[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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 <0.0001). The correction factor of 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%.
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.
Archives of Cardiovascular Diseases Supplements 04/2014; 6:3.
[Show abstract][Hide abstract] ABSTRACT: Purpose
The aim of the study was to Validate and to recalibrate the Framingham’s score Hard coronary heart disease (HCHD score) in a coronary Tunisian population.
Baseline data were collected between 1997 and 2004 in 146 patients. We excluded from the analysis all patients who died during the first 30 days of hospitalization. Vital status was checked and causes of death were obtained in 2011 after a mean follow up of 9.6 years. We also noticed myocardial infarction during the same period. The expected incidence of the composite event cardiovascular death and/or myocardial infarction was calculated by applying the HCHD equation on the basis of the level of risk factors in diabetic and non-diabetic populations and was compared with the observed incidence of the composite event in each group. Correction factor was calculated for each group. For the risk thresholds 20 % and that determined from the ROC curve of the HCHD score sensitivity, specificity values ??were calculated.
The total number of patients who developed the composite event cardiovascular death and/or myocardial infarction was 34 (23.3%). The average of HCHD score in our population is 16.2 +/−7.2% with a range from 2 to 30%. The HCHD score is significantly associated with cardiovascular death event and/or myocardial infarction in our population (p = 0.029). The correction factor score is 2 in diabetic group, 1.1 in non-diabetics group and 1.4 for the total population. The relative risk of HCHD score is calculated to 1.59 for the composite event cardiovascular death and/or myocardial infarction at 10 years.For the risk threshold for 20%, sensitivity was calculated at 41.11% and specificity at 76.7%.
HCHD 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.
Archives of Cardiovascular Diseases Supplements 04/2014; 6:2.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Few studies have examined the incidence of the composite event cardiovascular death and/or myocardial infarction in long term in patients who presented with acute coronary syndrome with ST segment elevation (STEMI) treated with fibrinolysis or percutaneous angioplasty.
This is a prospective longitudinal trial held between August 1997 and September 2011 in La Rabta Hospital. Between August 1997 and august 2004, were randomly included 146 patients who had had a first nonfatal myocardial infarction non-fatal during the first 30 days. After a mean follow up of 9.6 years, we recorded the composite event cardiovascular death and/or myocardial infarction.
The total number of patients who developed the composite event cardiovascular death and/or myocardial infarction was 34 (23.3%). The average time of occurrence of the composite event is 8.4+/−4.1 years. No factors of the characteristics of the population were significantly associated with nonfatal myocardial infarction at 10 years in univariate analysis. Factors significantly predictive of the composite event cardiovascular death and/or myocardial infarction at 9.6 years in univariate analysis are the same factors predictive of cardiovascular death age (p = 0.002), diabetes (p = 0.01) and multivessel coronary disease (p = 0.05). There is a tendency to correlation of the composite event at 9.6 years with history of hypertension (p = 0.06). In multivariate analysis, independent factors predictive of the composite event, cardiovascular death and/or myocardial infarction are age >55 years (OR=.53, 95% CI: 1.97, 36.96, p = 0.004), diabetes (OR=4.3, 95% CI: 1.31, 14.15, p = 0.016) and the anterior territory of the myocardial infarction (OR=5.5, 95% CI: 1.02, 29.66, p = 0.047).
In our population predictors of the composite event cardiovascular death and/or myocardial infarction in the multivariate analysis were age, anterior territory of the infarction and diabetes. Better control and management could reduce the long-term mortality.
Archives of Cardiovascular Diseases Supplements 03/2014; 6:1.
[Show abstract][Hide abstract] ABSTRACT: Elevated total plasma homocysteine (tHcy) is an established risk factor for occlusive vascular disease and is thought to increase the risk of pregnancy loss, birth defects, and cognitive impairment in the elderly.
[Show abstract][Hide abstract] ABSTRACT: Background and aims
Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a transcriptional co-activator involved in adaptive thermogenesis, skeletal muscle metabolism, fatty acid oxidation, and gluconeogenesis. Several studies have suggested that the common PGC-1α polymorphism Gly482Ser (rs8192678) may be associated with risk of type 2 diabetes (T2D), with conflicting results. The aim of this study was to analyze whether the Gly482Ser variant is a risk factor for development of T2D in Tunisian population.
In a case–control study 487 unrelated patients with type 2 diabetes and 402 apparently healthy controls were recruited from January 2008 to August 2010. The Gly482Ser polymorphism was determined by PCR-RFLP analysis.
A significant difference in genotypes distribution was observed between patients (Gly/Gly: 34.1%; Gly/Ser: 47.1%; Ser/Ser: 18.5%) and controls (Gly/Gly: 43.8%; Gly/Ser: 42.3%; Ser/Ser: 13.9%) (χ2 = 9.44, p = 0.009). The T2D patient group showed a significant higher frequency of the Ser allele compared to the controls (43% vs. 34%; OR: 1.35, 95% [CI]: 1.11–1.65, p = 0.002). The association between the Gly482Ser polymorphism and T2D remained significant after adjustment for other well-established cardiovascular risk factors.
In the current study, a significant and independent association between the Gly482Ser polymorphism (rs8192678) of the PGC-1α gene and T2D in the Tunisian population was found.
Diabetes and Metabolic Syndrome Clinical Research and Reviews 11/2013;
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor α (TNFα) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The aim of the present study was to investigate the association between the -863C/A polymorphism in the promoter of the TNFα gene and type 2 diabetes in the Tunisian population.
The polymorphism -863C/A in the TNFα gene was determined in 211 type 2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis.
A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with type 2 diabetes had significantly higher frequency of the CA+AA genotypes compared to controls [35.5% vs. 22.3%; OR (95%CI), 1.91 (1.31-2.8); p=0.001]. The type 2 diabetes patient group showed a significant higher frequency of the A allele compared to the controls (0.19 vs. 0.11; p=0.001). After adjustment by a stepwise logistic regression method, hypertension, dyslipidemia, and CA+AA genotype were found to be significantly associated with T2D.
The present study showed a significant and independent association between the -863C/A polymorphism of the TNFα gene and type 2 diabetes in the Tunisian population.
Diabetes research and clinical practice 10/2013; · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the interaction between the G protein beta3 subunit (GNB3) C825T variant and angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism in hypertensive Tunisian population.
Analyses of ACE and GNB3 genotypes were performed in 388 hypertensive patients and 425 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The plasma ACE activity was determined by a spectrophotometric method.
The ACE genotype distribution and allele frequencies were not significantly different between the hypertensive and normotensive subjects (p > 0.05). This polymorphism was not associated with hypertension (HTA) (OR = 0.93, 95% CI = 0.75 - 1.15; p = 0.50). In cases, subjects carrying the DD genotype exhibited higher plasma ACE activity than those with ID and II genotypes (p = 0.001). In this group, a linear regression analysis revealed that the ACE I/D polymorphism is independently associated with plasma ACE activity (p = 0.017). The genotypic distribution and allelic frequencies of the GNB3 C825T polymorphism were not significantly different between the two groups. This polymorphism was found to have no effect on the risk of HTA (OR = 1.14, 95% CI = 0.93 - 1.39; p = 0.21). We did not observe a significant interaction between the GNB3 gene and the ACE gene with HTA.
In this study, the I/D polymorphism is a significant independent predictor for variability of plasma ACE activity but the ACE I/D and GNB3 C825T polymorphisms are not significant factors for HTA in the Tunisian population. Moreover, we found no interaction between ACE D allele and GNB3 825T allele solely or combined with respect to HTA in the Tunisian population.
[Show abstract][Hide abstract] ABSTRACT: Background: Hypertension is a polygenic disease. Various singlenucleotide gene polymorphisms of renin angiotensin system have been explored in hypertension. Angiotensin II, the major biologically active component of this system, exerts its effect via two pharmacologically distinct subtypes of angiotensin II receptors, the angiotensin II type 1 receptor and the angiotensin II type 2 receptor. Aim: To examine whether the 3123 C/A polymorphism of angiotensin II type 2 receptor gene is involved in hypertension in a sample of Tunisian population. Methods: Atotal of 403 normotensive subjects and 382 hypertensive patients were included in the study. Genotyping was performed by polymerase chain reaction followed by Alu I restriction digestion. Results: The frequency of "A" genotype was not significantly different between the two groups in men (¯2=1.18; p=0.16). The estimated odds prevalence for hypertension ("A" versus "C") was 0.77 (95% CI 0.49 to 1.22, p=0.27). After adjustment for confounding factors, the OR for hypertension remained no significant (OR: 1.49, 95% CI: 0.84-2.63, p=0.16). In women, genotype distributions for C3123A variant in hypertensive patients were not significantly different from normotensive subjects (¯2=3.16; p=0.20). Multiple logistic regression analysis showed that the AA genotype was not significantly associated with hypertension (OR: 1.09, 95% CI: 0.58-2.06, p=0.77). Conclusion: In the present study, we showed that the 3123 C/A polymorphism of AGT2R gene is not a significant factor for hypertension in a sample of Tunisian population.
[Show abstract][Hide abstract] ABSTRACT: 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.
Nutrition research 05/2012; 32(5):342-6. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
A protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.
[Show abstract][Hide abstract] ABSTRACT: Background: Economic development and socio-demographic changes have led to increased frequency of cardio-vascular disease and other chronic diseases in Tunisia. Objectives: To assess the prevalence of different types of dyslipidemia and to examine their association with socio-demographic characteristics in the Greater Tunis population. Methods: The study included 2712 subjects (1228 men and 1484 women) aged 35-70 years, recruited during the years 2004 and 2005 from the Greater Tunis population. Hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol were defined according to the National Cholesterol Education Program-Adult Treatment Panel III. Results: The prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol was 40.8% (34.9% in males and 45.8% in females; p<0.001), 29.2% (31.1% in males and 27.6% in females; p<0.05), and 21.2% (32.5% in males and 11.5% in females; p<0.001), respectively. The prevalence was higher in urban than rural regions. Hypercholesterolemia was more frequent in illiterate women and in men with high education level. Conclusions: Dyslipidemias are common in Tunisians, mainly in urban areas, in illiterate women as well as in men with high levels of education. Profound changes of life style and dietary habits of Tunisians are needed to reduce the risk of cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the relationship between the adiponectin levels and various characteristics of the metabolic syndrome (MS) in a sample of the Tunisian population. Three hundred and fifty-four individuals were included in this study. Body mass index, blood pressure, HDL-cholesterol, triglycerides, glucose, insulin, and adiponectin concentrations were measured. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). MS was identified with the NCEP-ATP III criteria. Subjects with MS showed significantly lower adiponectin levels compared to those without MS. For both genders, the prevalence and the number of MS components increased significantly as the adiponectin concentrations decreased. Subjects with the lowest adiponectin quartile had an increased risk of MS adjusted for age, gender, and HOMA-IR. Our findings suggest that hypoadiponectinemia is strongly associated with the risk of MS independent of insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: Accumulation of phenylalanine following a deficiency of phenylalanine hydroxylase activity generates a brain damage with mental retardation: phenylketonuria (PKU). In the developing countries, where PKU systematic neonatal screening program is not established yet, the management of PKU handicap is not properly carried out. The aim of this study was to estimate the frequency of the PKU diagnosed following clinical features anomalies, to provide information about the untreated PKU patients profile in Tunisia not covered by neonatal screening. Also it is stressed that treated patients have a normal development.
This is a retrospective study of 156 cases of PKU detected in Tunisia over 20 years following symptoms suggestive of inherited metabolic disease. Phenylalaninemia level was performed by fluorometric method. Among them 9 patients were treated.
The PKU estimated frequency was 1/7631. The diagnosis mean age was 4 years. The phenylalaninemia mean was 1680 μmol/L; the classical PKU form accounted for 85.3% of cases and the dominant clinical symptoms were: mental retardation (88.2%), motor delays (87.7%), speech difficulties (83.2%) and pigmentation anomalies (61.7%). The treated patients responded to treatment and showed a normal development.
The establishment of neonatal screening should be a priority to avoid cases of mentally retardation.
Clinical neurology and neurosurgery 08/2011; 113(9):727-30. · 1.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.
European Journal of Internal Medicine 08/2011; 22(4):407-11. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3±7.6 years) and 180 postmenopausal women (mean age 53.4±6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.