Xanthine oxidase inhibitors in ischaemic heart disease

Increased uric acid levels are correlated with cardiovascular disease, particularly with ischaemic heart disease. Xanthine oxidase inhibitors, especially allopurinol, lower the risk of ischaemic heart disease due to their effects on reactive oxygen species and endothelial function. In chronic stable angina pectoris, allopurinol increases the median time to ST depression, time to chest pain, and total exercise time. On the other hand, it has been reported that allopurinol has a beneficial effect on ischaemic patients referred for angioplasty, but there are insufficient data regarding its effect on acute myocardial infarction patients. Moreover, other important actions of allopurinol are regression of left ventricular hypertrophy and improvement in the results of cardiac rehabilitation. The efficacy of allopurinol has recently been acknowledged by the European Society of Cardiology guidelines for stable angina pectoris, but the particular role of allopurinol in ischaemic heart disease patients is not fully established.

Renin Genetic Polymorphism in Heart Failure Patients.

BACKGROUND: Genetic polymorphism of renin-angiotensin-aldosterone system affects the pathogenesis of hypertension (HTN), ischemic heart disease (IHD) and heart failure (HF). The purpose of our study is to analyze A/G renin genetic polymorphism in heart failure patients. METHODS: We investigated renin polymorphism in 83 subjects hospitalized in the Cardiology Department of the Rehabilitation Hospital Cluj-Napoca, using the PCR amplification method. 43 patients were diagnosed with heart failure [NYHA III-IV class], and 40 subjects without cardiovascular disease (control group). The NT-proBNP and the presence of cardiovascular risk factors were assessed. RESULTS: Heart failure etiology was IHD in 60.46% of patients. The average value of NT-pro BNP was 2991.24 ± 2034.6 pg/ml. As it was expected, HF patients presented low lipid levels: total cholesterol = 162.36 ± 38.28 mg/dl, LDL-Cholesterol = 104.88 ± 27.60 mg/dl, triglycerides= 109.12 ± 55.84 mg/dl, HDL-Co = 35.68 ± 9.55 mg/dl. A/G renin genetic polymorphism [with pathogenic potential] in heart failure patients was of 60.46% (homozygote 4.65% and heterozygote 55.81%). Conversely, pathogenic mutations were found only in 38.46% of hypertensive patients, but also in 55.88% and 22.22% patients with obesity/overweight and diabetes. The heterozygote form was found in only 37.5% of control subjects. CONCLUSION: This study showed no involvement of A/G renin polymorphisms in the pathogenesis of HF.

RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells.

The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 production and how interferon (IFN)-γ alters RSV-induced IL-15 production and MHC class I and MICA expression. We infected respiratory epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial cells with RSV and measured production of IL-15, expression of MHC I and MICA and the role of the transcription factor nuclear factor (NF)-κB. We report here that RSV increases IL-15 in respiratory epithelial cells via virus replication and NF-κB-dependent mechanisms. Furthermore, RSV infection of epithelial cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN-γ upregulated RSV induction of soluble IL-15 but inhibited induction of MICA. Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in activating immune responses to RSV by epithelial cells.

The acute effect of Metoprolol upon NT-proBNP level in patients with congestive heart failure.

UNLABELLED: Brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. The acute effect of beta blockers upon plasma BNP levels in CHF patients has been less studied but it is important because of the initial possible depressing effect upon LV function. PURPOSE: To investigate the acute effect of oral Metoprolol upon plasma proBNP levels in CHF patients. METHODS: There were included 56 patients with congestive heart failure, 38 with ischemic heart disease and 18 with idiopathic dilated cardiomyopathy, 40 males and 16 females, aged between 25 and 65 years, who were compared with 19 healthy individuals, 12 males and 7 females, of the same age. All patients were free of beta blockers treatment. Plasma Nt-proBNP was determined in fasting state using ELISA method (NV <250 fmol/mL). After this, every patient received 50 mg Metoprolol succinate and at three hours (considered as peak plasmatic concentration) venous blood samples were again obtained and Nt-proBNP determined. RESULTS: NT-pro BNP was increased (1400 +/- 130 fmol/mL) in heart failure patients and normal (187 +/- 17.2 fmol/mL) in healthy controls. After Metoprolol the plasmatic level of NT-proBNP was not significantly different in both healthy controls (162 +/- 13.3 fmol/mL) and heart failure patients (1419 +/- 133 fmol/ml) in comparison with baseline values. After Metoprolol NT-proBNP decreased (from 1266 +/- 121 to 1120 +/- 107, p>0.05) in III NYHA class patients and increased (from 1457 +/- 142 to 1530 +/- 150, p<0.05) in IV NYHA class patients. It remained unchanged in patients with LVEF >30% (1384 +/- 140 vs 1389 +/- 129 fmol/mL) and increased (from 1480 +/- 134 to 1690 +/- 161 fmol/mL, p<0.05) in patients with LVEF <30%; it was not significantly modified in patients with atrial fibrillation in comparison with those in sinus rhythm (1348 +/- 132 vs 1516 +/- 168 fmol/mL). CONCLUSION: Beta blockers do not have a severe depressant effect on left ventricular performance in all patients with systolic heart failure. A LVEF>30% suggests, but the lack of modification of NT-proBNP levels after administration of 50 mg Metoprolol confirm, that the beta blocking treatment can be initiated with higher doses than those recommended until now.

Rehabilitation in diabetic patients.

Physical activity is very important for diabetic patients. In normal subjects physical activity postpones diabetes mellitus and in diabetic patients postpones the cardiovascular complications. In diabetic patients with cardiovascular disease, physical training increases exercise capacity, decreases complications and prolongs survival. Physical activity can be applied in diabetic patients as physical activity counseling or physical training, the second being recommended to be ambulatory and supervised but, sometimes, also home rehabilitation can be useful. Aerobic exercises, but also resistance exercises will be applied for a 30-60 min duration at least 3x/ week, recommended 5x/ week, and optimal every day. Some specific aspects of diabetic patients as hyper or hypoglycemia, autonomic or peripheral neuropathy, retinopathy, have to be considered during physical rehabilitation and sometimes physical training has to be modulated according to them. In conclusion, physical activity and training represent a real chance for every diabetic patient and has to be recommended and applied in all of them.

Drug treatment of heart failure patients in a general Romanian hospital.

OBJECTIVE: It is very well known that in clinical practice, according to the published guidelines, the heart failure patients are undertreated. There are striking differences in applying the guidelines in various countries and, up to the present, there are no consistent data for Romania. MATERIAL AND METHODS: There were studied 459 heart failure patients admitted in the Cardiology Department of a general hospital in Cluj-Napoca, Romania. They were evaluated from the point of view of the drugs used during hospitalization and recommended to be taken after discharge. RESULTS: The patients, 393 males and 66 females, aged 61+9 years (lower in comparison with other countries) were included in NYHA III and IV class, except 3%, in NYHA II class. The ischemic etiology was registered in 56% of the patients. Drug treatment was as follows: diuretics--86.98%, ACEI--77.77%, beta blockers--55.95, ARB's--7%, digoxin--51.63%, aldosterone antagonists--49%, nitrates--61.28%, statins--24%, antithrombotic therapy--60% (antiplatelet--45.75%, anticoagulants--28.5%), antiarrythmics--27.91% (mainly amiodarone). In comparison with other European countries, the use of RAAS antagonists is similar, there are more beta blockers and nitrates used, but there is less use of antithrombotic therapy (especially anticoagulation) and of statins. CONCLUSION: Even though Romania still belongs to the group of developing countries, the drug treatment of heart failure patients does not much differ from the treatment applied in developed countries.

Physical training--beyond increasing exercise capacity.

Physical training has traditionally represented the main method used in cardiovascular rehabilitation of ischemic patients in the past years. Nowadays, cardiovascular rehabilitation has been extended to other cardiovascular diseases, such as heart failure. Also, cardiovascular rehabilitation included psychological, social and professional measures along with secondary prevention methods such as lifestyle changes. It has also been found that physical training has other additional effects which increased exercise tolerance. Effects on the risk factors regard beneficial effect on body weight, on the serum lipids levels, on psychosocial stress, on high blood pressure and on insulin resistance and diabetes mellitus. Physical exercise has also beneficial effects on the balance between sympathetic--vagal tone, inducing a vagal predominance, has anti-atherogenic and anti-ischemic effects, influencing the endothelial function, the inflammation (anti-inflammatory effect), both arteriogenesis and angiogenesis and thrombosis. Physical training could improve the symptoms of coronary patients by preconditioning, which has a protective effect for the myocardium. We may state that physical exercise has beneficial effects in cardiovascular patients because it increases exercise tolerance with positive consequences on the quality of life and professional reintegration, but also because it has positive effects beyond this. Thus, physical exercise should be practiced through cardiac rehabilitation programs, by all cardiovascular patients.

Arterial stenosis and atherothrombotic events in polycythemia vera and essential thrombocythemia.

UNLABELLED: Patients with polycythemia vera (PV) and essential thrombocythemia (ET) are at risk of developing arterial and venous thromboembolic complications. Given the complex interaction between blood cells and the vessel wall, it is possible that atherogenesis may also be accelerated in these patients. We used Doppler arterial ultrasound to assess the presence of arterial stenosis in a cohort of PV and ET patients. MATERIAL AND METHODS: A total of 37 patients, 29 with PV and 8 with ET, were investigated. Aside from an extensive clinical and hematological evaluation, arterial Doppler ultrasonography was performed in all patients; in 3 patients arteriography/coronarography was also performed. RESULTS: Twenty four patients (65%) had a history of atherothrombotic events including cerebral ischemic attacks (CIA) in 12 patients, ischemic heart disease (IHD) in 10 patients and peripheral occlusive arterial disease (POAD) in 12 patients. Eight patients had multiple atherothrombotic events. Twenty five patients (67%) had other atherosclerotic risk factors such as smoking, dyslipidemia, hypertension and diabetes. Significant arterial stenosis was found in 23 patients (62.1%), including 12 patients with carotid plaques, 10 with peripheral arterial stenosis, 3 with coronary stenosis, 2 with aortic plaque and 2 with common iliac artery stenosis. In 12 patients multiple arterial stenoses were found. The presence of arterial stenosis was significantly correlated with the occurrence or thrombotic events (p = 0.0003) and was also correlated with the concomitant presence of polyglobulia and thrombocytosis. Both the thrombotic risk and the probability of stenosis detection were augmented by additional risk factors such as smoking, hypertension and dyslipidemia. DISCUSSION AND CONCLUSIONS: The high incidence of arterial thrombotic events in our PV and ET patients was associated with a high incidence of stenosis detectable by arterial ultrasound. Hyperviscosity, endothelial damage due to leukocyte activation with subsequent thrombus formation, hyperhomocysteinemia and hyperexpression of activating genes such as JAK2 and STAT5 are all features characteristic of PV and ET that may contribute, along with other risk factors, to the development and progression of atherothrombosis. Cytotoxic treatment in PV and TE may be beneficial both through its antiproliferative effect on hematopoiesis and on the atherosclerotic plaques, atherogenesis being described as a proliferative disease of the vessel wall.

The effect of Simvastatin upon serum pseudocholinesterase and plasmatic factor VII.

UNLABELLED: The statins have a moderate lowering effect upon triglycerides, one hypothesis suggesting an inhibitory effect upon liver VLDL synthesis. Because VLDL synthesis is related to other hepatic protein synthesis we studied the effect of Simvastatin upon serum cholinesterase activity and factor VII activity, which are also synthetized at hepatic level. METHODS: 39 patients with ischaemic heart disease, proved by coronarography and moderate hypercholesterolaemia received for two months 20 mg Simvastatin (Zocor). The value of total Co, LDLCo, HDLCo, triglycerides, serum cholinesterase activity and factor VII activity were determined before and after treatment, by standard methods. RESULTS: Triglycerides were, together with total Co, significantly lowered during the two months treatment with Simvastatin, but the values of serum cholinesterase and factor VII activity were not significantly modified. This suggests that moderate doses of Simvastatin do not depress liver protein synthesis. CONCLUSION: Simvastatin does not lower the triglycerides level through depression of liver protein syntesis, other mechanisms being probably involved.