Quantitative evaluation of microvessels in Behçet's disease.
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Publications and source records attributed to A Palazzuoli.
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Platelets and monocytes are involved in atherothrombosis via tissue factor expression. Moreover, they are activated in hypercholesterolemia, a classic risk factor for atherothrombosis. Cholesterol-lowering drugs (statins) reduce cardiovascular risk either by decreasing cholesterol or non-lipidic actions, such as platelet and monocyte activity. The aim of our study was to evaluate the effect of several statins on platelet and monocyte activity in hypercholesterolemic subjects. Platelet activity (P-selectin, cytofluorimetric detection), tissue factor levels (ELISA) and activity (detected in whole blood and cellular preparations by a specific clotting assay) were measured in hypercholesterolemic subjects (41 males, 23 females, aged 34-65 years, total cholesterol 6.86+/-0.60 mmol/l) treated with atorvastatin 10 mg, simvastatin 20 mg, fluvastatin 40 mg, or pravastatin 40 mg for 6 weeks. P-selectin and tissue factor expression in whole blood and isolated cells were increased in hypercholesterolemic subjects with respect to controls (all P<0.001). Simvastatin, atorvastatin, and fluvastatin reduced monocyte procoagulant activity in whole blood and P-selectin (P<0.01). Tissue factor antigen and activity in isolated cells were further reduced (all P<0.05) independently of cholesterol lowering. Pravastatin decreased tissue factor expression in whole blood in direct relationship to reduction of P-sel and cholesterol (P<0.05). Our data show a different impact of several statins on monocyte tissue factor expression in whole blood, suggesting a possible role of decreased platelet activity and a direct action on monocytes. In contrast, pravastatin decreased monocyte procoagulant activity with relation to cholesteroldependent modifications of platelet function.
Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before echocardiography, it was an occasional autoptic finding. With the development of ultrasonographic techniques, it is currently possible to carry out diagnosis in vivo. We report the case of a young woman with cerebral ischemia who was successfully treated by intra-arterial fibrinolysis with complete clinical resolution. Transesophageal echocardiography (TEE) identified a papillary fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of the tumor was performed. Sudden cerebral or peripheral embolization is frequently linked to thrombotic material which surrounds the neoplasm, and thus can be successfully treated with local fibrinolysis.
Inflammatory and lipid factors share an important role in atherosclerosis. Recent studies showed the concomitant presence and increase of complement components and lipids both in the atherosclerotic plaque and the circulating blood. The aim of this study was to examine the relationship between the complement system and lipid disorders. We evaluated the circulating complement terminal complex C5b-9, a clear sign of complement activation, in three groups of 30 patients the first with hypercholesterolemia, the second with hypertriglyceridemia (associated with low values of HDL-cholesterol), the third with low levels of HDL-cholesterol compared with an equivalent group of matched normolipemic subjects. We found a significant increase of sC5b-9 in each group of patients compared with controls. The mean sC5b-9 level in the hypercholesterolemic population was 366.2 +/- 141.2 ng/ml (P<0.01), 395.4 +/- 118.2 ng/ml in the hypertrygliceridemic group (P<0.01), 414.8 +/- 126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0 +/- 40.8. ng/ml in the control group. Regression analysis showed a significant direct correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse correlation between sC5b-9, HDL-chol (r=-0.74), and apo-A1 (r=-0.68); no significant relationship was found between sC5b-9 and cholesterol. We suggest that complement activation is associated with the various lipid disorders and is more important in those dyslipidemic conditions in which other factors may be involved. In particular, hypertriglyceridemia may be associated with endothelial and fibrinolytic disturbances, and the decrease of HDL may induce the failure of the regulatory proteins transported by the same HDL.
BACKGROUND: Recent studies have shown that carvedilol therapy in patients with heart failure improves clinical outcome and survival, however, the effects of such treatment on left cardiac morphology and function in elderly patients with severe heart failure has not been widely studied. AIM: The purpose of this study was to establish the effect of carvedilol at short- and long-term on left ventricular size and performance with mono- and two-dimensional echocardiography, in subjects with dilated cardiomyopathy, NYHA III functional class, low LV ejection fraction (EF < 35%) and mean age of > 70 years. METHODS: We studied 48 patients, previously randomized to treatment with either carvedilol or placebo, and we performed echocardiographic evaluation at the start, and after 3 and 12 months. Left ventricular diameters, LV mass and fractional shortening were calculated by Deveraux formula; left ventricular volumes and ejection fraction were measured by area-length formula; pulmonary pressure was calculated by tricuspid reflow. RESULTS: After 3 months, only LV end-diastolic diameter was lower in the carvedilol group compared to the placebo group. Nevertheless, after 12 months, patients on carvedilol treatment showed a LV geometric and functional improvement compared to placebo. We found significant differences in: diastolic (P < 0.01) and systolic diameters (P < 0.001); on LV mass (P < 0.002); on LV systolic volume (P < 0.03); and on LV ejection fraction (P<0.01). Pulmonary pressure was also reduced in beta-blocker subjects (P < 0.001). CONCLUSIONS: Carvedilol therapy for 12 months reduced LV diameters and volumes. Thus, improving cardiac remodeling and LV systolic function in elderly patients with severe heart failure. Several months of therapy are required for these favorable effects to occur, as these changes do not occur in the short term.
The role of H. pylori infection in increasing the risk of ischemic heart diseases (IHD) is still debated. We determined serologically the prevalence of overall H. pylori and CagA-positive H. pylori infection in 63 consecutive patients with IHD and 189 gender- and age-matched controls. We also determined in patients the influence of the infection and the CagA serological status on the results of an exercise ECG test and other parameters considered possible variables that may enhance the risk of IHD. The prevalence of H. pylori infection in patients and controls was 79.3% and 73.0%, respectively (P = 0.403) and that of CagA-positive H. pylori infection was 69.8% and 42.3%, respectively (P = 0.0002). The scores of the ECG S-T segment and T-wave abnormalities in the course of an exercise ECG in uninfected patients and in patients infected by CagA-negative and CagA-positive H. pylori strains were (mean +/- SD): 1.59 +/- 0.67, 1.92 +/- 0.64, and 2.19 +/- 0.70, respectively; (P = 0.011, 95% confidence limits of difference 0.15-1.07, CagA-positive infected vs uninfected patients). There was no intergroup difference in the levels of peripheral white blood cells, glucose, cholesterol, triglycerides, creatinine, and systolic and diastolic pressure. In conclusion, genetic heterogeneity of H. pylori could possibly explain some conflicting results concerning the association of H. pylori infection with IHD. Coronary vessels of IHD patients infected by CagA-positive H. pylori strains may be damaged more severely than those of uninfected patients.
BACKGROUND: Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL-C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day-1), atorvastatin (10 mg day-1), fluvastatin (40 mg day-1) and pravastatin (40 mg day-1) on platelet function in hypercholesterolaemic subjects with relation to (LDL-C), oxidized-LDL (ox-LDL) and antiport mechanism modifications. MATERIALS AND METHODS: Sixteen subjects were assigned to each treatment (40 males, 24 females, mean age 48.7 +/- 13.4, LDL-C 5.13 +/- 0,23 mmol L-1) and evaluated for platelet surface P-selectin (P-sel), lipid profile, ox-LDL, platelet-associated ox-LDL (Pox-LDL), platelet cholesterol content, antiport mechanisms, and intracellular and systemic NO synthase every 7 days for one month. RESULTS: Our data show a strong relation between enhanced P-sel and Pox-LDL (r = 0.68, P < 0.01). Simvastatin, atorvastatin, fluvastatin and pravastatin reduce platelet activity after 1, 2, 3 and 4 weeks of treatment, respectively (P < 0.001, P < 0.001, P < 0.01, P < 0.05). Pox-LDL are modulated early by simvastatin, atorvastatin and fluvastatin Pox-LDL (r = 0.66, 0.65 and 0.52; P < 0.001, 0.001 and 0.01, respectively) whereas LDL-C and ox-LDL reductions associated to modifications of antiport activity act later. Moreover, they are the most relevant finding in pravastatin-related subjects. CONCLUSIONS: Our data suggest a different impact of several statins on platelet function, which is initially related to interference with Pox-LDL rather than LDL-C reduction.
BACKGROUND AND AIM: Platelets are strictly involved in arterial thrombosis and their hyperactivity has been shown in hypercholesterolemia. It has been reported that drugs affecting cholesterol metabolism (statins) decrease cardiovascular events by lowering lipid levels or by means of non-lipidic actions such as the direct inhibition of platelet function. The aim of this study was to detect the effect on platelet-dependent thrombin generation (PDTG) of a reduction in cholesterol obtained by means of a lipid-lowering diet or treatment with statins. METHODS AND RESULTS: We compared PDTG (T0) in 144 hypercholesterolemic subjects (94 males and 50 females of child-bearing age, mean age 48.2 +/- 13.8, plasma total cholesterol 6.93 +/- 0.64, high density lipoprotein cholesterol 1.25 +/- 0.14, triglycerides 1.15 +/- 0.19 mmol/L) and 70 normolipidemic controls (37 males and 33 females, mean age 43.1 +/- 12.6. After six weeks on an appropriate diet, the patients were randomised to receive different statin therapies if there was no reduction in their lipid profile and/or PDTG (T1). They were re-evaluated six weeks later, and the drug doses were maintained or increased on the basis of the variables (T2). A final evaluation was made after a further six weeks (T3). All of the data were evaluated using ANOVA and Spearman's correlation coefficent. The results showed increased PDTG in hypercholesterolemic subjects (418.2 +/- 29.2 mIU/mL, p < 0.001 vs controls). Diet alone did not reduce PDTG (380.2 +/- 28.5 mIU/mL, p = 0.226 vs controls). At T2, simvastatin and atorvastatin significantly decreased PDTG (P < 0.001 vs T0-1) and low-density lipoprotein cholesterol (LDL-C). No correlation was found between the two variables in the simvastatin group (r = 0.16). Cerivastatin reduced PDTG without significantly decreasing LDL-C (p < 0.001 and p = 0.476, r = 0.14). Pravastatin and fluvastatin significantly reduced thrombin generation only at T3 (40 mg/day); pravastatin was also associated with a decrease in LDL-C (p < 0.01, r = 0.66). CONCLUSIONS: Our results confirm an increased PDTG in patients with type IIa hyperlipoproteinemia, which is not reduced by diet. Statins at different doses significantly decrease PDTG but do not correlate with a reduction in LDL-C.
To determine whether there is a correlation between fibrinolytic activity and dyslipidemia, we performed a study of 72 subjects (20 patients with hypercholesterolemia, 20 with hypertriglyceridemia, 12 with isolated low high-density lipoprotein (HDL)-cholesterol (mean age 47.7 +/- 6.3, body mass index 24.7 +/- 0.4) and 20 healthy controls. Plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were detected at baseline and after venous occlusion test. We also measured at baseline lipidic pattern, soluble E and P selectins (sE-sel, sP-sel), prothrombin factor 1+2 (F1+2), lipoprotein(a), factor VII, plasma insulin, fibrinogen, homocysteine, and thrombin activable fibrinolysis inhibitor (TAFI) activity. Fibrinolysis was significantly reduced in hypertriglyceridemic patients compared with hypercholesterolemic patients and control subjects (PAP, p < 0.01 and p < 0.001) and was associated with increased PAI-1 (at baseline and after venous occlusion test, p < 0.001). sP-sel, F1 +2 and TAFI were not significantly different compared with controls, while hypercholesterolemic subjects showed a significant increase in these parameters (p < 0.001), which were related to decreased PAP only at the upper low-density lipoprotein (LDL)-cholesterol levels (>160 mg/dl) (p < 0.001, r = -0.76). Moreover, there was no significant difference in PAI-1 activity (at baseline and after venous occlusion test) compared with controls. In conclusion, endothelial dysfunction was the main mechanism of decreased fibrinolysis in subjects with hypertriglyceridemia and low HDL-cholesterol, while enhanced thrombin generation and TAFI activity were the main determinants in hypercholesterolemia.
Pathologies of cerebral circulation are one of the most frequent causes of mortality and morbidity among the populations of Western countries. The incidence of ischemic events presumed to have a cardioembolic origin varies from 13% to 34% in the largest international multi-center studies. However, some authors have reported an incidence of general cardiogenic stroke ranging from 23% to 36% in younger patients. Transesophageal echocardiography (TEE) is a useful investigation for identifying cardiac sources of embolism in patients without vascular alterations involving the carotid and vertebral districts. This study comprised 73 patients with unexplained stroke who were investigated by both transthoracic echocardiography (TTE) and TEE. Vascular echocolor sonography had been performed in all of them with negative results. TEE demonstrated: atrial or ventricular thrombosis in 6 patients (8%), intracavitary neoplasm in 2 (2%), spontaneous echocontrast in 11 (13%), valve strands in 6 (7%), complex aortic plaque in 10 (11%), patency of the foramen ovale in 17 (19%), atrial septal aneurysm in 9 (11%), dystrophy and mitral calcifications in 9 (11%). In the other 18 patients, TEE did not reveal any anomalies. Definite sources of stroke (clots and tumors) were identified in 14% of all the lesions; however, the majority (86%) were potential sources. A comparison of the two echocardiographic techniques demonstrated a greater sensitivity and specificity of TEE. Although TEE was superior to TTE for identifying and evaluating potential embolic sources, we found both methods to be useful and would advise performing TTE before TEE. While TTE is not capable of identifying the majority of anomalies, it does provide useful information to guide subsequent transesophageal investigations.
In a 70-year-old man admitted to our hospital because of repeated episodes of transient disorientation, an ECG showed a recent inferior myocardial infarction. A two-dimensional echocardiography detected hypo-akinesia in the apex region, where a hyperechogenic oval and pedunculated mass with a maximum diameter of 1.5 cm, attributable to an organized thrombus, was located. After 20 days of therapy with calcium-heparin at a dose of 12,500 IU every 8 h, a two-dimensional echocardiography showed the complete disappearance of the mass. This and other recent reports confirm the thrombolytic activity of the drug and the possibility of postponing the immediate surgical removal of intraventricular thrombi in favour of heparin treatment.
The aim of this study was to establish if the physiologic adaptations following a prolonged physical training could influence the diastolic function in a professional Olympic male runner group. From February to December 1999 we studied 25 athletes (Group I) during the period of maximal training compared with 18 healthy sedentary subjects of matched age and sex (Group II). We used mono and bidimensional Echocardiography to assess left ventricular structure and systolic function. The diastolic function was evaluated by Doppler method assessing transmitral and venous pulmonary flow. From the comparison between the two groups, we found great differences in the interventricular septum and the posterior wall thickness; the analysis of the systolic function demonstrated a significant increase in ejection fraction, stroke volume, left ventricular mass, and end-diastolic volume in the athletes' population. Fluximetric study of transmitral and pulmonary venous flow showed that ventricular diastolic function is not influenced by hypertrophy. Our data indicate that diastolic function remains normal or improves in some cases after physical training; left ventricular hypertrophy and concentric remodeling do not involve diastolic changes like hypertrophic and hypertensive heart diseases.
Carvedilol is a cardiovascular drug of multifaceted therapeutic potential, with beta-blocker and vasodilatative activity. These actions confer to the above mentioned betablocker some beneficial properties on several processes involving cardiovascular system. Carvedilol provides haemodynamic, antiischemic, antiproliferative and antiarrhytmic benefits, for its antioxidant neurohumoral and electrophysiological effects. All these actions provide the basis for usefulness of the drug in the treatment of hypertension, coronary heart disease, and congestive heart failure. In this review we report the beneficial properties of Carvedilol and we analyze the rational clinical use of this betablocker taking special attention on recent clinical trial in heart failure where it appears an evidence supporting an important, favourable effect of the drug.