[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.

Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease.

Platelet glycoprotein IIb/IIIa is a membrane receptor which plays a key role in coronary artery disease and thrombotic events. However, there is a considerable controversy regarding the clinical impact of glycoprotein IIIa platelet antigen 1 (PlA1)/platelet antigen 2 (PlA2) polymorphism as a risk factor for myocardial infarction. To evaluate the association between glycoprotein IIIa PlA1/PlA2 polymorphism and 1-year cardiovascular events occurrence in aspirin-treated patients with stable coronary artery disease. We prospectively included 188 postacute coronary syndrome patients (183 men) aged 59 ± 10 years and receiving aspirin (250 mg/day). The clinical outcome at 1 year was the composite end point of nonfatal myocardial infarction, stroke, recurrent unstable angina or cardiac death. Genotyping for PlA1/PlA2 polymorphism was conducted using PCR and restriction fragment length polymorphism analysis. The genotype distribution of glycoprotein IIIa PlA1/PlA2 polymorphism was PlA1/PlA1, 55.3%; PlA1/PlA2, 39.3% and PlA2/PlA2, 4%. Incidence of composite end point in homozygous PlA1/PlA1 carriers was significantly higher than in PlA2/PlA2 and PlA1/PlA2 patients [14.4 vs. 3.6% odds ratio 4.5 (1.2-16.6, 95% confidence interval); P = 0.012]. Multivariate analysis identified three strong predictive factors of cardiac death: age more than 65 years [odds ratio = 6.8, (1.4-34, 95% confidence interval); P = 0.018], ventricular ejection fraction less than 50% [odds ratio = 8.6, (1.7-42.6, 95% confidence interval); P = 0.008] and homozygous PlA1/PlA1 genotype [odds ratio = 8.8, (1.0-78.6, 95% confidence interval); P = 0.014]. Our results demonstrated that glycoprotein IIIa PlA1/PlA1 genotype carriers have a significantly increased risks of acute vascular ischemic events associated with a poor prognosis at 1 year. These postacute coronary syndrome patients might require an optimized secondary antithrombotic prophylaxis strategy.

Association of the C677T MTHFR polymorphism with homocysteine, ox-LDL levels, and thiolactonase activities in the severity of coronary syndrome.

Coronary artery diseases (CAD) are influenced by multiple genes of modest effect as the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, related to MTHFR activity and total plasma homocysteine (tHcy) concentration. This study was designed to evaluate tHcy, oxidized low-density lipoprotein (LDL) (ox-LDL), high-sensibility C-reactive protein (Hs CRP) levels, and homocysteine thiolactonase (HTase) activities as new risk factors for CAD and to investigate an association between MTHFR polymorphism tHcy concentrations and coronary syndrome severity. Our results showed significantly higher levels of tHcy and ox-LDL in patients associated with lower HTase activities. These levels increased proportionally to disease severity. Total plasma Hcy levels were negatively correlated to HTase activities in patients where the TT genotype was significantly more frequent. In a multivariate analysis, tHcy level was the only independent factor affecting the coronary syndrome severity. High tHcy levels are associated with coronary syndrome severity and may be explained either by the elevated prevalence of TT genotype or by the diminished HTase activities.

Response variability to aspirin and one-year prediction of vascular events in patients with stable coronary artery disease.

The aim of this study was to assess the association between "aspirin non responsiveness" in patients with coronary artery diseases (CAD) and the risk of major adverse cardiovascular events (MACE). 204 patients with CAD receiving aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI-CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the patients aspirin responsiveness. The clinical primary endpoint was the occurrence of MACE including: cardiovascular death, MI, stroke or transient ischemic attack. The secondary endpoint was the occurrence of Recurrent Acute Vascular Event (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%; P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7-2.4; P = 0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2-32.2; P = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated with an increased risk of either MACE or RAVE. Our results, reinforce the importance of being able to diagnose laboratory "aspirin non responsiveness", and extend the evidence that aspirin non responsiveness may explain in part the occurrence of RAVE.

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.

[A comparison of the effect of oral captopril and nicardipine in hypertensive crisis]. / Effets compares du captopril et de la nicardipine orale dans la crise hypertensive.

BACKGROUND: Hypertensive crisis is defined as a severe elevation in blood pressure (BP) without target organ injury. There are few data about the efficacy and safety of comparative oral antihypertensive drugs. AIM: To compare the efficacy and safety of oral captopril (25 mg) and nicardipine (20 mg) in hypertensive crisis. METHODS: This prospective, randomized study included 50 patients attended at the emergency department with a hypertensive crisis (arterial blood pressure of at least 180/110 mmHg without target organ damage confirmed after 15 min of rest. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were assessed at several intervals during 4 h after the drug administration. Therapeutic success was defined by a SBP< or =160 and DBP< or =90 mmHg two hours after drug administration. The initial clinical characteristics as age, sex, initial systolic and diastolic BP and HR were no different in the two groups. RESULTS: BP levels started to significantly decrease within 15 minutes. At 2 hours, SBP and DBP dropped were similar in captopril group and nicardipine group,respectively to 162/94 vs 161/89 mmHg; p=ns. The therapeutic success at the second hour has been obtained in 68% of cases in the two groups. Age >70 years was a predictor's factor of therapeutic failure in the captopril group. Heart rate significantly dropped after 30 min in the captopril group (82.3 +/- 11.8 vs 77.6 +/- 12.7 c/min; p=0.037). This effect was maintained over four hours. There were no side effects in this study. CONCLUSION: Oral captopril or nicardipine are efficacy and safe in the treatment of hypertensive crisis.

Hyperhomocysteinaemia and parameters of antioxidative defence in Tunisian patients with coronary heart disease.

BACKGROUND: An imbalance between oxidative damage and antioxidative protection in association with the pathophysiology of atherosclerosis has been suggested. The aim of this study was to test the parameters of antioxidative defence and to assess their association with hyperhomocysteinaemia and the severity of coronary heart disease (CHD) in Tunisian patients. METHODS: The study population included 100 patients with CHD and 120 healthy controls. The severity of CHD was expressed as the number of affected vessels. Superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity and total antioxidant status (TAS) concentrations were measured using commercially available methods. Plasma total homocysteine (tHcy) concentration was determined by direct chemiluminescence assay. Serum zinc (Zn) was measured by a colorimetric method. RESULTS: Compared with healthy control subjects, patients with CHD had significantly lower activities of SOD (P < 0.01), GPx (P < 0.001), and serum Zn concentrations (P < 0.001) and significantly higher tHcy concentration (P < 0.001). However TAS concentrations were not significantly different between the groups. SOD and GPx activities were negatively correlated with tHcy concentration (P < 0.05, P < 0.001, respectively). Patients with hyperhomocysteinaemia showed a lower GPx and SOD activities than patients with normohomocysteinaemia. Antioxidant enzyme activities tended to be decreased in CHD patients presenting with 0- to 3-vessel stenosis. CONCLUSIONS: This study indicates that low activity of GPx, SOD and Zn concentration are associated with CHD patients. We hypothesize that hyperhomocysteinaemia and low antioxidant enzyme activities may increase the extent of CHD.

[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.

Plasma metalloproteinase-12 and tissue inhibitor of metalloproteinase-1 levels and presence, severity, and outcome of coronary artery disease.

Several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the development and outcome of coronary artery disease (CAD). We investigated whether MMP-12 and TIMP-1 levels were associated with risk, severity, and outcome of CAD. Plasma MMP-12 and TIMP-1 levels are measured in 50 and 44 patients with CAD, respectively, by enzyme-linked immunosorbent assay. Of all patients, 16 were taking statins. Patients who were not on statins were classified into 3 groups according to number of >50% stenotic vessels. Compared with 29 volunteers without CAD, patients without statins (n = 34) had higher MMP-12 concentrations (1.71 vs 1.08 ng/ml, p = 0.021). MMP-12 levels were significantly lower in patients with than in those without statin treatment (0.99 vs 1.71 ng/ml, p = 0.008). There was no association between MMP-12 levels and number of >50% stenotic vessels. MMP-12 concentrations were not associated with outcome of CAD. However, plasma TIMP-1 levels were associated with restenosis independently of number of stenotic vessels and age (p = 0.035) but not with risk or severity of CAD. In conclusion, plasma MMP-12 concentration was associated with the presence of CAD. Statin therapy decreases plasma MMP-12 levels in patients with CAD. Increased TIMP-1 levels may prevent restenosis after angioplasty.

Screening for aspirin resistance in stable coronary artery patients by three different tests.

BACKGROUND: Aspirin (ASA) failure to inhibit in vitro platelet function had been termed ASA resistance. The prevalence of this phenomenon as measured with different platelet function tests varies widely among studies. OBJECTIVES: In this study, we propose to determine the prevalence of ASA non-responsiveness in stable coronary artery patients using three different tests. PATIENTS AND METHODS: One hundred ninety-one patients with a stable coronary artery disease and receiving secondary ASA prophylaxis (250 mg/day) were tested. For each patient the ASA-induced platelet inhibition was determined using three different tests: Ivy Bleeding time (BT), collagen/epinephrine closure time (CEPI-CT; PFA-100, Dade-Behring) and urinary 11-dehydrothromboxane B2 (uTxB2) excretion level. The agreement between these tests was evaluated by kappa statistics test. RESULTS: The prevalence of biological ASA resistance was 15.7% (n=30), 20.4% (n=39) and 24.6% (n=47) by BT, PFA-100 and UTxB2, respectively. Only fourteen patients (7.3%) were non-responders for two tests: 6 (3.1%) BT/ PFA-100; 1 (0.5%) BT/UTxB2; 7 (3.7%) PFA-100/UTxB2). A poor agreement was found between these three methods and only 3 patients were resistant with all the tests (1.6%). CONCLUSION: The lack of agreement supposed that different types of aspirin resistance exist. Thus, combination of two tests or more could be a primary solution for a better identification of ASA resistant patients. This hypothesis must be confirmed by a large-scale randomized study with clinically well-defined endpoints.

Hyperhomocysteinemia, endothelial nitric oxide synthase polymorphism, and risk of coronary artery disease.

BACKGROUND: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population. METHODS: We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. RESULTS: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity. CONCLUSION: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.

Balloon mitral commissurotomy for patients with mitral stenosis in atrial fibrillation: ten-year clinical and echocardiographic actuarial results.

BACKGROUND AND AIM OF THE STUDY: Controversy persists as to whether atrial fibrillation (AF) has a direct negative effect on the outcome of percutaneous balloon mitral commissurotomy (PBMC). The study aim was to assess the effect of AF on immediate and 10-year clinical and echocardiographic actuarial results of patients with rheumatic mitral stenosis undergoing PBMC. METHODS: A total of 195 consecutive patients with AF (group 1) was analyzed and compared with 195 patients in sinus rhythm (group 2), matched for the severity of mitral valve morphological changes. RESULTS: Group 1 patients were older (43.8 + 12 versus 30.5 +/- 12.7 years; p <0.001), and a greater proportion had grade 1 mitral regurgitation (25.1 versus 9.7%; p <0.0001). The procedural success was 89.8% in group 1 and 92.3% in group 2 (p = NS), but group 1 patients had a smaller mitral valve area (2.1 +/- 0.4 versus 2.3 +/- 0.4 cm2; p <0.0001). Patients in AF had a lower 10-year survival (91.4 versus 99.4%; p = 0.018), a lower 10-year event-free-survival (60.3 versus 70%; p = 0.02), and a lower 10-year freedom from restenosis (40 versus 66%; p = 0.048). AF was an independent predictor of overall mortality (OR = 10.79; p <0.033) and of combined events (death, redo PBMC or mitral valve surgery; OR = 1.95; p <0.012), and was a univariate predictor of restenosis (p = 0.048). CONCLUSION: Patients with AF have good immediate results, but poorer long-term outcome after PBMC. AF a marker of worse prognosis in patients with mitral stenosis as it is in the general population.

[Cardiac amyloidosis revealing multiple myeloma]. / Amylose cardiaque révélatrice d'un myélome multiple.

INTRODUCTION: Amyloidosis is a rare disease characterized by an extracellular accumulation of a protein polysaccharid complex (Amyloid). Cardiac involvement is considered as a major prognostic factor. OBSERVATIONS: We report the case of two women, hospitalized for heart failure. The diagnosis of cardiac amyloidosis was suggested by echocardiography: Left ventricular concentric hypertrophy and typical amyeloid infiltration with hyperechoic, shiny and granite-like aspect of the interventricular septum. The histological confirmation was obtained by gastric biopsy in the first case and biopsy of the salivary glands in the second revealing an amyloidosis AL. This cardiac amyloidosis was secondary to multiple myeloma: monoclonal Gammopathy with immunoglobulin Lambda in the first and Kappa in the second, and the presence of a plasmocyte infiltration in the sternal puncture. CONCLUSION: Amyloidosis is a rare pathology, the cardiac involvement is frequent in the type AL and can occur with or without clinical manifestations. Echocardiography should be systematic in patients with confirmed amyloidosis.

Intracardiac thrombus in Behçet's disease: two case reports.

UNLABELLED: Intracardiac thrombus in Behçet's disease is an extremely rare manifestation. We report two such cases. A 20-year-old man presented with dyspnoea, cough and haemoptysis. Right heart thrombus associated with pulmonary artery aneurysm and thromboembolism was identified by helical CT and transoesophageal echocardiography. The second case was a 29-year-old male admitted for fever and chest pain. A diagnosis of right atrial thrombosis associated with pulmonary embolism and hyperhomocysteinemia was made. Due to the absence of haemodynamic compromise, medical management consisting of immunosupressive and anticoagulation therapy was adopted which resulted in complete dissolution of the thrombus with dramatic clinical improvement in both cases of clinical status. CONCLUSION: intracardiac thrombus is a rare complication of Behçet's disease. As shown in our patients, medical treatment should be considered as the first line.

[Role of cholesteryl ester transfer protein activity and genetic polymorphism in ischemic heart disease in type 2 diabetic patients]. / Rôle de l'activité et du polymorphisme génétique de la protéine de transfert des esters de cholestérol (CETP) dans les cardiopathies ischémiques chez les diabétiques type 2.

Cholesteryl Ester Transfer Protein (CETP) facilates the exchange of triglycerides (TG) and cholesteryl ester between lipoproteins particles. Diabetic subjects have been reported to have higher TG levels and lower high density lipoprotein-cholesterol (HDL-C) levels which contribute to the increased cardiovascular risk observed in some of these patients. The CETP activity was shown to be more important in a group of 93 non insulino-dependant diabetics with coronary artery disease than in a group of 92 healthy subjects (p = 0.033). Several polymorphisms have been reported in the CETP gene. The common Taq IB polymorphism is associated with decreased CETP activity and increased HDL-C. We have observed a frequency of 0.31 for B2 allele in deference to those reported in subjects from Caucasian population. An association between the presence of the B2B2 genotype, decreased CETP activity and increased of plasma HDL-C was observed in healthy subjects but not in diabetics with coronary artery disease.

[Correlation of clinical and angiographic morphology in unstable angina]. / Corrélations cliniques et angiocoronarographiques au cours de l'angor instable.

The goal of this study was to compare the clinical presentation and angiographic morphology of patients having an unstable angina pectoris. A total of 321 patients were consecutively studied and underwent cardiac catheterization, mean age 59 + 6 years. According to Braunwald classification, class III was predominant (58%) On coronary angiography, 148 patients had single vessel disease, double-vessel in 92 and triple-vessel in 64. Morphology of coronary artery lesions was classified according to Ambrose's classification, 100 patients had simple lesions (type I or IIA), 204 patients had complex lesions (type IIB, III, intracoronary thrombus or total occlusion). Thoracic rest pain (class III) or postinfarction angina (class C), were associated with the presence of complex lesions. This subgroup of high risk patients would benefit from either Glycoprotein IIb/IIIa blockers with an early revascularisation strategy.

[Multicenter study of atrial fibrillation]. / La fibrillation auriculaire. Etude multicentrique.

1134 patients presented a first episode of atrial fibrillation (AF) between January 1985 and December 2000. Age average was 58.6 years (15-60). 656 (57.8%) were male and 478 (42.2%) were female. The first etiology of AF was rheumatic carditis (36.1%). AF was idiopathic in 27.7% of cases. Morbi-mortality was significantly higher in patients with AF versus those with sinus rhythm; five years survival was respectively 96% and 85%. Success rate was 70% with electrical cardioversion versus 40% with pharmacological cardioversion. Results of AF reduction was independent of left atrium diameter. Only long standing of AF predicted failure of AF reduction.

[Mobile right atrial thrombus complicated by severe pulmonary embolism treated with low molecular weight heparin]. / Thrombus "flottant" de l'oreillette droite compliqué d'embolie pulmonaire massive traité par héparine de bas poids moléculaire.

Right heart emboli-in-transit have been echocardiographically documented in up to 4 to 23% of patient with acute pulmonary embolism. The most appropriate therapeutic approach still remains an unresolved problem because there are no prospective and randomized trials to definitively answer this question. Thrombolysis seems to be the more attractive alternative. We report a case of 44 years old man presented with a right atrial thrombus complicated by severe pulmonary embolism treated successfully by low molecular weight heparin.

Eighteen-year experience with echinococcosus of the heart: clinical and echocardiographic features in 14 patients.

We present a retrospective analysis of clinical symptoms and echocardiographic features in 14 patients having cardiac hydatic cysts and screened during the 18 last years, with surgical correlations in 13. The heart was the sole location of the cyst in six patients. The revealing symptoms were precordial pain (six patients), dyspnea (two patients). A systolic murmur of false pulmonic stenosis was present in three patients. In 13 patients, two-dimensional echocardiographic images of hydatic cysts were those of masses of liquid content with a well-contrasted capsule, which was single in eight patients and multiple in five, one of which had a honeycomb appearance. The mass was solid and calcified in one patient. The outlines of the cysts were particularly sharp on transesophageal echocardiograms (six patients). The cyst size ranged from 1.8 to 11 cm in diameter. Cysts were located in the intramyocardium in 10 patients (left ventricle in four patients, interventricular septum in four patients, right ventricle in two patients), the pericardium in three and the mediatinum in one. There were a Doppler pulmonary valve gradient in three patients. Computed tomography (eight patients) and coronary arteriography (seven patients) have no additional diagnosis value than echocardiography. Nuclear magnetic resonance imaging (three patients) was helpful in determining extracardiac extension of the cysts. Transthoracic and transesophageal two-dimensional echocardiography have a central role in diagnosing cardiac hydatic cysts.