Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan.

Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.

Irritable bowel syndrome in haemodialysis: Prevalence, link with quality of life and depression.

AIM: Health-related quality of life (HRQOL) is decreased in haemodialysis (HD) patients. Irritable bowel syndrome (IBS) is highly prevalent in general population. This study evaluated the prevalence of IBS and its association with HRQOL and depression in HD. METHODS: Sociodemographic and laboratory variables were recorded. Severity of depressive symptoms and HRQOL were assessed by the Beck Depression Inventory (BDI) and Short Form 36 (SF-36), respectively. Diagnosis of IBS was based on Rome II criteria. RESULTS: Among 236 patients 69 (29.2%) had IBS. Patients with IBS had lower SF-36 scores and had higher depressive symptoms than patients without IBS. Presence of IBS was associated with sleep disturbance (odds ratio (OR) = 2.012; P = 0.045), physical component summary score (OR = 0.963, P = 0.029), mental component summary score (OR = 0.962, P = 0.023), BDI score (OR = 1.040, P = 0.021) and albumin (OR = 0.437, P = 0.01). CONCLUSION: IBS is highly prevalent in HD patients. Presence of IBS is closely related with HRQOL and depression.

Reduced left ventricular ejection fraction and sudden cardiac death in patients undergoing revascularization: time to remember the other players of the game.

We strongly believe that relying solely upon ameliorating myocardial ischemia by coronary revascularization may be an inadequate clinical strategy for the prevention of sudden cardiac death (SCD) in dialysis and chronic obstructive pulmonary disease (COPD) patients. More importantly when predicting SCD risk in patients with coronary artery disease one should assess not only left ventricular ejection fraction but also the other clinical parameters such as renal replacement therapy and COPD.

Antibody response following hepatitis B vaccination in dialysis patients: does depression and life quality matter?

Previously, it was demonstrated that antibody production against hepatitis B virus (HBV) surface antigen (anti-HBs) achieved in hemodialysis patients is suboptimal. Decreased health-related quality of life (HRQOL) and depression is common among hemodialysis patients. This study evaluated whether HRQOL and depressive behavior are associated with antibody response against HBV surface antigen in hemodialysis patients. Depressive symptoms and HRQOL were assessed by Beck Depression Inventory (BDI) and Medical Outcomes Study Short Form (SF-36), respectively. Patients were separated into non-seroconversion (anti-HBs antibody titers <10 IU/L) and seroconversion (anti-HBs antibody titers > or =10 IU/L) groups. Among 188 patients, 37 (19.7%) were diagnosed as nonresponsive to vaccination (anti-HBs antibody titers <10 IU/L). Anti-HBs response is positively associated with Physical Component Summary Score of SF-36 (odds ratio: 1.44; P: 0.009) and albumin (odds ratio: 10.615, P: 0.007), and negatively with BDI score (odds ratio: 0.903, P: 0.007). We concluded that HRQOL and depression is closely related with antibody response following HBV vaccine in hemodialysis patients.

Impact of admission glomerular filtration rate on the development of poor myocardial perfusion after primary percutaneous intervention in patients with acute myocardial infarction.

AIMS: We aimed to investigate the impact of admission estimated glomerular filtration rates (eGFR) on the development of poor myocardial perfusion after primary percutaneous coronary intervention (pPCI) in patients presenting with acute ST-segment-elevation myocardial infarction (STEMI). MATERIALS AND METHODS: Study population consisted of 80 patients with STEMI (64 men, mean age=67.5+/-6.6 years) undergoing pPCI. Myocardial perfusion was evaluated by using thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG). Patients were divided into two groups according to TMPG after pPCI. Group 1 and 2 consisted of 40 patients with TMPGs 0-1 and 40 patients with TMPGs 2-3, respectively. GFR was calculated based on the abbreviated Modification of Diet in Renal Disease study equation. RESULTS: Admission serum creatine kinase-MB isoenzyme (CKMB) levels and the percentage of lower eGFR (<60 ml/min/1.73 m2) values of the patients with TMPGs 0-1 were significantly higher than those of the patients with TMPGs 2-3 after primary PCI (P=0.007, P<0.001, respectively). Univariate analysis identified pain-to-balloon time, eGFR lower than 60 ml/min/1.73 m2, peak CKMB, and TIMI flow grade 0/1 as the predictors of poor myocardial perfusion. In multivariate analysis peak CKMB, left ventricular ejection fraction less than 35%, admission TIMI flow grade 0/1, lower eGFR and pain-to-balloon time continued to have statistically significant independent association with poor myocardial perfusion in the model. Adjusted odds ratios were calculated as 12.05 for low eGFR [P=0.005; confidence interval (CI): 2.11-68.70], 8.10 for admission TIMI grade 0/1 (P=0.04; CI: 1.37-47.91), 7.04 for pain-to-balloon time (P<0.001; CI: 2.37-20.90), 6.76 for low left ventricular ejection fraction (P=0.03; CI: 1.12-40.61), and 1.02 for CKMB (P=0.01; CI: 1.00-1.04). CONCLUSION: Decreased GFR on admission in patients with STEMI is independently associated with the risk of poor myocardial perfusion following after primary PCI.

Plasma adiponectin and insulin resistance in new onset hypertension.

OBJECTIVE: The data related to association among hypertension, insulin resistance, and plasma adiponectin concentration is controversial. We aimed to evaluate the relationships among these factors in a young hypertensive group who had no confounding factors. DESIGN AND METHODS: Thirty newly diagnosed and formerly untreated hypertensive males (mean age 23.4 +/- 4.0 yr; body mass index: 24.9 +/- 2.2 kg/m2), and 60 healthy control subjects (mean age 22.5 +/- 3.2 yr; body mass index: 24.6 +/- 1.6 kg/m2) were enrolled. Insulin resistance was calculated by homeostasis model assessment (HOMA). RESULTS: The two groups were similar in terms of age, body mass index, fasting glucose, total cholesterol, HDL and LDL cholesterol, adiponectin, insulin, HOMA, and hsCRP levels. Mean triglyceride levels in hypertensive patients were significantly higher than the controls (p = 0.02). CONCLUSIONS: These results indicate that young, newly diagnosed, uncomplicated patients with hypertension have similar plasma adiponectin levels and insulin sensitivities when compared to healthy controls. We suggest that high blood pressure itself may not be associated with insulin resistance or low adiponectin levels in patients with new onset, uncomplicated hypertension.

Asymptomatic kindred of patients with coronary events have increased peripheral T-cell activities.

T cells are involved in the pathogenesis of atherosclerosis. We aimed to search for any association between the peripheral T-cell activities and atherogenic risk factors in healthy subjects. Fifty male volunteers (age 22.0 +/- 2.4 years) were enrolled. No subject had any chronic disease or was under any drug treatment. Lymphocytes were isolated from heparinized venous blood and the proliferative responses to phytohemagglutinin (PHA) were measured from the amount of radioactive thymidine uptake by the lymphocyte DNA. T-cell activity responses of patients with a family history of coronary events were compared with others. The activity responses of smokers were compared with nonsmokers. Subjects with a positive family history of coronary events had higher PHA stimulated T-cell response and delta cpm (P < 0.05 for each). Total and low-density lipoprotein cholesterol levels of the subjects with a positive family history of cardiovascular events were positively correlated with the PHA-activated T-cell responses (P = 0.022, r = 0.604 and P = 0.015, r = 0.635, respectively). There was no significant difference between the T-cell activity responses of smokers and nonsmokers. No correlation was found between the biochemical parameters and T-cell activities in these groups. Peripheral T-cell activity responses to PHA are higher in the asymptomatic relatives of patients with coronary events. This may be a clue for the familial tendency of atherosclerotic diseases. Further follow-up studies are necessary to investigate the relationship.

The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia.

OBJECTIVE: There is controversy about the effects of statins on insulin resistance and plasma adiponectin. The aim of this study was to investigate the effects of fluvastatin treatment on these parameters in a group of dyslipidaemic patients who had no confounding factors for insulin resistance or alterations in plasma adiponectin. DESIGN AND PATIENTS: Forty-nine patients [27 males, 22 females; mean age 47.2 +/- 10.3 years; body mass index (BMI) 29.64 +/- 3.2 kg/m2] with dyslipidaemia and 20 controls (six males, 14 females; mean age 45.3 +/- 9.31 years; BMI 30.07 +/- 4.04 kg/m2) were enrolled. All patients were treated initially with therapeutic lifestyle changes (TLC) for 6 weeks. Six out of 49 subjects were excluded from the study. Then, 24 out of 43 patients with high blood cholesterol despite TLC were allocated to fluvastatin 80 mg daily plus TLC, and the remaining 19 patients with normal cholesterol were subjected to TLC alone for additional 12 weeks. MEASUREMENTS: Plasma adiponectin, immunoreactive insulin levels, BMI, waist circumference, blood pressure, lipids, and glucose were determined. The insulin sensitivity index was quantified using the homeostasis model assessment (HOMA). RESULTS: TLC caused significant improvement in plasma insulin (P = 0.02) and elevation in plasma adiponectin (P = 0.02). Fluvastatin treatment decreased total cholesterol and low density lipoprotein (LDL)-cholesterol significantly (P = 0.01 and P = 0.02, respectively). No significant effect of fluvastatin was observed on plasma insulin or adiponectin or on the HOMA index. CONCLUSIONS: Fluvastatin does not improve plasma adiponectin levels and insulin sensitivity, despite its beneficial effects on lipid levels. Our data, however, were limited by the fact that a more accurate method of assessing insulin sensitivity, the euglycaemic-hyperinsulinaemic glucose clamp technique, was not used.

Association of plasma adiponectin concentrations with chronic lymphocytic leukemia and myeloproliferative diseases.

Adiponectin, an adipocyte-secreted hormone, is an important negative regulator in the immune system and hematopoiesis. In this study, we investigated the association of adiponectin levels with chronic lymphocytic leukemia (CLL) and myeloproliferative diseases (MPDs). We measured adiponectin levels in 19 patients with CLL and 30 patients with MPD (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were compared with results from a control group of healthy volunteers who were matched according to age, sex, and body mass index. The adiponectin levels in patients with CLL were lower than in the controls (4.71 +/- 1.33 microg/mL versus 16.61 +/- 3.91 microg/mL; P <.001). They were also significantly lower in patients with MPD than in the controls (8.95 +/- 1.33 microg/mL versus 16.16 +/- 4.77 microg/mL; P <.001). In addition, we compared the adiponectin levels of MPD patients who were treated with interferon (IFN) to the levels of patients who were not treated with IFN. Adipnectin levels were significantly higher in IFN-treated patients (11.03 +/- 1.39 microg/mL versus 6.87 +/- 1.79 microg/mL; P <.001). These results suggest that lymphopoiesis and myelopoiesis negatively influence adiponectin levels. Adiponectin may be related to inflammatory cytokine release. IFN therapy appears to have a positive influence on adiponectin secretion by suppressing inflammatory cytokines. Future studies are needed to prove causality and to provide insight about this hormone's mechanism of action and its potential role regarding the etiology and progression of CLL and MPD.

Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients.

OBJECTIVES: To determine the effects of nebivolol on oxidative stress, insulin resistance, adiponectin and plasma soluble P-selectin levels in hypertensive patients in comparison with metoprolol. MATERIAL AND METHODS: Eighty newly diagnosed hypertensive patients in grade 1 hypertension according to the European Society of Hypertension and European Society of Cardiology guidelines were enrolled in this prospective, blinded, randomized study. Seventy-two patients completed the study. After baseline assessment, each patient was randomly allocated to a 5 mg daily dose of nebivolol (n = 37, 20 male) or a 100 mg daily dose of metoprolol (n = 35, 18 male) and treated for 6 months. Blood pressure, heart rate, oxidative stress (malonyldialdehyde), homeostasis model assessment: insulin resistance, adiponectin and plasma soluble P-selectin levels were measured before and after treatment. RESULTS: At the end of treatment, nebivolol and metoprolol significantly decreased blood pressure and heart rate, with a more pronounced bradycardic effect of metoprolol. Nebivolol, but not metoprolol, significantly lowered oxidative stress (P = 0.03), the insulin resistance index (P = 0.003) and plasma soluble P-selectin levels (P = 0.008), and increased adiponectin levels (P = 0.04). CONCLUSION: Nebivolol, in contrast to metoprolol, improved oxidative stress, insulin sensitivity, decreased plasma soluble P-selectin and increased adiponectin levels in hypertensive patients. These beneficial effects of nebivolol may contribute to a reduction in cardiovascular risk in hypertensive patients.

Subacute cholestatic hepatitis likely related to the use of senna for chronic constipation.

We report a case of senna-induced cholestatic hepatitis which was not diagnosed at presentation. A 77 year old male was referred with abdominal pain, jaundice and elevated transaminase levels. A diagnosis of extrahepatic cholestasis was first suspected, due to the observation of a duodenal diverticulum and dilated proximal choledocus. However, the sphincterotomy did not improve cholestasis. At further evaluation, HBsAg was positive but serological work up was compatible with a healthy-carrier status. Further interrogation of the patient revealed a history of chronic senna intake to treat a chronic constipation. Liver biopsy showed bridging hepatocellular necrosis as well as canalicular cholestasis. Drug withdrawal resulted in a slow and progressive reduction in bilirubin levels and liver enzymes. In this case senna was likely the cause of a subacute cholestatic hepatitis exemplifying again the potential role of herbal related liver injury.

The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan.

OBJECTIVES: Afghanistan is one of the endemic regions of chloroquine resistant P. falciparum. Mefloquine and doxycycline are among the recommended prophylactic regimes. The aim of the study was to compare the efficacy and tolerability of the two regimes on the Turkish soldiers settled in Kabul, Afghanistan. METHODS: A total number of 1400 soldiers were subjected to prophylactic regimes with either doxycycline 100 mg/day (n=986) or mefloquine 250 mg/week (n=414). Prophylaxis lasted about 12 weeks. The side effects and compliances were investigated by questionnaires. All soldiers were monitored up to 6 months after returning home. RESULTS: No malaria case was observed and there was no severe side effect in either group. The total side effects in doxycycline group were significantly higher (P<0.001). The compliance of mefloquine takers was better than the doxycycline takers (P<0.05). CONCLUSIONS: The tolerability of the mefloquine regime is better than the doxycycline regime in malaria prophylaxis.

The comparative effects of telmisartan and ramipril on P-wave dispersion in hypertensive patients: a randomized clinical study.

BACKGROUND: Prolongation of P-wave times and increase of P-wave dispersion (PWD) were shown to be independent predictors of atrial fibrillation (AF). Angiotensin II receptor blockers (AARBs) and angiotensin-converting enzyme inhibitors (ACEIs) have beneficial effects on atrial conduction times. However, there are not enough data about the comparative effects of those drugs on PWD. HYPOTHESIS: We aimed to compare the effects of telmisartan and ramipril on PWD after 6-month treatment in hypertensive patients. METHODS: In all, 100 newly diagnosed hypertensive patients were enrolled in the study and were randomly assigned to two groups. Group 1 and Group 2 each consisted of 50 patients, taking daily doses of 80 mg telmisartan and 10 mg ramipril, respectively. Twelve-lead surface electrocardiograms (ECG) were recorded from all patients before and after 6-month drug therapy. The P-wave duration (Pdur) measurements were calculated from the 12-lead surface ECG. RESULTS: When pretreatment PWD and Pmaximum values were compared with post-treatment values, a statistically significant decrease was found in both groups after 6 months (Group 1 and 2; p < 0.001 for PWD and Pmaximum). P-wave dispersion and Pmaximum values after treatment in Group 1 were statistically significantly lower than those in Group 2 after the 6-month treatment period (p = 0.01 for PWD; p = 0.008 for Pmaximum). CONCLUSIONS: Telmisartan has a much greater lowering effect on PWD and Pmaximum values than ramipril. This finding may be important in the prevention of AF in hypertensive patients.

Effects of statins on oxidative stress.

Free oxygen radicals and insufficient antioxidant enzymes have been implicated in the pathogenesis of hypercholesterolemia (HC). Trace elements function as cofactors in antioxidant enzymes. Antioxidant system and trace elements were investigated in many different studies including HC, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in hypercholesterolemic patients given fluvastatin therapy. We examined malondialdehyde (MDA), copper zinc-superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activities together with copper (Cu), iron (Fe), and zinc (Zn) levels in erythrocytes of 35 patients with HC and 27 healthy control subjects. It was found that in patients with HC, erythrocyte MDA was significantly higher than those of controls and erythrocyte CuZn-SOD and GSH-Px activities were significantly lower in patients with HC. Erythrocyte iron levels were significantly higher than those of controls, and erythrocyte copper and zinc levels were significantly lower in patients with HC. Plasma lipid levels and the oxidative state were analyzed in statin-treatment groups given fluvastatin therapy before and after a 3-mo treatment period. In conclusion, we found that fluvastatin has significant antioxidant properties and these effects might be very important in managing dyslipidemia by improving endothelial function.

Increased sucrose permeability in Behçet's disease.

Behçet's disease (BD) is a chronic, relapsing, systemic vasculitis with unknown etiology. During the progression of the disease, gastrointestinal involvement can be observed. The aim of this study was to find out the predictive value of the sucrose permeability test in detecting gastrointestinal mucosal damage in BD. Twenty-six male Behçet's patients and 21 age- and sex-matched controls were enrolled in the study. Seventeen patients had active disease, while nine did not. Active disease was defined as having elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels or at least two of the diagnostic criteria in the previous month. Patients and controls were investigated with the upper gastrointestinal permeability test. Of all the patients, 25 were investigated endoscopically. The urine sucrose levels were significantly higher in patients than in the control group (P = 0.0001) and in patients with active disease than those with inactive disease (P < 0.0001), while urine sucrose of patients with inactive disease and the control group did not differ. The endoscopic findings were not specific to BD. Active and inactive BD had similar endoscopic findings. Increased upper gastrointestinal permeability was established in patients with BD. This increased permeability was not related to a specific gastrointestinal BD lesion. Further studies with larger series must be performed in order to determine the value of the sucrose permeability test in detecting mucosal involvement in BD.

Fluvastatin improves insulin resistance in nondiabetic dyslipidemic patients.

Statins have multiple actions, independent of their classical effects on lipoproteins. The data about the effects of statins on insulin resistance is controversial. This study was designed to search the statin effects on nondiabetic dyslipidemic patients. Thirty-five (17 male, 18 female) consecutive dyslipidemic patients 54.25 +/- 8.81 yr were enrolled in the study. After a standard follow-up period of lifestyle modification, the patients were given fluvastatin 40 mg/d for 8 wk. Serum analyses were done both before and after treatment. Insulin resistance was assessed by homeostasis assessment model (HOMA). Fasting plasma triglyceride, total and LDL cholesterol, fasting insulin, and HOMA index were significantly reduced and HDL cholesterol was improved after fluvastatin treatment. HOMA-IR was not correlated with triglycerides, LDL, HDL, or total cholesterol levels. The same situation was present for both fasting plasma insulin and fasting plasma glucose levels. Also age was not associated with HOMA-IR and fasting plasma insulin levels. As a conclusion, the present study indicates that fluvastatin treatment improves insulin resistance in dyslipidemic patients who do not have diabetes or impaired fasting glucose. Also, the effect of fluvastatin on insulin resistance is not associated with the lowering of triglycerides. The latter finding indicates that the effect of statins on insulin sensitivity may not be related with the lowering of triglycerides in dyslipidemic patients.