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Biomedical subjects

Dennis V Cokkinos

Publications and source records attributed to Dennis V Cokkinos.

At least 19 recordsLinked to original sources
PubMed2007

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking.

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Myocardial viability estimation during the recovery phase of stress echocardiography after acute beta-blocker administration.

BACKGROUND: Myocardial viability assessment in severely dysfunctional segments by dobutamine stress echocardiography (DSE) is less sensitive than nuclear scanning. AIM: To assess the additional value of using the recovery phase of DSE after acute beta-blocker administration for identifying viable myocardium. METHODS: The study included 49 consecutive patients with ejection fraction (LVEF) or=4 viable segments were considered viable. Coronary revascularization followed within 3 months in all patients. Radionuclide evaluation of LVEF was performed before and 12 months after revascularization. RESULTS: Viability with DISA-SPECT was detected in 463 (59%) segments, while 154 (19.7%) segments presented as scar. The number of viable segments increased from 415 (53%) at DSE to 463 (59%) at DSE and recovery, and the number of viable patients increased from 43 to 49 respectively. LVEF improved by >or=5% in 27 patients. Multivariate regression analysis showed that, DSE with recovery phase was the only independent predictor of >or=5% LVEF improvement after revascularization (OR 14.6, CI 1.4-133.7). CONCLUSION: In this study, we demonstrate that the recovery phase of DSE has an increased sensitivity for viability estimation compared to low-high dose DSE.

Adrenergic beta-Antagonists↗
PubMed2006

Thyroid hormone changes cardiomyocyte shape and geometry via ERK signaling pathway: potential therapeutic implications in reversing cardiac remodeling?

It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. This effect may be of therapeutic relevance. Therefore, the present study has investigated potential signaling mechanisms underlying the thyroid hormone action on cardiac myocyte shape and geometry. Neonatal cardiomyocytes were treated with T(3) while untreated cells served as controls. T(3) administration for 48 h significantly increased the ratio of the major to minor cell axis and changed their shape from an almost circular to an elongated form. Cell area and protein synthesis were increased and T(3) treated cells expressed 51% alpha-MHC and 49% beta-MHC as compared to 100% beta-MHC expression in non-treated cells. This response was accompanied by a 1.9-fold increase in phospho-ERK levels early at 8 min which, within 60 min, returned to the levels of the untreated cells. Phospho-JNK levels were significantly reduced within 60 min after T(3) treatment while no changes in the expression of phospho-Akt and phospho-p38 MAPK were found between the T(3) treated and untreated cells. Administration of PD98059 (an inhibitor of ERK signaling) prevented the thyroid hormone induced changes in cardiomyocyte geometry and shape without a significant reduction in cell area and protein synthesis. In conclusion, T(3) induced changes in cardiomyocyte shape and geometry involve the ERK kinase signaling. This response is independent of the effects of T(3) on cell size and protein synthesis.

Animals↗
PubMed2006

Correlation between R wave amplitude, exercise ischemic electrocardiographic indices and thallium-201 imaging defects in patients with known coronary artery disease.

We investigated the relation between R wave amplitude (RWA) and ST depression as well as the presence and extent of reversible ischemia in thallium-201 scanning in patients with known coronary artery disease (CAD) and found that RWA both at rest and during exercise testing (ET) correlates with the magnitude of ST depression in the same leads. Greater ST changes appear on leads with highest RWA. Thus lead selection strongly influences interpretation of ECG ischemic changes during ET in patients with CAD. An electrocardiographic result negative for ischemia in patients with low RWA should prompt the alternative use of echocardiography and scintigraphy.

Adult↗
PubMed2006

Pre-treatment with Irbesartan attenuates left atrial stunning after electrical cardioversion of atrial fibrillation.

AIMS: Left atrial (LA) stunning, the transient impairment of LA function, is responsible for an increased thrombo-embolic risk after cardioversion of atrial fibrillation (AF). Angiotensin receptor blockers (ARBs) attenuate atrial remodelling in AF and could theoretically influence LA stunning. We studied the effect of Irbesartan on LA stunning. METHODS AND RESULTS: We prospectively assigned 50 patients from the outpatient clinic undergoing electrical cardioversion for AF with duration of >4 weeks, into two matched groups: 25 patients were treated with Irbesartan (228+/-93 mg/day) for at least 2 weeks prior to cardioversion (Irbesartan group); 25 patients did not receive ARBs (control group). The groups did not differ concerning age (64+/-13 vs. 63+/-13 years, respectively), AF duration (20+/-18 vs. 20+/-19 weeks), underlying disease, LA diameter (46+/-7 vs. 47+/-9 mm), left ventricular dimensions, and ejection fraction (47.7+/-11.6 vs. 49.7+/-14.5%). We assessed LA appendage emptying velocities (LAAEV) and LA spontaneous echo contrast (LASEC) by transoesophageal echocardiography before and after cardioversion and at 2 weeks, and the A-wave by transthoracic echocardiography after cardioversion, at 2 and at 4 weeks. LA stunning was significantly attenuated in the Irbesartan group. The reduction of LAAEV immediately after cardioversion was significantly less in the Irbesartan group (LAAEV reduction of 9+/-49% from 28+/-9 cm/s before cardioversion to 25+/-13 cm/s immediately afterwards) than in the control group (reduction of 48+/-20% from 34+/-15 cm/s before cardioversion to 16+/-6 cm/s afterwards) (P = 0.048). New or increased LASEC occurred in eight patients (32%) in the Irbesartan vs. 16 patients (64%) in the control group (P = 0.046). CONCLUSION: Irbesartan significantly attenuates LA stunning after electrical cardioversion of AF. Therefore, ARBs may represent an important pharmacological supplementation in patients being prepared for cardioversion.

Adult↗
PubMed2006

Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution.

Central issues in intracoronary infusion (ICI) of bone marrow (BM)-cells to damaged myocardium for improving cardiac function are the cell number that is feasible and safe to be administrated as well as the retention of cells in the target area. Our study addressed these issues in eight patients with chronic ischemic cardiomyopathy undergoing ICI of selected BM-progenitors. We could immunomagnetically isolate 0.8 +/- 0.32 x 10(7) CD133(+) cells and 0.75 +/- 0.24 x 10(7) CD133(-)CD34(+) cells from 310 +/- 40 ml BM. After labeling these cells with (99m)Tc-hexamethylpropylenamineoxime, they were infused into the infarct-related artery without any complication. Scintigraphic images 1 (eight patients) and 24 hours (four patients) after ICI revealed an uptake of 9.2% +/- 3.6 and 6.8% +/- 2.4 of the total infused radioactivity in the infarcted area of the heart, respectively; the remaining activity was distributed mainly to liver and spleen. We conclude that through ICI of CD133(+) and CD133(-)CD34(+) BM-progenitors a significant number of them are preferentially attracted to and retained in the chronic ischemic myocardium.

AC133 Antigen↗
PubMed2006

Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study.

BACKGROUND: It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF. METHODS: 197HF patients (EF <35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo. RESULTS: Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p<0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8+/-5.3 at baseline, 30.7+/-10 at 2 years, p<0.05). CONCLUSIONS: (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome.

Aged↗
PubMed2006

High glucose protects embryonic cardiac cells against simulated ischemia.

In the present study we investigated whether acute glucose administration could be protective against hypoxic stress. H9c2 cells were exposed to either 4.5 mM or 22 mM of glucose for 15,min and then were submitted to simulated ischemia. Cell death was microscopically assessed by combined staining with propidium iodide (PI) and Hoeschst 33358. Intracellular content of glucose was measured by enzymatic analysis. Clucose content of H9c2 cells was 48.24+/- 7.94 micromol/L in the 22 mM vs 23.86+/- 4.8 micromol/L in the 4.5 mM group (p < 0.05). PKCepsilon expression was increased 1.6 fold in the membrane fraction after pretreatment with high glucose (p < 0.05), while was decreased 1.6 fold in the cytosol (p < 0.05). In addition, no difference to PKCdelta translocation was observed after pretreatment with low glucose. After hypoxia, in the 22 mM group, cell death was found to be 17.36+/- 2.66% vs 38.2+/- 5.4% in the 4.5 mM group (p < 0.05). In the presence of iodoacetic acid, a glycolytic inhibitor, cell death was not different between the two groups (23.54+/- 3.2% in 22 mM vs 22.06+/- 5.3% in 4.5 mM). Addition of chelerythrine did not change the protective effect of high glucose (13.4+/- 1.7% cell death in 22 mM vs 27.5+/- 5.5% in 4.5 mM, p < 0.05). In conclusion, short pretreatment with high glucose protects H9c2 cells against hypoxia. Although this protective effect is associated with translocation of PKCepsilon and increased glucose uptake, it was abrogated only by inhibition of glycolysis.

Animals↗
PubMed2006

Postprandial lipaemia in menopausal women with metabolic syndrome.

BACKGROUND: The metabolic syndrome (MetS) is associated with an increased incidence of coronary heart disease (CHD). Postprandial hypertriglyceridaemia is also associated with CHD. The aim of this study was to evaluate the postprandial lipaemia after an oral fat tolerance test (OFTT) in women with MetS. METHODS: OFTT, was given to 21 menopausal women with MetS (defined by the Adult Treatment Panel III) and to 12 healthy menopausal women. Triglyceride (TG) levels were measured before and 2, 4, 6 and 8h after the OFTT. The postprandial response was quantified by the areas under the curve (AUC) of TG levels. MetS women were subdivided according to body mass index (BMI) < or > or =30kg/m(2), and to fasting TG levels < or > or =150mg/dl. RESULTS: The response to the OFTT was significantly higher in the MetS group compared to healthy [AUC(S.D.), in mg/dl/h; 2014(933) versus 732(197), p<0.001]. The subjects with BMI < or > or =30kg/m(2) had similar fasting TG levels [157(60)mg/dl versus 158(67) mg/dl] and AUC [1975(898) versus 2072(1044), respectively]. The MetS women with TG> or =150mg/dl had higher AUC compared to those with TG<150mg/dl [2502(854) versus 1281(441), p=0.002]. In linear regression analysis, where BMI, high-density lipoprotein cholesterol, fasting TG, HOMA-IR and QUICKI were the independent variables, only fasting TGs significantly predicted the AUC (coefficient B=11.866, p=0.008). CONCLUSIONS: The fasting TG concentration is the main determinant of postprandial lipaemia. The obesity state was not an additional determinant for exaggerated postprandial response in MetS women. The abnormal postprandial lipaemia could be added as an important metabolic disturbance to the MetS.

Area Under Curve↗
PubMed2006

Coronary artery ectasias: imaging, functional assessment and clinical implications.

Coronary artery ectasia is a relatively common entity characterized by inappropriate dilatation of the coronary vasculature. The exact mechanism of its development is unknown, but evidence suggests a combination of genetic predisposition, common risk factors for coronary artery disease and abnormal vessel wall metabolism. It frequently coexists with aneurysms elsewhere, mostly involving the aorta. In this review, the flow disturbances that are associated with this condition and the imaging modalities, which can be used for diagnosis and prospective follow-up are described. The prognosis of coronary ectasias is controversial and prospective studies focusing on conservative or invasive strategies to prevent cardiac complications are needed.

Coronary Artery Disease↗
PubMed2006

Magnetic resonance angiography, function and viability evaluation in patients with Kawasaki disease.

OBJECTIVES: We evaluated the ability of magnetic resonance imaging to perform a noninvasive assessment of coronary arteries, function and viability in one examination in a population with Kawasaki disease. BACKGROUND: Magnetic resonance angiography (MRA) can identify coronary abnormalities in patients with Kawasaki disease (KD). Contrast enhanced cardiovascular magnetic resonance (CeCMR) is the current gold standard for scar detection. Steady-state, free precession (SSFP) cine is a reliable technique to evaluate myocardial function and wall motion. METHODS: Twenty patients with KD aged 7-12 yrs, were examined. Coronary MRA was performed using a 1.5 T system with two ECG-triggered pulse sequences. CeCMR images were acquired 15 minutes after the i.v. injection of 0.1 mmol/kg Gd-DTPA using an inversion recovery sequence. SSFP cines were acquired using 6-mm short-axis slices from the atrioventricular ring to the apex. RESULTS: Aneurysms of the coronary arteries were identified in 7 patients and coronary ectasia was present in the remaining 12 patients while 1 patient had both. Transmural anterior-apical scar was detected by ceCMR in two cases, while small inferior necrosis was identified in another 2 cases. Left ventricular function was deteriorated only in the two patients with antero-apical infarction. The presence of myocardial infarction was detected in the territory supplied by the involved coronary artery. CONCLUSION: In Kawasaki disease MRA, SSFP cine and ceCMR are able to perform noninvasive coronary artery evaluation, function and infarct detection in a single study.

Child↗
PubMed2006

Postprandial lipemia in postmenopausal women with high fasting high-density lipoprotein cholesterol.

BACKGROUND: Several groups of patients at high risk for cardiovascular disease have been found to show an exaggerated postprandial hypertriglyceridemia. Postprandial lipemia (PPL) therefore has been implicated as a potential additional risk factor that has been evading us. The purpose of this study was to test the effect of high fasting high-density lipoprotein cholesterol (HDL-C) levels on PPL in postmenopausal females. METHODS: Oral fat tolerance test, as quantified by the areas under the curve (AUC) of triglyceride (TG) levels, was given to 3 groups: normal postmenopausal females (control), postmenopausal females with exceptionally high HDL-C and a familial history of longevity (longevity syndrome), and postmenopausal females that were heterozygotes of familial hypercholesterolemia (hFH) with exceptionally high HDL-C. RESULTS: The PPL was not different between the control and longevity syndrome groups but was significantly higher in the hFH group; AUC (SD), in mg/dl/h; 749 (195), 882 (278) and 1244 (497) respectively, p=0.002. In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 11.779, p < 0.001). CONCLUSIONS: In subjects with longevity syndrome the PPL is similar to controls, which means that high fasting HDL-C has not any beneficial influence on PPL. The fasting TG concentration is the main determinant of PPL. Furthermore, postmenopausal females with hFH have higher TG response postprandially, even in the case of high fasting HDL-C. Whether there is a threshold below or above, where HDL-C becomes a significant independent determinant of PPL is a question to be answered by future research.

Aged↗
PubMed2006

Metabolic syndrome and gender differences in postprandial lipaemia.

BACKGROUND: Postprandial hyperlipidaemia may be a predictor of vascular risk. DESIGN: We evaluated postprandial lipaemia after an oral fat tolerance test (OFTT) in men (n=41) and women (n=21) with metabolic syndrome (MetS). METHODS: Triglyceride (TG) levels were measured before and 2, 4, 6 and 8 h after the fat load. RESULTS: Men showed a greater plasma TG response 8 h after the fat load (284+/-117 versus 224+/-126 mg/dl, P=0.029). Only fasting TG levels significantly predicted the TG area under the curve (AUC) and incremental AUC. CONCLUSIONS: Men had a more pronounced postprandial hypertriglyceridaemia and seem to have delayed TG clearance.

Coronary Disease↗
PubMed2006

Lipid profile of women qualifying for hypolipidaemic treatment.

OBJECTIVE: Death rates from coronary heart disease continue to rise in women despite a marked decrease in men for the past two decades. Our study aimed to evaluate essential risk factors in high-risk adult women. METHODS: Lipid profiles of 547 dyslipidaemic adult women aged 57.5 +/- 10.6 years (mean +/- standard deviation) were evaluated and stratified according to fasting plasma lipid levels. Classification of the cohort was performed based on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels and correlations between TG and HDL-C were estimated. RESULTS: Patients with TG > or =150 mg/dl had lower HDL-C levels compared to those with TG <150 mg/dl (p < 0.001). Patients with HDL-C <40 mg/dl had lower TC levels and higher TG levels compared to those with HDL-C > or =40 mg/dl (p = 0.012 and p < 0.001, respectively). In the cohort and the subgroups an inverse correlation between TG and HDL-C was observed (r = -0.428, slope = -0.048, p < 0.001). CONCLUSIONS: The expected inverse correlation between fasting high TG and low HDL levels was confirmed. The novelty of the study is that this correlation persists even in the case of low fasting TG levels.

Adult↗
PubMed2006

Cholesteryl ester transfer protein gene polymorphisms and severity of coronary stenosis.

PURPOSE: Cholesteryl ester transfer protein (CETP) gene is involved in the reverse cholesterol transport in humans. Thus, it is a candidate for studying the susceptibility to coronary heart disease (CHD). The goal of the current investigation was to determine any association between CETP polymorphisms (I405V and TaqIB), and severity of coronary stenosis, since the extent of coronary artery narrowing has been considered as a primary determinant of survival in CHD patients. METHODS: The severity of coronary stenosis was estimated by Gensini (GS) and Duke Jeopardy (JS) scores in 130 men with documented CHD (mean age 61 +/- 10 yr). Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The allele frequencies for both TaqIB and I405V were found in Hardy-Weinberg equilibrium. Homozygotes for I had lower GS compared with heterozygotes (IV) and homozygotes for V [72(95% CI 51-92) vs. 122(95% CI 88-157) and 136 (95% CI 74-198), P = 0.009, P = 0.010, respectively]. In addition, GS differed between carriers of I and carriers of V allele [86(95% CI 72-101) vs. 128(95% CI 102-154), P = 0.003]. A correlation was found between the GS and I405V polymorphism (r = 0.250, P = 0.005), but not with JS. CONCLUSION: Homozygosity for I405 favours less severe coronary stenosis. Our findings indicate that the I405V polymorphism may have potential importance in screening individuals at high risk for developing CHD, establishing efficient prevention measures, and searching for other risk factors for CHD. However, further prospective investigations in larger populations are required to confirm these findings.

Base Sequence↗
PubMed2005

Enhanced sensitivity of dobutamine stress echocardiography by observing wall motion abnormalities during the recovery phase after acute beta-blocker administration.

Dobutamine stress echocardiography (DSE) has a modest sensitivity for detecting single-vessel coronary artery disease (CAD). This study assessed the additional diagnostic value of new or worsening wall motion abnormalities during recovery after acute administration of beta blockers. The study population consisted of 200 patients (mean 59 +/- 11 years of age, 144 men), who underwent DSE. Images were acquired at rest, low dose, peak dose, and during recovery. Patients received intravenous metoprolol (1 to 5 mg/min). The dose was adjusted to achieve a recovery heart rate within a 10% range of heart rate at rest. Coronary angiography was performed within 2 months. Inducible new wall motion abnormalities were observed in 168 patients (84%) at peak stress. An additional 14 patients (7%) developed new or worsening wall motion abnormalities during recovery. CAD was detected in 182 patients (86 had single-vessel CAD). Sensitivity, specificity, and accuracy of DSE were 88%, 65%, and 73% at peak stress and 97%, 65%, and 74% during recovery. Sensitivity was particularly higher during recovery than during peak stress in patients with single-vessel CAD (98% vs 81%, p <0.001). In conclusion, assessment of wall motion abnormalities during the recovery phase after acute beta blockade improves sensitivity of DSE, particularly in patients with single-vessel CAD.

Adrenergic beta-Antagonists↗
PubMed2005

Activity questionnaires; a useful tool in accessing heart failure patients.

AIM: The aim of the study was to correlate the score derived from Specific Activity Questionnaire (SAQ), Left Ventricular Dysfunction 36 (LVD 36) and the Minnesota Living with Heart Failure Questionnaire (LIhFE) with peak oxygen consumption measured during maximal treadmill exercise spirometry in patients with heart failure. METHODS: We prospectively studied 106 patients, average age 47+/-15.5 (mean+/-SD), with symptomatic heart failure. All were asked to answer the questions of the above mentioned questionnaires. Subsequently patients underwent treadmill exercise spirometry to measure peak oxygen consumption (VO2 peak ml/kg/min) using the Dargie protocol and to derive functional class according to the Weber classification system. RESULTS: SAQ had a very high performance in classifying patients with a VO2 peak <20 ml/kg/min and those with a VO2 peak <14 ml/kg/min. The correlation between VO2 peak achieved and the METs corresponding to the score derived from SAQ according to the given answers was r=0.77 (p<0.01). The correlation between VO2 peak achieved and the score from LVD 36 was r=-0.74 (p<0.01). The correlation between VO2 peak achieved and the score from LIhFE was r=-0.71 (p<0.01). CONCLUSION: The Specific Activity Questionnaire, the Left Ventricular Dysfunction and the Minnesota Living with Heart Failure Questionnaire were used to predict aerobic capacity and all correlated significantly with peak VO2 achieved from exercise spirometry. The above questionnaires represent a useful method to access heart failure patients and are valuable for those unable to undergo a treadmill test.

Adolescent↗