Domenico Melina

Ghrelin Improves Endothelial Function in Patients With Metabolic Syndrome

Background— Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect endothelial function in metabolic syndrome. Methods and Results— Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 &mgr;g/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P=0.008) in patients with metabolic syndrome (n=12, 5 female) compared with controls (n=12, 7 female), whereas the vasodilator response to SNP was not different between groups (P=0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls (P=0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (P<0.001) and resulted in a potentiation of the vasodilator response to acetylcholine (P=0.001 versus saline) but not to SNP (P=0.22). This effect was likely related to enhanced nitric oxide bioavailability because, in a group of patients with metabolic syndrome (n=6, 2 female), ghrelin had no effect on the vasodilator response to acetylcholine (P=0.78 versus saline) after nitric oxide inhibition by NG-monomethyl-l-arginine. Conclusions— These findings indicate that ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in these patients, might play a role in the pathobiology of atherosclerosis.

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.

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.

Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis.

OBJECTIVEnImpaired endothelium-dependent vasodilator function may contribute to vascular damage in patients with systemic sclerosis (SSc). This study was undertaken to investigate whether increased activity of the endothelin 1 (ET-1) system plays a role in the occurrence of endothelial dysfunction in patients with SSc.nnnMETHODSnIn 12 patients with SSc (6 with diffuse cutaneous SSc [dcSSc] and 6 with limited cutaneous SSc [lcSSc]), forearm blood flow responses to graded doses of acetylcholine (ACh) and sodium nitroprusside (SNP) given intraarterially were assessed by plethysmography, during infusion of saline and following selective blockade of ETA receptors with BQ-123 (10 nmoles/minute).nnnRESULTSnDuring saline infusion, the vasodilator response to ACh was blunted in patients with SSc as compared with that in healthy controls (P<0.001), whereas the response to SNP was not different between groups (P=0.27). The vasodilator effect of ETA receptor antagonism was higher in patients than in controls (P<0.001), indicating enhanced ET-1-mediated vasoconstriction in SSc. In patients, ETA receptor blockade resulted in a potentiation of the vasodilator response to ACh (P<0.001 versus saline), but did not affect the response to SNP (P=0.31). Notably, both the vasodilator effect of ETA receptor antagonism and the improvement in the responsiveness to ACh following BQ-123 infusion were higher in patients with dcSSc than in those with lcSSc (P<0.01).nnnCONCLUSIONnET-1-dependent vasoconstrictor tone is increased predominantly in the subgroup of SSc patients with dcSSc, in whom acute blockade of ETA receptors was able to improve impaired endothelium-dependent vasodilator function. Our results suggest novel vasculoprotective effects of ETA receptor antagonism and support further exploration of strategies that target the ET-1 pathway in SSc.

Blood Pressure Variations, Hemorheological Determinants, and Platelet Aggregation in Hypertensive Patients with Unstable Angina

Plasma viscosity, fibrinogen, haematocrit and beta-thromboglobulin were assessed on venous blood samples taken within 24 hours of admission from 20 consecutive male hypertensive patients with unstable angina and 20 male hypertensive patients with stable angina, matched for clinical variables. Besides, all patients underwent automated indirect blood pressure monitoring for 24 hours, starting just after hospitalization. Despite similar average 24-hour, day-time and night-time systolic and diastolic blood pressure, hypertensive patients with unstable angina showed an increased variability of 24-hour (p <0.01) and day-time (p < 0.05) systolic and disatolic blood pressure, together with higher values of all haemorhelogical parameters (plasma viscosity, fibrinogen and haematocrit) (p < 0.01) and beta-thrombogobulin (p< 0.05), when compared with hypertensive patients with stable angina. Moreover, significant correlations between plasma viscosity and 24-hour systolic (r = 0.42, p < 0.01) and diastolic (r = 0.39, p < 0.05) blood pressure variability were shown in hypertensive patients with unstable angina. Besides, in the same patients, the haematocrit was positively correlated with 24-hour systolic blood pressure variability (r = 0.37, P < 0.05). Our data further support the relevance of rheological determinants, platelet activation and haemodynamic factors in the genesis of the high risk condition of unstable angina.

Heart rate variability and ventricular ectopic activity in hypertensive patients

In order to investigate whether the severity of ventricular ectopic beats in hypertensive patients is influenced by the autonomic drive to the heart, we evaluated the relationship between the degree of dysrhythmias and 24-h spontaneous heart rate variability, an index of sympatho-vagal balance at cardiac level. Ambulatory 24-h ECG monitoring was used to examine 42 untreated essential hypertensives, previously scored for the presence and the extent of hypertensive target organ damage. No significant difference was found in the prevalence of complex ventricular ectopic beats in patients with a heart rate variability that was lower and higher than the arbitrary cut off points selected to divide subjects into groups. Neither heart rate variability nor the degree of arrhythmias was correlated with blood pressure levels, whereas the degree of ectopy was influenced by the presence of target organ damage and left ventricular hypertrophy (by ECG). Our results seem to exclude an association between dysrhythmias in hypertensives and autonomic outflow to the heart as detected by the analysis of heart rate variability.

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.

ACUTE ABDOMINAL SYMPTOMS IN MALIGNANT HYPERTENSION: CLINICAL PRESENTATION IN FIVE CASES

Malignant hypertension causes anatomical and functional damage in several target organs, in particular brain, retina, heart and kidneys. Although vascular lesions in the gastroenteric tract are known to occur in several instances, their clinical relevance is unknown. In this study five cases of malignant hypertension, presenting with acute abdominal symptoms, are reported. A history of essential arterial hypertension was present in three patients; while one patient had a previous diagnosis of renovascular hypertension and one patient had renoparenchymal hypertension. However, in all cases the antihypertensive treatment was discontinued and inadequate before the accelerated malignant phase. The acute abdominal symptoms at presentation were due to intestinal infarction in 3 patients and acute pancreatitis in 2 patients. One patient with intestinal infarction died of postoperative cardiogenic shock. Our data are in agreement with previous reports describing the possible intra-abdominal complications of malignant hypertension. The therapeutic approach in such conditions should always consider an effective antihypertensive treatment in conjunction with surgical options.

Ambulatory blood pressure and left ventricular mass in alcohol-associated hypertension

Abstract Twenty-five hypertensive male alcoholic patients and 25 men with mild-to-moderate essential hypertension underwent echocardiographic examination, followed by ambulatory blood pressure monitoring for 24 hours. (Twenty normotensive men served as controls.) The left ventricular mass index of the hypertensive alcoholic patients was significantly higher than that of the patients with essential hypertension ( P P r = .52; P r = .44; P r = .54; P