Marco Mettimano

Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have endothelial dysfunction, which may predispose them to the risk of premature atherosclerosis. This study investigated the involvement of tumor necrosis factor (TNF) α in the pathophysiologic characteristics of this abnormality by use of the TNF‐α‐neutralizing antibody infliximab.

Eradication of Helicobacter pylori Infection Improves Blood Pressure Values in Patients Affected by Hypertension

Background.  Arterial hypertension is a risk factor for atherosclerosis of whose pathogenesis is unknown. Growing evidence underscores the causative role of endothelial dysfunction. A possible association between Helicobacter pylori infection and cardiovascular and autoimmune disorders has been found. The release of cytotoxic substances either of bacterial origin or produced by the host may represent mediators of these systemic sequelae. The aim of our study was to determine the prevalence of H. pylori infection in hypertensive patients and the effects of H. pylori eradication on blood pressure and on digestive symptoms.

Diastolic function: the influence of pneumoperitoneum and Trendelenburg positioning during laparoscopic hysterectomy

Background and objective Several reports concerning the haemodynamic changes during gynaecologic laparoscopy have been published so far, and the effects of head-down tilt and pneumoperitoneum have not been clearly separated. However, its main effect seems to be an increase in systemic vascular resistance. We investigated how the augmented afterload can affect diastolic function. Methods : Our study involved 20 healthy women, classified as having ASA status I: 10 undergoing laparoscopic hysterectomy and 10 undergoing conventional open hysterectomy. Measurements were made in awake patients and after induction of anaesthesia and then repeated after carbon dioxide insufflation and head-down positioning and at the end of surgery. Diastolic function was primarily studied by transthoracic echocardiography. Results We observed that pneumoperitoneum caused a significant reduction in stroke volume, cardiac output and left ventricular end-diastolic volume; the diastolic filling times showed a progressive reduction in the E-velocity (the velocity of early mitral inflow, corresponding to the ventricular passive filling phase, measured by pulsed-wave Doppler), a prolonged deceleration time and an augmented isovolumetric relaxation time. After head-down tilting, stroke volume, cardiac output and left ventricular end-diastolic volume increased in both laparoscopic hysterectomy and conventional open hysterectomy groups. Conclusion We have found that pneumoperitoneum has important effects on left ventricular volumes, causing a drop in left ventricular end-diastolic volume; it also affects diastolic function with a delay in deceleration time and isovolumetric relaxation time without any effects on intracavitary pressures.

Tumor Necrosis Factor-α Antagonism Improves Vasodilation During Hyperinsulinemia in Metabolic Syndrome

OBJECTIVE—Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-α. We assessed the effects of TNF-α neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. RESEARCH DESIGN AND METHODS—Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. RESULTS—Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. CONCLUSIONS—TNF-α neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.

Association between altered circadian blood pressure profile and cardiac end-organ damage in patients with renovascular hypertension

Background: Patients with renovascular hypertension (RVH) have a higher degree of cardiovascular end-organ damage compared to patients with essential hypertension (EH). The precise mechanisms underlying this phenomenon, however, have not been fully elucidated. This study investigated the relationship between circadian blood pressure (BP) profile and cardiac involvement in patients with RVH and EH. Methods: Twenty patients with RVH and 20 with EH, matched for demographic characteristics, underwent simultaneous 24-hour ambulatory BP recording and Holter ECG monitoring. Also, each participant underwent echocardiographic assessment of left ventricular mass. Cardiac damage was defined as the presence of left ventricular hypertrophy, myocardial ischemia or arrhythmias. Results: Casual BP was similar in both groups, whereas 24-hour ambulatory BP values were higher in RVH than in EH patients; moreover, RVH patients had higher blood pressure variability and blunted nocturnal BP fall compared to those with EH. Left ventricular mass, as well as the prevalence of myocardial ischemia and the presence and severity of cardiac arrhythmias, were higher in RVH than in EH patients. Conclusions: Patients with RVH have altered circadian BP profile compared to those with EH. This abnormality might contribute to their increased prevalence of cardiac damage and might adversely affect the prognosis of these patients.

Differences between diabetic and non-diabetic hypertensive patients with first acute non-ST elevation myocardial infarction and predictors of in-hospital complications.

Objectives This investigation was undertaken to compare diabetic and non-diabetic hypertensive patients with a first acute non-ST segment elevation myocardial infarction (NSTEMI) and to assess the impact of clinical and laboratory parameters on the occurrence of in-hospital complications. Methods The study population comprised 112 consecutive male hypertensive patients with their first NSTEMI, who were divided into two groups according to the presence of type 2 diabetes mellitus. All patients underwent echocardiography and 24-h electrocardiographic (ECG) and blood pressure monitoring within 48 h from admission. Results Diabetic hypertensive patients had significantly higher mean daytime, night-time, 24-h systolic blood pressure and heart rate and hypertensive peaks (P < 0.01), more episodes of asymptomatic ST segment depression (P < 0.05), which were also more severe and prolonged (P < 0.01), and more episodes of non-sustained ventricular tachycardia (P = 0.01). Diabetic patients showed a greater left ventricular mass index (LVMI) and a lower left ventricular ejection fraction (LVEF) (P < 0.01). In-hospital adverse clinical events were more frequent in diabetic hypertensives compared to non-diabetics (40.3% versus 18.1%, P = 0.01). In particular, heart failure occurred during hospitalization in 33.3% versus 14.5% (P = 0.02). The difference in transient cerebral ischaemic attacks did not reach statistical significance (7.0% versus 1.8%, P = 0.18). Multivariate Cox proportional hazards analysis showed that the only independent predictors for the occurrence of in-hospital adverse clinical events in diabetic patients were: 24-h systolic blood pressure variability [relative risk (RR) = 1.013, 95% confidence interval (CI) = 1.001–1.025, P = 0.03]; mean 24-h heart rate (RR = 7.05, 95% CI = 1.35–35.9, P = 0.02) and the LVMI (RR = 1.9, 95% CI = 1.121–3.785, P = 0.02). Conclusions This study indicates that in-hospital complications, including heart failure and transient cerebral ischaemia, occur frequently during the acute phase of a first NSTEMI in patients with both diabetes and hypertension. The coexistence of diabetes and hypertension doubles the risk of complications with respect to hypertension alone. In addition, adverse events may appear despite an initial uncomplicated clinical presentation, which can be predicted by the early assessment of heart rate and blood pressure behaviour and by the echocardiographic assessment of left ventricular mass.

NT-proBNP: A marker of preclinical cardiac damage in arterial hypertension.

BACKGROUND The cardiac left ventricle responds to pressure overloads with mechanisms culminating in irreversible structural/functional cardiac alterations (left ventricular hypertrophy and/or diastolic dysfunction), inducing myocardial cells to secrete natriuretic peptides (NT-proBNP) antagonists of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the diagnostic accuracy of serum NT-proBNP levels in order to detect structural/functional cardiac diseases assessed by echocardiography. METHODS A total of 126 consecutive newly diagnosed, never before treated, hypertensive patients (30-67 years) were enrolled, and clinical, echocardiography parameters and biochemical data were collected. Our reference was the presence of structural/functional cardiac disease (CSFD) and our index text was the serum NT-proBNP levels. RESULTS NT-proBNP levels in CSFD patients were ~2 times higher than in non-CSFD subjects (median 61 vs 29 ng/L, n=50 and 76, respectively); in addition, 60% of CSFD subjects (only 14% of which with pathological levels, >125 ng/L), and 30% without CSFD showed NT-proBNP concentrations higher than 50 ng/L. However, ROC curves demonstrated a low specificity (38%) (calculated at 90% sensitivity at a cut-off of 22.5 ng/L). DISCUSSION NT-proBNP levels, as a screening tool for cardiac structural/functional disease, appear to be limited, because of the low specificity. However, the strong association between its concentration and the establishment of irreversible cardiac hypertrophy prompts successive studies aimed to ascertain the use of its serum levels as an early alert indicator of disease severity.

Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators

Endothelial expression of cell adhesion molecules (CAMs) plays an important role in atherosclerosis. Atherosclerosis is increased in hyperinsulinemic states, but whether insulin per se is proatherogenic remains unclear. To investigate the effects of hyperinsulinemia on CAM expression, plasma levels of ICAM-1, VCAM-1 and E-selectin were measured before and after forearm infusion of insulin in healthy subjects. Insulin administration for 2 h resulted in signifi-cant hyperinsulinemia, whereas no significant change was observed in soluble CAMs (all p > 0.05). Because insulin stimulates endothelial release of both endothelin-1 (ET-1) and nitric oxide (NO), which may modulate the expression of CAMs, we also investigated the response of CAMs to ET-1 receptor blockade, alone and in combination with NO synthesis inhibition. ET-1 receptor blockade during hyperinsulinemia resulted in a vasodilator response, but did not affect soluble CAMs (all p > 0.05). Superimposition of NO inhibition by l-NMMA reversed the vasodilator effect of ET-1 blockade, without affecting soluble CAMs (all p > 0.05). In conclusion, acute hyperinsulinemia, alone or during ET-1 and NO pathway blockade, does not affect soluble CAMs. These results do not support a direct effect of insulin on endothelial cells to affect leukocyte adhesiveness to the vascular wall.