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Biomedical subjects

John Lekakis

Publications and source records attributed to John Lekakis.

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

Myocardial ischemia induces interleukin-6 and tissue factor production in patients with coronary artery disease: a dobutamine stress echocardiography study.

BACKGROUND: Interleukin-6 (IL-6) and macrophage colony stimulating factor plasma levels are elevated in acute coronary syndromes. IL-6 has an inherent negative inotropic action and, with tissue factor (TF), mediates the ischemia-reperfusion myocardial injury. We hypothesized that inducible ischemia leads to cytokine production, TF expression, and consequently persistent left ventricular dysfunction after dobutamine stress echocardiography (DSE) in coronary artery disease patients. METHODS AND RESULTS: DSE was performed in 103 patients with angiographically documented coronary artery disease. Blood samples were obtained at rest, at peak stress, and 30 minutes after cessation of dobutamine infusion for measurement of macrophage colony stimulating factor, IL-6, and TF. New or worsening wall motion abnormalities at peak stress and their duration into recovery were noted. Median IL-6 and TF levels were increased at peak stress and at 30 minutes into recovery compared with rest (2.7 and 2.4 versus 2.1 pg/mL for IL-6, 310 and 385 versus 266 pg/mL for TF [P<0.01] in patients with an ischemic response; n=55). Compared with rest, a greater release of IL-6 at peak stress and recovery was observed in patients with increasing number of ischemic segments at peak DSE (2 versus 3 to 4 versus 5 to 6 versus 7 to 8 segments; P=0.03). The time to recovery of wall motion abnormalities was also associated with IL-6 levels at peak stress and recovery (r=0.51 and r=0.39, P<0.05). Macrophage colony stimulating factor levels remained unchanged throughout DSE. CONCLUSIONS: Reversible ischemia induced during DSE increases IL-6 and TF plasma levels. IL-6 is related to the extent of left ventricular dysfunction at peak stress and to persistent LV dysfunction during recovery.

Adult↗
PubMed2005

Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure.

In this randomized, placebo-controlled study, it was found that a 24-hour levosimendan infusion improves echocardiographic markers of abnormal left ventricular diastolic function (transmitral flow patterns and mitral annulus velocities, as assessed by transthoracic pulse-wave Doppler and tissue Doppler imaging, respectively) and reduces substances of excessive neurohormonal activation (plasma B-type natriuretic peptide and interleukin-6) in patients with advanced heart failure. Moreover, levosimendan-treated patients had fewer events and longer progression-free survival during a 5-month follow-up compared with those who received placebo. Thus, levosimendan seems to be effective in improving left ventricular diastolic function and reducing neurohormonal activation in patients with severe heart failure.

Aged↗
PubMed2005

Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina.

BACKGROUND: Oxidative stress contributes to endothelial dysfunction, an important step to the pathogenesis of atherosclerosis and coronary events. Latest studies revealed the existence of pleiotropic and especially antioxidant properties of statins. We sought to examine the effects of pravastatin on lipid peroxidation and endothelial function, independently from lipid-lowering, in patients with unstable angina (UA). METHODS: Thirty-seven patients (males), 64.46+/-9.09 years, suffering from UA enrolled in the study. Patients were not on statin medication before admission and they received after randomization either 40 mg pravastatin daily (group A, n = 20), or placebo (group B, n = 17). Malondialdehyde (MDA) concentration, an index of lipid peroxidation and plaque instability, flow-mediated dilatation (FMD) of the brachial artery and blood lipids were measured on the second day of hospitalization and 10 days later. RESULTS: MDA decreased significantly in both groups (A, p = 0.008; B, p = 0.003). FMD increased significantly in group A (p = 0.007), whereas in group B it did not change. Serum lipids remained unaltered in all three groups. CONCLUSIONS: Pravastatin administration improved FMD within 10 days and this favorable effect occurred before any significant reduction in blood lipids, revealing its pleiotropic effects during the early phase of an acute coronary syndrome. Circulating lipid peroxidation products in patients with UA decreased significantly during the same period independently of endothelial function and pravastatin therapy.

Aged↗
PubMed2005

Increased circulating C-reactive protein and macrophage-colony stimulating factor are complementary predictors of long-term outcome in patients with chronic coronary artery disease.

AIMS: We investigated, in a 6 year follow-up study, whether circulating levels of C-reactive protein (CRP) and macrophage colony stimulating factor (MCSF) have an independent or complementary prognostic value in patients with chronic coronary artery disease (CAD). METHODS AND RESULTS: MCSF and CRP were measured in 100 patients with chronic CAD. Of 95 (33%) patients, 31 who completed the 6 year follow-up presented adverse events (death, myocardial infarction, and unstable angina). In multivariable analysis (including traditional risk factors and medications), the upper tertiles of MCSF (> or =814 pg/mL) and CRP (> or =2.5 mg/L) levels were independently associated with a 13- and 6-fold increase in risk of events, respectively (P<0.01). Patients with combined high CRP and MCSF had a higher absolute risk of events than patients with elevated MCSF or CRP alone (75 vs. 59 vs. 32%, respectively, P<0.01). The mean event-free time was 39, 64, and 52 months in patients with elevated MCSF, elevated CRP, and their combination, respectively. CONCLUSION: In patients with chronic CAD, the prognostic value of MCSF is independent and complementary to that of CRP. MCSF is a particularly useful prognostic marker when CRP levels are low, but also provides additional information concerning risk and time-course of events in patients with elevated CRP.

Adult↗
PubMed2005

Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: should we consider monitoring central blood pressure?

BACKGROUND: Data concerning blood pressure changes, acutely induced by caffeine consumption, are conflicting. Furthermore, limited data exist regarding central hemodynamic response to caffeine ingestion by healthy young subjects. We investigated the acute effect of coffee (80 mg of caffeine) and decaffeinated coffee on peripheral and central hemodynamics, as well as on wave reflections. SUBJECTS: For this purpose, 16 healthy volunteers (eight females and eight males, mean age 29+/-3.2 years) were investigated. METHODS: Repeated measurements were performed at baseline and 30, 60, 90 and 120 min after oral administration of each beverage in a double-blind crossover design. Aortic blood pressures, augmentation index (AI) and pressure (AP) and timing of reflected waves were evaluated by using applanation tonometry and pulse wave analysis. RESULTS: Regular coffee increased central systolic (SBP) and diastolic pressure (DBP) from 96.2+/-9.9 to 101.1+/-10.1 mmHg, p=0.011 and from 72.6+/-9.4 to 76.5+/-9.0 mmHg, p=0.027, respectively, but no change was observed following consumption of decaffeinated coffee. Peripheral systolic blood pressure did not change significantly after the administration of either coffee. Augmentation index increased significantly following regular coffee consumption. The change in AI was significantly higher following regular compared to decaffeinated coffee consumption as shown by analysis of variance (ANOVA) for repeated measures (p=0.001). CONCLUSIONS: These caffeine effects reveal an unfavourable effect on wave reflections and therefore on left ventricular (LV) pulsatile afterload. It also revealed a significant acute effect of caffeine consumption on central hemodynamics which is not observed at peripheral pressures.

Adult↗
PubMed2005

Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease: effects of aspirin treatment.

BACKGROUND: Smoking is associated with endothelial dysfunction. Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets. We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin. METHODS AND RESULTS: Plasma macrophage-colony-stimulating factor (M-CSF) and C-reactive protein (CRP) were measured in 100 patients with chronic CAD, 60 of whom were chronic smokers. Prothrombin fragments 1+2 and urinary 11-dehydro-thromboxane B2 (TXB2) were additionally measured in 60 of 100 patients (30 of whom were smokers) and in 24 healthy controls. Smokers (n = 20) matched for age, myocardial ischemia, and other risk factors with 20 nonsmokers entered a double-blind crossover trial of aspirin (300 mg/d for 3 weeks) versus placebo. Blood and urine measurements were repeated after each treatment. Compared with nonsmokers, smokers had 3-fold median M-CSF (1499 vs 476 pg/mL), 2-fold CRP (1.5 vs 0.8 mg/L), and higher 11-dehydro-TXB 2 (3.6 vs 2.1 ng/mg creatinine, P < .01 for all comparisons). After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB 2 , and prothrombin fragments 1+2 remained higher in smokers compared with nonsmokers despite a significant reduction of these markers by aspirin (P < .05). M-CSF remained related to 11-dehydro-TXB 2 excretion during both treatment phases (P < .01) suggesting that cytokine-mediated thromboxane A 2 production was not altered by aspirin. CONCLUSIONS: Smoking is associated with increased M-CSF, CRP, and platelet activity. Although aspirin treatment reduces the proinflammatory and procoagulant markers in smokers, it does not abolish the proinflammatory effects of smoking in patients with chronic CAD.

Adult↗
PubMed2005

Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease.

BACKGROUND: It has been shown that acute intake of red wine improves endothelial-dependent vasodilatation. It is not clear, however, which constituents of red wine are responsible for this effect. We examined whether acute intake of a red grape polyphenol extract has a positive effect on brachial artery flow-mediated dilatation. METHODS: We recruited 30 male patients with coronary heart disease. They were randomly assigned either to a red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 0.47 mg rutin, 0.42 mg epsilon-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the brachial artery was evaluated after reactive hyperemia induced by cuff obstruction of the forearm, using high-resolution ultasonography. Particularly, flow-mediated dilatation was measured after fasting and 30, 60 and 120 min after the intake of the grape extract or placebo. RESULTS: Intake of the red grape polyphenol extract caused an increase in flow-mediated dilatation, peaking at 60 min, which was significantly higher than the baseline values (4.52+/-1.34 versus 2.6+/-1.5%; P < 0.001) and the corresponding values at 60 min after the intake of placebo (4.52+/-1.34 versus 2.64+/-1.8%, P < 0.001). There was no change in FMD values after the intake of placebo throughout the whole duration of the study. CONCLUSION: Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. These results could probably, at least partly, explain the favorable effects of red wine on the cardiovascular system.

Blood Flow Velocity↗
PubMed2005

Experimental and clinical study of the combined effect of arterial stiffness and heart rate on pulse pressure: differences between central and peripheral arteries.

1. Pulse pressure (PP) constitutes an independent predictor of cardiovascular events and mortality in various populations. Heart rate (HR) and arterial stiffness, in addition to their independent predictive value for cardiovascular complications, seem to interact with regard to the modification of PP. The aim of the present study was to investigate the association of PP with HR under different levels of arterial compliance (AC), revealing their synergistic effects. 2. Seventy-one normotensive and untreated hypertensive subjects were examined. Arterial compliance was measured by the 'area' method, whereas central blood pressures and wave reflections were evaluated using the Sphygmocor system (AtCor Medical, Sydney, NSW, Australia). A hydraulic Windkessel model was also used to evaluate the independent effect of HR and AC on PP. Peripheral PP was associated only with mean pressure and AC. In contrast, central PP was further related to HR (20 b.p.m. decrease in HR resulted in central PP augmentation by 5.6 mmHg) regardless of mean pressure, stroke volume, age and gender. However, this association was statistically significant only for subjects with lower AC (< 1.1 mL/mmHg) and not for those with more compliant arteries. These findings are also in accordance with the experimental data. 3. Aortic PP is affected to a greater degree by HR changes compared with peripheral PP. This response was observed only at high levels of arterial stiffness. 4. The present study provides the first evidence regarding the combined effect of AC and HR on aortic PP, which may lead to larger clinical or epidemiological studies aiming to optimization of drug treatment and to a possible reduction of cardiovascular risk.

Arteries↗
PubMed2004

Aortic elastic properties and left ventricular diastolic function in patients with Adamantiades-Behcet's disease.

OBJECTIVES: We investigated whether Adamantiades-Behcet's disease (ABD) is related to impaired aortic (Ao) elastic properties and left ventricular (LV) function. BACKGROUND: Adamantiades-Behcet's disease is an inflammatory disorder characterized by vasculitis leading to vascular complications and, rarely, myocarditis. METHODS: We studied 82 patients with ABD (age: 40 +/- 12 years) and 24 normal control subjects by echocardiography. Abdominal Ao diameter (mm/m(2)) and Ao elastic indexes--namely, Ao strain (%), distensibility (cm(2) x dyn(-1)x 10(-6)), stiffness index, and pressure strain modulus (Ep) (cm(2) x dyn(-1) x 10(-6))--were calculated from the echocardiographically derived thoracic Ao diameters (mm/m(2)), and the measurement of pulse pressure obtained by cuff sphygmomanometry. Isovolumic relaxation time (IVRT) (ms), deceleration time (DT) (ms), and flow propagation velocity (FPV) (cm/s) were measured by Doppler echocardiography to assess diastolic LV function. The duration of disease and presence of vascular complications were noted. RESULTS: Patients versus control subjects had increased Ao diameters (p < 0.01), lower mean Ao strain and distensibility (4 vs. 9 and 1.4 vs. 3.4, respectively, p < 0.01), higher mean aortic stiffness index and Ep (15.6 vs. 6 and 1.17 vs. 0.44, respectively, p < 0.01), and impaired IVRT and FPV (p < 0.01). Aortic function indexes were related to the duration of disease (p < 0.01) and increased DT (p < 0.01). Deceleration time >190 ms predicted vascular complications with 80% sensitivity and 71% specificity (odds ratio 6.52 [confidence interval: 2.23 to 19.03]). CONCLUSION: Aortic elastic properties and diastolic LV function are impaired in patients with ABD and are interrelated. The link between diastolic LV dysfunction and vascular complications suggests the presence of a common pathophysiologic pathway and provides a possible marker of risk for vascular disease.

Adult↗
PubMed2004

The significance of serum HDL phospholipid levels in angiographically defined coronary artery disease.

OBJECTIVES: To evaluate discriminant serum lipid components associated with the presence and extent of coronary artery disease, with particular emphasis on the role of HDL phospholipids as an important predictor for disease severity. DESIGN AND METHODS: Total serum lipoprotein and phospholipids levels of 157 adult male patients (grouped based on degree of coronary artery occlusion) who underwent coronary angiography were analyzed. RESULTS: Patients showed elevated triglyceride (P < 0.001) and VLDL (P < 0.001) levels whereas a significant reduction was observed at LDL (P < 0.01), HDL (P < 0.01), and HDL-phospholipids (P < 0.001) concentrations. Correlation with disease progression (from one to three occluded vessels) showed significant rise in levels (P < 0.001) and markedly decreased HDL phospholipids (P < 0.001). CONCLUSIONS: Triglyceride levels and HDL phospholipids are better indicators of the presence and extent of coronary artery disease compared to the other lipoproteins studied. Furthermore, the HDL phospholipids/Total Cholesterol ratio is proposed as additional information of the degree of coronary artery occlusion.

Aged↗
PubMed2004

Monitoring of arterial stiffness indices by applanation tonometry and pulse wave analysis: reproducibility at low blood pressures.

OBJECTIVE: Aortic pulse wave analysis (PWA) reveals valuable information related to several hemodynamic characteristics mainly in normotensive and hypertensive patients. The main indices determined by PWA are augmentation index (AI) and reflection time index (RTI), which provide an indirect estimate of arterial stiffness and pulse wave velocity. The objective of the present study was to assess the reproducibility of aortic AI and RTI obtained by an automated and commercially available system (SphygmoCor) applied in patients with low blood pressures where such data are lacking. METHODS: The study population consisted of 19 patients with cardiogenic shock due to acute myocardial infarction who underwent mechanical assistance with intraaortic balloon pump. Aortic pressure waveforms were derived from peripheral waveforms--recorded by applanation tonometry of the radial artery--by applying generalized transfer functions. On every occasion, a well-trained operator performed two measurements with 2 min interval. Multiple pairs of measurements were obtained per patient in order to study a wide range of different hemodynamic conditions. Thus, a total of 91 pairs of measurements were performed and analyzed using Bland-Altman plots. RESULTS: AI and RTI ranged within 30-184% and 10-27%, respectively. Within-observer difference was 0.10 +/- 5.82% for aortic AI and 0.14 +/- 1.2% for RTI. CONCLUSION: Pulse wave analysis and radial artery tonometry can be used to measure AI and RTI with satisfactory reproducibility even in low blood pressures. Ongoing research is required to establish PWA utility in clinical practice especially at patients with low blood pressures.

Aged↗
PubMed2004

Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease.

BACKGROUND: Several studies suggest that red wine is beneficial in coronary artery disease (CAD). Although the long-term effect of moderate red wine consumption on endothelial function is currently under investigation, there is little knowledge about its effect on postprandial endothelial function and haemostatic factors. The aim of the present study was to investigate the postprandial effects of alcohol content and the antioxidants of red wine on endothelial function and fibrinogen levels in CAD patients. METHODS: Fifteen males with angiographically documented CAD were recruited for the study. All volunteers ingested 250 ml of either red wine or de-alcoholized red wine on two different days. Blood samples (for analysis of fibrinogen and blood lipids) were collected and flow-mediated dilatation (FMD) was determined before and 30, 60 and 90 min following consumption of each beverage RESULTS: FMD was higher following the consumption of de-alcoholized red wine [type of wine effect, P=0.05 repeated measures analysis of variance (ANOVA)]. Furthermore, the pattern of the response was different between the two beverages, as FMD increased following the ingestion of de-alcoholized red wine, but it decreased after consumption of regular red wine (type of wine by time interaction effect, P=0.006 repeated measures ANOVA). Fibrinogen concentrations were unaltered CONCLUSIONS: Acute ingestion of red wine without alcohol led to higher FMD than ingestion of regular red wine in CAD patients. The acute effect of red wine on endothelial function may be different than its long-term effect and it could be attributed to its constituents other than alcohol.

Antioxidants↗