGF-β and Il-10) cytokine secretion was determined (Elisa) in monocytes incubated for 48 hours with lypopolysaccharide (100 ng/ml) and in 48 hour PHA activated lymphocytes. The results obtained demonstrated a similar proliferative response and cytokine secretion in lymphocytes from both groups. Cytokine secretion was moreover similar in LPS activated monocytes, but IL-6 secreted from PCOS was significantly higher (as evaluated by Mann-Whitney U and Kolmogorov-Smirnov tests, p=0.01 and p<0.05, respectively) in all experiments performed. Although markers of inflammation (CRP, leucocytes, fibrinogen) were all within normal range and a comparable basal secretion cytokine was observed in both groups, activation with LPS invariably produced an increased secretion of IL-6 in PCOS adolescents. Since Il-6 is an acknowledged cause on inflammation to the arterial wall and a stimulator of CRP, we suggest that in a life-long time, an excessive IL-6 response to numerous microbial and metabolic stimuli may constitute a hazard for the arterial wall. PO26-418
ASSOCIATION OF ADIPONECTIN WITH INSULIN RESISTANCE AND LIVER ENZYMES IN DYSLIPIDEMIC SUBJECTS: RELATIONSHIP TO NONALCOHOLIC FATTY LIVER DISEASE?
H. Vaverkova 1 , D. Jackuliakova 1 , D. Karasek 1 , D. Novotny 2 , J. Lukes 2 . Department of Internal Medicine, Medical Faculty and University Hospital Olomouc, Olomouc, Czech Republic; 2 Department of Clinical Biochemistry, University Hospital Olomouc, Olomouc, Czech Republic 1 3rd
The aim of our study was to evaluate the interrelationship of adiponectin, parameters of insulin resistance and liver enzymes ALT and GMT as markers of fatty liver disease in dyslipidemic subjects. Material: We examined 371 dyslipidemic subjects, their first degree relatives and spouses, until now not treated with hypolipidemic drugs.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background: Gonadotropin releasing hormone (GnRH) agonists are the cornerstone of metastatic prostate cancer treatment. Fibrinolytic system components play a central role in cardiovascular risk and atherosclerosis. In this study, we investigated the short term effects of GnRH agonists on plasma fibrinolytic parameters in patients with metastatic prostate cancer. Methods: Eleven patients (mean age 69.3±6.5) with metastatic prostate cancer and a clinical indication for GnRH agonist therapy were selected. Plasma plasminogen activator inhibitor (PAI-1) antigen (Ag), tissue plasminogen activator (t-PA) Ag and trombin-activatable fibrinolysis inhibitor (TAFI) Ag levels were measured. All patients received the first dose of GnRH agonist, Goserelin Acetate (Zoladex ® , s.c administration, 10.8 mg). Plasma PAI-1 Ag, t-PA Ag and TAFI levels were measured at 4 weeks after Goserelin Acetate administration. Results: Serum Prostate Spesific Antigen (PSA) levels significantly decreased from 36,6±19.3 ng/ml to 1.1±0.3 ng/ml after Goserelin acetate treatment (p=0.005). Significant changes in these fibrinolytic parameters were noted at 4 weeks after treatment with GnRH agonists. Plasma t-PA levels decreased (16.3±4.9 vs. 12.2±2.8 p=0.047) after the treatment. In contrast, plasma PAI-1 Ag (59.0±48.5 vs. 56.4±30.5, p=0.8), and TAFI Ag levels (130.6±9.5 vs. 124.2±26.5, p=0.3) did not change significantly. After GnRH agonists, PAI-1/t-PA molar ratio (4.8±3.6 vs. 6.6±3.4, p=0.16) increased without reaching statistical significance. Conclusion: This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels, and increasing PAI-1/t-PA Ag ratio. PO25-416
practice patterns concerning coronary heart disease, arterial hypertension, diabetes mellitus, and lipid disorders. DETECT is a large multistage cross-sectional and prospective study of 60000 consecutive patients in over 3000 primary care offices, nationwide. A subset of 6336 patients was characterized by an extensive standardized laboratory program. Results: NT-proBNP was associated with New York Heart Association functional class, left ventricular hypertrophy, peripheral vascular disease, and cerebrovascular disease. NT-proBNP was positively related to age, female sex, hypertension, and C-reactive protein and negatively related to body mass index and glomerular filtration rate. Dyslipidemia, type 2 diabetes mellitus, and coronary artery disease were more frequent in patients with high concentrations of NT-proBNP (>400 ng/L) compared to patients with normal NT-proBNP (<100 ng/L). Conclusions: NT-proBNP was associated with cardiovascular risk factors and related to cardiovascular and cerebrovascular disease. The measurement of NT-proBNP may contribute to the risk assessment of cardiovascular diseases in the general population.
SHORT TERM EFFECTS OF GNRH AGONISTS ON PLASMA FIBRINOLYTIC SYSTEM IN METASTATIC PROSTATE CANCER
O. Baykan 1 , A. Cincin 1 , A. Tekin 2 , F. Sengor 2 , M. Demir 3 , M. Agirbasli 1 . 1 Department of Cardiology, Marmara University School of Medicine, Istanbul, Turkey; 2 Department of Urology, Haydarpasa Numune Hospital, Istanbul, Turkey; 3 Department of Internal Medicine, Division of Hematology, Trakya University School of Medicine, Edirne, Turkey
119