Mid-term subclinical myocardial injury detection in patients who recovered from COVID-19 according to pulmonary lesion severity.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) may cause damage to the cardiovascular system during the acute phase of the infection. However, recent studies reported mid- to long-term subtle cardiac injuries after recovering from acute coronavirus disease 2019 (COVID-19). This study aimed to determine the relationship between the severity of chest computed tomography (CT) lesions and the persistence of subtle myocardial injuries at mid-term follow-up of patients who recovered from COVID-19 infection. Methods: All patients with COVID-19 were enrolled prospectively in this study. Sensitive troponin T (hsTnT) and chest CT scans were performed on all patients during the acute phase of COVID-19 infection. At the mid-term follow-up, conventional transthoracic echocardiograph and global longitudinal strain (GLS) of the left and right ventricles (LV and RV) were determined and compared between patients with chest CT scan lesions of < 50% (Group 1) and those with severe chest CT scan lesions of greater or equal to 50% (Group 2). Results: The mean age was 55 ± 14 years. Both LV GLS and RV GLS values were significantly decreased in group 2 (p = 0.013 and p = 0.011, respectively). LV GLS value of more than -18 was noted in 43% of all the patients, and an RV GLS value of more than -20 was observed in 48% of them. The group with severe chest CT scan lesions included more patients with reduced LV GLS and reduced RV GLS than the group with mild chest CT scan lesions [(G1:29 vs. G2:57%, p = 0.002) and (G1:36 vs. G2:60 %, p = 0.009), respectively]. Conclusion: Patients with severe chest CT scan lesions are more likely to develop subclinical myocardial damage. Transthoracic echocardiography (TTE) could be recommended in patients recovering from COVID-19 to detect subtle LV and RV lesions.

Long-term predictors of death among Tunisian patients presenting for non ST-elevation acute coronary syndrome.

BACKGROUND: Coronary artery disease is the leading cause of death in emerging countries. Contemporary data about clinical profile and prognosis in Tunisian patients presenting for non ST-elevation acute coronary syndrome (NSTE-ACS) are lacking. AIM: We sought to study the risk profile and 3-year mortality predictors in Tunisian patients presenting for NSTE-ACS in the contemporary setting. METHODS: In this single center study, data about all consecutive patients presenting to our center for NSTE-ACS from April 2014 to July 2016 were extracted and outcomes exhaustively updated. 3-year mortality predictors were determined by multivariable survival analysis. RESULTS: A total of 340 patients were included, of which 204 (61.8%) were male. Mean age was 63.6 ± 10.3 years. Prevalence of diabetes mellitus, hypertension and smoking was 57.3%, 62.4%, and 45.3%, respectively. In-hospital, 6, 12 and 36-month mortality rate was 2.3%, 3.2%, 7.1% and 15.2%, respectively. In multivariable survival analysis, independent predictors of death were age >75 (HR=5.45, 95% CI: 2.9-10.03, p<0.001), ST-segment deviation (HR=1.86, 95% CI: 1.04-3.33, p=0.036), anemia (HR=2.56, 95% CI: 1.41-4.67, p=0.002), left ventricular ejection fraction (LVEF) <40% (HR=3.5, 95% CI: 1.84-6.67, p<0.001) and a Global Registry of Acute Coronary Events (GRACE) score ≥140 (HR=2.38, 95% CI: 1.02-5.57, p=0.044). CONCLUSION: In Tunisian patients presenting for NSTE-ACS, long-term mortality was high. Advanced age, ST-segment deviation, anemia, LVEF <40% and a GRACE score ≥140 were independent long-term predictors of death.

Left atrial appendage closure with Watchman device: Insights from the first-ever Tunisian experience and six-year follow-up.

BACKGROUND: Stroke is a major complication of nonvalvular atrial fibrillation (AF). Despite its proven efficacy in stroke prevention, oral anticoagulation (OAC) is associated to a significant increase in bleeding complications. New techniques such as percutaneous left atrial appendage (LAA) closure were developed. AIM: To evaluate immediate, mid- and long-term outcomes after percutaneous LAA closure in Tunisian patients presenting with nonvalvular AF. METHODS AND RESULTS: Nineteen patients with nonvalvular AF were prospectively enrolled for percutaneous LAA closure between February 2013 and June 2014. The Watchman device was used in all LAA closure procedures. Clinical and echocardiographic follow-up were carried-out at 1, 6, 12 months and six years in all patients. Mean age was 68.4 ± 7.5 years. Thirteen patients were female, 16 had hypertension, 12 had diabetes mellitus and seven had a history of stroke or transient ischemic attack (TIA). Average CHA2DS2VASc (Congestive Heart Failure/Left Ventricular Dysfunction, Hypertension, Age≥75, Diabetes mellitus, Stroke/Transient Ischemic Attack/Thromboembolic event, Vascular disease,Age≥65, Sex category) score was 4.2 ± 1.5 and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding tendency, Labile INR, Age≥65, Drugs) score was 3.5 ± 1. Ten patients had a history of severe bleeding. Procedural success was achieved in all patients. Pericardial effusion with tamponade was reported in one case. No post-procedural death was reported. Regular follow-up at 1, 6 and12 months then every year up to 6 years reported no stroke, no thromboembolic event, no Watchman device thrombosis and three cases of death caused by a respiratory problem and cancers. CONCLUSION: According to this study, LAA closure with Watchman device was safe and effective in preventing stroke in patients with nonvalvular AF and contra indication to OAC.

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What's behind the scenes?

BACKGROUND: Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3). Mutations in SCN5A gene coding for the α-subunit of the NaV1.5 cardiac sodium channel are identified in 15-30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of the protein-coding portions and flanking intronic regions of SCN5A. This excludes the 5'UTR and 3'UTR from the routine genetic testing. METHODS: We here screened the coding sequence, the flanking intronic regions as well as the 5' and 3'UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with BrS. RESULTS: A new SCN5A-Q1000K mutation was identified along with two common polymorphisms (H558R and D1819). Multiple genetic variants were identified on the SCN5A 3'UTR, one of which is predicted to create additional microRNA binding site for miR-1270. Additionally, we identified the hsa-miR-219a-rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes. CONCLUSIONS: The absence of genotype-phenotype concordance within all the identified genetic variants in this family gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors, rather than a single variant. Most SCN5A variants were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities.

Prognostic value of hyperglycemia on-admission in diabetic versus non-diabetic patients presenting with ST-elevation myocardial infarction in Tunisia.

BACKGROUND: Hyperglycemia on-admission is a powerful predictor of adverse events in patients presenting for ST-elevation myocardial infarction (STEMI). AIM: In this study, we sought to determine the prognostic value of hyperglycemia on-admission in Tunisian patients presenting with STEMI according to their diabetic status. METHODS: Patients presenting to our center between January 1998 and September 2014 were enrolled. Hyperglycemia was defined as a glucose level ≥11mmol/L. In-hospital prognosis was studied in diabetic and non-diabetic patients. The predictive value for mortality of glycemia level on-admission was assessed by mean of the area under receiver operating characteristic (ROC) curve calculation. RESULTS: A total of 1289 patients were included. Mean age was 60.39±12.8years and 977 (77.3%) patients were male. Prevalence of diabetes mellitus was 70.2% and 15.2% in patients presenting with and without hyperglycemia, respectively (p<0.001). In univariate analysis, hyperglycemia was associated to in-hospital death in diabetic (OR: 8.85, 95% CI: 2.11-37.12, p<0.001) and non-diabetic patients (OR: 2.57, 95% CI: 1.39-4.74, p=0.002). In multivariate analysis, hyperglycemia was independently predictive of in-hospital death in diabetic patients (OR: 9.6, 95% CI: 2.18-42.22, p=0.003) but not in non-diabetic patients (OR: 1.93, 95% CI: 0.97-3.86, p=0.06). Area under ROC curve of glycemia as a predictor of in-hospital death was 0.792 in diabetic and 0.676 in non-diabetic patients. CONCLUSION: In patients presenting with STEMI, hyperglycemia was associated to hospital death in diabetic and non-diabetic patients in univariate analysis. In multivariate analysis, hyperglycemia was independently associated to in-hospital death in diabetic but not in non-diabetic patients.

Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype?

PURPOSE: Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). METHODS: We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. RESULTS: We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759). CONCLUSIONS: Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. TRIAL REGISTRATION: Clinical Trials.gov NCT03373552 (Registered 13 December 2017).

Clinical features and prognosis of infective endocarditis in children: Insights from a Tunisian multicentre registry.

BACKGROUND: Infective endocarditis (IE) is a rare condition in the paediatric setting. No data on the epidemiology and prognosis of IE in children are available from North African countries. AIM: To investigate the epidemiological profile and prognosis of IE in children in Tunisia. METHODS: All patients aged≤18 years presenting with IE in three Tunisian tertiary care centres between January 1997 and September 2013 were included. Clinical features and 30-day and 6-month mortality rates were studied. Factors predictive of death at 6-month follow-up were determined. RESULTS: A total of 73 patients were included in the present study. The mean age was 12±4.8 years; 35 (50.7%) patients were male. Rheumatic heart disease (RHD) was the underlying heart disease in 17 (23.3%) cases and IE occurred in a structurally normal heart in 36 (49.3%) cases. Staphylococcus species were isolated in 17 (23.3%) cases. Regarding IE localization, the mitral valve was involved in 28 (38.4%) cases and the aortic valve in 14 (19.2%) cases. Recourse to surgery was reported in 37 (50.7%) cases. Thirty-day and 6-month mortality rates were 13.6% and 19.2%, respectively. Heart failure on admission or during the hospital course, acute renal failure and neurological complications were significantly associated with death at 6-month follow-up in the univariate analysis and after adjustment for age and sex. CONCLUSIONS: In the Tunisian context, IE in children is still characterized by the high prevalence of RHD as an underlying heart disease. Short- and long-term mortality rates remain high. Heart failure, acute renal failure and neurological complications are significantly associated with death at 6-month follow-up.

Prevalence and prognostic significance of anemia in patients presenting for ST-elevation myocardial infarction in a Tunisian center.

BACKGROUND: Anemia on admission is a powerful predictor of major cardiovascular events in patients presenting for acute coronary syndromes. We sought to determine the prevalence and prognostic impact of anemia in patients presenting for ST-elevation myocardial infarction (STEMI). METHODS: We analyzed data from a Tunisian retrospective single center STEMI registry. Patients were enrolled between January 1998 and October 2014. Anemic and nonanemic patients were compared for clinical and prognostic features and according to four prespecified hemoglobin level subgroups. In patients with severe anemia, factors associated with in-hospital death were studied. RESULTS: A total of 1498 patients were enrolled. Mean age was 60.47 ± 12.7 years and prevalence of anemia was 36.6%. Anemic patients were more likely to be elderly, hypertensive, and diabetic in comparison to nonanemic patients. In-hospital mortality was significantly higher in anemic patients (14.9% vs. 5%, p < 0.001). Lower hemoglobin levels were significantly associated with a higher prevalence of heart failure on admission, cardiogenic shock, and in-hospital mortality (p < 0.001 for all). In univariate analysis, factors associated with in-hospital death in patients with severe anemia were hypertension (p = 0.044), heart failure on admission (p < 0.001), renal failure on admission (p < 0.001), and primary percutaneous coronary intervention (pPCI) use (p = 0.016). The absence of pPCI use was independently associated with in-hospital death in multivariate analysis (odds ratio = 2.22, 95% confidence interval: 1.07-4.76, p = 0.033). CONCLUSION: According to this study, anemic patients presenting for STEMI have a higher in-hospital mortality rate. The absence of pPCI use was independently associated with in-hospital death.

Risk profile and in-hospital prognosis in elderly patients presenting for acute ST-elevation myocardial infarction in the Tunisian context.

OBJECTIVES: Little is known about the risk profile and in-hospital prognosis of elderly patients presenting for ST-elevation myocardial infarction (STEMI) in Tunisia. We sought to determine in-hospital prognosis of elderly patients with STEMI in a Tunisian center. METHODS: The study was carried out on a retrospective registry enrolling 1403 patients presenting with STEMI in a Tunisian center between January 1998 and January 2013. Patients ≥75 years old were considered elderly. Risk factors and in-hospital prognosis were compared between elderly and younger patients, and then predictive factors of in-hospital death were determined in elderly patients. RESULTS: Out of the overall population, 211 (15%) were part of the elderly group. Compared to younger patients, elderly patients were more likely to have arterial hypertension but less likely to be smokers and obese. Thrombolysis was significantly less utilized in the elderly group (22.3% vs. 36.6% in the younger group, p<0.001), whereas the use primary percutaneous coronary intervention was comparable between the two sub-groups (24.2% vs. 28.8%, p=0.17). The incidence of in-hospital complications was higher in the elderly group, and so was the in-hospital mortality rate (14.2% vs. 8.1%, p=0.005). Heart failure on-admission, renal failure on-admission, and inotropic agents use were independently associated to in-hospital death in the elderly group. CONCLUSIONS: In the Tunisian context, elderly patients presenting with STEMI have higher prevalence of risk factors and a worse in-hospital course in comparison to younger patients. Clinical presentation on-admission has a strong impact on in-hospital prognosis.

Absence of family history and phenotype-genotype correlation in pediatric Brugada syndrome: more burden to bear in clinical and genetic diagnosis.

Brugada syndrome (BrS) is an autosomal-dominant genetic cardiac disorder caused in 18-30 % of the cases by SCN5A gene mutations and manifested by an atypical right bundle block pattern with ST segment elevation and T wave inversion in the right precordial leads. The syndrome is usually detected after puberty. The identification of BrS in pediatric patients is thus a rare occurrence, and most of the reported cases are unmasked after febrile episodes. Usually, having a family history of sudden death represents the first reason to perform an ECG in febrile children. However, this practice makes the sporadic cases of cardiac disease and specially the asymptomatic ones excluded from this diagnosis. Here, we report a sporadic case of a 2-month-old male patient presented with vaccination-related fever and ventricular tachycardia associated with short breathing, palpitation and cold sweating. ECG changes were consistent with type 1 BrS. SCN5A gene analysis of the proband and his family revealed a set of mutations and polymorphisms differentially distributed among family members, however, without any clear genotype-phenotype correlation. Based on our findings, we think that genetic testing should be pursued as a routine practice in symptomatic and asymptomatic pediatric cases of BrS, with or without family history of sudden cardiac death. Similarly, our study suggests that pediatrician should be encouraged to perform an ECG profiling in suspicious febrile children and quickly manage fever since it is the most important factor unmasking BrS in children.

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the risk of ischemic stroke in a Tunisian population.

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, extracellular matrix remodeling, plaque rupture and myocardial infarction. MMP gene polymorphisms contribute to the risk of developing cardiovascular diseases. In this study, we investigated, for the first time, the association between MMP-1-16071G/2G, MMP-12 -82A/G and MMP-12 1082A/G genotypes and haplotypes and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). To examine whether these genetic polymorphisms are associated with susceptibility to IS, 196 patients with IS and 192 controls were examined by PCR-based RFLP. When the analyses were adjusted for multiple risk factors, no interaction between T2DM and MMP-1-1607 1G/2G polymorphism on the risk of ischemic stroke was found (p=0.074). However, MMP-12 polymorphisms genotypes were associated with the higher risk of IS in diabetic patients compared with total patients. The -82G-1082G haplotype of MMP-12 polymorphisms was associated with higher risk of ischemic stroke in diabetic patients [AOR=2.33; 95% CI (1.25-3.62), P=0.032]. These findings showed that there was an important joint effect of the MMP-12 polymorphisms and T2DM on the risk of IS and therefore it can be considered as a potential marker of cerebrovascular disorders in diabetic patients.

[Association between oxidative stress parameters and inflammation markers according to the gravity of the acute coronary syndrome]. / Association entre les paramètres du stress oxydatif et les marqueurs de l'inflammation selon la gravité du syndrome coronaire aigu.

BACKGROUND: Cardiovascular disease is the consequence of appearance and development of atherosclerosis lesions of associated with a inflammatory complication. AIM: To elucidate a possible association between several inflammation and oxidative stress markers according to the severity of coronary artery disease. METHODS: This study was carried on 93 coronary subjects with: unstable angina (UA; n=42); stable angina (SA; n=15) and acute myocardial infarction (AMI; n=36) and 140 control subjects to whom lipidic, oxidative and inflammatory parameters were determined. RESULTS: In addition to a moderate hyperhomocysteinemia observed in the coronary artery disease, a significant higher levels of the oxidized LDL (ox-LDL) were found among these patients (p< 0.001). A positive correlation was found between the markers of the inflammation and the gravity of the acute coronary syndrome. One note a significant increase of the rate of ox-LDL and high sensitive CRP to AMI by reports in UA and SA (p=0.00, and p=0.001 respectively) which is linked to an elevation of the plasmatic concentration of the total homocysteine. CONCLUSION: This study suggests an association between the markers of the inflammation and oxidative parameters in the acute coronary syndrome.

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease.

OBJECTIVES: To verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport. DESIGN AND METHODS: We investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n=36), those without CAD (n=20), and 37 healthy subjects. RESULTS: Plasma APF concentrations were decreased in diabetics with CAD compared to controls (p<0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p<0.01 and p<0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls. CONCLUSIONS: APF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.

TNF-alpha -308G>A and IL-6 -174G>C polymorphisms in Tunisian patients with coronary artery disease.

OBJECTIVE: Our aim was to evaluate the contribution of tumor necrosis factor (TNF)-alpha -308G>A and interleukin (IL)-6 -174G>C gene promoter variants to the presence of coronary artery disease (CAD) in Tunisians. DESIGN AND METHODS: Study subjects comprised 418 angiographically proven CAD patients and 406 age-, gender-, and ethnic origin-matched controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: There were no significant differences in the allelic distribution of TNF-alpha -308A (19.6% vs. 19.0%, P=0.73), and IL-6 -174C (15.6% vs. 14.3%, P=0.47) promoter polymorphisms between CAD patients and control subjects, respectively. In addition, single locus analysis revealed no differences in genotype frequencies between the two study groups, and the combined distribution of both genotypes did not differ significantly between controls and CAD patients (P>0.05). CONCLUSION: There is no allelic or genotypic association of TNF-alpha -308G>A and IL-6 -174G>C promoter polymorphisms with CAD in Tunisians, thereby confirming an ethnic-selective contribution of both gene variants to CAD presence.

Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome.

INTRODUCTION: Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD). OBJECTIVES: We evaluated the relationship of tHcy and HTase with paraoxonase 1 (PON1) gene polymorphism according to CAD severity. DESIGN AND METHODS: 118 healthy volunteers and 91 CAD patients were compared. RESULTS: Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 48% in CAD patients and were associated with significantly lower levels of HDL cholesterol (p=0.02) and 42% of decrease in HTase activities (p<0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels (r=-0.622, p=0.00 and r=-0.355, p=0.007 respectively) but positively associated with apoB and triglyceride levels (r=0.35, p=0.042 and r=0.308, p=0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls (P<0.05), while its frequency was similar between the two subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease (p=0.029). CONCLUSIONS: High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients.

Reverse modulation of the HDL anionic peptide factor and phospholipid transfer protein activity in coronary artery disease and type 2 diabetes mellitus.

OBJECTIVES: The high density lipoprotein Anionic Peptide Factor (HDL(3)-APF) was previously described as an apolipoprotein that promotes the reverse cholesterol transport. Since phospholipid transfer protein (PLTP) is involved in such mechanism we attempted to focus on the two APF and PLTP proteins. DESIGN AND METHODS: We recruited 56 type 2 diabetic patients with (n=36) or without (n=20) coronary artery disease (CAD) and 19 CAD patients. The three groups were compared to 39 healthy control subjects. In all groups, lipid profile was determined and plasma APF concentrations and PLTP activity were measured. RESULTS: In all patients, the PLTP activity was significantly increased in comparison with controls (p<0.01), in concomitance with a plasma APF level decrease in groups with CAD (with and without type 2 diabetes) (p<0.01). Multiple linear regression analysis demonstrated that, when apoA-I, HDL-C, HDL-phospholipids and PLTP activity were taken into account as independent variables (after univariate regression analysis), HDL-PL was positively and independently related to APF (p<0.0001 in whole population; p=0.0090 in controls) and PLTP activity was negatively and independently related to APF in whole population and all patients' groups (all p<0.05), but positively and independently associated to APF in controls (p=0.0005). CONCLUSIONS: APF could be considered as a specific marker against CAD and type 2 diabetes mellitus and our results confirm the atherogenic behavior of PLTP in CAD. Thus, these two proteins are likely to be regulated in a reverse manner.

Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease.

AIM: To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD). METHODS: In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured. RESULTS: Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role. CONCLUSION: Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism.

Relationship between thiolactonase activity and hyperhomocysteinemia according to MTHFR gene polymorphism in Tunisian Behçet's disease patients.

BACKGROUND: Behçet's disease (BD) is a multisystemic immuno-inflammatory disorder. Inflammatory processes may cause lipid peroxidation, alteration of lipid profile and increase the risk of atherosclerosis. The aim of this study was to evaluate the association between thiolactonase (HTLase) activity and plasma homocysteine levels (tHcy) in a BD population and to investigate their association with methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype. METHOD: A total of 35 BD patients were compared to 39 healthy volunteers. RESULTS: Significantly higher tHcy levels associated with lower HTLase activities were found in BD patients as compared to healthy controls (p<0.001). These patients also exhibited lower values of triglycerides and high-density lipoprotein cholesterol (HDL-C). Homozygosity for the T allele of the MTHFR gene was more frequent in BD patients (14.3% vs. 7.7%). It was associated with significantly higher tHcy levels (16.9 micromol/L for n=17 vs. 13.1 micromol/L for n=18; p<0.05) and markedly lower HTLase activity (362.6+/-156.7 U/L vs. 414.2+/-180.2 U/L) for the (TT+CT) and CC genotypes, respectively. Moreover, HDL-C levels were inversely correlated with tHcy (r=-0.5; p=0.004) but positively associated with HTLase activity (r=0.374; p=0.038). These correlations were also present in several clinical manifestations, such as ocular, neurological involvement or thrombosis. CONCLUSIONS: Homozygosity of the T allele of the MTHFR gene is prevalent in BD patients. High levels of tHcy associated with low HTLase activities may be one of the causes leading to thrombosis in BD patients.

[Abnormalities of the interatrial septum associated with cerebral ischemia in young adults: contribution of trans-oesophageal echocardiography]. / Anomalies du septum inter-auriculaire complique d'ischemie cerebral chez le sujet jeune: apport de l'echographie trans-oesophagienne.

BACKGROUND: About 40% of the mechanism of ischaemic stroke in young adults remains unclear. A paradoxical embolism associated with persistence of a patent foramen ovale and/or the presence of an atrial septal anevrysm are significantly more frequent in patients examined for ischaemic stroke of unknown cause than in control subjects. AIM: was to evaluate the contribution of trans-oesophageal echocardiography to the diagnosis of abnormalities of the interatrial septum and to identify the role played by this condition in unexplained ischemic stroke. METHODS: In 30 consecutive patients, trans-oesophageal echocardiography recording were made during a saline contrast study. RESULTS: Abnormalities of the interatrial septum was diagnosed in 23.3% cases. The proportion of patent foramen ovale was 10% (3 patients); atrial septal anevrysm was detected in 6.6%(2 patients). The prevalence of patent foramen ovale associated with atrial septal anevrysm was 6.6% (2 patients). CONCLUSION: Transesophageal echocardiography with contrast appears to be an effective exam in diagnosis of abnomalities of the interatrial septum and our study was suggestive of their embolic nature.