Frangiskos I. Parthenakis

Early Effects of Simvastatin versus Atorvastatin on Oxidative Stress and Proinflammatory Cytokines in Hyperlipidemic Subjects

The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n=132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p=0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p=0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p=0.014 and p=0.001, respectively). TNF-a demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p=0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.

Androgen Deficiency and Endothelial Dysfunction in Men with End-Stage Kidney Disease Receiving Maintenance Hemodialysis

Objectives and Methods: Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testoster- one levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). Results: Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = –0.44 and r = –0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = –0.32, p < 0.003, and r = –0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. Conclusion: The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficiency.

Restrictive filling pattern is associated with increased humoral activation and impaired exercise capacity in dilated cardiomyopathy.

Although heart failure (HF) is characterized by increased proinflammatory cytokines, natriuretic peptide levels and impaired exercise capacity, the effect of concomitant diastolic dysfunction on those parameters has not been adequately studied.

Alteration of proximal aorta biophysical properties in patients with end stage renal disease

Objective: To present a novel, non-invasive echocardiographic application to assess the structural and functional properties of the complex composition of the proximal aorta in patients with end stage renal disease (ESRD). Methods: 71 haemodialysis patients (mean (SD) age 61.3 (9.3) years, dialysis duration 79.2 (51.6) months) and 62 age matched controls were studied. From the suprasternal view, the distance between ascending and descending aorta was measured with two dimensional ultrasound. The aortic flow wave transit time was measured with pulsed wave Doppler. M mode echocardiography, with simultaneous blood pressure estimates, was used to assess the diameters of the aortic annulus and of the ascending aorta. Pulse pressure, pulse wave velocity (PWV), pressure strain elastic modulus, characteristic impedance, and β index were calculated. Results: Patients had increased pulse pressure (68.0 (7.2) v 51.4 (5.0) mm Hg, p < 0.001), PWV (6.1 (1.1) v 3.9 (0.6) m/s, p < 0.001), characteristic impedance (174 (58) v 111 (31) m/s·cm2, p < 0.001), pressure strain elastic modulus (872 (254) v 541 (140) mm Hg, p < 0.001), and β index (8.9 (3.4) v 5.5 (1.4), p < 0.001) compared with controls. In patients PWV was correlated with age and time on haemodialysis (r  =  0.44, p < 0.001, and r  =  0.51, p < 0.001, respectively). Conclusion: A novel application of duplex ultrasound of the proximal aorta showed that patients with ESRD have impaired proximal aortic function compared with controls. The data indicate that these non-invasive measurements can be used to describe status and change in aortic biophysical properties and may be used as a marker for cardiovascular disease risk.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia and troponin release. Myocarditis or the "hot phase" of the disease?

A 21-year-old man was admitted due to sustained palpitations and an episode of presyncope. Twelve-lead resting ECG revealed sustained ventricular tachycardia with an average rate of 220 bpm, LBBB configuration and superior axis (Fig. 1A). The patient was hemodynamically stable with arterial blood pressure 110/80 mm Hg and was converted to sinus rhythm (SR) with bolus infusion of 150 mg amiodarone over 10 min. After conversion to SR, a new 12-lead ECG exhibited inverted T waves in leads V1 to V4 and frequent ventricular extrasystoles of LBBB type and axis similar to that of VT (Fig. 1B). Detailed history revealed that at the age of 15, the patient had suffered similar episodes of sustained palpitations and presyncope, especially after exercise. Cardiac evaluation at that time demonstrated inverted T waves in leads V1 and V2 on 12-lead ECG but no functional/ structural alterations on two-dimensional echocardiography were reported. Therewas no family history of cardiac disease or sudden cardiac death. Furthermore, he denied any recent infection. The patient underwent two-dimensional echocardiography that revealed dilatation of the right ventricle (RV outflow tract enddiastolic diameter was 36 mm and 41 mm, on parasternal long axis

Differential effect of telmisartan and amlodipine on monocyte chemoattractant protein-1 and peroxisome proliferator-activated receptor-gamma gene expression in peripheral monocytes in patients with essential hypertension.

Monocyte chemoattractant protein-1 (MCP-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) play a significant role in monocyte activation, vascular inflammation, and atherogenesis. Angiotensin receptor blockers and calcium channel blockers are antihypertensive drugs with established efficacy and a favorable safety profile. We investigated the effect of telmisartan--an angiotensin receptor blocker with PPAR-γ agonist activity--and amlodipine on the activation state of peripheral blood monocytes with respect to MCP-1 and PPAR-γ gene expression in hypertensives. We recruited 31 previously untreated patients with essential hypertension who were randomly assigned to receive treatment with telmisartan (n = 16) or amlodipine (n = 15). Blood samples were taken before and 3 months after therapy initiation. Mononuclear cells were isolated and mRNAs of MCP-1 and PPAR-γ were estimated by real-time quantitative reverse transcription-polymerase chain reaction each time. The 2 treatments decreased all blood pressure components significantly (p <0.001). In contrast, in the amlodipine group, MCP-1 gene expression was significantly downregulated after treatment with telmisartan (from 21.4 ± 20.5 to 8.1 ± 6.5, p = 0.009), whereas the amlodipine group did not show any significant change (12.5 ± 8.5 vs 17.6 ± 16.4, p = NS). In addition, PPAR-γ mRNA levels showed a significant increase in telmisartan-treated patients (from 20 ± 18.5 to 42.6 ± 36, p = 0.006) and no significant alterations in the amlodipine group (from 29.6 ± 42.5 to 24.2 ± 27.7, p = NS). In conclusion, treatment with telmisartan results in a significant attenuation of MCP-1 gene expression and an increase of PPAR-γ gene expression in peripheral monocytes in patients with essential hypertension. Our findings may provide new insights into the cardiovascular protection of telmisartan in hypertensives.

Diagnosing acute aortic syndromes: The role of specific biochemical markers

Acute aortic syndromes (AAS) remain one of the most challenging medical emergencies. Making a prompt and accurate diagnosis is a race against time, where delay may be disastrous for the patients life. Prompt and accurate diagnosis using imaging modalities has been available for many years, but the major concern is how the clinicians suspicion should be aroused concerning the possibility of an acute aortic syndrome, especially in cases of atypical clinical presentation and/or poor signs during clinical examination. Since the first case report publication in 1995, novel biochemical markers have been used for the rapid diagnosis of AAS, such as smooth muscle myosin heavy chains, serum soluble elastin fragments, and d-dimers, with the latter being the most widely used in clinical trials. Despite their potential, all these substances need to be re-evaluated in large randomized trials before they can be included as biomarkers of high sensitivity and specificity in clinical practice.

Isolated Left Ventricular Apical Hypoplasia: A Newly Recognized Unclassified Cardiomyopathy

We describe two relatively asymptomatic cases diagnosed with the newly recognized unclassified cardiomyopathy, isolated left ventricular apical hypoplasia. The disease has been described mainly in cardiac magnetic resonance, whereas this study presents the echocardiographic characteristics of this new cardiomyopathy.

NT‐proBNP response to dobutamine stress echocardiography predicts left ventricular contractile reserve in dilated cardiomyopathy

Brain natriuretic peptide (BNP) and left ventricular (LV) inotropic reserve are major prognostic indexes in heart failure (HF).

Altered proximal aortic stiffness and endothelin plasma levels in diabetic patients with end-stage renal disease.

Peripheral artery stiffness is altered in diabetic patients with end-stage renal disease (ESRD), whereas few data exist to confirm this trend for proximal aortic stiffness. The pulse wave velocity of the proximal aorta (PWVr) and of the carotid-to-femoral aortic segment (PWVcf) were determined by ultrasound imaging in 160 patients with ESRD (70 diabetic) and in 160 matched control subjects. Also, plasma levels of endothelin, homocysteine, and high-sensitivity C-reactive protein were determined in both groups. Patients with ESRD had increased pulse pressure, left ventricular (LV) end-diastolic diameter, LV mass index, PWVr, and PWVcf compared with control subjects (p < 0.05). Diabetic patients had increased LV mass index, PWVr, and PWVcf compared with nondiabetic patients with ESRD (p < 0.05). Endothelin levels exhibited a strong relation with PWVr (r = 0.32, p < 0.001) and PWVcf (r = 0.33, p < 0.001) measurements in ESRD patients. Multivariate linear regression analysis revealed that age, diabetes, and plasma levels of endothelin were major determinants of increased PWVr measurements in the total ESRD population. After adjustment for age, body surface area, time on dialysis, systolic blood pressure, history of hypertension, and plasma endothelin levels, diabetes was an independent factor associated with PWVr in ESRD subjects. Diabetic patients with ESRD had significantly increased proximal aortic stiffness and significantly altered plasma levels of endothelin as compared with the nondiabetic.