P13
Coronary heart disease with depression and studies of serum interleukin-6 level
G Maimaitiming
First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
Topic: Behavioural medicine
Objectives: this study was conducted to explore the relationship between interleukin –6(IL-6) and coronary heart disease with depression, and sought prognostic role of IL-6, in order to come up with intervention strategy on treating coronary heart disease patients who were developed depression. Methods:90 patients with coronary heart disease were recruited into our study, -according to ZUNG self depression scale (SDS) score, subjects were divided into two groups as, coronary heart disease with depression (group A) and coronary heart disease without depression (group B).
Results: 57.78% of subjects had varying degree of depression, patients with mild depression were 24 (26.67 %), patients with moderate and severe depression were 28(31.11%); 57.59% of male patients had depression, and 57.89% of female patients had depression, there was no statistical difference between two genders when compare the concomitance rate of depression (P< 0.05); the levels of serum IL-6 in the A group [M(P25, P75)] were [0.04(0.01, 0.06)] ng/ml, B group were [0.02(0.01,0.05)] ng/ml, group A were significantly higher than the B group (P<0.05); In the group A, the levels of serum IL-6 patients with moderate and severe depression were [0.05(0.02,0.08)] ng/ml higher than in patients with mild depression [0.04(0.01,0.05)] ng/ml, (P<0.05); In the group A the serum IL-6 levels was positively correlated with cholesterol? low-density lipoprotein? C-reactive protein and left ventricular internal diameter at the end diastolic left ventricular internal diameter (P<0.05), negatively correlated with left ventricular ejection fraction (P<0.05), there was no obvious correlation with triglyceride and high-density lipoproteins. In the group B the serum IL-6 levels was not obviously correlated to cholesterol? triglyceride? low-density lipoprotein? high-density lipoproteins, C-reactive protein, left ventricular internal diameter at the end-diastolic and left ventricular ejection. fraction.
Conclusion: the concomitance rate of depression in the coronary heart disease patients were higher, the level of serum inflammatory markers in coronary heart disease patients with depression were higher than coronary heart disease patients without depression; In moderate to severe depressed patients with higher levels of inflammatory markers than in mild depression patients. Depression is a sign of activation of inflammatory responses; inflammatory responses play invariably role in coronary heart disease with depression.
Key words: Coronary heart disease; Depression; IL-6.
P409
Prevention of oxidative-nitrosative stress activity by atorvastatin at high dose in patients undergoing aorta-femoral bypass operation
Y V Shchukin, AN Vachev, EI Selesnev, EA Medvedeva, EA Surkova, II Berezin
Samara State Medical University, Samara, Russian Federation
Topic: Lipids and atherosclerosis
Objective: To study atorvastatin influence on the molecular mechanisms of decrease in oxidative-nitrosative stress, which is the pathogenetic factor for cardiac complications after the aorta-femoral bypass (AFB) operation.
Methods: 126 patients with atherosclerosis undergoing AFB operation, were included in the study. the intensity of oxidative-nitrosative stress was determined by the levels of oxidized low-density lipoproteins (ox-LDL), 3-nitrotyrosine (3-NT) and secretory phospholipase A2 type IIA (sPLA-A2 IIA) activity. Antioxidant protection system was estimated by glutathione peroxidase (GPx), extracellular superoxide dismutase (EC-SOD) activity and the level of protein thiol (−SH) groups. the postoperative myocardial ischemia was determined by means of electrocar-diography monitoring (Holter). Patients were divided into two groups: 1 group − 62 patients received atorvastatin 60 mg per day during 10–15 days before operation, 2 − 64 patients were prepared in traditional way. the control group included 36 healthy people.
Results: Before treatment we found increase of oxidative-nitrosative stress in both patients groups. After atorvastatin treatment we observed increase in activity of GPx (24%, p<0,05), EC-SOD (22%, p<0,05), level of protein thiol (−SH) groups and decrease in level of 3-NT (27%, p<0,05), ox-LDL - (24%, p<0,05), sPLA- A2 IIA - (23%, p<0,05). In the second group changes were not observed. On the first day after operation indicators of oxidative stress were increased in both patients group, but in the first group less than in the second group difference between groups was 35–40%. We also found increase in the rate of postoperative myocardial infarction and ischemia in the second group in comparison with the first one.
Conclusion: Preoperative atorvastatin significantly reduces adverse cardiac events after AFB operation in patients with atherosclerosis. It may be connected with reduction of vascular and myocardial oxidative-nitrosative stress.
P410
Combined effect of genetic factors, vitamin status and renal function on plasma homocysteine level in Russian patients with stable CAD
OO Olga Shakhmatova1, AL Komarov1, DV Rebrikov2, I Kofiady2, TI Kotkina1, AV Bolvacheva1, EP Panchenko1
1
Russian Cardiology Research & Production Center, Moscow, Russian Federation, 2DNA-technology, Moscow, Russian Federation
Topic: Genetic-environmental interactions
Moderate hyperhomocysteinemia is an important risk factor for CAD. Common polymorphisms (MthFR C677T, MthFR A1298C, MTR A2756G, MTRR A66G, TCN C776G) and some clinical factors (reduced folat and cobalamin level, diabetes mellitus (DM), renal insufficiency and atherosclerotic burden) may contribute to increased homocysteine (Hcy) level.
Purpose: To investigate clinical and genetic determinants of hyperhomocysteinemia in Russian pts with stable CAD.
Methods: 506 pts (388 male, age 59.4±12.2 years) with stable CAD were enrolled. Atherosclerosis in other vascular beds (cerebrovascular and peripheral vascular diseases) was assessed. Renal function was estimated by creatinine clearance (CrCl), Cocroft-Gault formula. Hcy, folat and vitamin B12 plasma concentrations were measured. Polymorphisms were detected based on the real-time PCR.
Results: Mean Hcy was 14.3±4.6çmol/l. 432 (85.4%) pts had hyperhomocysteinemia (Hcy>10ç-mol/l). the frequency of polymorphisms was as follows (hetero-/homozygote): MthFR 677T 43.3/8.5%, MthFR 1298C 43.3/12.4%, MTR2756G 37.0/17.2%, MTRR66G 38.7/23.6%, TCN 776G 44.7/22.3%. Prevalence of other factors of interest was: low folat plasma level (<7.2 ng/ml) − 55.5%, low B12 plasma level (<200 pg/ml) − 9.7%, DM − 19%, CrCl<90 ml/min − 53.4%, coexisting CVD and/or PAOD − 28.8%.
According to univariate analysis, Hcy was related to folat plasma level (Spearman rank –0.23, p<0.0001), B12 plasma level (Spearman rank –0.24, p<0.001) and renal dysfunction (Hcy level: 15.2çmol/l for CrCl <90 ml/min vs 13.5çmol/l for CrCl > 90 ml/min, p<0.02). According to ANOVA with continuous covariances (using the nested models), folat plasma level (beta-coefficient — 3.86, p<0.0001), cobalamin plasma level (beta –5.73, p<0.0001) and MTRR 66AA genotype (beta 10.71, p<0.0005) were the only three independent predictors of hyperhomocysteinemia. Also Hcy level was related to some combined conditions: MTRR 66G mutation + folat plasma level (beta 1.12, p<0.0001), MTRR 66AA genotype + cobalamin plasma level (beta 0.012, p<0.0001), TCN 776G mutation + cobalamin plasma level (beta –0.03, p<0.0001), TCN 776G mutation + folat plasma level (beta 0.58, p<0.0009), MTR 2756G mutation + cobalamin plasma level (beta 0.004, p<0.002), MTRR 66G mutation + CrCl <90 ml/min (beta 0,08, p<0.001) and TCN 776G mutation + CrCl <90 ml/min (beta 0,07, p<0.0007).
Conclusion: in Russian pts with stable CAD Hcy level is related to vitamin plasma concentrations, MTRR66AA genotype and MTR 2756G, MTRR 66G, TCN 776G mutations with account taken of vitamin status and renal insufficiency.
P413
Acute exercise increases paracrine activity of circulating angiogenic cells in sedentary patients with chronic heart failure
E Van Craenenbroeck, V Hoymans, P Beckers, N Possemiers, C Vrints, V Conraads
Antwerp University Hospital, Edegem, Belgium
Topic: Exercise physiology, testing and training
Purpose: the production of angiogenic cytokines is one of the putative mechanisms by which circulating angiogenic cells (CAC) participate in maintaining normal structure and function of the endothelial cell-layer. Migratory capacity of CAC is impaired in patients with CHF. this functional deficit might partially explain endothelial dysfunction, which characterizes CHF patients and determines exercise capacity. the paracrine function of CAC has not been investigated in CHF. therefore, we studied the production of vascular endothelial growth factor (VEGF) by CAC obtained in CHF patients and healthy subjects. Furthermore, the effect of a single exercise bout, known to improve CAC migratory capacity, was studied.
Methods: Venous blood was sampled from 21 sedentary CHF patients and 5 healthy subjects before and after a graded exercise test (GXT). Peripheral blood mononuclear cells were cultured for 7 days in an endothelial cell medium (EGM-2MV) to generate acLDL+UEA-I+CAC. After 7 days, migratory capacity towards VEGF and SDF-1a was assessed in vitro. For paracrine activity, cultured CAC were switched to basal medium (no supplemental growth factors) for 72 hours. Conditioned media were collected and assayed for VEGF using ELISA. Supernatant from human dendritic cells served as negative controls.
Results: Compared to dendritic cells supernatant (no VEGF detected), VEGF levels in supernatant of CAC cultures from healthy subjects ranged from 75.0 to 143.6 pg/ml. VEGF concentration was significantly lower in supernatant obtained from CAC from CHF patients (61.7 ± 11.0 pg/ml, mean ± SD) compared to controls (101.3 ± 12.0 pg/ml, p= 0.05). Acute exercise significantly affected VEGF production by CAC. In healthy subjects, VEGF levels decreased with 41.5 ± 7.4% post-GXT, whereas in the CHF group an increase of 24.8 ± 16.1 % was observed (p=0.002). Migratory capacity towards VEGF and SDF-1a showed a similar pattern. there was a significant correlation between the change in VEGF levels and the change in migratory capacity following GXT (p=0.004, r=0.541).
Conclusion: Paracrine activity of CAC is impaired in CHF patients and this deficit could contribute to impaired endothelial repair and hence, endothelial dysfunction. Acute exercise is a powerful stimulus to improve CAC paracrine function in these patients.
(W) P414: Comparison of predicted dose vs. actual dose using pharmacogenomic algorithms in 483 patients on long term warfarin therapy
B Diug1, L Sheffield2, M Dooley3, J Lowthian1, S Evans1, E Maxwell4, A Street3, J Mcneil1
1
Monash University, Melbourne, Australia, 2Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Australia, 3the Alfred Hospital, Melbourne, Australia, 4Melbourne Pathology, Melbourne, Australia
Topic: Genetic-environmental interactions
Purpose: this study aims to compare the predicted dose against the actual dose using pharmacogenomics in patients on long-term warfarin therapy in the community. Previous studies have focussed on pharmacogenomics during initial titration phase however, there is limited information on its impact on maintenance dosing in patients on long- term warfarin therapy.
Method: Acase control study was conducted with patients recruited by a metropolitan pathology provider. Warfarin predicted dose was calculated by application of two pharmacogenomic algorithms. Actual dose was attained from the patient and confirmed by the pathology provider where by mean absolute percentage error was calculated (MAPE). Cases had an elevated INR=6.0 whilst controls were within their therapeutic range for at least 3 months. Patient interviews investigated demographic and clinical risk factors, time in range and dosage. Height, weight, waist circumference were measured with DNA obtained through a cheek brush sample for analysis of genes CYP2C9 and VKORC1.
Results: A total of 483 patients were recruited: 156 cases (mean age 75.4 yrs, range 25–96) and 327 controls (mean age 75.5 yrs, range 36–92). Primary indication for long-term warfarin therapy was atrial fibrillation (55%) and the predominant race was white (85%) in this cohort. Patients had a mean height of 167cm (139–198), mean weight of 79.5kg (36–175). Duration of therapy showed no difference between the two groups with cases on warfarin for a median of 4 years (0.3–31) and controls 5 years (0.3–31). Mean dosage for cases was 4.5 mg (1–12) whilst controls were 4.3 mg (0.75–14.5).
Conclusions: Our findings show no difference between the results from the NEJM and Gage algorithms. However, MAPE showed significant variations between expected and predicted dosages between our cases and controls in community-based patients on long -term warfarin maintenance therapy. Further, assessment of these findings is required.
