Konstantinos Pappas

Rifaximin Improves Systemic Hemodynamics and Renal Function in Patients With Alcohol-Related Cirrhosis and Ascites

Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α increase with intestinal bacterial overgrowth and translocation, and are believed to be involved in the pathogenesis of hyperdynamic circulatory syndrome and functional renal failure in patients with advanced cirrhosis. We investigated the effects of the antibiotic rifaximin on systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. We measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound, systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma renin activity, levels of plasma aldosterone, the glomerular filtration rate by plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin, and serum levels of IL-6 and TNF-α in 13 patients at baseline and after 4 weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO and significantly increased systemic vascular resistance, in association with a significant decrease in plasma rennin activity. The therapy also significantly increased the glomerular filtration rate and natriuresis while reducing levels of endotoxin, IL-6, and TNF-α. Intestinal decontamination with rifaximin improved systemic hemodynamics and renal function in patients with advanced cirrhosis.

Determinants of vascular function in patients with type 2 diabetes

BackgroundType 2 diabetes mellitus (T2DM) is independently associated with an increased risk for cardiovascular diseases that is primarily due to the early development of advanced atherosclerotic vascular changes. The aim of our study was to investigate the predictors of vascular dysfunction in T2DM patients.MethodsWe studied 165 T2DM patients without known macrovascular or microvascular disease. Standard demographic (age, gender, cardiovascular risk factors, medications), clinical (body mass index, blood pressure) and laboratory (glucose, glycated hemoglobin, lipids, renal function) parameters were included in analyses. Brachial artery flow-mediated dilation (FMD), nitrate mediated dilation (NMD) and Carotid-Femoral Pulse Wave Velocity (PWV) were measured.ResultsMedian age was 66 years and duration since T2DM diagnosis was 10 years, 70% were females and 79% hypertensives, while only 10% had a glycated hemoglobin <7%. FMD was positively associated with NMD (r 0.391, P < 0.001), while PWV was inversely associated with FMD (r -0.218, P = 0.014) and NMD (r -0.309, P < 0.001). Time since diagnosis of diabetes was the single independent predictor of FMD (β -0.40, P = 0.003). Increased age and fasting glucose and the presence of hypertension were independent predictors of decreased NMD (P < 0.001). Increased age and systolic blood pressure were independently associated with increased PWV (P < 0.001).ConclusionsIn T2DM patients, impairment of endothelium-dependent vasodilation was independently associated only with longer diabetes duration while no association with other established risk factors was found. Vascular smooth muscle dysfunction and increased arterial stiffness were more prominent in older T2DM patients with hypertension. Worse glycemic control was associated with impaired vascular smooth muscle function.

Pioglitazone vs glimepiride: Differential effects on vascular endothelial function in patients with type 2 diabetes

OBJECTIVE The aim of this study was to compare the effect of glimepiride and pioglitazone on endothelial function in patients with type 2 diabetes already on metformin. METHODS Twenty-eight patients with type 2 diabetes already on metformin, without known cardiovascular disease, were randomized in 2 groups; glimepiride (4 mg od) was added in group A (n=14) and pioglitazone (30 mg od) in group B (n=14) for 6 months. Flow-mediated dilation (FMD) in the brachial artery was assessed in all patients, at baseline and at follow-up. RESULTS The 2 groups did not differ in age (mean+/-S.D., 63.6+/-7.3 years vs 62.8+/-7.2 years respectively), or any measured variable at baseline. Fasting glucose and glycated haemoglobin improved similarly in both groups. There were significant differences between the 2 groups in the absolute changes observed at follow-up in waist circumference, +1.86+/-3.11 cm vs -1.86+/-1.88 cm in groups A and B respectively; fasting insulin levels, +14.79+/-12.56 pmol/L vs -25.84+/-28.09 pmol/L; homeostasis model assessment (HOMA), +0.66+/-1.01 vs -1.83+/-1.38; HDL cholesterol levels, -0.07+/-0.22 mmol/L vs +0.14+/-0.20 mmol/L and FMD, +0.14+/-1.09% vs +2.02+/-2.05% (p<0.05 for all). The only independent predictor factor of the FMD improvement was treatment-induced changes in HOMA (R(2): 0.488, slope: -0.782, [95% CI: -1.128, -0.436], p=0.0001). CONCLUSIONS In patients with type 2 diabetes already on metformin, addition of pioglitazone as compared to glimepiride, improved endothelial function despite similar glycemic control. The improvement in endothelial function was mainly due to a reduction in insulin resistance.

Paradoxical protective effect of central obesity in patients with suspected stable coronary artery disease

Increased body mass index (BMI) has been paradoxically inversely associated with the presence of angiographic coronary artery disease (CAD). Central obesity measures, considered to be more appropriate for assessing obesity‐related cardiovascular risk, have been little studied in relation to the presence of CAD. The aim was to investigate the association of central obesity with the presence of angiographic CAD as well as the prognostic significance of obesity measures in CAD prediction when added to other cardiovascular risk factors.

Rosiglitazone improves endothelial function in patients with type 2 diabetes treated with insulin

An increased incidence of myocardial infarction with rosiglitazone in patients with type 2 diabetes mellitus (T2DM) has been reported. This study aimed to assess the effect of rosiglitazone on endothelial function, assessed by flow-mediated dilation (FMD), in 34 patients with advanced T2DM treated with insulin without known cardiovascular disease. Patients were randomised into two groups: no additional treatment was given in 17 patients, while 17 patients were given rosiglitazone for 6 months. Addition of rosiglitazone significantly reduced glycosylated haemoglobin (HbA1c) (p < 0.0005) and fasting glucose (p < 0.05) and improved FMD (p < 0.005). No significant changes were observed in the insulin-only group. The single independent predictor of FMD improvement was rosiglitazone treatment (p = 0.048). These results show that, in patients with advanced T2DM treated with insulin, addition of rosiglitazone may have a beneficial effect on endothelial function. Further research is needed to investigate why this beneficial effect does not translate into improved cardiovascular prognosis in these patients.

Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas

Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA1C and HOMA-IR (p < 0.05 for all) and increased FMD (p = 0.002). Metformin induced a significant decrease in HbA1C (p = 0.02) and only a trend for increase in FMD (p = 0.08). The greater improvement in FMD with pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.

Increased Aortic Pulse Wave Velocity Is Associated With the Presence of Angiographic Coronary Artery Disease in Overweight and Obese Patients

BACKGROUND Increased arterial stiffness assessed by carotid-femoral pulse wave velocity (CFPWV) and central augmentation index (AIx), has been associated with a worse cardiovascular prognosis and increased prevalence of angiographic coronary artery disease (CAD). Obesity, a well-recognized cardiovascular risk factor, has been related to increased arterial stiffness, although not consistently. The aim of this work was to investigate the association of arterial stiffness indices with obesity measures in patients undergoing coronary angiography and to study any potential association of arterial stiffness with angiographic CAD in relation to obesity. METHODS Three hundred ninety-three patients with suspected stable CAD (aged 61±10 years; n = 303 men) referred for diagnostic coronary angiography were included. Body mass index (BMI), waist circumference (WC), and traditional cardiovascular risk factors were measured. Arterial stiffness was assessed by CFPWV and AIx using applanation tonometry in all patients. RESULTS CFPWV was not associated with obesity measures in multiple-adjusted logistic regression analysis (P > 0.05), whereas AIx was inversely associated with BMI and WC (P < 0.05 for both). Increased CFPWV was associated with CAD in overweight and obese patients (BMI ≥25kg/m(2); WC ≥94cm in men and ≥80cm in women; P < 0.05). No association of AIx with CAD was found (P > 0.05). CONCLUSIONS Arterial stiffness indices were not consistently associated with obesity, opposite to what might have been expected. The association of increased CFPWV with the presence of angiographic CAD in patients with increased BMI or WC values warrants further research.

The value of transesophageal echocardiography for embolic strokes of undetermined source

Objective: Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic strokes of undetermined source (ESUS). Methods: We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups. Results: We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points [interquartile range: 3–8]). TEE revealed additional findings in 52% (95% confidence interval [CI]: 40%–65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% [95% CI: 9%–28%]) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%–10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ (p = 0.315) among patients with cryptogenic stroke (6.9% [95% CI: 4.9%–9.6%]), ESUS (8.1% [95% CI: 3.4%–18.1%]), and IS (9.4% [95% CI: 7.5%–11.8%]). Conclusions: Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS.

Inflammation, Endothelial Dysfunction and Increased Left Ventricular Mass in Chronic Kidney Disease (CKD) Patients: A Longitudinal Study

Introduction Within this longitudinal study we investigated the association of inflammation markers C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) and endothelial dysfunction markers intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with left ventricular mass indexed for height2·71 (LVMI) in hypertensive predialysis CKD patients. Material and Methods From 2004 to 2005, 182 incident consecutive adult patients from the outpatient CKD clinics of two hospitals in Greece with CKD and hypertension or using antihypertensive medication, were included. Of these, 107 patients underwent CRP (mg/l) and LVMI (g/height2·71) measurements annually for three years. Results In the longitudinal analyses, using linear mixed modeling, a higher IL-6 (ß = 1.9 (95%ci:0.38;3.5), inflammation score based on CRP, IL-6 and TNF-α (ß = 5.0 (95%ci:0.72; 9.4) and VCAM-1 (ß = 0.01 (95%ci:0.005;0.02) were associated with higher LVMI. These models were adjusted for age, gender and primary renal disease, and for confounders that on top changed the beta with ≥10%, i.e. diuretic use (for IL-6 and inflammation score). Conclusion The results suggest that in predialysis CKD patients, inflammation as well as endothelial dysfunction may play an important role towards the increase in LVMI.

An Epidemiologic Study of Acute Coronary Syndromes in Northwestern Greece

Acute coronary syndromes (ACS) represent the most common cause of morbidity and mortality in the Western world. Relative epidemiologic data for Greece, a Mediterranean country, are sparse. The aim of the study was to determine the incidence and the clinical presentations of ACS. Over a 1-year period we conducted a prospective, population-based survey of ACS cases in an isolated area of northwestern (NW) Greece with 170,000 inhabitants. Every patient living in the study area, aged <80 years, without history of coronary artery disease, who presented with symptoms suspicious for ACS and was hospitalized for at least 24 hours was eligible for inclusion in the study. For sudden cardiac deaths, relative information was obtained from the autopsy report or the physician who documented death. Additional information regarding timing and associated conditions was obtained from relatives. The diagnosis and classification of the studied cases was performed according to World Health Organization and European Society of Cardiology criteria. The authors identified 352 patients (265 men, 87 women, mean age 62.5 ±10 and 68 ±9.5 years, respectively) with first-appeared ACS (174 non-ST elevation, 105 ST elevation, 73 sudden cardiac deaths). Fifty-six patients with other forms of ischemic heart disease (stable angina, heart failure, and silent ischemia) were not included in the analysis. Moreover, 154 patients with chest pain and normal appearing EGG at rest, normal values for enzymes (CK, troponin), and negative exercise testing, as well as 77 patients with normal findings from coronary angiography studies, were also excluded. The annual incidence for the age group of 30-79 was 39/10,000 inhabitants (60.6 for men and 19 for women). The incidence of ACS increased with age in both sexes and was higher in men even after the age of 70. About one third of the ACS and half of the sudden cardiac deaths occurred in the age group of 70-79. Only 3 patients were successfully resuscitated. ACS are common in this area of NW Greece and the majority of them present in a form amenable to therapeutic manipulations. Twenty percent of patients died suddenly, and a very small percentage of these were successfully resuscitated. Preventive measures and acute management facilities need to be improved, even in a Mediterranean country where the incidence of ischemic heart disease is relatively lower than in northern European countries.