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Biomedical subjects

Dimitris Tousoulis

Publications and source records attributed to Dimitris Tousoulis.

At least 37 records · Page 2Linked to original sources
PubMed2005

Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major.

BACKGROUND: Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. METHODS: The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6+/-0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. RESULTS: Patients had significantly lower levels of total cholesterol (125+/-4.5 vs. 207+/-7 mg/ml, p<0.01), ApoA1 (120+/-3 vs. 129+/-5 mg/ml, p<0.05), ApoB (60.5+/-2 vs. 95+/-4 mg/ml, p<0.01), ApoE (3+/-2 vs. 4+/-0.2 mg/ml, p<0.01) and Lp(a) (7.9+/-1.3 vs. 14.5+/-3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03+/-0.31 pg/ml) than controls (1.15+/-0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513+/-31 and 368+/-25.5 ng/ml, respectively) than controls (333+/-13.8 and 272+/-14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1+/-0.3 ml/100 ml tissue/min and 49+/-2.8%, respectively) than controls (8.26+/-0.32 ml/100 ml tissue/min and 86.3+/-5.57%, respectively, p<0.01 for both). CONCLUSIONS: Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.

Apolipoprotein A-I↗
PubMed2005

Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction.

OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event.

Female↗
PubMed2005

Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure.

BACKGROUND: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. AIM: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. METHODS: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. RESULTS: RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all). CONCLUSIONS: Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.

Aged↗
PubMed2005

Early atherosclerosis in childhood: diagnostic approaches and therapeutic strategies.

The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. Injury to the endothelium is a critical step in atherosclerotic process. Conventional and novel risk factors for coronary artery disease operate from early in life. Noninvasive methods, using mostly ultrasound techniques, have enabled the assessment of early functional and structural arterial disease progression even from the first decade of life. These measures have been shown to be good surrogate markers for atherosclerotic disease progression and future clinical cardiovascular events. Lifestyle and dietary modifications as well as pharmacological interventions have beneficial effects in prevention and restoration of the early arterial changes.

Adolescent↗
PubMed2005

The impact of early administration of low-dose atorvastatin treatment on inflammatory process, in patients with unstable angina and low cholesterol level.

BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in patients with stable angina or multiple risk factors. However, the effects of lipid-lowering treatment on inflammatory process during and immediately after the acute phase of unstable angina remain unclear. In this study we assessed the effects of low-dose atorvastatin treatment, on inflammatory process in patients admitted for unstable angina with low cholesterol level. METHODS: Forty-seven normocholesterolemic patients with unstable angina were randomized into two groups, and received atorvastatin 10 mg/day (n = 24) or no statin (n = 23) for 6 weeks. Circulating levels of inteleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and soluble vascular cell adhesion molecule (sVCAM-1) were measured by their admission, and at the 1st and 6th week of the study. RESULTS: Serum levels of MCP-1 and sVCAM-1 were significantly increased in the control group (p < 0.05) while remained unaffected in the atorvastatin-treated group six weeks after admission. However, IL-6 and TNF-alpha levels were similarly decreased in both atorvastatin-treated and control groups. CONCLUSION: Low-dose atorvastatin treatment modifies inflammatory process in patients with unstable angina and low cholesterol level, an effect seen at 6 weeks but not 1 week after admission.

Angina, Unstable↗
PubMed2005

Inflammation and endothelial dysfunction as therapeutic targets in patients with heart failure.

Evidence suggests that vascular endothelium plays key role in the regulation of vascular tone, in the process of inflammation and in the thrombotic mechanisms. Recent studies indicate that it is an important component of the pathophysiological mechanisms of heart failure. Heart failure may induce endothelial dysfunction by different mechanisms, such as reduced synthesis and release of nitric oxide (NO), increased degradation of NO or by increased production of endothelin-1. In addition, endothelial dysfunction has been associated with the progression of heart failure. Alterations in neurotransmitters, hormones and also in physiological stimuli are present in heart failure and affect the vascular endothelium. Treatments with beneficial effects on endothelial dysfunction may also improve prognosis in patients with heart failure.

Animals↗
PubMed2005

Left atrial function, cytokines and soluble apoptotic markers in mitral stenosis: effects of valvular replacement.

BACKGROUND: Patients with mitral stenosis (MS) and heart failure (HF) are characterized by changes in the left atrial (LA) function and activation of the apoptotic process. The purpose of the present study was the evaluation of the effect of mitral valve replacement on the LA function, on inflammatory process and apoptotic markers in patients with MS and HF. METHODS: We studied 30 patients with MS and HF (15 in NYHA III-IV and 15 in NYHA IV) in sinus rhythm (mean age 56.2 +/- 4.6 years), and 20 age and gender matched healthy volunteers. Blood samples were obtained before and 6 months after surgical mitral valve replacement, and plasma levels of soluble Fas/APO-1 receptor (sFas), tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were measured. Echocardiographically, LA volumes were measured at mitral valve opening (Vmax), at the onset of left atrial systole (P wave of the electrocardiogram, Vp) and at the mitral valve closure (Vmin). LA contractile function was assessed by the LA active emptying fraction (ACTEF). RESULTS: After mitral valve replacement, TNF-a, IL-6 and sFas levels, as well as the Vmax LA volume, were significantly reduced (p < 0.05). ACTEF showed a significant postoperative decrease (0.29 +/- 0.09 vs. 0.23 +/- 0.06, p < 0.01) and it was significantly correlated with sFas (r = -0.88, p = 0.001), TNF-a (r = -0.81, p = 0.001) and IL-6 (r = -0.74, p = 0.001) levels. CONCLUSION: The present findings indicate that mitral valve replacement in patients with mitral valve stenosis, reduces the size of the left atrium, improves left atrial contractile function and depresses inflammatory and apoptotic process.

Adult↗
PubMed2005

Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta.

It is well documented that in patients with coarctation of the aorta life expectancy is not normal even after successful coarctation repair (SCR), primarily due to cardiovascular events. We examined endothelial function in the forearm circulation, the mechanical properties and intima/media thickness in carotid and femoral arteries and the inflammatory process in normotensive patients, after coarctation repair. Fifteen patients, 29+/-2 years old, 12+/-2.9 years after SCR and 16 age- and sex-matched controls were enrolled in our study. Forearm blood flow was determined by gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was expressed as the %change from baseline to post-reactive hyperemia blood flow. High resolution ultrasound was used for determination of intima/media thickness and elastic properties of carotid and femoral arteries. Serum levels of soluble vascular adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), E-selectin, and interleukines 1b (IL-1b) and 6 (IL-6) were determined by ELISA. Reactive hyperemia was significantly decreased in patients compared to controls (p<0.01). Patients with SCR had higher intima/media thickness and decreased distensibility in the carotid arteries than controls (p<0.01 for both). Serum levels of sICAM-1, sSVCAM-1, E-selectin and IL-1b were higher in SCR group than in controls (p<0.05 for all). Adult patients after SCR have impaired endothelial function in the forearm circulation, increased intima/media thickness, decreased distensibility in the carotid arteries and increased levels of proinflammatory cytokines and adhesion molecules than healthy controls. These results may partly explain the high incidence of coronary artery disease in patients with repaired coarctation of the aorta.

Adult↗
PubMed2005

Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure.

Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure (HF) and normal cholesterol levels. HF is characterized by endothelial dysfunction and increased inflammatory process, while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients. We investigated the effect of 4-week atorvastatin treatment (10 mg/day) on endothelial function and inflammatory markers in patients with HF and cholesterol levels <220 mg/dl. Patients were randomly allocated into groups and received atorvastatin (n=19) or no statin (n=19). Forearm blood flow was measured using gauge-strain plethysmography. Serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule (sVCAM-1) were determined with ELISA. Data are expressed as median [25th-75th percentile]. Forearm vasodilatory response to reactive hyperemia was significantly improved in atorvastatin-treated patients (from 38.1% [32.0-59.1] to 70.0% [61.1-106.3], P<0.01), while it remained unaffected in the control group. Levels of IL-6, TNF-alpha and sVCAM-1 were decreased in atorvastatin-treated group (from 7.8 pg/ml [4.8-9.5], 3.2 pg/ml [2.7-4.8] and 595 ng/ml [440-810] to 5.6 pg/ml [2.5-9.0], 2.8 pg/ml [2.0-3.6] and 289 ng/ml [169-368], respectively, P<0.05 for all) but not in the control group. These findings indicate that atorvastatin may improve forearm vasodilatory response to reactive hyperemia and depress inflammatory process in patients with heart failure and normal baseline cholesterol levels.

Aged↗
PubMed2005

Left ventricular diastolic dysfunction is accompanied by increased aortic stiffness in the early stages of essential hypertension: a TDI approach.

OBJECTIVE: To investigate the inter-relationship between aortic stiffness and left ventricular (LV) diastolic function in subjects with newly diagnosed uncomplicated essential hypertension. METHODS: We studied 106 consecutive newly diagnosed subjects (aged 51 years, 80 males) with stage I-II essential hypertension, and 50 normotensives matched for age, sex and body mass index. LV diastolic function was estimated by pulsed tissue Doppler imaging (TDI) echocardiography, averaging diastolic mitral annular velocity measurements (Emav, Amav, Emav/Amav ratio) from four separate sites (basal septal, lateral, anterior, and inferior LV wall). Moreover, aortic stiffness was evaluated by non-invasive carotid-femoral pulse wave velocity (c-f PWV) measurement. RESULTS: Hypertensives compared with normotensives exhibited greater LV mass index and Amav (110 versus 95 g/m and 10 versus 8.8 cm/s, respectively, P < 0.001 for both cases), and greater c-f PWV (8.47 versus 7.48 m/s, P < 0.03), as well as lower Emav and Emav/Amav values, (8.4 versus 10 cm/s and 0.82 versus 1.15, respectively, P < 0.001 for both cases). In the group of hypertensives, a univariate analysis revealed that c-f PWV was negatively associated with Emav (r = -0.305, P = 0.005), as well as with Emav/Amav ratio (r = -0.437, P < 0.001). Moreover, a multivariate analysis showed that the TDI-derived Emav/Amav ratio was significantly associated with age (P = 0.001), relative wall thickness (P = 0.006) and c-f PWV (P = 0.03), while the conventional Doppler-derived E/A ratio was significantly associated only with age (P = 0.001). CONCLUSIONS: TDI-detected LV diastolic dysfunction is accompanied by increased aortic stiffness in newly diagnosed essential hypertension, suggesting that there may be a common pathophysiological pathway linking these two entities.

Adult↗
PubMed2004

Combined effects of smoking and hypercholesterolemia on inflammatory process, thrombosis/fibrinolysis system, and forearm hyperemic response.

The combined effects of smoking and hypercholesterolemia on the inflammatory process, the thrombosis/fibrinolysis system, and forearm hyperemic response were investigated. It was shown that smokers with hypercholesterolemia (n = 25) had a reduced and delayed forearm hyperemic response compared with healthy smokers (n = 24), patients with hypercholesterolemia (n = 26), and healthy controls (n = 75; p <0.01 for all). This phenomenon was associated with a respective increase in the inflammatory process and changes in the thrombosis/fibrinolysis system.

Adult↗
PubMed2004

Effects of smoking on nitric oxide synthesis in epicardial normal and atheromatous coronary arteries.

The effects of an intracoronary infusion of N(G)-monomethyl-L-arginine (LNMMA) followed by intracoronary administration of nitroglycerin in non-stenotic proximal and distal coronary segments were studied in 11 patients with coronary artery disease and in 19 subjects with "normal arteriograms". In normal subjects, LNMMA induced significant constriction (p<0.01) of proximal and distal vessels in non-smokers and smokers. In normal non-smokers, the reduction in coronary luminal diameter of proximal segments was significantly greater compared to normal smokers (p<0.05). In patients with coronary artery disease, LNMMA induced significant constriction of proximal and distal vessels in smokers, and only distal constriction in non-smokers (p<0.01). The reduction in coronary luminal diameter of the distal segments in normal smokers, and in both groups in patients with coronary artery disease was significantly greater compared with proximal segments (p<0.05). Therefore, the difference in vasomotor response to LNMMA in relation to smoking is localised to the proximal coronary segments.

Adult↗
PubMed2004

Endothelial function and proinflammatory cytokines in patients with ischemic heart disease and dilated cardiomyopathy.

BACKGROUND: Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are important mediators of immune response, associated with endothelial dysfunction in patients with coronary artery disease (CAD) or heart failure. We compared endothelial function and levels of IL-6 and TNF-alpha between patients with ischemic heart failure, dilated cardiomyopathy, CAD and healthy controls. METHODS: The population consisted of 20 patients with dilated cardiomyopathy, 48 patients with ischemic cardiomyopathy, 26 patients with CAD and normal left ventricle function and 14 healthy controls. Forearm blood flow was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate were considered as indexes of endothelium-dependent and endothelium-independent dilation, respectively. RESULTS: Levels of IL-6 were significantly higher in ischemic cardiomyopathy compared to CAD patients (P<0.05) or controls (P<0.05) and in patients with dilated cardiomyopathy compared to controls (P<0.05). TNF-alpha levels were significantly higher in both groups with ischemic or dilated cardiomyopathy compared to CAD (P<0.05) or controls (P<0.05). RH% was significantly lower in ischemic and dilated cardiomyopathy compared to CAD (P<0.05) or controls (P<0.001) and higher in dilated than ischemic cardiomyopathy (P<0.05). CONCLUSIONS: Impaired endothelial function and increased inflammatory process were found in both types of heart failure. A greater endothelial dysfunction was observed in patients with ischemic heart failure compared to those with dilated cardiomyopathy, implying that the underlying atherosclerosis may participate in this process.

Adult↗
PubMed2004

Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study.

BACKGROUND: Individuals with the metabolic syndrome (MS) are at high risk for coronary heart disease and may benefit from aggressive lifestyle modification. In this study, we evaluated the effect of leisure time physical activity (PA) and the Mediterranean diet (MD) on the prevalence of the MS. METHODS: The ATTICA study is a health and nutritional survey. On the basis of a multistage, random sampling, 1128 men and 1154 women (>18 years old) without any evidence of cardiovascular disease or diabetes mellitus were enrolled from the greater Athens area during 2001 to 2002. The MS was defined according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. PA was determined from a detailed questionnaire and graded according to the kcal/min expanded. MD was assessed through a validated nutrient questionnaire. RESULTS: The overall prevalence of the MS was 453 of 2282 subjects (19.8%). Of these subjects, 284 (25.2%) were men and 169 (14.6%) were women (P <.001). The prevalence of the MS increased accordingly to age (P for trend <.001). With multiple logistic regression analysis, the odds ratio of having the MS when the participant consumed the MD was 0.81 (95% CI, 0.68-0.976), and when even a little to moderate PA (<7 kcal/min)was reported, the odds ratio was 0.75 (95% CI, 0.65-0.86). The higher levels of inflammation and coagulation markers among participants with MS did not explain much of the aforementioned effect of lifestyle modification. CONCLUSION: MS is common in Greece and is becoming even more common in the middle-aged population. The suggested therapeutic lifestyle approach may contribute to the reduction of the prevalence of the MS, beyond the levels of several lipid, inflammation, and coagulation markers.

Adult↗
PubMed2003

Significance of exercise-induced ST changes in leads aVR, V5, and V1. Discrimination of patients with single- or multivessel coronary artery disease.

BACKGROUND: It is known that exercise-induced ST-segment elevation in lead V1 (V1-E) detects left anterior descending (LAD) stenosis. It was also postulated that ST elevation in aVR and simultaneous ST depression in V5 (aVR-E + V5-D) is a marker of ischemia due to significant stenosis of the LAD in patients with single-vessel disease. HYPOTHESIS: This study was undertaken to investigate the significance of the concomitant appearance of both electrocardiographic (ECG) ischemic markers, and of each of them alone during exercise, to detect either LAD stenosis as single-vessel coronary artery disease (CAD), or multivessel CAD involving LAD stenosis. METHODS: A total of 196 consecutive patients (152 men and 44 women, mean age 54 +/- 7 years) with at least one of these ECG markers, who underwent treadmill exercise testing with the Bruce protocol and coronary arteriography, were studied. RESULTS: Patients were divided into three groups. In Group A (83 patients with V1-E + aVR-E & V5-D), 93% of patients with single-vessel disease had significant LAD stenosis (p<0.001), whereas 75% of patients with double-vessel disease had significant stenoses of the LAD and the left circumflex (LCx) coronary arteries (p<0.01). In Group B (97 patients with aVR-E & V5-D but without V1-E), 43% of patients with single-vessel disease had significant LAD stenosis (p<0.08), whereas 85% of patients with double-vessel disease had significant stenoses of the LAD and the right coronary artery (RCA) (p<0.01). In Group C (16 patients with only V1-E), 60% of patients with single-vessel disease had significant LAD stenosis (p<0.05), whereas 75% of patients with double-vessel disease had significant LAD and LCx stenoses (p<0.05). CONCLUSIONS: The concomitant appearance of exercise-induced ST elevation in lead V1, ST elevation in lead aVR, and ST depression in lead V5, as well as the isolated appearance of ST elevation in lead V1 detect significant LAD stenosis as single-vessel disease, or significant stenoses of LAD and LCx arteries in patients with double-vessel disease, whereas the appearance of ST elevation in aVR & ST depression in V5 but without ST elevation in V1 correlates strongly with significant LAD and RCA stenoses and usually indicates double-vessel disease.

Adult↗