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Biomedical subjects

Claudio Ferri

Publications and source records attributed to Claudio Ferri.

At least 19 recordsLinked to original sources
PubMed2007

Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease.

BACKGROUND: Hypertensives with a blunted nocturnal blood pressure (BP) decrease have increased risk of developing atherosclerotic disease. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. Therefore, we evaluated the relationship between circulating sCD40L levels, circadian BP profile, and early carotid atherosclerosis in essential hypertensives. METHODS: Plasma sCD40L concentrations were assessed in two groups of 25 never-treated hypertensives, without additional cardiovascular risk factors, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (nondippers) of daytime values, and in 25 matched normotensives. Carotid intima-media thickness (IMT) was also measured in all participants. RESULTS: Plasma sCD40L concentrations were higher in nondippers (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/- 0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P < .0001). The IMT was higher in both hypertensive groups than in normotensives (P < .0001). In the entire hypertensive population IMT directly correlated with circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P = .004). CONCLUSIONS: Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.

Blood Pressure↗
PubMed2006

Inhibition of phosphodiesterase type 5 with tadalafil is associated to an improved activity of circulating angiogenic cells in men with cardiovascular risk factors and erectile dysfunction.

Circulating angiogenic cells (CACs) contribute to repair of the vessel wall and dysfunctional CACs are associated to endothelial dysfunction in men with vascular risk factors (VRFs). We investigated whether inhibition of phosphodiesterase type 5 (PDE5) in men with erectile dysfunction (ED) and VRFs is accompanied to changes of CACs and to changes of endothelial function. Thirty-six men with ED and VRFs were randomised to 4 weeks of tadalafil (20mg/other day) or placebo treatment. The number of ex vivo expanded functional CAC's, identified by uptake of 1,1'-dioctadecyl-3, 3,3', 3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (DiLDL) and concomitant Ulex europaeus agglutinin I (UEA-1) binding, was determined at baseline and after treatment. The number of cells double positive for DiLDL and for UEA-1, per high-power field fluorescence microscopy was significantly reduced in patients compared to 10 controls (26.88+/-6.3 and 74.41+/-17.1, respectively; P<0.0001) and was markedly increased after tadalafil treatment (40.69+/-13.07 versus 25.82+/-6.49; P<0.0001). The percentage variation of CACs number and of flow-mediated dilation in the brachial artery by ultrasound after treatment was significantly associated to the presence of endothelial dysfunction at baseline. In conclusion, the increased number of functional CACs after tadalafil treatment suggests a beneficial effect of prolonged PDE5 inhibition on vascular homeostasis.

Adult↗
PubMed2006

Enhanced soluble CD40 ligand and Alzheimer's disease: evidence of a possible pathogenetic role.

It has been suggested that cerebrovascular factors contribute to Alzheimer's disease. Soluble CD40 ligand (sCD40L) is directly involved in the development of vascular damage. We tested the hypothesis that sCD40L may be enhanced in Alzheimer's disease and predictive of its clinical course. Plasma sCD40L levels were evaluated in three groups of 40 consecutive patients each referring for mild or moderate or severe Alzheimer's disease, as assessed by the Clinical Dementia Rating (CDR), and in 40 healthy subjects. Seventy-seven patients with mild or moderate disease were re-evaluated after 2 years. Cross-sectional comparisons revealed higher plasma sCD40L levels in Alzheimer's disease patients than in controls (9.3+/-4.7 ng/mL versus 3.4+/-1.3 ng/mL, p<0.0001). Circulating sCD40L levels significantly increased through the three CDR stages (p=0.0011 or less) and were correlated with MMSE (r=-0.574, p<0.0001) and ADAS-cog subscale (r=0.538, p<0.0001) scores. Longitudinal evaluation identified sCD40L as an independent predictor of MMSE (beta=-0.157, t=-3.650, p=0.0005) and ADAS-cog subscale (beta=0.484, t=3.890, p=0.0002) score changes after 2 years. Patients with plasma sCD40L level>or=6.0 ng/mL, identified by ROC curve analysis as the best discriminating value for disease progression, had a three-fold increase in the risk of progression toward a worse CDR stage (odd ratio: 3.0, C.I. 95% 1.2-8.1). In conclusion, circulating sCD40L is enhanced in patients with Alzheimer's disease and independently associated with the severity and progression of the disease. These data might suggest a pathogenetic role for sCD40L in Alzheimer's disease.

Aged↗
PubMed2006

A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients.

OBJECTIVES: We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. BACKGROUND: The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. METHODS: Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+ and K+ in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) > or =50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). RESULTS: A total of 1,180 patients (age 46 +/- 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. CONCLUSIONS: In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.

Adrenal Cortex Neoplasms↗
PubMed2006

Renal damage in primary aldosteronism: results of the PAPY Study.

Primary aldosteronism (PA) has been associated with cardiovascular hypertrophy and fibrosis, in part independent of the blood pressure level, but deleterious effects on the kidneys are less clear. Likewise, it remains unknown if the kidney can be diversely involved in PA caused by aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Hence, in the Primary Aldosteronism Prevalence in Italy (PAPY) Study, a prospective survey of newly diagnosed consecutive patients referred to hypertension centers nationwide, we sought signs of renal damage in patients with PA and in comparable patients with primary hypertension (PH). Patients (n = 1180) underwent a predefined screening protocol followed by tests for confirming PA and identifying the underlying adrenocortical pathology. Renal damage was assessed by 24-hour urine albumin excretion (UAE) rate and glomerular filtration rate (GFR). UAE rate was measured in 490 patients; all had a normal GFR. Of them, 31 (6.4%) had APA, 33 (6.7%) had IHA, and the rest (86.9%) had PH. UAE rate was predicted (P < 0.001) by body mass index, age, urinary Na+ excretion, serum K+, and mean blood pressure. Covariate-adjusted UAE rate was significantly higher in APA and IHA than in PH patients; there were more patients with microalbuminuria in the APA and IHA than in the PH group (P = 0.007). Among the hypertensive patients with a preserved GFR, those with APA or IHA have a higher UAE rate than comparable PH patients. Thus, hypertension because of excess autonomous aldosterone secretion features an early and more prominent renal damage than PH.

Albuminuria↗
PubMed2006

Limitations and discrepancies of transthoracic and transoesophageal echocardiography compared with surgical findings in patients submitted to surgery for complications of infective endocarditis.

OBJECTIVE: Transoesophageal echocardiography (TEE) is recognized to be superior to transthoracic echocardiography (TTE) in evaluating complications of infective endocarditis (IE). The aim of this study was to compare results from TTE and TEE with surgical findings, and to assess limitations and discrepancies of TEE as compared with surgical findings. METHODS: A retrospective analysis was carried out in 63 consecutive patients undergoing surgical intervention for IE-related complications. All patients were submitted to TTE and TEE before surgery. Clinical, anaesthesiological and surgical data were reviewed for all patients as well as the TTE and TEE examinations recorded on S-VHS videotape. Patients were divided into two groups according to the time elapsed from TEE to surgery (> 72 h in group A and < 72 h in group B). RESULTS: The study population included 44 patients with native valve endocarditis and 19 patients with prosthetic valve endocarditis for a total of 76 affected valves (54 native and 22 prosthetic valves). No significant differences were observed between groups in number of patients (31 vs. 32; P = NS), of native valves (29 vs. 27; P = NS), and of prosthetic valves (10 vs. 12; P = NS). Discrepancies between TEE and surgical findings were found in 14 cases (11/31 in group A vs. 3/32 in group B; P = 0.01). CONCLUSIONS: Time between TEE and surgery seems to be an important factor affecting comparison. Lesion characteristics appear to be more precise and concordant with surgical findings the shorter the time elapsed from TEE to surgery. Changes resulting from disease progression require repeat TEE evaluation prior to surgical intervention for IE-related complications. This could be useful in providing the surgeon with a more accurate definition of valvular lesions for optimal planning of intervention.

Abscess↗
PubMed2005

Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.

Adult↗
PubMed2005

Early activation of vascular endothelial cells and platelets in obese children.

Obesity in adulthood is combined with vascular endothelial cell and platelet activation. In this study we evaluated whether or not such activation is already present in obese children. Forty obese (10.3 +/- 2.5 yr) and 40 nonobese (10.3 +/- 2.3 yr) children were studied. Circulating levels of soluble (s) intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, as indices of vascular endothelial cell activation, were assessed in both groups. Plasma concentrations of sP-selectin and sCD40 ligand, as indices of platelet activation, were also measured. Circulating levels of highly sensitive C-reactive protein (hs-CRP) and the lipid peroxidation product 8-iso-prostaglandin (PG)F(2alpha) were evaluated because of their ability to promote vascular endothelial cell and platelet activation. Circulating levels of all of the assessed markers were higher in obese than in nonobese children (sICAM-1, +38.8 +/- 13.3%; sVCAM-1, +26.5 +/- 13.7%; sE-selectin, +31.3 +/- 17.3%; sP-selectin, +31.7 +/- 16.9%; sCD40 ligand, +36.9 +/- 22.1%; total 8-iso-PGF(2alpha), +24.0 +/- 20.2%; hs-CRP, +76.6 +/- 12.9%; P < 0.0001). Significant correlations (P < 0.004) between plasma total 8-iso-PGF(2alpha) levels and circulating sICAM-1 (r = 0.485), sVCAM-1 (r = 0.506), sP-selectin (r = 0.449), sCD40 ligand (r = 0.498), and hs-CRP (r = 0.520) concentrations were found in obese children. In conclusion, an early activation of vascular endothelial cells and platelets was present in obese children. Increased lipid peroxidation was also present in these children and likely contributed to the observed proinflammatory phenotype.

Area Under Curve↗
PubMed2005

Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons.

BACKGROUND: Numerous studies indicate that flavanols may exert significant vascular protection because of their antioxidant properties and increased nitric oxide bioavailability. In turn, nitric oxide bioavailability deeply influences insulin-stimulated glucose uptake and vascular tone. Thus, flavanols may also exert positive metabolic and pressor effects. OBJECTIVE: The objective was to compare the effects of either dark or white chocolate bars on blood pressure and glucose and insulin responses to an oral-glucose-tolerance test in healthy subjects. DESIGN: After a 7-d cocoa-free run-in phase, 15 healthy subjects were randomly assigned to receive for 15 d either 100 g dark chocolate bars, which contained approximately 500 mg polyphenols, or 90 g white chocolate bars, which presumably contained no polyphenols. Successively, subjects entered a further cocoa-free washout phase of 7 d and then were crossed over to the other condition. Oral-glucose-tolerance tests were performed at the end of each period to calculate the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI); blood pressure was measured daily. RESULTS: HOMA-IR was significantly lower after dark than after white chocolate ingestion (0.94 +/- 0.42 compared with 1.72 +/- 0.62; P < 0.001), and QUICKI was significantly higher after dark than after white chocolate ingestion (0.398 +/- 0.039 compared with 0356 +/- 0.023; P = 0.001). Although within normal values, systolic blood pressure was lower after dark than after white chocolate ingestion (107.5 +/- 8.6 compared with 113.9 +/- 8.4 mm Hg; P < 0.05). CONCLUSION: Dark, but not white, chocolate decreases blood pressure and improves insulin sensitivity in healthy persons.

Adult↗
PubMed2005

Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension.

An enormous number of studies in the last two decades have been devoted to investigating the role of the endothelium in cardiovascular diseases. Nonetheless, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, molecular genetic tests and invasive and non-invasive tools with and without pharmacological and physiological stimuli have been introduced. Furthermore newer pharmacological tools have been proposed. However, the application of these methodologies should fulfil a number of requirements in order to provide conclusive answers in this area of research. Thus, the most relevant methodological issues in the research on endothelial function and dysfunction are summarized in this paper.

Endothelium, Vascular↗
PubMed2005

Endothelial activation. Sliding door to atherosclerosis.

The vascular endothelium has been long viewed as a simply physical separation between blood and tissue [1]. Over the last two decades a consistent bulk of data demonstrated that endothelium is a widely distributed organ, with a variable degree of heterogeneity among and within tissues [2, 3] and deeply involved in vascular physiology and pathophysiology, rather than a cellophane-like membrane that lines the circulatory system [1]. Being positioned at the interface of blood and tissue, the vascular endothelium is able to sense changes in hemodynamic forces and biochemical stimuli and promptly responds to local changes in biological needs by modulating vasomotion, hemostasis, angiogenesis, and vascular growth [1]. The vascular endothelium also modulates the trafficking of circulating blood cells by up-regulating adhesion molecules on cell surface [1, 4, 5]. These cell membrane-associated molecules are critic for leukocyte migration into specific organs under physiologic conditions and accelerate migration towards sites of inflammation [1, 4, 5]. Recently, the multi-step cascade of events that results in the local recruitment of leukocytes to sites of inflammatory challenge, also known as endothelial activation, has been considered as a crucial step in the initiation of atherosclerosis process, as well as in the development of advanced atherosclerosis [6].

Atherosclerosis↗
PubMed2004

Endothelial cell activation in men with erectile dysfunction without cardiovascular risk factors and overt vascular damage.

PURPOSE: Endothelial cell activation (ECA) is an initiating event in atherosclerosis. Biochemical measures of ECA were evaluated in patients with erectile dysfunction (ED) associated or not associated with cardiovascular risk factors (VRFs) to assess whether ED is a sentinel of atherosclerosis. MATERIALS AND METHODS: Circulating soluble P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and endothelin-1 concentrations were assessed in 45 men with ED but no VRFs, 45 men with ED associated with VRFs and 25 healthy men. Ultrasound intima-media thickness of carotid arteries and pharmacologically stimulated peak systolic velocity of cavernous arteries were used to assess vascular damage. RESULTS: Measures of ECA were higher in men with ED but no VRFs than in controls (p <0.01) and all were comparable among groups of men with ED. Levels of endothelin-1 in men with ED and no VRFs versus healthy men of the same age resulted in the best independent predictor for ED after adjusting for the confounding effect of increased body mass index and smoking (OR 5.37, 95% CI 2.12 to 19.70). Intima-media thickness of carotid arteries was comparable in controls and in men with ED but no VRFs, and ruled out the bias of overt damage of large arteries in the latter. Peak systolic velocity of cavernous arteries excluded vasculogenic ED in the majority of patients with no VRFs. CONCLUSIONS: Increased biochemical measures of ECA were associated with ED independent of coexisting VRFs and overt vascular damage, suggesting that ED is a sentinel of early atherosclerosis.

Adult↗
PubMed2003

Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty.

BACKGROUND: Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). CD40-CD40L interaction is involved in the pathogenesis of atherosclerosis; however, its role in the pathophysiology of restenosis is still unclear. We tested the hypothesis that soluble CD40L (sCD40L) may be involved in the process of restenosis and that it exerts its effect by triggering a complex group of inflammatory reactions on endothelial and mononuclear cells. METHODS AND RESULTS: We studied 70 patients who underwent PTCA and who had repeated angiograms at 6-month follow-up. Plasma sCD40L was measured before and 1, 5, 15, and 180 days after PTCA, whereas plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 were measured before and 24 hours after PTCA. Furthermore, the release of adhesion molecules and MCP-1 and the ability to repair an injury in endothelial cells, as well as the generation of O2- in monocytes, were analyzed in vitro after stimulation with serum from patients or healthy control subjects. Restenosis occurred in 18 patients (26%). Restenotic patients had preprocedural sCD40L significantly higher than patients with favorable outcomes (2.13+/-0.3 versus 0.87+/-0.12 ng/mL, P<0.0001). Elevated sCD40L at baseline was significantly correlated with adhesion molecules and MCP-1 generation after PTCA and with lumen loss at 6-month follow-up. Furthermore, high sCD40L was directly associated in vitro with adhesion molecules and MCP-1 generation and impaired migration in endothelial cells and with enhanced O2- generation in monocytes. CONCLUSIONS: We conclude that increased sCD40L is associated with late restenosis after PTCA. This may provide an important biochemical link between restenosis and aspirin-insensitive platelet activation. These results provide a rationale for studies with new antiplatelet treatments in patients who underwent PTCA.

Angioplasty, Balloon, Coronary↗
PubMed2003

Genetic determinants of nonmodulating hypertension.

We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and chi2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 -344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.

Age Factors↗
PubMed2003

Angiotensin II inhibits endothelial cell motility through an AT1-dependent oxidant-sensitive decrement of nitric oxide availability.

OBJECTIVE: The migratory capability of vascular endothelial cells plays a pivotal role in the maintenance of vessel wall integrity and is stimulated by nitric oxide (NO). Angiotensin II increases NAD(P)H oxidase activity in endothelial cells, thereby promoting reactive oxygen species (ROS) generation. Because ROS can both reduce NO synthase activity and increase NO breakdown, thus impairing NO availability in endothelial cells, we evaluated the effect of angiotensin II on human vascular endothelial cell (HUVEC) motility. METHODS AND RESULTS: Angiotensin II dose- and time-dependently reduced HUVEC migration. Besides inhibiting HUVEC motility, angiotensin II altered intracellular glutathione redox status. The generation of ROS by cultured HUVECs was significantly increased by angiotensin II. Furthermore, angiotensin II reduced NO metabolite concentrations in culture media. The angiotensin II type 1 receptor antagonist candesartan cilexetil attenuated the inhibitory action exerted by angiotensin II on HUVEC motility, reversed the angiotensin II-induced increase in intracellular oxidative stress, and restored NO availability. Similar effects were exerted by the flavonoid inhibitor diphenylene iodinium and the antioxidant agent N-acetyl-L-cysteine. CONCLUSIONS: All together, our data demonstrate that angiotensin II inhibits HUVEC motility by reducing NO availability. Such reduction is due to an angiotensin II type 1 receptor-dependent increment in intracellular ROS generation.

Angiotensin II↗