Harisios Boudoulas

Effect of static magnetic field exposure of up to 8 Tesla on sequential human vital sign measurements

To determine if increasing static magnetic field strength exposures up to 8 Tesla (T) affect vital signs or electrocardiograms (ECGs) in normal human volunteers.

Etiology of valvular heart disease

The etiology of valvular heart diseases (VHD) has changed in the last 50 years in the industrialized countries. A significant reduction in the incidence of rheumatic fever and its sequelae, increase in life expectancy, recognition of new causes of VHD and advancement in technology are responsible for the metamorphosis of the etiology of VHD. Heritable disorders of connective tissue (marfan syndrome, Ehlers–Danlos syndrome, adult polycystic kidney disease, floppy mitral valve/mitral valve prolapse); congenital heart disease (bicuspid aortic valve); inflammatory/immunologic disorders (rheumatic fever, AIDS, Kawasaki disease, syphilis, seronegative spondyloarthropathies, systemic lupus erythematosus, antiphospholipid syndrome); endocardial disorders (nonbacteremic thrombotic endocarditis, infective endocarditis, endomyocardial fibroelastosis); myocardial dysfunction (ischemic heart disease, dilated cardiomyopathy, hypertrophic cardiomyopathy); diseases and disorders of other organs (chronic renal failure, carcinoid heart disease); aging (calcific aortic stenosis, mitral annular calcification); postinterventional valvular disease; drugs and physical agents are all clinical entities associated with VHD. It should be emphasized that VHDs still constitute a major health problem which will increase with the aging population.

Cardiovascular Effects of Type 1 Diabetes Mellitus in Children

Previous studies have shown that type 1 diabetes mellitus (DM) is associated with cardiovascular abnormalities. Early detection and treatment of these abnormalities may help to prevent the natural progression of the disease. The present study was undertaken to define early cardiovascular abnormalities in children with type 1 DM. Simultaneous evaluation of multiple cardiovascular parameters was performed in 14 children with type 1 DM and 14 age- and gender-matched normal subjects. Measurements of carotid artery intima-media thickness (cIMT, echocardiography), carotid and aortic (ascending and abdominal) distensibility (echocardiography, brachial artery blood pressure), aortic pulse wave velocity (carotid to femoral artery, Doppler), and left ventricular dimensions, mass, and function (echocardiography) were performed. Diabetic children demonstrated a greater cIMT (0.36 ±0.04 mm vs 0.31 ±0.03 mm, p=0.002) and decreased carotid artery distensibility (4.4 ±1.6 cm2·dynes-1·10-6 vs 6.0 ±1.9 cm2·dynes-1·10-6, p<0.01) compared to control. Aortic pulse wave velocity was increased in DM (6.70 ±0.39 vs 6.30 ±0.31, p=0.02) compared to control. Left ventricular diameters, mass, and systolic and diastolic function did not differ between the 2 groups. Simultaneous assessment of multiple cardiovascular parameters in children with type 1 DM revealed impaired carotid artery structure and function, and decreased elastic properties of the aorta, before demonstrable changes in left ventricular structure and function could be detected.

The role of red blood cells in the progression and instability of atherosclerotic plaque

This review attempts to present a focused summary of selected areas of the rapidly growing knowledge regarding the red blood cells role in atherosclerotic plaque progression and instability. A summary of the characteristics of the erythrocyte membranes is provided, followed by a brief review of the in vitro and in vivo work that has helped clarify their role in atherosclerosis. Mechanisms by which erythrocytes enter the atherosclerotic plaque and contribute to its progression and instability are presented. Finally, some elements that may be clinically important regarding erythrocytes in coronary artery disease are discussed.

Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3‐year follow‐up study

Eur J Clin Invest 2010; 40 (4): 288–293

Effects of exercise training on the severity and composition of atherosclerotic plaque in apoE-deficient mice.

Aim: To investigate the effects of exercise on atherosclerotic plaque composition, the concentration of matrix metalloproteinases (MMPs) in the atherosclerotic plaque and the systemic circulation. Methods: Ninety apolipoprotein E-deficient (apoE–/–) mice (45 male) were randomized to the following groups (n = 15 each): control male/female; sedentary male/female; exercise male/female. Mice were kept on a 16-week high-fat diet. Subsequently, the control groups were sacrificed, while the rest of the animals were placed on a normal diet for 6 more weeks. During the latter period, the exercise groups were trained daily on treadmill. At the end of the study, mice were euthanized, and blood samples as well as aortic root specimens were obtained. Results: Compared to control and sedentary animals, exercise training reduced atherosclerotic plaques (–30%; p < 0.01) and increased elastin and collagen content in both genders (p < 0.05). Body weight or lipid profile did not change significantly. Decreased macrophages and MMP-9 as well as increased tissue inhibitor of metalloproteinases 1 (TIMP-1) levels were observed in the atherosclerotic plaques of the exercise-treated groups (p < 0.05). Plasma concentrations of MMP-9 decreased, while plasma TIMP-1 levels increased in the exercise compared to control and sedentary groups (p < 0.05). Conclusions: Exercise training had a favorable effect on the size and composition of the atherosclerotic plaque in apoE–/– mice, associated with suppressed MMP activity.

Interleukin-8 is increased in the membrane of circulating erythrocytes in patients with acute coronary syndrome

AIMSnStudies have shown that erythrocyte membranes are present within necrotic cores in atherosclerotic plaques, and that circulating erythrocytes in patients with acute coronary syndrome (ACS) have increased total cholesterol content (CEM). Interleukin-8 (IL-8) binds to erythrocytes and during intraplaque haemorrhage it is released into the plaque and thus may contribute to inflammatory cascade and atherosclerotic plaque instability. The present study was undertaken to test the hypothesis that erythrocyte membrane IL-8 is elevated in patients with ACS compared with those with chronic stable angina (CSA).nnnMETHODS AND RESULTSnConsecutive patients who presented with CSA (n = 120, 92 men, 62 +/- 9 years), ACS (n = 118, 90 men, 62 +/- 10 years) or with chest pain who had normal coronary arteries (n = 36, 26 men, 60 +/- 7 years), were studied prospectively. IL-8 concentrations in erythrocyte membranes (rIL-8) and in plasma (pIL-8), C-reactive protein (CRP) and CEM were measured. rIL-8 levels [mean +/- 1 SD (standard deviation)] were higher in ACS (102.9 +/- 70.1 pg/mL) compared with CSA (44.7 +/- 22.8 pg/mL) (P < 0.001). No difference in pIL-8 levels between the two coronary artery disease groups was observed (P = 0.280). Serum CRP levels were correlated with rIL-8 levels (r = 0.294, P < 0.001); no association was found between CRP and pIL-8 levels (r = 0.025, P = 0.706). Further, rIL-8 had an independent association with ACS, when CRP and CEM were taken into consideration.nnnCONCLUSIONnThis study shows for the first time that rIL-8 content was significantly higher in ACS, compared with CSA. These findings endorse results from our previous studies suggesting that erythrocytes may play an important role in the development of unstable atherosclerotic plaque.

Associations Between Collagen Synthesis and Degradation and Aortic Function in Arterial Hypertension

BACKGROUNDnStudies have suggested that collagen accumulation in the aortic wall may contribute to the stiff aorta in arterial hypertension. However, data in human hypertension are limited. In this investigation, relations between markers of collagen metabolism and aortic function in patients with arterial hypertension were evaluated.nnnMETHODSnWe studied 72 hypertensive patients (age 53 +/- 5 years) and 27 age- and gender-matched normotensive individuals. Elastic properties of the aorta were assessed by aortic pulse wave velocity (carotid-to-femoral pulse wave velocity (PWVc-f)). Free amino-terminal propeptides of precollagen type I (PINP, reflecting collagen I synthesis), serum telopeptides of collagen type I (CITP, an index of collagen I degradation), free amino-terminal propeptides on precollagen type III (PIIINP, reflecting collagen III metabolism), prometalloproteinase-1 (proMMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined by commercially available immunoassays.nnnRESULTSnPatients with arterial hypertension had greater PWVc-f (P = 0.01); and higher levels of PINP/CITP compared to control (P = 0.04). PWVc-f was significantly associated with PINP/CITP ratio (analysis of variance (ANOVA), P = 0.03). Hypertensive patients had significantly higher levels of proMMP-1/TIMP-1 (P = 0.04); PWVc-f was significantly associated with proMMP-1 (ANOVA, P = 0.03) and proMMP-1/TIMP-1 (ANOVA, P = 0.04). Associations between PWVc-f and proMMP-1 and between PWVc-f and PINP/CITP ratio remained significant after adjustment for PWVc-f confounders and antihypertensive treatment.nnnCONCLUSIONSnAlterations in collagen turnover that favor collagen type I synthesis; as well as proMMP-1 expression are related to increased aortic stiffness in treated hypertensive individuals without left ventricular (LV) hypertrophy.

Relationship between plasma osteopontin and oxidative stress in patients with coronary artery disease

Background: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. Objectives: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). Methods/results: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 ± 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that ln-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R2 = 0.278, p = 0.0004 and β regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 ± 36.2 ng/ml versus 56.1 ± 30.9 ng/ml, p = 0.02 and 2.5 ± 0.5 μM versus 2.0 ± 0.5 μM, p = 0.002, respectively). Conclusions: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis.

Factors Determining Left Atrial Kinetic Energy in Patients with Chronic Mitral Valve Disease

Background:Increased left atrial (LA) work is a major contributornto LA fatigue, LA failure and atrial fibrillation in patientsnwith mitral stenosis (MS) and mitral valvular regurgitationn(MVR). The present study was undertaken to define factorsnthat determine LA work in patients with chronic mitral valvendisease.nPatients and Methods: Peak left atrial kinetic energy (LAKE)nwas used as an index of LA work in 14 patients with MS, 14 withnMVR, and 19 normal subjects matched for age and gender withnMS and MVR patients. LA stroke volume and ejection fractionnwere measured from the biplane area-length method usingnecho techniques. Peak LAKE was obtained from the formula 1/2nmv2, where m = LA stroke volume x 1.06 (blood’s specific gravity)nand v = transmitral Doppler A-wave velocity.Results: Stepwise regression analysis of ten clinical and echocardiographicnparameters demonstrated that in MS, mitral valvenarea (r2 = 0.43) and LA maximal volume (r2 = 0.62), in MVR, onlynLA maximal volume (r2 = 0.42) contributed independently tonLAKE. LAKE was greater in MS and MVR compared to control subjectsnwhile LA ejection fraction was similar in all groups.Conclusions: It is concluded that LA work is markedly increasednin patients with chronic mitral valve disease. Increased LAnwork in chronic mitral valve disease may contribute to LA fatigue,nLA failure, and atrial fibrillation.Hintergrund: Eine erhöhte linksatriale Arbeit ist der Hauptfaktor,nder zur Insuffizienz des linken Vorhofs und Vorhofflimmernnbei Patienten mit Mitralstenose und Mitralinsuffizienznführt. Die Studie wurde durchgeführt, um Determinanten dernlinksatrialen Arbeit bei Patienten mit chronischer Mitralklappenerkrankungnzu identifizieren.Patienten und Methoden: Die maximale linksatriale kinetischenEnergie wurde als Index für die linksatriale Arbeit bei 14 Patientennmit Mitralstenose, 14 Patienten mit Mitralklappeninsuffizienznund 19 gesunden Kontrollpersonen für Alter und Geschlechtnohne Mitralstenose und ohne Mitralklappeninsuffizienz verwandt.nDas LA Schlagvolumen und die Ejektionsfraktion des linkennVorhofs wurden nach der biplanen Flächen-Längen-Methodenmittels Echokardiographie bestimmt. Die linksatriale kinetischenEnergie wurde nach folgender Formel berechnet: 1/2 m x v2, m = linkes Vorhofvolumen x 1,06 (spezifisches Gewicht desnBlutes), v = transmitrale Doppler A-Wellen-Geschwindigkeit.Ergebnisse: Die stufenweise Regressionsanalyse für zehn klinischenund echokardiographische Echoparameter demonstrierte,ndass bei Mitralstenose die Mitralklappenöffnungsflächena2 X 0,43) und das maximale linksatriale Volumen (an0,62) und bei Mitralklappeninsuffizienz nur das linksatrialenVolumen (a2 = 0,42) als unabhängige Variablen zur linksatrialennkinetischen Arbeit bestehen. Die linksatrialen kinetischenArbeit war bei Mitralstenose und Mitralinsuffizienz größer alsnbei Kontrollpersonen während die linksatriale Ejektionsfrakionnin allen Gruppen ähnlich groß war.Schlussfolgerung: Es kann davon ausgegangen werden, dassndie linksatriale Arbeit für Patienten mit chronischen Mitralklappenerkrankungnwesentlich erhöht ist. Die erhöhte linksatrialenbei ei chronischen Mitralklappenerkrankung trägt ZurnInsuffizienz des linken Vorhofs und Vorhofflimmern bei.