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.

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-alpha 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)-alpha. We assessed the effects of TNF-alpha 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-alpha 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.

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.

The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly.

The aim of this longitudinal study was to evaluate the echocardiographic outcome of acromegalic heart disease in patients undergoing different therapeutic approaches, in order to investigate whether SSA could provide therapeutic advantages as compared with neurosurgery. In total of 36, consecutive patients undergoing SSA treatment after neurosurgery were enrolled in this study (Gr.Surg.-SSA). After 12 months of treatment, 21 patients had a controlled disease, while the remaining 15 patients displayed uncontrolled disease. Twelve acromegalic patients who did not undergo SSA treatment due to controlled disease after neurosurgery were enrolled as control group (Gr.Surg). The echocardiographic-Doppler study was performed before neurosurgery and after 12-months of follow-up. After follow-up, a significant reduction in serum GH and IGF-I values, Left Ventricular Mass index (LVMi) and LVH rate with an improvement in diastolic function was observed in both groups of patients. We found a significant reduction of LVMi either in patients with controlled disease or in those with poorly controlled disease undergoing SSA treatment. Diastolic function and of LVH percentage improved in all groups, but significantly so only in controlled patients, no significant difference in any echocardiographic parameters and in the prevalence of the LVH rate were observed between the three groups of patients at the end of follow-up. Therefore, our data appear to show that for echographic parameters medical treatment additive beneficial effects is compared to neurosurgery alone. SSA also appears to contribute to the improvement of acromegalic cardiomyopathy also in patients who did not achieve biochemical control of the disease.

Selective cardiac neuroadrenergic abnormalities in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: Increased sympathetic drive to the heart might contribute to the development and progression of myocardial damage in hypertensive patients (HTs). This study assessed the possible presence of abnormalities in myocardial uptake of (123)I-metaiodobenzylguanidine (MIBG), a marker of sympathetic activity, in HTs with left ventricular hypertrophy (LVH). METHODS: Eleven HTs with LVH and 10 matched normotensive controls underwent clinical and laboratory examination, as well as LVH determination by echocardiography. The presence of myocardial ischemia was ruled out by exercise stress testing. Global and regional myocardial uptake of (123)I-MIBG was determined in both groups using planar and single proton emission tomography scintigraphy. In addition, thallium-201 (Tl-201) myocardial scintigraphy was performed in HTs. The heart/mediastinum (H/M) ratio on planar (123)I-MIBG images at different time points was compared between HTs and controls. Moreover, regional cardiac uptake of (123)I-MIBG was compared between groups and, within the HTs group, with regional Tl-201 uptake. RESULTS: At all study times, the H/M ratio was lower in HTs than in controls (all p <0.05). A significant reduction in (123)I-MIBG uptake in the mid-inferolateral and mid-inferior segments was observed in HTs compared to controls. Also, a significant reduction in (123)I-MIBG uptake compared to Tl-210 uptake was observed in non-septal segments of HTs. CONCLUSIONS: Cardiac abnormalities in global and regional uptake of (123)I-MIBG, as well as impaired (123)I-MIBG compared to Tl-201 uptake, are present in HTs with LVH. Given the effect of sympathetic nervous system on the heart, these abnormalities might play a role in hypertension-related cardiac damage.

Blood pressure regulation by CCR genes.

New genetic evidence strongly supports a role for the immune system in the pathogenesis of essential hypertension (EH) through chemokines and their receptors (CCR) involvement. The aim of the present study was to evaluate the possible relation between CCR2 and CCR5 alleles and blood pressure (BP) levels in hypertensive subjects. In all, 118 essential hypertensive outpatients (male 90, female 28; stage I and II; age 27-54 years; not previously treated with antihypertensive drugs) were selected for the study. All of the subjects underwent office BP measurement. Subsequently, 24-h ambulatory BP monitoring (ABPM) was performed with a Spacelabs 90207 monitor during a regular working day. CCR264I and CCR5Delta32 polymorphisms were determined by polymerase chain reaction (PCR), following the standard molecular biology protocols. Allelic frequencies were the following: CCR5Delta32= 0.097, CCR264I=0.101. Logistic regression analysis showed an association between the CCR5Delta32 allele and the following: 24-h systolic BP (SBP >140 mmHg; p = 0.027), values over the 50th percentile of 24-h SBP (p = 0.032), and the values over the 50th percentile of nighttime SBP (p = 0.039). Office BP showed an association with the Delta32 allele in a range over the 75th percentile of SBP (p = 0.087) and the 75th percentile of DBP (p = 0.085). No significant association was observed for CCR264I and BP levels or between physiological nocturnal BP decline and genotype. The observed results not only support the role of the immune system in the development and maintenance of hypertension, but they also indicate an influence of CCR5Delta32 polymorphism on the establishment of BP levels.

Intravascular tumor necrosis factor alpha blockade reverses endothelial dysfunction in rheumatoid arthritis.

BACKGROUND: 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) alpha in the pathophysiologic characteristics of this abnormality by use of the TNF-alpha-neutralizing antibody infliximab. METHODS: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside, respectively, were assessed by strain-gauge plethysmography in patients (n = 10) with early RA during saline solution infusion and after intra-arterial infusion of infliximab (200 microg/min). RESULTS: Circulating markers of systemic inflammation (C-reactive protein and interleukin 6) were higher in patients than in control subjects (n = 10, both P < .05), whereas plasma levels of TNF-alpha and soluble TNF receptor types 1 and 2 were similar in both groups (all P > .05). During saline solution infusion, the vasodilator response to acetylcholine was blunted in patients with RA compared with control subjects (14.2 +/- 9.2 mL . min-(1). dL-(1) versus 23.7 +/- 9.2 mL . min-(1). dL-(1) at the highest dose, P = .004) whereas vasodilation to sodium nitroprusside was not different between groups (P = .10). In patients with RA infliximab did not modify circulating C-reactive protein levels (P = .29, versus saline solution) but did potentiate the vasodilator response to acetylcholine (21.0 +/- 11.1 mL . min-(1). dL-(1); P = .004, versus saline solution). The response to sodium nitroprusside, in contrast, was not modified by infliximab (P = .28 versus saline solution). CONCLUSIONS: Intravascular administration of anti-TNF-alpha antibody ameliorates endothelial function in patients with RA but does not concurrently affect systemic inflammatory changes. Our findings suggest that enhanced TNF-alpha generation within the vessel wall, rather than systemic mechanisms, plays a role in the pathobiologic features of endothelial dysfunction in RA.

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 2h resulted in significant 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.

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.

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. MATERIALS AND METHODS: Seventy-two hypertensive patients (34 male and 38 female; mean age 53 +/- 12 years) and 70 normotensive controls (35 male and 35 female; mean age 52 +/- 10 years) were enrolled. All patients were subjected to a first ambulatory blood pressure monitoring (ABPM) at enrollment, a 13C urea breath test and a test for IgG-CagA antibodies, and completed the validated dyspepsia questionnaire. H. pylori-positive patients were treated with triple therapy (amoxicillin, clarithromycin and ranitidine bismute citrate) for 7 days. Control of eradication was assessed by 13C urea breath test, and all patients underwent a second ABPM 6 months after enrollment. RESULTS: H. pylori infection was 55% in hypertensive patients, with 90% CagA positivity, and 50% in controls, with 60% CagA positivity. At the first ABPM, blood pressure values were similar in H. pylori-positive and -negative individuals; positive patients showed a significant increase in pyrosis and epigastric pain compared to negative patients. H. pylori was eradicated in 80% of patients and in 85% of controls. At the second ABPM, we found a statistically significant decrease in 24-hour mean blood pressure values when compared to the first ABPM only in the eradicated hypertensive group. CONCLUSIONS: Our study demonstrated a significant decrease in blood pressure values, in particular in diastolic blood pressure values, after H. pylori eradication in hypertensive patients. A high prevalence of CagA positivity was found. The association between cardiovascular disease and H. pylori infection seems pronounced only in CagA-positive patients. The possible links between hypertensive disease and H. pylori infection may involve the activation of the cytokine cascade with the release of vasoactive substances from the primary site of infection, or molecular mimicry between the CagA antigens of H. pylori and some peptides expressed by endothelial cells and smooth muscle cells.