Salem Abdessalem

Association of a DNA polymorphism of the apolipoprotein AI-CIII-AIV gene cluster with myocardial infarction in a Tunisian population

BACKGROUND Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high-density lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population. METHODS A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (co-dominant model odds ratio [OR]: 1.53, 95% confidence interval [CI]: 1.0-2.35, p=0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p=0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p=0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls. CONCLUSION In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Association between endothelial nitric oxide gene intron 4a4b VNTR polymorphism and plasma homocysteine concentrations in Tunisian male patients with myocardial infarction.

Many studies have shown that hyperhomocysteinemia may be an independent risk factor for coronary artery disease. However, not all prospective studies support an association between elevated plasma homocysteine levels and coronary artery disease. Nitric oxide (NO) plays a relevant role in various events during atherogenesis, and in vitro data suggest that NO may modulate total homocysteine (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide (NOS3) gene have been reported to be related to an increased risk of myocardial infarction (MI) and hyperhomocysteinemia, but the results have been controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a determinant of tHcy concentrations and tested this in 310 patients with MI and 250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by polymerase chain reaction analysis. There was no significant difference in the homocysteine levels between patients with MI and controls. The frequencies of the NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different from those in the control group. In patients with MI, plasma tHcy concentrations were significantly different among the NOS3 genotypes (13.5±4.5, 18.5±3.9, and 20.4±2.1 μmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P<.001). However, no significant difference was observed for tHcy concentrations in the control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a allele) is associated with MI and influences plasma tHcy concentrations in patients with MI in the Tunisian male population.

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients.

OBJECTIVES The aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population. DESIGN AND METHODS A total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP. RESULTS Subjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR=0.44, 95% CI=0.28-0.72, p=0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR=0.30, 95% CI=0.21-0.43, p<0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR=0.58, 95% CI=0.42-0.80, p<0.001). CONCLUSION A protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.

Coronary angiogram video compression adapted to medical imaging applications

H.264/AVC coder has proven to use the most advanced video compression, but, at the cost of high computational complexity. On the other hand, analysis of coronary x-ray images reveals large areas containing no diagnostically important information. In this paper, we propose to exploit the energy characteristics in slice equal size regions to determine the active zones in coronary x-ray sequences to be encoded as normal using the H.264 coding system. The other regions, are compressed using conventional low complex approaches. Experimental results have shown that this procedure reduces the coder computing time of about 20% while attaining the same compression performance. A clinical subjective assessment by three expert physicians in interventional cardiology leads to a compression ratio of about 30:1 which insures both a diagnosis adequacy and a sufficient compression in regards to storage and transmission requirements.

0025: Validation of genetic risk score predicting cardiovascular death and/or myocardial infarction in a coronary Tunisian population: a 9.6 follow up study

Background After myocardial infarction, patients have a very heterogeneous risk of cardiovascular death and/or reinfarction. Furthermore, no genetic approach score, as part of secondary prevention, was found in the literature. Aim This is a prospective longitudinal study (mean follow up of 9.6 years) including 146 patients, hospitalized between August 1997 and August 2004 for a myocardial infarction (MI) who survived the 30 first day after the MI. Depending on the composite event cardiovascular death and/or myocardial infarction, the genetic score was derived from 43 single nucleotide polymorphisms (SNP) belonging to 26 different genes. In the same study 3 clinical and biological scores were calculated (European SCORE, Hard coronary heart disease and coronary heart death score of Framingham scores). A multivariate analysis using logistic regression was used. Results Mortality at 10 years was 12.3% with a median time of 5.2± 4.8 years. The incidence of the composite event cardiovascular death and/or myocardial infarction was 23.4% with a mean of 8.4±4.1 years.The genetic score predicting the composite event cardiovascular death and/or myocardial infarction is an equation that included age (OR=1.04, 95% CI: 0.98, 1.1) and the following polymorphisms eNOS894 (OR=1.87, 95%: 0.64, 5.43); rs2781665AT arginase (OR = 1.63, 95% CI: 0.69, 3.85); 45TG adiponectin (OR=1.62, 95% CI: 0.65,4.02); eNOS4a4b (OR=1.29, 95% CI: 0.53, 3.14) and MTP (OR=0.78, 95% CI: 0.35,1.74). The clinical and biological scores were all correlated with the long-term corrsponding predicted. Correction factors were calculated for each score. The genetic score had the best reliability with a Sensitivity = 73.3%, a Specificity = 61.3%, a predictive positive value =31.11%, a predictive negative value = 90.74%. Conclusion It seems that using a genetic score provides a good prediction of event cardiovascular death and/or myocardial infarction at long term. A validation of our genetic score and a combined clinical-genetic approach to a large population remains our future hope (table next page). Abstract 0025 – Table: Genetic factor tested in univariate analysis Genetic factors Cardiovascular death P non fatal MI Composite event Âge a l’inclusion 0,002 0,19 0,012 MTP 0,23 0,09 0,053 XbaI 0,83 0,03 0,1 MspI 0,54 0,25 0,54 PPAR 0,85 1 0,74 Prostacycline synthase 0,43 0,44 0,19 Insertion / delection(ApoB) 0,5 0,75 0,98 Apo CIII 0,05 0,17 0,2 Apo AI 0,77 0,79 0,69 EcoRI 0,27 0,5 0,79 Apo E 0,83 0,17 0,32 LFABP 0,46 0,3 0,85 eCNOS786 0,81 0,63 0,81 eNOS894 0,76 0,3 0,22 eNOS4a4b 0,43 0,05 0,44 MS 0,64 0,64 0,48 CYP1A1 0,88 0,47 0,93 MCP1 0,44 0,48 0,36 leptine 223A/G 0,84 0,085 0,29 leptine 2548G/A 0,43 0,62 0,81 Enzyme de conversion 0,001 0,76 0,38 Bradykinine 0,3 0,24 0,21 CD14 0,64 0,34 0,3 Andino45TG 1 0,03 0,02 rs2781666GT 0,005 0,22 0,39 Apo A51131CT 0,89 0,36 0,72 PON1Q192R 0,16 0,31 0,25 ApoA 51131CT 0,89 0,36 0,72 CBS ins/del 0,68 0,68 0,75 rs2781665AT 0,04 0,77 0,19 CCR2 0,92 0,65 0,81 CBS1080 0,98 0,55 0,57 rs17599586CT 0,63 0,95 0,89 PON2 0,82 0,52 0,43 res420 0,56 0,58 0,7 PPARC161T 0,001 0,4 0,002 rs2781668 0,74 0,76 0,65 TNF863CA 0,81 0,02 0,09 TNF1031TC 0,94 0,71 0,65 PON1L55M 0,6 0,69 0,58 Adiponectine4522CT 0,22 0,32 0,48 TNF308 0,52 0,74 0,56 MTHFRC337 0,38 0,45 0,93 MTHFR1298 0,12 0,12 0,12 MI : Myocardial infarction. Full-size table Table options View in workspace Download as CSV

PW150 Predictive Factors of Long-Term Cardiovascular Death After A First Myocardial Infarction: A 9.6-Year Follow-Up Study

Introduction: Although drug eluting stents (DES) are known to minimize the risk of restenosis, some of the cases are still selecting plain old balloon angioplasty (POBA) for some reasons. Objectives: The aim of this study is to clarify the characteristics and trends of POBA in current DES era. Methods: We examined the cases of POBA performed in our institute during years of 2008 to 2012 retrospectively. For control, bare metal stents (BMS) and DES implantation done in 2011 were analyzed. Results: During the period, 85 POBA, 63 BMS, 132 DES cases were identified. POBA cases were significantly older than BMS (69.5+/-10.7, 64.0+/-10.1, 67.6+/-9.5 year-old, POBA, BMS, DES, respectively, p<0.05). The device used were significantly smaller diameter in POBA than others (2.69+/-0.55, 3.07+/-0.49, 2.94+/-0.41 mm, POBA, BMS, DES, respectively, p<0.01). Within 218 cases (POBA 63, BMS 47, DES 108) completed follow up angiography, the rate of restenosis was significantly higher in POBA than BMS and DES (39.7%, 14.9%, 3.7%, POBA, BMS, DES, respectively, p<0.001). Unlike other strategies, restenosis cases in POBA used significantly larger devices than the other (2.90+/-0.64 vs. 2.61+/-0.49 mm, restenosis or not, p<0.05). After extracting the cases unable to classify, we create 3 categories for the reason of selecting POBA. 1; stent delivery failure or expected difficulty for stent delivery due to calcification etc. (n1⁄414), 2; intervention for in-stent restenosis or stent thrombosis (n1⁄434), 3; successful POBA for small vessels without complication (n1⁄414). According to it, category 1 showed significantly high probability for restenosis than others (1; 10/14, 71.4%, 2; 12/34, 35.3%, 3; 2/14, 14.3%, p<0.05) while category 3 showed nearly as good as BMS. Conclusion: POBA was done for older cases with smaller devices and showed significantly high probability for restenosis. We can interpret the categories of reason for POBA as follows; category 1 for negative selection, 3 for positive selection. Cases forced to select POBA had still unfavorable results whereas cases intentionally avoid stent implantation had tolerable outcome in current DES era. Disclosure of Interest: None Declared

0015: Validation and recalibration of the Systematic coronary risk evaluation (SCORE) in a coronary Tunisian population

Purpose Development of a validated risk prediction model for cardiovascular death in coronary patients is a high priority for strategies of therapy. We sought to validate and recalibrate of the SCORE (Systematic coronary risk evaluation) risk chart based on Tunisian national mortality data and average major cardiovascular risk factor levels. Methods Baseline data were collected between 1997 and 2004 in 146 male patients aged 52.4 ± 9 years hospitalized with STEMI treated with fibrinolysis in 68 % of patients and not revascularized early in 32% of patients. Vital status was checked and causes of death were obtained in 2011 after a mean follow up of 9.6 years. The expected cardiovascular mortality was calculated by applying the SCORE equation for high risk populations on the basis of the level of risk factors in the total population, in the diabetic and non-diabetic population and was compared with the observed mortality in each group. Correction factor was calculated for each group. Univariate analysis was used for statistical analysis. The optimum threshold of SCORE , allowing for an optimal sensitivity and specificity, was determined by the ROC curve (receiver operating characteristic). For risk thresholds 5% and that determined from the ROC curve of the European SCORE sensitivity, specificity values were calculated. Results The total number of cardiovascular death at 10 years is 18 with a mortality of 12.3%. The average of SCORE in our population was 8.73+/-5.12% with extremes ranging from 1 to 32%. The European SCORE was strongly correlated in our cohort to the occurrence of cardiovascular death at 10 years (p SCORE is calculated to 2.7 in diabetic group, 1 in non-diabetic group and 1.4 for the total population. The ROC curve has a c index ( AUC ) = 0.73 corresponding to the risk threshold of 9.12%. The relative risk of cardiovascular death at 10 years of SCORE for the 9.12% threshold is calculated at 3.6. For the risk threshold for 9.12%, sensitivity was calculated at 66.7% and specificity at 68.8%. For the risk threshold for 5%, sensitivity was calculated at 94.9% and specificity at 17.96%. Conclusion SCORE is validated in coronary male Tunisian patients with and recalibrated using correction factors. Validation on a larger population and multi-ethnic remains our future desire.

0062: TIMI risk score predicts risk of death at ten-year follow-up in STEMI patients

Background TIMI Risk Score for ST-elevation myocardial infarction (STEMI) is a score designed for prediction of mortality occuring 30 days after a STEMI. It was validated in the literature at 1 years and 5 years after STEMI. Aim We applied the TIMI risk score to our cohort of STEMI patients treated in majority with fibrinolysis to validate the possibility to predict 10 years survival. Methods TIMI risk score was developed in a cohort of 146 male Tunisian (mean age 52.4±9 years) hospitalized during the period 1997 to 2004 with STEMI treated with fibrinolysis in 68% of patients and non revascularised early in 32% of patients. STEMI was diagnosed based on typical criteria: chest pain or ECG changes and rise in creatinin kinase in all patients. We excluded from the analysis all patients who died during the first 30 days. After a mean follow up of 9.6 years, we recorded cardiovascular death. TIMI Risk Score for STEMI was calculated and they were divided into three groups: Low risk (0–2 points), medium risk (3–7) and high risk (>7 points). Univariate analysis was used for statistical analysis. Results At the inclusion 94 (65.4%) of our patients had had a low risk (TIMI between 0 and 2), 48 patients (32.3%) had had an intermediate risk (TIMI between 3 and 7) and 4 (2.2%) had had a high risk (TIMI between 8 and 14). Median TIMI risk score was 2.3 (ranging from 0 to 11). During follow-up there were 18 deaths (12.3%). Mortality was 5.7% in the low risk group, 25.6% in the intermediate risk group and 0% in the high risk group. Mortality increased significantly with TIMI risk score in patient with TIMI score 8, our study did not allow us to draw any conclusions. We calculated Mortality predicted by corrected TIMI score (Mortality predicted at 1 year – Mortality predicted at 30 days). In patients with TIMI risk score Conclusions TIMI Risk Score accurately defines the population of STEMI patients who are at high risk of death not only during the first 30 days, but also during 10 years of follow-up. This simple score should be included in the discharge letters because it contains very useful information for further care.

234: Association of the porothrombin 20210GA variant with myocardial infarction in Tunisian population

Introduction The prothrombin is the precursor of the serine protease thrombin, a key enzyme in hemostasis and thrombosis. Prothrombin 20210GA polymorphism was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant and fibrinolytic system. 20210GA curriers have an increased risk of thrombosis. In this study, we propsed to determine the prevalence of 20210GA prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction (MI). Methods This study included 1007 unrelated male Tunisians divided into 399 MI patients and 608 healthy controls. Both groups were aged between 35-70 years. The prothrombin 20210GA polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. Results The distribution of genotypes was in accordance with Hardy-Weinberg equilibrium (P >0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 97% for GG genotype and 3% for GA + AA genotype. The control group had a frequency of 99% for the GG genotype and 1% for the GA + AA genotype (χ2=6.95, p=0.031). The MI patient group showed a significant higher frequency of the 20210A allele compared to the controls 0.02 vs. 0.01 [OR=3.60 (95% CI=1.29-10.53), p =0.005]. Conclusion Our work showed a significant association between the 20210GA polymorphism of the prothrombin gene and MI in the Tunisian population.