Systemic oxidoreductive balance and vascular function in individuals without clinical manifestation of atherosclerosis.

INTRODUCTION: Endothelial dysfunction is recognized as the earliest disorder in the development of atherosclerosis, in the pathogenesis of which oxidative stress plays a crucial role. The aim of this study was to determine the relationships between non-invasive parameters of vascular dysfunction and oxidative stress. MATERIAL AND METHODS: Forty-eight individuals without clinical manifestation of atherosclerosis were studied. The plasma concentrations of the following were determined in all 48 subjects: retinol, ascorbic acid, α-tocopherol and uric acid, as well as the products of oxidative DNA damage repair: 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in blood leukocytes and urine, and 8-oxo-7,8-dihydroguanine (8-oxoGua) in urine. The following parameters of vascular dysfunction were also examined: flow- (FMD) and nitroglycerin- (NMD) mediated dilatation of the brachial artery, pulse pressure (PP), distensibility coefficient (DC), pulsation (PI) and resistance (RI) index, carotid intima-media thickness (cIMT), and ankle-brachial index (ABI). RESULTS: Individuals with an FMD value of ≥ 8.8% had significantly higher blood concentrations of antioxidative vitamins and lower concentrations of 8-oxodG in their urine and blood leukocytes than their counterparts. Blood concentration of alpha-tocopherol or ascorbic acid positively correlated with FMD, PI, RI, DC and ABI and negatively with PP and cIMT. The reverse was the case for 8-oxodG in urine and leukocytes. In multiple regression analysis, markers of oxidative DNA damage positively determined the variance in PP and ABI. CONCLUSIONS: In persons without clinical manifestation of atherosclerosis, oxidative stress was an independent factor associated with vascular wall dysfunction, and a better predictor than smoking and blood concentrations of glucose, lipids and creatinine.

Does morphology of carotid plaque depend on patient's oxidative stress?

OBJECTIVES: This study explored the relationship between oxidative stress biomarkers and stability of carotid plaque. We decided to analyze the broad range of parameters describing oxidative stress in patients with carotid stenosis. DESIGN AND METHODS: 124 consecutive patients undergoing carotid endarterectomy were enrolled in the study group. The control group consisted of 49 patients without symptoms of atherosclerosis. The stability of carotid plaques was assessed using GSM (gray-scale median) scoring system and the study group was divided into three subgroups according to echogenicity of the plaque. The following parameters of oxidative stress/DNA damage were analyzed: i) urinary excretion of the products of oxidative DNA damage repair; ii) the background level of 8-oxo-7,8-dihydro-2'-deoxyguanosine in leukocytes' DNA and in atherosclerotic plaques; and iii) the concentrations of antioxidant vitamins, uric acid and C-reactive protein in plasma. RESULTS: Oxidative stress (described by redox status) was higher in the patient group than in the control group. There is a correlation between oxidative stress of the patients and stability of the plaque, echolucent plaques (GSM<25) being associated with the highest antioxidant level and lowest excretion of DNA repair markers. CONCLUSIONS: The plaque formation/morphology may depend on local environment and is independent of oxidative stress/inflammation observed on the level of the whole body.

Improvement in health-related quality of life after therapy with omeprazole in patients with coronary artery disease and recurrent angina-like chest pain. A double-blind, placebo-controlled trial of the SF-36 survey.

BACKGROUND: Many patients with coronary artery disease (CAD) have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs). The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL) in patients with CAD. STUDY: 48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy. RESULTS: Patients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health), as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being. CONCLUSIONS: A double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo.

Treatment with double dose of omeprazole increases ß-endorphin plasma level in patients with coronary artery disease.

INTRODUCTION: The proton pump inhibitor empirical trial, besides the analysis of symptoms, is the main method in the diagnosis of gastro-oesophageal reflux disease-related chest pain. ß-Endorphin acts as an endogenous analgesia system. The aim of the study was verify whether ß-endorphin plasma level is affected by omeprazole administration and influences the severity of anginal symptoms and outcome of the "omeprazole test" in patients with coronary artery disease (CAD) and chest pain of suspected non-cardiac origin. MATERIAL AND METHODS: Omeprazole was administered to 48 patients with CAD in a randomized, placebo-controlled, crossover study design. At the beginning of the study, and again after the 14-day omeprazole and placebo treatment, the ß-endorphin plasma concentration was determined. RESULTS: The level of plasma ß-endorphin after the administration of omeprazole was significantly greater than at the start of the study and following the placebo. Responders to omeprazole had an average lower ß-endorphin plasma concentration than subjects who failed to respond to this therapy. Subjects with symptoms in class III (according to the Canadian Cardiovascular Society classification) after omeprazole administration had a greater ß-endorphin plasma level than subjects in class II for anginal symptom severity. CONCLUSIONS: Fourteen-day therapy with a double omeprazole dose significantly increases the ß-endorphin plasma concentration in patients with CAD. Circulating ß-endorphin does not seem to be involved in the mechanism for the "omeprazole test" outcome, although an individually different effect on pain threshold cannot be excluded.

[Pheochromocytoma--a disease which is worth to keep in mind]. / Guz chromochlonny nadnercza--choroba, o której warto pamietac.

The case of 25 years old male patient with symptoms of hypertensive storm in the course of pheochromocytoma was presented. For some years he had been suffering from moderate increase in arterial blood pressure whose secondary cause was not suspected by physicians examining this patient. In presented case the course of pheochromocytoma has special characteristics, such as: clinical presentation in young age, the course alternate between periods of hypertension and phases of normal blood pressure, physical signs of Marfan's syndrome, increase of troponin level within hypertensive storm, and attributes of malignant hypertension presented as transient proteinuria and glycosuria within normoglycemia.

The effect of double dose of omeprazole on the course of angina pectoris and treadmill stress test in patients with coronary artery disease--a randomised, double-blind, placebo controlled, crossover trial.

BACKGROUND: Gastroesophageal reflux (GER) and coronary artery disease (CAD) frequently overlap, making the proper diagnosis of chest pain more difficult. GER symptoms may mistake anginal chest pain, and oesophageal acidification may induce myocardial ischaemia both in the rest and in the effort. Increase of oesophageal pH should prevent these conditions. AIM: To estimate the effect of double omeprazole dose on the course of angina pectoris and treadmill stress test in patients with coronary artery disease (CAD), using double-blind, crossover randomised, placebo-controlled study design. METHODS: We studied 48 patients with angina pectoris symptoms and significant narrowing of coronary vessels in angiography. After baseline examination and treadmill stress test all subjects were randomised to treat either with omeprazole (20 mg b.i.d.) or placebo for 14 days, using a double-blind, crossover placebo controlled design. RESULTS: Seventeen (35%) subjects reported more than by half decrease in symptoms severity after omeprazole and 6 (12%) after placebo (p=0,01). Omeprazole significantly decreased the number of chest pain episodes and number of nitroglycerin doses taken in the second week of both study phases, as well as the percentage of subjects with significant decrease of ST interval during the stress test (64% vs. 73%, p<0,05). However majority of other stress test parameters (i.e. test duration, DUKE index) have improved both after omeprazole and placebo administration (by 9-38%). CONCLUSION: Double dose of omeprazole significantly decreased symptoms severity in 35% of patients with CAD, as well as frequency of some electrocardiographic signs of myocardial ischaemia during stress test.

[Gastroesophageal reflux disease and coronary heart disease--coexistence or interrelationship?]. / Choroba refluksowa przelyku a choroba wiencowa-- wspólistnienie czy zaleznosc?

There is the normal coronary artery appearance in 20-30% of coronarographies, made in patients with chest pain and/or positive noninvasive cardiological tests. The simple explanation of this fact is the presence of diseases which may affect coronary perfusion via mechanism independent to the diameter of main coronary arteries. One of them is gastroesophageal reflux disease (GERD). The presence of GERD symptoms in general population concerns about 30-40% of individuals, while non-physiological reflux is stated in 50-65-85% of patients with coronary heart disease (CHD). That means, that GERD is twice more frequent in patients with CHD than in general population. One explanation of the increased frequency of gastroesophageal reflux appearance in patients with CHD is the adverse effect of drugs used in treatment of cardiological diseases. Morover, one of potential mechanisms explaining the influence of esophagal disturbance on the appearance of coronary hipoperfusion may be their common neurological control of the functions. There are three aspects of it: vagal reflexes (esophageal-cardiac reflex), the disturbances of autonomic nervous system balance and changes in visceral pain perception threshold. Visceral reflex can combine GERD and CHD with mechanism of vicious circle: acid gastroesophageal reflux via vagal reflex may cause coronary hipoperfusion, and the products of anaerobic metabolism of cardiomyocytes may cause relaxation of lower esophagus sphincter, facilitating reflux. Additional mechanism connecting GERD and CHD is inflammation caused by Helicobacter pylori infection. The relationship between digestive tract pathology and evolution, as well as progression and complications of atherosclerosis together with similarity of clinical presentation imply the necessity of precise diagnosis of chest pain causes and caution in interpretation of laboratory examination results.

Suppression of gastric acid production may improve the course of angina pectoris and the results of treadmill stress test in patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) and gastro-esophageal reflux disease (GERD) often coexist in the same patients. The aim of this study was to estimate the effects of gastric acid output suppression with rabeprazole on course of angina pectoris and results of the treadmill stress test in patients with CAD. MATERIAL/METHODS: We studied 34 patients with stable angina pectoris. In all subjects a medical history, a physical examination, and a stress test were performed at the beginning of the study and after two weeks of add-on rabeprazole therapy (20 mg b.i.d.). RESULTS: Rabeprazole therapy significantly improved the outcome of the stress test in 27 patients (79%), prolonging mean stress exercise time (449+/-147 vs. 489+/-156s, p=0.027) and exercise time, leading to a maximum ST interval depression (360+/-167 vs. 467+/-148s, p=0.001), and also decreasing ST interval depression delta (1.9+/-1.1 vs. 1.5+/-0.9; p=0.013). CONCLUSIONS: In 79% of our study subjects, rabeprazole improved stress test results in CAD patients, which implies that at least some of their symptoms were related to GERD. A proton pump inhibitor exerted a favorable effect on the frequency of angina-like chest pain and the results of the treadmill stress test.