Association between haptoglobin 2-2 genotype and coronary artery disease and its severity in a tunisian population.

Haptoglobin (Hp) polymorphism generates three common human genotypes (Hp1-1, Hp2-1, and Hp2-2), having functional differences, related to the risk of development of cardiovascular diseases. These functions are a consequence of hemoglobin binding that leads to the synthesis of an antioxidant like ferritin. We explored the association of Hp polymorphism with significant coronary stenosis (SCS) and its severity within 400 Tunisian patients, using genotyping, biochemical parameters, and the Gensini score. After adjustments for age and gender, Hp2-2 was associated with the highest ferritin but the lowest Hp concentrations. After adjustments for confounding parameters, the OR of SCS associated with Hp2-2 was 1.74 (95% CI 1.18-2.58; p = 0.005). This effect was enhanced within diabetics (OR 1.90, 95% CI 1.11-3.24; p = 0.018), obese subjects (OR 1.98, 95% CI 1.10-4.86; p = 0.034), and smokers (OR 4.17, 95% CI 1.54-1.29; p = 0.005). The Hp2-2 genotype is associated with an increase in SCS especially in diabetics, the obese, and smokers.

Association of PON1 and PON2 polymorphisms with PON1 activity and significant coronary stenosis in a Tunisian population.

PON1 and PON2 have attracted considerable attention as candidate genes for coronary heart disease because their enzymes function as key factors in lipoprotein catabolism pathways. We studied the distribution of PON1 and PON2 polymorphisms, including genotyping, lipid profile, and PON1 activity, and their association with PON1 activity and significant coronary stenosis (SCS) in a Tunisian population. PON1 activity was lower in patients with SCS than in controls. It increased with the R allele (QQ < QR < RR) in PON1-192 genotypes and with the L allele (MM < ML < LL) in PON1-55 genotypes. In the presence of metabolic syndrome and diabetes, PON1-192RR and PON2-311CC were associated with an increased risk of SCS and PON1-55MM seems to have lower risk. This association was evident among nonsmokers for PON1-55MM and among smokers for PON1-192RR and PON2-311CC. The GTGC haplotype seemed to increase the risk of SCS compared with the wild haplotype in a Tunisian population.

Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population.

Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoprotein particles (Chylomicrons and very-low-density lipoprotein). LPL polymorphisms' effects on lipids and coronary artery disease are controversial among studies and populations. Our aim was to study the association between six polymorphisms, haplotypes and significant coronary stenosis (SCS), disease severity and lipid parameters in Tunisian patients. LPL PvuII, 93 T/G, 188 G/E, HindIII, N291S and D9N polymorphisms were analyzed in 316 patients who underwent coronary angiography. Assessment of coronary angiograms identified SCS as the presence of stenosis >50 % in at least one major coronary artery. The stenosis severity was determined by using Gensini score and vessels number. A significant association of SCS with TT of the HindIII polymorphism was showed (odds ratio (OR): 2.84, 95 % CI, 1.19-7.40, p = 0.017) and TG (OR: 1.77, 95 % CI, 1.99-2.82, p = 0.033). The mutated HindIII genotype was significantly associated with increased TG and ApoB/ApoA-I ratio and with decreased HDL-C. Haplotype analysis showed that OR of SCS associated with the CTGTAG haplotype was 2.12 (95 % CI 1.05-4.25, p = 0.032) and with CGGGAA was 0.71 (95 % CI 0.26-1.95, p = 0.022) compared to the CTGTAA. Significant difference in Gensini score was observed among HindIII genotype and haplotypes. A significant association between the mutated genotype of HindIII polymorphism and decreased HDL-C level and increased ApoB/ApoA-I ratio and TG level was showed. Our results suggest that HindIII and D9N polymorphisms and CTGTAG haplotype seem to be considered as marker of predisposition to coronary stenosis. In another hand, HindIII and haplotypes were related to stenosis severity.

Design and Rationale of the National Tunisian Registry of Atrial Fibrillation: Protocol for a Prospective, Multicenter Trial.

BACKGROUND: Atrial fibrillation (AF) is an important health problem in Tunisia. A significant change in the epidemiological pattern of heart disease has been seen in the last 3 decades; however, no large prospective multicenter trial reflecting national data has been published so far. Robust data on the contemporary epidemiological profile and management of AF patients in Tunisia are limited. OBJECTIVE: The aim of this study is to analyze, follow, and evaluate patients with AF in a large multicenter nationwide trial. METHODS: A total of 1800 consecutive patients with AF by electrocardiogram, reflecting all populations of all geographical regions of Tunisia, will be included in the study, with the objective of describing the epidemiological pattern of AF. Patients will be officially enrolled in the National Tunisian Registry of Atrial Fibrillation (NATURE-AF) only if an electrocardiogram diagnosis (12-lead, 24-hour Holter, or other electrocardiographic documentation) confirming AF is made. The qualifying episode of AF should have occurred within the last year, and patients do not need to be in AF at the time of enrollment. Patients will be followed for 1 year. Incidence of stroke or transient ischemic attack, thromboembolic events, and cardiovascular death will be recorded as the primary end point, and hemorrhagic accidents, measurement of international normalized ratio, and time in therapeutic range will be recorded as secondary end points. RESULTS: Results will be available at the end of the study; the demographic profile and general risk profile of Tunisian AF patients, frequency of anticoagulation, frequency of effective treatment, and risks of thromboembolism and bleeding will be evaluated according to the current guidelines. Major adverse events will be determined. NATURE-AF will be the largest registry for North African AF patients. CONCLUSIONS: This study would add data and provide a valuable opportunity for real-world clinical epidemiology in North African AF patients with insights into the uptake of contemporary AF management in this developing region. TRIAL REGISTRATION: ClinicalTrials.gov NCT03085576; https://clinicaltrials.gov/ct2/show/NCT03085576 (Archived by WebCite at http://www.webcitation.org/6zN2DN2QX). REGISTERED REPORT IDENTIFIER: RR1-10.2196/8523.

Epidemiology of infective endocarditis in Tunisia: a 10-year multicenter retrospective study.

BACKGROUND: Since the first description of infective endocarditis, the profile of the disease has evolved continuously with stable incidence. However, epidemiological features are different in developing countries compared with western countries. OBJECTIVE: To describe epidemiological, microbiological and outcome characteristics of infective endocarditis in Tunisia. PATIENTS AND METHODS: This was a descriptive multicenter retrospective study of inpatients treated for infective endocarditis from 1991 to 2000. Charts of patients with possible or definite infective endocarditis according to the Duke criteria were included in the study. RESULTS: Four hundred and forty episodes of infective endocarditis among 435 patients (242 males, 193 females; mean (SD) age=32.4 (16.8) years, range 1-78 years) were reviewed. The most common predisposing heart disease was rheumatic valvular disease (45.2%). Infective endocarditis occurred on prosthetic valves in 17.3% of cases. Causative microorganisms were identified in 50.2% of cases: streptococci (17.3%), enterococci (3.9%), staphylococci (17.9%), and other pathogens (11.1%). Blood cultures were negative in 53.6% and no microorganism was identified in 49.8%. Early valve surgery was performed in 51.2% of patients. The in-hospital mortality was 20.6%. CONCLUSION: Infective endocarditis is still frequently associated with rheumatic disease among young adults in Tunisia, with a high frequency of negative blood cultures and high in-hospital mortality, given that the population affected is relatively young.

[Left coronaroventricular microfistula]. / Les microfistules coronaro-ventriculaires gauches.

Left coronaroventricular microfistulae is a rare malformation. The authors report 11 cases of microfistulae between coronary arteries and left ventricle diagnosed by coronary arteriographies. These cases include 6 men and 5 women. Patient's mean age was 54.4 years. The symptoms were suggestive of coronary pathology. The ECG showed myocardial ischemia signs in 5 cases. The other patients had a positive exercise-test. Microfistulae originated from the left anterior descending artery were seen in 5 cases, from the right coronary artery in 2 cases, from the circumflex in 1 case and from the lateral artery in 1 case. The microfistulae originated from both left anterior descending artery and right coronary artery were observed in 2 patients. The main mechanism of myocardial ischemia seems to be related to the coronary steal phenomenon. The diagnosis of the microfistulae is based on coronary arteriography with late recorder angiographic images. The treatment is essentially medical. Surgical and transcatheter treatments are exceptional and must be considered in only severe forms with refractory medical treatment.

Four polymorphisms of cholesteryl ester transfer protein gene and coronary stenosis in a Tunisian population.

AIMS: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is under debate. We studied the association of four polymorphisms (Taq1B, I405V, R451Q and A373P) in the CETP gene with lipid profile and coronary artery disease. METHODS: Four CETP polymorphisms were studied in 316 Tunisian patients undergoing coronary angiography. Patients were clinically examined and their lipid profiles were estimated. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The 451Q allele, associated with lower high-density lipoprotein-cholesterol (HDL-C) and higher total cholesterol and apolipoprotein B (ApoB) concentrations, was also significantly associated with an increased risk of significant stenosis [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.15-2.61, P = 0.007]. The B2 allele of Taq1B polymorphism had an increase in HDL-C concentration and was associated with a decreased risk of coronary stenosis, as described earlier. It was also associated with low risk of hypoHDLaemia [OR = 0.615, 95% CI 0.377-1.002, P = 0.035]. No significant effect of different A373P and I405V alleles was found on the lipid profile and on coronary stenosis. When CETP polymorphisms were combined in haplotypes possessing R451Q, A373P, I405V, Taq1B polymorphisms, the 1112 haplotype (where 1 is the wild genotype and 2 represents carriers of the variant allele) seems to be the most protective against significant stenosis (OR = 0.71, 95% CI 0.188-0.983; P = 0.014), whereas 2111 was probably the most atherogenic, with an OR = 2.17, 95% CI 1.06-5.88; P = 0.039. CONCLUSION: The Q allele of the R451Q polymorphism was associated with decreased HDL-C, increased ApoB concentrations and increased risk of coronary stenosis. In haplotype analysis, we found that 1112 seems to be a protective haplotype, whereas 2111 has an atherogenic effect in a coronary Tunisian population.

Association of three polymorphisms of scavenger receptor class BI gene (exon8, exon1, intron5) with coronary stenosis in a coronary Tunisian population.

BACKGROUND: The potential role of scavenger receptor class BI (gene name SCARB1) in the regulation of lipoproteins metabolism and atherosclerosis has attracted considerable interest. We tested the relationship of SCARB1 polymorphisms with significant coronary stenosis (SCS) and lipid profile in a coronary Tunisian population. METHODS: Three SCARB1 polymorphisms (exon8 (C/T), exon1 (G/A), intron5 (C/T)) were studied in 316 Tunisian patients undergoing coronary angiography. SCS was defined as a luminal narrowing of ≥ 50% in at least one major coronary artery. Lipid profile was measured. Genotyping was performed using PCR-RFLP. RESULTS: Individuals with TT genotypes of exon8 were associated with higher concentrations of plasma HDL-C and ApoAI in the group without SCS. Carriers of T allele of exon8 were associated with 41% lower risk of SCS. This protective effect seemed to be particularly significant in women, nondiabetics and nonsmokers. Subjects homozygous for the variant allele of intron5 were significantly associated with an increased risk of SCS, particularly in smokers. AA genotype of exon1 was associated with an increased risk of SCS in diabetics and in patients with metabolic syndrome. The (CAT) haplotype was associated with increase in the risk of SCS compared to the wild haplotype and had a 4-fold greater risk of SCS than patients with haplotype (TGC) which seems to be the most protective against SCS. CONCLUSION: Carriers of T allele of exon8 in SCARB1 seemed to increase HDL-C and ApoAI concentrations and reduce the risk of SCS. The intron5, exon1 and (CAT) haplotype seemed to have an atherogenic effect.

Single-nucleotide polymorphisms at the adiponectin locus and risk of coronary artery disease in Tunisian coronaries.

OBJECTIVE: Adiponectin is an adipocyte-derived hormone and an essential modulator of insulin sensitivity. Several studies suggest an important role of adiponectin in the process leading to atherosclerosis, thus indicating the adiponectin gene as a potential candidate for coronary artery disease. Two single-nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) have been associated with low circulating adiponectin levels, insulin resistance and type 2 diabetes. The objective was to examine the association of two SNPs (45T/G and 276G/T) with coronary artery disease in a Tunisian population. METHODS: We have recruited 316 Tunisian patients, documented by coronary angiography. Significant coronary stenosis (SCS) was defined as a luminal narrowing of at least 50% in at least one major coronary artery. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism. Lipids and apolipoproteins were measured. RESULTS: After adjustments for confounder parameters, odds ratio (OR) of SCS associated with 276G/T mutated genotypes was 0.472 [95% confidence interval (CI) 0.195-0.842, P=0.046]. The mutated genotypes at the +45T/G polymorphism were significantly associated with increased SCS only in obese patients (OR 3.31, 95% CI 0.996-11.05, P=0.049 versus OR 1.71, 95% CI 0.467-6.269, P=0.418 in non-obese individuals). A potential protective effect was also observed for the haplogenotype TT/TT (OR 0.548, 0.306-0.982, P=0.043) in all the studied population. CONCLUSION: Mutated genotypes at +45T/G (GG + TG) were associated with an increase in SCS only in the obese group. Mutated genotypes at +276G/T (TT + GT) seem to reduce the risk of SCS in the studied population. When the two SNPs were combined, the TT/TT haplogenotype (normal genotype at 45T/G and mutated genotype at 276G/T) was associated with a protective effect.

Associations between common polymorphisms of adenosine triphosphate-binding cassette transporter A1 and coronary artery disease in a Tunisian population.

BACKGROUND: The adenosine triphosphate-binding cassette transporter A1 (ABCA1) protein plays an important role in the first step of the reverse cholesterol transport system. AIMS: We studied the association of four polymorphisms in the ABCA1 gene (G1051A, G2706A, G2868A and -565C/T) with lipid profile and coronary artery disease. METHODS: Overall, 316 Tunisian patients underwent coronary angiography. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured. RESULTS: Only carriers of the G2706A allele were associated with a decreased risk of significant stenosis (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.22-0.92, p = 0.029), without pronounced effects on high-density lipoprotein (HDL) cholesterol. This protective effect was significant in smokers and diabetes. Carriers of the G1051A allele were associated only with increased concentrations of HDL cholesterol (p = 0.032). G2868A and -565C/T did not show any association with lipids or risk of significant stenosis. When ABCA1 polymorphisms were combined in haplotypes possessing G1051A, G2706A, G2868A and -565C/T, (AAGC) seemed to be most protective against significant stenosis (OR 0.5, 95% CI 0.29-0.96, p = 0.048) whereas (GGAT) was probably the most atherogenic (OR 1.26, 95% CI 1.03-1.56, p = 0.025). CONCLUSION: Only the G2706A allele seems to be associated with a reduced risk of significant stenosis without important modification of HDL-cholesterol concentration, and appears to be more protective for smokers and diabetic patients. We found that (AAGC) seems to be a protective haplotype whereas (GGAT) has an atherogenic effect in a Tunisian population.

Elevated liver enzymes in metabolic syndrome are associated with coronary stenosis in a Tunisian population.

BACKGROUND: Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. The aim of this study was to investigate if there is a relationship between elevated liver enzymes and coronary stenosis associated with metabolic syndrome in a Tunisian population. METHODS: We enrolled 192 patients who underwent coronary angiography. Significant coronary stenosis (SCS) was diagnosed in the presence of coronary stenosis with lumenal narrowing >or=50%. Metabolic syndrome was defined according to the International Diabetes Federation criteria. RESULTS: Frequencies of subjects with liver enzyme activities belonging to quartile 4 were higher in the group with metabolic syndrome. Association of SCS with metabolic syndrome was more significant in the quartile 4 of gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Odds ratios of SCS associated with metabolic syndrome were: [1.40 (0.66-2.9) for quartile 1 versus 4.20 (1.3-9.9) for quartile 4 of GGT; 1.52 (0.29-3.7) for quartile 1 vs. 5.30 (1.39-18.9) for quartile 4 of ALT]. CONCLUSIONS: Elevated liver enzyme activity was associated with metabolic syndrome and only GGT and ALT seem to be associated with an increase of the coronary stenosis in the studied population with metabolic syndrome.

Metabolic syndrome is a risk factor for coronary artery disease in a tunisian population.

BACKGROUND: Metabolic syndrome is a constellation of disorders that produces a high risk of atherosclerosis. The prevalence of metabolic syndrome clearly varies depending on ethnicity. The aim of this study was to investigate the prevalence of metabolic syndrome and its relationship with significant coronary stenosis (SCS) in a Tunisian population. METHODS: Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. SCS was defined as a luminal narrowing of more or equal to 50% in at least 1 major coronary artery, as judged by coronary angiography. A total of 192 subjects documented by coronary angiography were recruited from the cardiology department. RESULTS: In all, 54.2% (n = 104) of patients presented with metabolic syndrome, with a higher prevalence among women (65.9% vs. 45.5%; P = 0.004). In the subjects with metabolic syndrome, the fasting hyperglycemia was the most common metabolic disorder (86.5%). The risk of SCS increased approximately 3-fold in the presence of metabolic syndrome [odds ratio (OR) = 3.38, P = 0.004]. In addition, SCS risk was increased according to the increase in the number of metabolic syndrome components. The most atherogenic profile was that which assembled five metabolic syndorme components (OR = 4.18, P = 0.001). There was a significant relationship between the homeostasis model of insulin resistance (HOMA-IR) and the risk of SCS in the presence of metabolic syndrome. In fact, the OR of SCS associated with metabolic syndrome was (4.96, P = 0.001) in participants in the highest quartile of HOMA-IR. CONCLUSIONS: This study suggests that metabolic syndrome is a risk factor for SCS. The detection, prevention, and treatment of the underlying risk factors of metabolic syndrome should become an important approach for reduction of the cardiovascular disease burden in our study population.

5' ins/del and 3' VNTR polymorphisms in the apolipoprotein B gene in relation to lipids and coronary artery disease.

BACKGROUND: Studies that considered apolipoprotein B (APOB) gene polymorphisms as risk factors for coronary artery disease (CAD) have reported conflicting results. We sought to analyze the association between 5' ins/del and 3' VNTR polymorphisms of APOB, lipid parameters and CAD risk. METHODS: We recruited 251 patients with CAD, documented by coronary angiography, and 94 controls. Genotyping was performed by PCR. Lipids and apolipoproteins were measured. RESULTS: 5' ins/del (ins/ins, ins/del, del/del) and 3' VNTR (LL, SS, LS) polymorphism frequencies were significantly (p<0.05) different between controls and CAD patients. LL and del/del were significantly associated with higher levels of apolipoprotein B (apoB), total cholesterol/high-density lipoprotein cholesterol ratio and apoB/apoA-I ratio (p<0.05) and with increased risk of CAD. The odds ratio for significant coronary stenosis associated with del/del was 3.2 (95% CI 1.6-36.42) (p=0.032) and with LL was 2.2 (95% CI 1.1-5.1) (p=0.042). CONCLUSIONS: The two polymorphisms exert an impact on lipid levels and contribute to the susceptibility to the development of CAD.

Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population.

BACKGROUND: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is undergoing debate. AIMS: In this prospective study, we sought to explore the role of the CETP Taq1B variant in coronary artery disease risk, and its association with plasma lipid and apolipoprotein concentrations. METHODS: DNA was extracted from 316 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured by enzymatic and nephelometric assays. RESULTS: In our study population, the B2 allele frequency was 0.29. B2 allele carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype (1.041+/-0.294 versus 0.995+/-0.277; p=0.039). After adjusting for age, sex, smoking status, diabetes, hypertension and dyslipidaemia, the odds ratio (OR) for significant stenosis associated with the B2 allele was 0.82 (95% confidence interval (CI) 0.60-0.97; p=0.039), suggesting that the B2 allele is associated with an 18% lower risk of significant stenosis. This protective effect seemed to be more significant in male nonsmokers (38% lower risk; OR 0.62, 95% CI 0.29-0.92; p=0.029). No significant protective effects were observed in women or male smokers. CONCLUSION: Our data suggest that the B2 allele is associated with higher concentrations of HDL-C, which confer a protective effect with regard to coronary atherosclerosis. This effect seems to be more significant in men than in women and in nonsmokers than in smokers.