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Biomedical subjects

C Stefanadis

Publications and source records attributed to C Stefanadis.

At least 37 records · Page 2Linked to original sources
PubMed2004

Vascular endothelium and inflammatory process, in patients with combined Type 2 diabetes mellitus and coronary atherosclerosis: the effects of vitamin C.

AIMS: Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non-diabetic subjects. METHODS: Thirty-seven patients with DM + CAD, 17 patients with DM without CAD and 21 non-diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium-dependent dilation. RESULTS: Baseline levels of IL-6 and TNF-alpha were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM-1, TNF-alpha and IL-6 in any of the groups. CONCLUSIONS: Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.

Antioxidants↗
PubMed2003

FH-Pyrgos: a novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia.

In a patient with familial hypercholesterolemia (FH), we have identified a new mutation (-45delT) in repeat 3 of the low-density lipoprotein receptor (LDLR) gene promoter. Analysis of a neutral polymorphism in the LDLR mRNA from the patient's white blood cells showed that the expression of one allele was significantly reduced, and cells have only 24% of LDLR activity by binding and uptake of DiI-LDL. Transient transfection studies using a luciferase gene reporter revealed that the -45delT mutation considerably reduces the transcriptional activity of the LDLR promoter and strongly suggest that the mutation is the cause of the FH phenotype.

Adolescent↗
PubMed2003

Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment.

This study was designed to test the hypothesis that plasma concentrations of matrix metallo-proteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P=0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances <1440 dyn s/cm(5) exhibited higher values of MMP-2 (P=0.005) and MMP-9 (P=0.001) than hypertensive patients with systemic vascular resistances >1440 dyn s/cm(5). Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P=0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.

Adult↗
PubMed2003

Effects of L-arginine on flow mediated dilatation induced by atrial pacing in diseased epicardial coronary arteries.

OBJECTIVE: To examine the effects of L-arginine on basal coronary tone and flow mediated dilatation induced by atrial pacing in patients with coronary artery disease and stable angina. DESIGN: Atrial pacing was performed during intracoronary infusions of normal saline and L-arginine (150 micromol/min) in 8 patients with coronary artery disease and stable angina. The luminal diameter of epicardial coronary arteries was assessed by quantitative angiography. RESULTS: L-arginine administration significantly increased the diameter of all the coronary segments and stenoses. During atrial pacing with saline infusion, luminal diameter of the proximal, distal, and stenosis reference segments increased significantly (p < 0.01 versus saline) but stenosis diameter did not change. L-arginine administration did not change the magnitude (NS) of atrial pacing induced dilatation in proximal and distal segments and in coronary stenoses and their reference segments. CONCLUSIONS: Non-stenotic segments of diseased coronary arteries dilate in response to atrial pacing but stenoses do not. L-arginine dilates coronary segments and stenoses but does not increase the magnitude of the response to atrial pacing in proximal and distal segments and in coronary stenoses and their reference segments. These findings provide evidence that the shear stress responsive mechanism is absent at stenoses but present in non-stenotic segments of diseased coronary arteries. They also indicate a relative deficiency of L-arginine, except in the shear response mechanism.

Angina Pectoris↗
PubMed2003

Inflammatory and thrombotic mechanisms in coronary atherosclerosis.

Many molecular and cellular mechanisms link inflammation and haemostatic mechanisms. Inflammation, and perhaps chronic infection, may play important roles in the initiation and progression of atherosclerosis. Atherosclerotic lesions are heavily infiltrated by cellular components associated with inflammation (macrophages and T lymphocytes), and acute plaque rupture is also associated with inflammatory components. Several markers of systemic inflammation may predict future cardiovascular events in apparently healthy subjects as well as in patients with chronic and acute syndromes. There may thus be therapeutic potential in modifying the atherosclerotic, vasomotor, and thrombotic components of ischaemic heart disease.

Arteritis↗
PubMed2002

Microalbuminuria is associated with unfavourable cardiac geometric adaptations in essential hypertensive subjects.

We sought in this study to examine the relationship between microalbuminuria and cardiac geometry since a slight increased urinary albumin excretion (UAE) and increased left ventricular (LV) mass have both been identified as predictors of cardiovascular events in hypertensive subjects. For this purpose, microalbuminuria was determined in three non-consecutive 24-h urine samples as UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects. Echocardiographic classification of patients into LV geometric patterns was based on relative wall thickness values and on gender-specific values for LV mass index (LVMI). The group of patients with microalbuminuria (n = 119) was matched for age, sex, body mass index, smoking status and plasma cholesterol level with the group of patients without microalbuminuria (n = 130). Subjects with microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001), relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P < 0.005). For the pooled population, UAE was positively correlated to LVMI (r = 0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire population, normal LV geometry, concentric LV remodelling, eccentric and concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The prevalence of normal LV geometry was significantly higher in normoalbuminuric compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the prevalence of concentric LV hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001). Multiple regression analysis revealed that concentric LV hypertrophy was significantly associated with increased values of UAE and mean arterial pressure. In conclusion, the higher prevalence of unfavourable LV geometric patterns in hypertensive subjects with microalbuminuria compared with those without microalbuminura, may account for the worse cardiovascular outcomes associated with the presence of an increased UAE in hypertensive subjects.

Adult↗
PubMed2002

The effect of the combination of Mediterranean diet and leisure time physical activity on the risk of developing acute coronary syndromes, in hypertensive subjects.

The World Health Organization reports that the number of hypertensives, worldwide, is estimated to be 600 million people. In addition a considerable proportion of hypertensive subjects remains untreated or uncontrolled. In this work we investigated the combined effect of physical activity and Mediterranean diet on coronary risk, in hypertensives. Thus we randomly selected, from all Greek regions, 848 hospitalised patients (695 males, 58 +/- 10 years old and 153 females, 65 +/- 9 years old) with a first event of coronary heart disease (CHD) and 1078 paired, by sex, age, region controls, without any suspicions for CHD. Physically active were those who reported non-occupational physical activity more than once per week. Subjects 'closer' to the Mediterranean diet were assessed through a special nutrient questionnaire. A total of 418 (49%) of the patients and 303 (28%) of the controls were hypertensive. Of these, 115 (27%) patients and 70 (23%) controls were untreated, 148 (35%)-111 (36%) were uncontrolled and 155 (38%)-122 (41%) were controlled (P-value <0.01). One hundred and sixty-two (19%) of the patients and 265 (25%) of the controls (P < 0.01) were 'closer' to the combination of Mediterranean type of diet and physical activity. The analysis showed that the previous combination is related to a 25% reduction of the coronary risk in controlled hypertensive subjects (OR = 0.75, P < 0.01), a 11% reduction in untreated (OR = 0.89, P < 0.05) and 17% reduction (OR = 0.83, P < 0.05) in uncontrolled, after adjusting for age, sex, educational and financial level and the conventional cardiovascular risk factors. Consequently, the adoption of Mediterranean diet by physically active subjects seems to reduce significantly the coronary risk and prevent, approximately, the one-third of acute CHD, in controlled hypertensive subjects.

Aged↗
PubMed2002

Statin treatment is associated with reduced thermal heterogeneity in human atherosclerotic plaques.

AIMS: Heat released from atherosclerotic plaques as a result of the local inflammatory process, may be measured in vivo by a thermography catheter. Statins seem to have an antiinflammatory effect which results in plaque stabilization. The aim of this study was to investigate the effect of statins on plaque temperature. METHODS AND RESULTS: The study population included 72 patients: 21 with effort angina, 32 with unstable angina and 19 with acute myocardial infarction. In the study group, 37 patients received statins for more than 4 weeks and 35 were not receiving statins. We measured the temperature difference (deltaT) between the atherosclerotic plaque and the proximal vessel wall (background temperature) using a thermography catheter. The statistical analysis showed that the mean value of deltaT was higher in the untreated group compared to the treated-with-statin, group (0.56+/-0.41 vs 0.29+/-0.33 degrees C, P<0.01). Moreover, a progressive increase in deltaT by type of clinical syndrome was observed in both groups (statin group; effort angina: 0.24+/-0.15, unstable angina: 0.26+/-0.26, acute myocardial infarction: 0.40+/-0.28, vs untreated group; effort angina: 0.41+/-0.26, unstable angina: 0.44+/-0.28, acute myocardial infarction: 0.84+/-0.52, P<0.05). Multivariate analysis showed that treatment with statins was an independent factor in temperature variation, after taking into account the effect of the clinical syndrome (P<0.05). CONCLUSIONS: Patients on statin treatment produce less heat from the culprit coronary lesion than those not treated. Thus, statins seem to have a favourable effect on heat release from atherosclerotic plaques, and whether this effect has an impact on plaque stabilization needs to be investigated in future studies.

Arteriosclerosis↗
PubMed2002

Association between exposure to environmental tobacco smoke and the development of acute coronary syndromes: the CARDIO2000 case-control study.

OBJECTIVE: To investigate the association between environmental tobacco smoke (ETS) exposure (at least 30 minutes a day) and the risk of developing acute coronary syndromes (ACS). DESIGN AND SETTING: The CARDIO2000 is a case-control study which was conducted in Greece from 2000 to 2001. Cases included 847 individuals with a first event of ACS and 1078 cardiovascular disease-free controls. Cases and controls were frequency matched on age (within three years of age), sex, and region. MAIN OUTCOME MEASURES: ACS was defined as a diagnosis of first acute myocardial infarction or unstable angina. Main independent variable: Exposure to ETS was measured by self report as follows: after the second day of hospitalisation for the cases, and at the entry for the controls, participants were asked whether they were currently exposed to tobacco smoke from other people (home and/or work) for more than 30 minutes a day. The responses were categorised into three levels: no exposure, occasional exposure (< 3 times per week), and regular exposure. In addition participants were asked how many years they had been exposed. Because these were self reported assessments and prone to bias, the results were compared to reports obtained from subjects' relatives or friends, using the Kendal's tau coefficient that showed high agreement. RESULTS: 731 (86%) of the patients and 605 (56%) of the controls reported current exposure of 30 minutes per day or more to ETS. Among current non-smokers, cases were 47% more likely to report regular exposure to ETS (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.26 to 1.80) compared to controls. Exposure to ETS at work was associated with a greater risk of ACS compared to home exposure (+97% v +33%). The risk of ACS was also raised in active smokers (OR 2.83, 95% CI 2.07 to 3.31) regularly exposed to ETS. CONCLUSIONS: This study supports the hypothesis that exposure to ETS increases the risk of developing ACS. The consistency of these findings with the existing totality of evidence presented in the literature supports the role of ETS in the aetiology of ACS.

Adult↗
PubMed2001

Biochemical changes involved in the mechanism of vasovagal syncope.

Vasovagal syncope elicits one of the most powerful transient vasodilatory responses in humans. Many studies have shown an altered neurohumoral response to tilting in patients with vasovagal syncope. Vasopressin (VP) has been of particular interest, but its exact role remains unclarified, whereas the possible role of the potent vasoactive end products of arachidonic acid metabolism has not yet been addressed. We determined the changes in plasma levels of VP, thromboxane (TXA2), and prostacyclin (PGI2) in 34 syncopal patients undergoing a standardized head-up tilt-table testing protocol and compared these changes between patients with positive and negative test results. Blood samples were collected at baseline, 15 minutes in the head-up position, and at the termination of the tilt test (the induction of syncope or the completion of a negative test). Sixteen patients had a positive test result, whereas 18 completed the test without developing any syncopal symptoms. In the tilt-positive group, VP levels presented a 20-fold increase at the time of syncope when compared with baseline levels (p = 0.0000), without any increase at earlier stages. No change was detected at any stage in the tilt-negative patients. We did not find any difference in the levels of PGI2 at any stage in any group of patients or between the 2 groups. TXA2 levels increased significantly at 15 minutes in the upright position in both tilt-positive and tilt-negative patients. No further increase was noticed at the time of syncope in the tilt-positive group, whereas in patients with a negative test result, there was a tendency to decline at the time of the test's completion. It is concluded that although VP is markedly increased during tilt-induced vasovagal syncope, vasoactive amines such as TXA2 and PGI2 play a minor role in the vasodilatory component of the response.

Adolescent↗
PubMed2001

Therapeutic modification of the L-arginine-eNOS pathway in cardiovascular diseases.

L-Arginine is the substrate for nitric oxide production. Endothelium dysfunction could be attributed to L-arginine deficiency or the presence of L-arginine endogenous inhibitors. This hypothesis leads to the assumption that provision of L-arginine could be the key for endothelial function improvement. Many studies have proven that L-arginine has a beneficial effect on endothelium dependent vasoreactivity, as well as on the interaction between vascular wall, platelets and leucocytes. Therefore, individuals with risk factors for atherosclerosis and patients with coronary artery disease or heart failure, could benefit from therapy with L-arginine.

Animals↗
PubMed2001

Increased temperature of malignant urinary bladder tumors in vivo: the application of a new method based on a catheter technique.

PURPOSE: The aim of this study was to investigate the existence of any thermal difference between malignant tumors and inflammatory benign lesions of the human urinary bladder and to determine whether it correlates with tumor angiogenesis quantification. PATIENTS AND METHODS: A new method, developed in our institute, is introduced to detect temperature in human urinary bladder, in vivo. This method is based on a thermography catheter. We calculated the differences of the temperature of the solid tumor and of a normal area (Delta T) on 20 subjects (mean age, 72.5 years; 95% confidence interval [CI], 68.5 to 76.4). According to the biopsy histology, Eight (40%) patients had benign tumors, and 12 (60%) had malignant tumors. RESULTS: We found significant differences of Delta T between patients with benign and malignant tumor (P <.001). Also, differences were found for the mean values of angiogenesis level between malignant and benign tumors (P =.0261), and a moderated positive correlation was estimated between the degree of angiogenesis and Delta T (P =.02). Based on logistic regression analysis, we found that a 1-degree increase of Delta T triples the odds of a patient having a malignant tumor (odds ratio = 2.91; 95% CI, 1.97 to 7.78; P <.001), adjusted for the degree of angiogenesis (P =.0236) and the grade of tumor (P <.001). A threshold point of Delta T = 0.7 degrees C was determined, with sensitivity 83% and specificity 75%. CONCLUSION: These findings suggest that the calculated difference of temperature between normal tissue and neoplastic area could be a useful criterion in the diagnosis of malignancy in tumors of the human urinary bladder.

Aged↗
PubMed2001

Stent deployment in calcified lesions: can we overcome calcific restraint with high-pressure balloon inflations?

Although significant coronary artery (CA) calcification is believed to affect stent deployment, the exact impact on stent deployment after high-pressure balloon inflations is unknown. Intracoronary intravascular examination (ICUS) was performed in 27 moderate-severe calcified CA lesions before and after stent implantation. In case of unsatisfactory results (in-stent area < 90%, minimal in-stent diameter/maximal in-stent diameter < 0.8), further inflations up to 20 atm guided by ICUS were applied. Initially, stent expansion was adequate in 10 stents (37%) and symmetric in 19 (70%). After inflation at 20 atm, stents with adequate expansion increased to 16 (59%, P = 0.0036), but stents with symmetry decreased to 13 (48%, P = 0.0045). Stent expansion was inversely correlated to the arc of calcium (r = -0.8, P < 0.0001). There were five patients with clinical restenosis at 6 months (18%). Increases in stent lumen area with high-pressure balloon inflations in moderate-severe calcified CA lesions are at the expense of symmetry. This may affect clinical restenosis.

Aged↗
PubMed2001

Thermography of human arterial system by means of new thermography catheters.

In this case report, we present the first clinical application of three thermography catheters for temperature measurements in the coronary arteries, the aorta, and the femoral arteries. The entire procedure was performed successfully without complications. Larger clinical studies are required in order to examine the feasibility for the application of the aortic and the peripheral artery thermography catheters and the clinical significance of temperature measurements in these arteries. Cathet Cardiovasc Intervent 2001;54:51-58.

Aorta↗
PubMed2001

Identification of patients with coronary artery disease by assessing diastolic abnormalities during isometric exercise.

BACKGROUND: Previous clinical studies using invasive and noninvasive methods have shown handgrip-induced diastolic abnormalities in patients with coronary artery disease (CAD). HYPOTHESIS: The study was undertaken to determine the utility of Doppler echo- and pressocardiography during hand-grip in discriminating patients with coronary artery disease (CAD) and in those with normal coronary arteries. METHODS: Both methods were obtained in 96 patients with suspected CAD within 24 h before coronary angiography. An abnormal handgrip-Doppler was defined by an early (E) to late (A) transmitral flow velocities ratio (E/A) < 1 during handgrip and a positive handgrip pressocardiographic test (HAT) by an abnormal increase in the A wave/total excursion or prolongation of the absolute or relative (heart-rate corrected) total relaxation time during isometric exercise. RESULTS: Of the 96 patients studied, 23 had normal coronary arteries and 73 showed CAD. In patients with normal coronary arteries, handgrip-Doppler showed an abnormal average E/A at rest and during handgrip, whereas all variables of HAT were within normal limits. In patients with CAD, handgrip-Doppler showed only a moderate handgrip-induced increase in average A (+ 19%, p < 0.001), whereas HAT showed a significant (p < 0.001) increase in mean A wave/total excursion (+ 60%) and decrease in the relative total relaxation time (- 17%). Furthermore, handgrip-Doppler and HAT were abnormal in 15 of 23 (65%, specificity 35%) and the HAT in 5 of 23 (22%, specificity 78%) patients with normal coronary arteries, as well as in 57 of 73 (sensitivity 78%) and 69 of 73 (95%) patients with CAD. CONCLUSIONS: Our study demonstrates that these noninvasive stress tests can become a useful new diagnostic modality for detecting patients with unknown or suspected CAD.

Adult↗
PubMed2001

Chemokines in patients with ischaemic heart disease and the effect of coronary angioplasty.

Percutaneous coronary transluminal angioplasty (PTCA) may release inflammatory mediators such as chemokines. Monocyte chemoattractant protein-1 (MCP-1) and eotaxin (EOX) are monocyte- and eosinophil-specific chemokines involved in the inflammation and pathogenesis of coronary atherosclerosis. A total of 28 patients undergoing elective PTCA, 20 coronary artery disease (CAD) patients undergoing coronary angiography and 28 healthy controls were studied. In PTCA patients before the procedure, MCP-1 plasma levels (441+/-64 pg/ml) were similar to those of CAD patients (430+/-24 pg/ml), and significantly higher compared with controls (145+/-17 pg/ml, P<0.01). MCP-1 rose significantly after 3 and 6 months following PTCA (696+/-89 and 876+/-86 pg/ml, respectively, P<0.01 vs. before PTCA). EOX plasma levels (155+/-14 pg/ml) were similar to those of CAD patients (157+/-14 pg/ml), but significantly higher compared with controls (83.2+/-10 pg/ml, P<0.05). EOX rose significantly 24 h (273+/-41 pg/ml, P<0.05) but not 3 months after PTCA (160+/-20 and 158+/-19 pg/ml, respectively). These findings indicate that chemokine-induced monocyte- and eosinophil-specific chemoattraction is stimulated in patients with coronary artery disease. MCP-1 levels remain significantly elevated for at least 6 months following elective PTCA, suggesting an inflammatory stimulation.

Angioplasty, Balloon, Coronary↗