Mouna Turki

Atherogenic Lipid Profile in Behçet’s Disease: Evidence of Alteration of HDL Subclasses

BACKGROUND AND AIMSnBehçets disease (BD) is an inflammatory vasculitis, most common in the Mediterranean area and Asia. Evidence for accelerated atherosclerosis in BD has been observed. The relationship between cardiovascular risk factors and accelerated atherosclerosis in patients with BD is still controversial. The aim of this study was to evaluate the lipid profile and to investigate the low-density lipoprotein (LDL) size and the distribution of high-density lipoprotein (HDL) subpopulations in BD patients.nnnMETHODSnThirty six BD patients were compared to 36 healthy controls. Total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C) levels were measured using standard techniques. HDL subclasses and LDL-C size were estimated using polyacrylamide linear gradient gel electrophoresis. The LDL-C/HDL-C ratio was also calculated. High-sensitive C-reactive protein (hsCRP) level was measured by a turbidimetric method. Homocysteine (Hcy) level was determined using a liquid chromatography tandem mass spectrometry (LC/MS/MS).nnnRESULTSnIn BD patients, HDL-C levels as well as its subfraction levels were decreased (respectively, p <10(-6) and p <10(-3)). Percentage of HDL2 subpopulation was also decreased (p=0.02). HDL3 subfraction was significantly higher (p=0.02). The LDL-C/HDL-C ratio and CRP level were increased (respectively, p=10(-4) and p=0.003). TC was correlated with CRP. HDL-C and its subfractions were correlated with CRP and TG levels. HDL subparticle percentages were also correlated with age.nnnCONCLUSIONSnOur findings of a reduction of HDL-C and HDL2 subpopulation and an increase HDL3 subclass and a higher LDL-C/HDL-C ratio may be considered as important predictors of cardiovascular events in BD patients.

Value of Serum Cholinesterase Activity in the Diagnosis of Septic Shock Due to Bacterial Infections.

Background: We aimed to investigate whether serum cholinesterase (SChE) activity can be helpful for the diagnosis of septic shock and to evaluate its usefulness in comparison with procalcitonin (PCT) and C-reactive protein (CRP). Methods: A prospective single-blinded study conducted in an intensive care unit of university hospital. Patients were classified as having cardiogenic shock, septic shock, or hemorrhagic shock. We also included a control group without neither hemodynamic instability nor sepsis. For all included patients, SChE, PCT, and CRP were simultaneously sampled. Results: The comparison of sepsis markers between all groups showed that the mean values of PCT and CRP were significantly higher in patients with septic shock. However, SChE activity was significantly lower in this group. The SChE activity was found to be more accurate than PCT and CRP for the diagnosis of septic shock. In fact, an SChE activity ≤ 4000 UI/L predicted the diagnosis of septic shock with a sensitivity of 78%, a specificity of 89%, a predictive negative value of 97%, and a predictive positive value of 65%. However, the prognostic value of SChE activity was poor in multivariate analysis. Conclusion: The SChE activity level was significantly decreased in patients with septic shock. However, its prognostic value is poor. Our results suggest that SChE activity is useful for the diagnosis of septic shock. Further studies are warranted to confirm our findings.

Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria

L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been proposed as an endo- and exogenous cytotoxic organic acid that induces free radical formation and generation of reactive oxygen species (ROS). In this report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous families the south of Tunisia. The patients were diagnosed with L2HGA disease confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH gene in all probands and identified the same c.241A>G homozygous mutation, which was previously reported in Tunisia. We also used intragenic single nucleotide length polymorphisms (SNPs) and two extragenic microsatellites flanking the L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied cases. In addition, we carried out the measurement of the oxidative stress parameters in the plasma of L2HGA patients which revealed a significant increase in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the reduced glutathione (GSH). A diminution of the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also observed.

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients

ObjectivesThe study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2Rxa0→xa03R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.MethodsA total of 185 patients with RA were included. Homocysteinexa0(Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcyu2009>u200915xa0µmol/L.ResultsMTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; pu2009=u20090.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; pu2009=u20090.035).ConclusionsThe MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.

Cystatin C: A prognostic marker after myocardial infarction in patients without chronic kidney disease

Aims Cystatin C is an endogenous marker of renal function. It is a well established better marker of glomerular filtration rate than serum creatinine. There is also evidence that cystatin C is associated with atherosclerotic disease. The present prospective study evaluated the prognostic value of cystatin C after myocardial infarction in patients without chronic kidney disease. Methods and results A total of 127 patients who underwent coronary angiography after an acute coronary syndrome (ACS) were included. Cystatin C was associated with the severity of coronary artery disease (CAD). Cystatin C levels were significantly higher in patients with 3-vessels disease and severe CAD according to GENSINI score (p = 0.01 and p < 0.001 respectively). Among the patients admitted for ST elevation myocardial infarction, Cystatin C concentration was correlated with the initial TIMI flow in the culprit artery (p < 0.001). Mean duration of the follow-up period was 10.76 ± 2.1 months. High Cystatin C concentrations were associated to the occurrence of unfavourable outcomes and cardiovascular mortality during follow-up (1.19 ± 0.4 vs. 1.01 ± 0.35 mg/L, p = 0.01 and 1.21 ± 0.36 vs. 0.96 ± 0.27 mg/L, p = 0.03). Among different laboratory parameters, cystatin C was the best marker to predict the occurrence of major adverse cardiovascular events during the follow-up (Area under the receiveroperating characteristic curve = 0.743). Conclusion High cystatin C levels are associated with the severity of coronary artery disease in patients presenting an acute coronary syndrome and a normal renal function. Cystatin C is also associated to unfavourable cardiovascular outcomes during follow-up and appears as a strong predictor for risk of cardiovascular events and death.

0519: Cystatin C: a novel marker of cardiovascular risk in a hypertensive cohort

Introduction Arterial hypertension (HTN) is a major cardiovascular factor which leads to several diseases. We hypothized that cystatin C may reflect the cardiovascular risk in hypertensive patients. Patients and Methods we studied 31 hypertensive patients with no exertional dyspnea and 30 age and sex-matched healthy subjects. Patients didn’t experience any history of diabetes, coronary or valvular heart disease. Kidney and liver dysfunction were also exclusion criteria in our study. 2D and 3D echocardiography was performed with use of speckle tracking imaging. Serum cystatin C was also calculated. Cardiovascular risk scoring was calculated according to the European charts (SCORE). Results Mean patients’ age was 51±10 years. Mean left ventricular ejection fraction was similar in both hypertensive and healthy subjects (65±4 vs.64,4±4,5%, p=0,5). However, LV mass and relative wall thickness were significantly greater in HTN group (116±19 vs. 75±18g/m 2; p Conclusion Serum cystatin C may reflect the cardiovascular risk in hyper-tensive patients with good sensitivity and specificity.

0363: Acute coronary syndrome complicated with left ventricular diastolic dysfunction: what is the contribution of brain natriuretic peptid?

Background nThe utility of Brain Natriuretic Peptide (BNP) for detecting leftventricular (LV) diastolic dysfunction in patients presenting an acute coronary syndrome without heart failure symptoms is unclear. In this study, we investigated the relation between BNP plasma levels and LV diastolic dysfunction in patients with postmyocardial infarction without systolic dysfunction. nMethods nWe studied 81 patients (12 women, mean age 55±11.79) admitted in our center for myocardial infarction with or without ST segment elevation. Patients with heart failure symptoms or abnormal systolic function were excluded. LV diastolic function was assessed with conventional Doppler, by means of mitral inflow and with tissue Doppler echocardiography by means of mitral annulus. The ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic E’ wave velocities (E/E’), was used to detect LV filling pressures. Patients were divided in three groups according to E/E’ ratios 15 (group III). n n n n n n nAbstract 0109 – Table: Patients’ baseline characteristics n n n Patients’baseline characteristics n BMS (n=30) DES (n=300) p nSex, M/F 30/0 30/0 1 nAge, y 52,03±6,35 50,2±8,45 0,34 nBody mass index*, kg/m2 25,79±2,56 25,00±2,97 0,28 nHypertension, % 16,66 1,66 1 nDyslipidemia, % 33,33 33,33 1 nDiabetes mellitus, % 0 0 1 nFamily history, % 26,66 6,66 0,07 nCigarette smoking, % 73,33 60 0,41 nPrevious CAD, Stroke, PAOD, % 0 0 1 nIndication of coronary angiography nAMI (STEMI/NSTEMI, % 86,66 76,66 0,5 nUA, % 13,33 16,66 1 nSCAD, % 0 6,66 0,49 nTime interval between PCI and blood sampling, d 39,16±7,68 38,73±6,76 0,81 nStent length, mm 16,3±4,24 17,56±5,71 0,33 nLVEF, % 58,66±7,30 61,13±6,18 0,16 nDrug therapies* nStatin, % 100 100 1 nASA, % 100 100 1 nSecond anti-platelet drug nClopidogrel, % 46,66 43,33 1 nPrasugrel, % 53,33 50 1 nTicagrelor, % 0 6,66 0,49 nβ-blocker, % 85,71 (n=28) 60 (n=25) 0,059 nACE inhibitor, % 0 (n=28) 0 (n=26) 1 nOAC, % 0 0 1 nBlood tests* nLDL cholesterol, g/L 0,75±0,18 0,68±0,19 0,19 nHDL cholesterol, g/L 0,39±0,10 0,43±0,11 0,19 nTriglyceride, g/L 0,96±0,32 0,93±0,29 0,72 nHemoblogin, g/dl 14,34±0,97 14,4±0,83 0,82 nPlatelets, G/L 242,93±55,90 239,56±49,61 0,8 nSerum creatinine, μmol/L 2,07±2,02 1,39±1,30 0,12 nFasted glycaemia, g/L 0,97±0,11 1,01±0,09 0,14 nHbA1c, % 5,74±0,39 5,73±0,40 0,92 n n n nContinuous variables are presented as sample mean and standard deviation. P-values reflect comparisons between patients with a BMS and patients with DES and are derived from Student’s t-tests for continuous variables whereas qualitative data were compared with Fisher’s exact test. n nThe characteristics marked with an asterisk were collected on the same day that blood was sampled (one month after PCI) n n nFull-size table n nTable options n n n nView in workspace n nDownload as CSV n n n n n n n nResults nThe BNP blood levels were positively correlated significantly with E/E’ ratio (p 15 (n = 27) had highest BNP (302±68xa0pg/ml) levels. E/E’ 10 to 15 group (n = 24) had a mean BNP level of 136.4±27xa0pg/ml, and those with E/E’ 15. The area under the ROC curve for BNP to detect any diastolic dysfunction was 0.757. A BNP value of 72.7xa0pg/ml had a sensitivity of 82.2% and a specificity of 66.7% for detecting a diastolic dysfunction. nConclusions nA rapid assay for BNP can detect the presence of diastolic abnormalities on echocardiography. In patients with preserved systolic function post myocardial infarction, elevated BNP levels might help to reinforce the diagnosis of LV diastolic dysfunction.

Impact de l’androgénothérapie sur les profils métabolique et inflammatoire chez l’homme hypogonadique

This study aims to evaluate the impact of androgen therapy on metabolic and inflammatoy profiles in male hypogonadic patients. Forty cases with isolated hypogonadism and 80 controls were enrolled. Clinical data were collected (age, weight, height, waist circonference and androgenothearapy). Blood tests were performed to evaluate testosterone, homeostasis index modal assessment (HOMA-IR), lipids and C reactive protein (CRP). Among hypogonadic patients, 14 of them were treated for 4 +/- 3.4 years. Amongst them testosterone levels were significantly elevated comparatively to non-treated patients and significantly lower than controls. Significant differences were noted on waist circumference between non treated patients and controls. Body mass index and HOMA-IR were significantly higher in non-treated patients. Triglycerides and HDLc were significantly decreased respectively in treated and non-treated patients. However, CRP levels were significantly decreased in controls. In conclusion, androgen therapy appeared to protect against obesity, insulin resistance, and hyperlipidemia. Effects on systemic inflammation seemed to be more discrete. Testosterone substitution should be strongly indicated in daily practice with careful prostate monitoring.

Markedly increased vitamin B12 concentration due to immunological interference

Presence of high serum cobalamin concentrations is generally detected in patients with hematologic disorders and hepatic diseases [1], but only seldom will it be detected in patients without evidence of cobalamin metabolism disturbance [2]. We report a case in which an analytical problem led to a falsely increased result.In April 2012, an 85 year old man presented to his general practitioner for a routine check-up. He was a known case of chronic kidney disease V, type 2 diabetes and Parkinson disease. [...]

Metabolic and inflammatory profiles in polycystic ovary syndrome associated to weight excess

Polycystic ovary syndrome (PCOS) and weight excess exhibited metabolic abnormalities and elevated cardiovascular risk. Our objective was to assess metabolic and inflammatory profiles in women with PCOS associated to weight excess; 85 women were enrolled. Four groups were then identified with and without PCOS and/or weight excess. Hyperlipidemia was significantly more observed in the two groups with weight excess. In whom insulinresistance and high sensitive C reactive protein were also elevated. Abnormalities observed when PCOS and weight excess are associated would mimic these observed in isolated weight excess with some particularities.