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Introduction: The diagnosis of cardiac amyloidosis (CA) is usually performed by endomyocardial biopsy; however, possible sampling errors and procedural risks such as cardiac tamponade, malignant arrhythmias and bleeding risk, limit its use. Therefore, a non-invasive diagnostic method appears to be necessary., Materials and Methods: Echocardiography plays an important role in this need. Conventional two-dimensional echocardiography appears able to detect some specific and distinguishing signs of cardiac amyloid infiltration., Results and Conclusions: Of these, thickened right and left ventricular (LV) myocardium, normal or small LV cavity size in contrast to enlarged biatrial cavities, diffuse hyper-refractile 'granular sparkling' appearance and 'mismatch' ECG/ECHO are the most specific findings. The magnitude of cyclic variation recorded with integrated backscatter reflects structural changes in the myocardium. In patients with CA, this magnitude is reduced because myocardial amyloid infiltration is characterized by a reduction of number of "contractile" fibers. Other informations concerning LV dysfunction CA-related can be obtained by Tei index. Finally, new echocardiographic imaging modalities, such as tissue Doppler, Doppler-based strain, speckle tracking imaging and three-dimensional echocardiography, can provide some findings regarding the preclinical stages of LV dysfunction when other echocardiographic measurements are showing normal; however, these are unable to provide a non-invasive diagnosis of cardiac amyloidosis.

Background: Left atrial volume (LAV) and function are connected to the left ventricular (LV) haemodynamic patterns. To define the changes of LAV and functions to counterbalance age-related LV diastolic impairment, this study was undertaken., Methods: 2D-Left Atrial Speckle Tracking Echocardiography (2D-LASTE) was used to define both LAV and functions in an aged healthy population (group II) respect to adult healthy controls (group I)., Results: Results showed an increasing of left atrial volume indices (LAVI) (maximum, minimum, pre-a) in old subjects in comparison with those obtained in adult healthy controls. On the contrary, LAVI passive emptying unchanged and LAVI passive fraction reduced with advanced age. Finally, LAVI active emptying increased with advancing age to compensate the age-dependent left ventricular diastolic dysfunction. The values of global systolic strain (S); systolic strain rate (SrS); early diastolic strain rate (SrE), and late diastolic strain rate (SrA) were also calculated. With reference to the function, our study confirmed that LA conduit function deteriorates with age while booster pump increases respect to adult controls and reservoir phase is maintained., Conclusions: The echocardiographic findings obtained with conventional and tissue Doppler confirmed the connection between LA functions and volumes and age-related LV dysfunction. Conclusively, 2D-LASTE appears to be a reliable tool to evaluate the role of LA to compensate the derangement of left ventricle happening with ageing., Competing Interests: Conflicts of Interest: None declared.

Cardiac hypertrophy is a key compensatory mechanism acting in response to pressure or volume overload, involving some alterations in signaling transduction pathways and transcription factors-regulation. These changes result in enhanced proteins' synthesis leading to Left Ventricular Hypertrophy (LVH). It is known that the main function of Ubiquitin-Proteasome System (UPS) is to prevent accumulation of damaged, misfolded and mutant proteins by proteolysis. But emerging evidences suggest that UPS also attends to the cells' growth, favoring proteins' synthesis, subsequently evolving in LVH. The role of the proteasome in to favor cellular hypertrophy consists in upregulation of the catalytic proteasome subunit, with prevalence of proteins-synthesis on proteins degradation. It is also evident that UPS inhibition may prevent cells' growth opposing to the hypertrophy. In fact in several experimental models, UPS inhibition demonstrated to be able to prevent or reverse cardiac hypertrophy induced by abdominal aortic banding (AAB). That can happen with several proteasome inhibitors acting by multifactorial mechanisms. These evidences induce to hypothesize that, in the future, in patients with the increased volume overload by systemic hypertension, some proteasome-inhibitors could be used to antagonize or prevent LVH without reducing peripheral high blood pressure levels too.

Inheired or acquired hyperhomocysteinemia (HHcy) is associated with several impairments, as certain tumors, deep venous thrombosis, tube neural defects, osteoporosis, early atherosclerosis and vascular acute events (IMA, stroke, PVD), mild cognitive impairments till Alzheimer's disease (AD). But, vascular and neuronal derangements are the most frequent HHcy-manifestations. As far as early atherosclerosis, some clinical trials demonstrated that folates and B6-12 vitamins supplementation is unable to reduce atherosclerotic lesions and cardiovascular events, even if it lowers HHcy levels. Thus, for atherosclerosis and its acute events (IMA, stroke, PVD) HHcy acts as a powerful biomarker rather than a risk factor. For that, the supplementation with folates and B vitamins to lower atherosclerotic lesions-events in hyperhomocysteinemic patients is not recommended. On the contrary, several clinical investigations demonstrated that folates and vitamins administration is able to reduce Hcy serum levels and antagonize some mechanisms favouring neurodegenerative impairments, as mild cognitive impairment, AD and dementia. Thus, contrarily to the atherosclerotic manifestations in hyperhomocysteinemic patients, preventive treatment with folates and B6-12 vitamins reduces Hcy concentration and could prevent or delay cognitive decline and AD.

Aim: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD)., Methods: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment., Results: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped., Conclusion: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

Aims: We analyzed the effects of tight glycemic control on regenerative potential of myocardium during acute myocardial infarction., Patients and Methods: Seventy-five patients with their first acute myocardial infarction undergoing coronary bypass surgery were studied: 25 patients with glycemia below 140 mg/dl served as the control group; hyperglycemic patients (glucose>140 mg/dl) were randomized to intensive glycemic control (IGC; n=20; glucose goal, 80-140 mg/dl), conventional glycemic control (CGC; n=20; glucose goal, 180-200 mg/dl), or glucose-insulin-potassium (GIK; n=10; glucose goal, 180-200 mg/dl) for almost 3 d before surgery, using insulin infusion followed by sc insulin treatment. During surgery, myocyte precursor cells (MPC) (c-kit/MEFC2/GATA4-positive cells), oxidation of MPC DNA (c-kit/8-hydroxydeoxyguanosine-positive cells), senescent MPC (c-kit/p16INK4a-positive cells), and cycling cardiomyocytes (Ki-67-positive cells) were analyzed in biopsy specimens taken from the peri-infarcted area., Results and Discussion: Before surgery, plasma glucose reduction was greater in the IGC group than in the CGC and GIK groups (P<0.001 for both). IGC patients had higher MPC (P<0.01) and cycling myocytes (P<0.01), as well as less oxidized (P<0.01) and senescent MPC (P<0.01) in peri-infarcted specimens compared with both CGC and GIK patients. Tight glycemic control, by reducing senescent MPC, may increase regenerative potential of the ischemic myocardium.

Background: To point out a possible correlation between left atrial volume index (LAVI) and left ventricular (LV) diastolic time interval to better define LV diastolic dysfunction, this study was performed., Methods: In 62 hypertensive-hypertrophic patients without LV systolic dysfunction, LV volumes, myocardial mass index, ejection fraction% (EF%) and LAVI were measured by two-dimensional echocardiography. Instead, tissue Doppler echocardiography (TDE) was used to measure myocardial performance index (MPI) and its systo-diastolic time intervals, such as: iso-volumetric contraction time (IVCT); iso-volumetric relaxation time (IVRT); ejection time. LAVI, TDE-MPI and time intervals where also measured in 15 healthy controls, to obtain the reference values., Results: Results shown a significant increase of LV volumes in hypertensives in comparison to the control group (p < 0.05). LV mass index also augmented (p < 0.001). Instead, EF% not significantly changed in hypertrophic patients in comparison with healthy controls. LAVI raised in hypertensives wih left ventricular hypertrophy, whereas IVCT resulted within the normal limits. On the contrary, IVRT significantly raised. Accordingly, MPI resulted higher in controls., Conclusion: LAVI, MPI and its time intervals appear as reliable tools to non-invasively individualize LV diastolic dysfunction in systemic hypertension, in absence of mitral valve disease.

Left ventricular hypertrophy (LVH) induced by systemic hypertension (SH) represents a maladaptive response to the increased overload. It is known that the LV pathological remodeling is associated with an increased risk of cardiovascular morbidity and mortality. Secretion and production of vasoactive peptides, such as angiotensin II, endothelin-1, norepinephrine, and Rho and Ras proteins, are increased during the process and play critical roles in the hypertrophic response to systemic hypertension. Oxidative stress, heat shock proteins, calcineurin, and some kinases are also involved in the hypertrophic process. Usually, antihypertensive treatments are able to reduce elevated blood pressure levels, but are not always useful to slow or prevent LVH. Experimental studies performed in animal models demonstrate that some humoral factors, by suppressing the biochemical hypertrophic responses, could prevent their cardiac complications independently of their possible anti-hypertensive effects. Cyclosporine-A, scutellarin, and spironolactone are also included among these antihypertrophic substances. Thus, new drugs deriving from these molecules and humoral factors could be employed to antagonize LVH., (Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Increased homocysteine levels can be responsible for arterial ischemic events, such as MI, stroke or peripheral vascular disease. Homocysteine is metabolized by two pathways: re-methylation and trans-sulfuration. Both involve folic acid, and vitamins B(6-12.) Several studies assumed that the folates and vitamins B supplementation or dietary source to normalize plasma homocysteine. But, even if tends to normalize homocysteine levels, lowering homocysteine by B-group vitamins and/or folates does not reduce cardiovascular risk. In fact, recent reports confirmed that hyper-homocysteinemia is not directly responsible for cardiovascular disease, but is merely present in individuals suffering for acute and/or chronic cardiovascular events, as a collateral finding. Reduced methylation potential (MP) [due to decreased S-adenosyl-methionine (AdoMet)/S-adenosyl-homocysteine (AdoHcy) ratio] induced by the elevated plasma homocysteine levels seems to be the true responsible for cardiovascular diseases (CVD). The pathogenic mechanisms responsible for CVD appear to be dependent of DNA hypomethylation inducing an inhibition of cyclin A transcription and a reduction of endothelial cells growth. But, other human studies performed in a wide range are requested.

Objective: Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes., Research Design and Methods: A total of 97 older individuals (mean +/- SD age 76 +/- 6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing., Results: At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean +/- SD values in the entire population were as follows: A1C 7.5 +/- 0.5%, fasting plasma glucose (FPG) 8.6 +/- 1.3 mmol/l, fasting plasma insulin (FPI) 148 +/- 74 pmol/l, MMSE 24.9 +/- 2.4, TMT-A 61.6 +/- 42.0, TMT-B 162.8 +/- 78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 +/- 58.1, and RAVLT 24.3 +/- 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (P(trend) < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (P(trend) = 0.024), executive efficiency (DIFFBA) (P(trend) = 0.026), and RAVLT memory test (P(trend) = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (P(trend) = 0.011). With use of linear mixed-effects models, the interaction term, FPI x time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (beta = -1.899; P = 0.009)., Conclusions: Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.

We evaluated the role of sterol-regulatory element binding protein (SREBP)-1c/peroxisome proliferator activated receptor-gamma (PPARgamma) pathway on heart lipotoxicity in patients with metabolic syndrome (MS) and aortic stenosis (AS). Echocardiographic parameters of heart function and structural alterations of LV specimens were studied in patients with (n = 56) and without (n = 61) MS undergoing aortic valve replacement. Tissues were stained with hematoxylin-eosin (H and E) and oil red O for evidence of intramyocyte lipid accumulation. The specimens were also analyzed with PCR, Western blot, and immunohistochemical analysis for SREBP-1c and PPARgamma. Ejection fraction (EF) was lower in MS compared with patients without MS (P < 0.001); no difference was found in aortic orifice surface among the groups. H and E and oil red O staining of specimens from MS patients revealed several myocytes with intracellular accumulation of lipid, whereas these alterations were not detected in biopsies from patients without MS. Patients without MS have low levels and weak immunostaining of SREBP-1c and PPARgamma in heart specimens. In contrast, strong immunostaining and higher levels of SREBP-1c and PPARgamma were seen in biopsies from the MS patients. Moreover, we evidenced a significative correlation between both SREBP-1c and PPARgamma and EF and intramyocyte lipid accumulation (P < 0.001). SREBP-1c may contribute to heart dysfunction by promoting lipid accumulation within myocytes in MS patients with AS; SREBP-1c may do it by increasing the levels of PPARgamma protein.

The role of surgically removing subcutaneous fat by abdominoplasty on circulating inflammatory markers and myocardial dysfunction, evaluated by myocardial performance index (MPI), were investigated. Twenty volunteers submitted to the abdominoplasty (abdominoplasty group), and other 28 women treated by hypocaloric diet (diet group) were evaluated. Echocardiographic parameters of MPI, circulating levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, were performed at baseline and 2 months later. Compared with nonobese women, obese women had increased concentrations of TNF-alpha (P < 0.01), IL-6 (P < 0.01), and higher MPI (P < 0.02), indicating ventricular dysfunction. Subcutaneous fat concentrations of TNF-alpha and IL-6 were related to MPI impairment. After 60 days, waist-to hip ratio was significantly reduced in the abdominoplasty group. Anthropometric changes were accompanied by a significant decline in plasma concentrations of TNF-alpha and IL-6 levels as well as by significant improvements of MPI in abdominoplasty group compared with diet group. Abdominoplasty may represent a safe method for ameliorating cardiac function in obese women.

The aim of this review was to describe the different ultrasonic modalities to non-invasively evaluate right cardiac chambers and pulmonary vascular bed function. M-Mode, 2-D, conventional pulsed doppler, tissue doppler imaging (TDI), strain rate imaging (SRI) and 3D echocardiography are illustrated in order to obtain both regional and global right heart and pulmonary function. The results have a good correlation with other invasive and non-invasive diagnostic techniques, as magnetic resonance imaging (MRI). All these echocardiograpic techniques can be employed to evaluate the morphologic and functional pictures of right heart and pulmonary circulation in presence of pulmonary hypertension (PH). The hemodynamic profile obtained consent to anatomically and functionally characterize PH. But, other experiences performed on more wide range of healthy and PH patients are necessary to confirm the described results.

Several experimental studies and some clinical experience have shown that metabolic syndrome and caloric restriction exert opposite effects on thrombosis, because these two nourishing conditions are at extreme ends of the same spectrum. The antithrombotic action induced by caloric restriction happens through Sirtuin 1 (SIRT1), a gene/protein activated by the reduction of calorie intake lower than is typical. The antithrombotic effect is due to the activation of SIRT1 acting through an increase of insulin sensitivity, which reduces endothelial dysfunction. Sirtuins have been implicated in several processes, including genomic stability, DNA repair, apoptosis, and adipogenesis. In addition, they have been shown to promote longevity in simple eukaryotes. Some compounds, such as resveratrol, mimic the action of SIRT1 and seem able to correct the prothrombotic state induced by metabolic syndrome. To confirm this, we demonstrated that resveratrol improved the left ventricular function of type 2 diabetics who suffered recent acute myocardial infarction (AMI) when a moderate red wine amount (containing resveratrol) was taken daily by patients receiving conventional antiischemic therapy, in comparison with another group treated with antiischemic compounds alone.

Background and Aims: Left ventricular (LV) function in the healthy aging heart is modified by biochemical changes with advancing age. We employed for the first time Tissue Doppler Imaging (TDI), to identify which phase of the cardiac cycle is involved., Methods: TDI was performed in 175 aging subjects, free of cardiovascular and/or respiratory disease (group II), and in 182 healthy adults enrolled as the control group (group I), to calculate the Myocardial Performance Index (MPI). The index derives from the values of Isovolumetric Contraction Time (ICT), Isovolumetric Relaxation Time (IRT) and Left Ventricular Ejection Time (LVET) measured in ms, according to the formula: (ICT+IRT)/LVET., Results: An increase in MPI in group II was shown, with significant lengthening of IRT in comparison with the same value obtained in the control group (group I), ICT and LVET were unchanged., Conclusions: The rise in IRT in the aging healthy heart is dependent on diastolic LV dysfunction consequent upon the formation of Advanced Glycosilation End-product (AGE) crosslinks with connectival proteins of interstitial myocardial tissue. Agerelated increase in oxidative stress also modifies some interstitial compounds, favoring hardening of ventricular walls. These changes are similar to those happening in the diabetic heart, and TDI seems to be able to define non-invasively which phase of the cardiac cycle is impaired.

Objective: To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women., Design: In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor alpha, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined., Results: The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857 mm/18 months in the placebo group (P<0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P<0.02), low-density lipoprotein cholesterol (P<0.02), soluble forms of intercellular adhesion molecule-1 (P<0.005) and vascular cell adhesion molecule-1 (P<0.04), E-selectin (P<0.02), interleukin-6 (P<0.005), tumor necrosis factor alpha (P<0.005) levels, and homeostatic model assessment index (P<0.005) and a significant increase in plasma adiponectin levels (P<0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio=0.41; 95% CI: 0.32-0.70)., Conclusion: Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.

The objective of this study was to investigate the relationship between insulin resistance (IR) and subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Carotid artery intima media thickness (IMT), using ultrasound evaluation, and other clinical and laboratory variables were investigated in 45 RA outpatients and in 48 controls with soft tissue disorders. IR was assayed by homeostasis model assessment (HOMA2) and metabolic syndrome by National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. Insulin resistance, as defined by HOMA2-IR>1, was seen in 40 (88.9%) RA patients and in three (6.2%) controls (p<0.001). No significant difference was detected in the prevalence of metabolic syndrome. The median IMT was greater in RA patients (0.76 mm; interquartile range [IQR] 0.65, 0.85) than in the controls (0.66 mm; IQR 0.60, 0.72) (p<0.001). Dividing the RA patients according to the cut-off IMT value (0.72 mm), a difference was detected in both systolic (p=0.04) and diastolic blood pressure (p=0.02), disease activity score (DAS28) (p=0.008), HOMA2-IR (p<0.001) and cumulative oral steroid dose (p=0.001). Moreover, the frequency of cases with increased IMT was higher in glucocorticoid users than in non-users (21/23 vs. 9/22, respectively) (p<0.001). Spearman's rho correlation showed a significant positive relationship between IMT and HOMA2-IR (p<0.001). Multivariate stepwise analysis selected HOMA2-IR plus diastolic BP plus glucocorticoid exposure as the best predictive model for subclinical atherosclerosis (R2c=0.577, F=21, p<0.001). In conclusion, this study showed a significantly higher prevalence of IR in RA patients and pointed out a significant association between IR and subclinical atherosclerosis. This relationship may be driven primarily by exposure to steroid therapy.

Ozonized autohemotransfusion has been used as a complementary therapy in patients with peripheral arterial disease (PAD). To determine whether ozone therapy could acutely modify artery vasodilatory capacity, a flow-mediated dilation test was performed at the brachial artery level before and after an ozonized autohemotransfusion in 16 patients with PAD, mean (± SD) age 55±1.8 years, and 14 healthy volunteers matched for age, sex and body mass index. Before ozonized autohemotransfusion, the mean baseline diameter of the brachial artery was higher in PAD patients than in healthy subjects (4.6±0.54 mm versus 3.6±0.54 mm, P<0.001) while mean flow-mediated brachial artery dilation and percentage of increase in flow were significantly lower in PAD patients than in controls (6.3±6.1% versus 11.8±2.4%, P<0.02; 433±61% versus 580±46%, P<0.02, respectively). No significant changes were observed after ozonized autohemotransfusion, indicating that ozonized autohemotransfusion does not modify endothelium-dependent ischemia-induced vascular reactivity.

Objectives: We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic and symptomatic patients and the effect of rosiglitazone, a peroxisome proliferator-activated receptor-gamma activator, in symptomatic plaques., Background: The role of the ubiquitin-proteasome system, the major pathway for non-lysosomal intracellular protein degradation in eucaryotic cells, in the progression of atherosclerotic plaque to instability is unclear., Methods: Plaques were obtained from 40 symptomatic and 38 asymptomatic patients undergoing carotid endarterectomy. Symptomatic patients received 8 mg rosiglitazone (n = 20) or placebo (n = 20) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-lymphocytes (CD3), inflammatory cells (HLA-DR), ubiquitin-proteasome activity, nuclear factor kappa B (NFkB), inhibitory kappa B (IkB)-beta, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay)., Results: Compared with asymptomatic plaques, symptomatic plaques had more macrophages, T-lymphocytes, and HLA-DR+ cells (p < 0.001); more ubiquitin-proteasome activity and NFkB (p < 0.001); and more markers of oxidative stress (nitrotyrosine and O2- production) and MMP-9 (p < 0.01) along with a lesser collagen content and IkB-beta levels (p < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated symptomatic plaques presented fewer inflammatory cells (p < 0.01); less ubiquitin, proteasome 20S, and NFkB (p < 0.01); less nitrotyrosine and O2- production (p<0.01); and greater collagen content (p<0.01), indicating a more stable plaque phenotype., Conclusions: Ubiquitin-proteasome overactivity is associated with enhanced inflammatory reaction in symptomatic plaques. The inhibition of ubiquitin-proteasome activity in lesions of symptomatic patients by rosiglitazone is associated with plaque stabilization, possibly by down-regulating NFkB-mediated inflammatory pathways.

The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma activator, in diabetic plaques. Plaques were obtained from 46 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Diabetic patients received 8 mg rosiglitazone (n = 23) or placebo (n = 23) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLA-DR), ubiquitin, proteasome 20S activity, nuclear factor (NF)-kappaB, inhibitor of kappaB (IkappaB)-beta, tumor necrosis factor (TNF)-alpha, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with nondiabetic plaques, diabetic plaques had more macrophages, T-cells, and HLA-DR+ cells (P < 0.001); more ubiquitin, proteasome 20S activity (TNF-alpha), and NF-kappaB (P < 0.001); and more markers of oxidative stress (nitrotyrosine and O2(-) production) and MMP-9 (P < 0.01), along with a lesser collagen content and IkappaB-beta levels (P < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated diabetic plaques presented less inflammatory cells (P < 0.01); less ubiquitin, proteasome 20S, TNF-alpha, and NF-kappaB (P < 0.01); less nitrotyrosine and superoxide anion production (P < 0.01); and greater collagen content (P < 0.01), indicating a more stable plaque phenotype. Similar findings were obtained in circulating monocytes obtained from the two groups of diabetic patients and cultured in the presence or absence of rosiglitazone (7.0 micromol/l). Ubiquitin-proteasome over-activity is associated with enhanced inflammatory reaction and NF-kappaB expression in diabetic plaques. The inhibition of ubiquitin-proteasome activity in atherosclerotic lesions of diabetic patients by rosiglitazone is associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by downregulating NF-kappaB-mediated inflammatory pathways.

In 44 patients affected by systemic lupus erythematosus (SLE) without any clinical signs of heart disease (group I) the myocardial performance index (MPI) was calculated to investigate left ventricular function. The index, as the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) divided by ejection time (ET), was measured by tissue Doppler echocardiography (TDE). Results achieved show a prolonged MPI with respect to the values recorded in healthy controls (group II). Its prolongation is due to a significant increase of IRT, whereas ICT and ET were within the normal limits. In patients with SLE without an evident cardiac engagement, this outcome seems to depend on a prevalent diastolic left ventricular dysfunction, perhaps due to a subclinical myocarditis. TDE is more precise than the conventional Doppler method in evaluating MPI and single time intervals, because their measurements are accomplished in concomitance of left ventricular wall motion rather than the flow movement.

Background: Morning blood pressure (BP) peak may be a risk factor for cardiovascular disease. Whether morning BP should be a target of hypertension treatment is not known. We investigated the relationship between morning BP variations, carotid internal-medial thickness (CIMT), circulating inflammatory markers, and sympathetic activity in hypertensive patients with different patterns of morning BP increase at baseline and after antihypertensive treatment., Methods: One hundred twenty-eight hypertensive patients with morning BP peak (MP+) were compared with 196 hypertensive patients without morning BP peak (MP-). All patients performed 24-h ambulatory BP monitoring, assessment of CIMT, circulating concentration of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), and urinary catecholamines., Results: Compared with MP- patients, MP+ patients had higher CIMT and urinary catecholamine output (P < .001), as well as CRP, IL-6, and IL-18 (P < .001). We randomly assigned 128 drug-naive MP+ patients to either metoprolol or carvedilol, two antihypertensive drugs with different effects on sympathetic activity. The primary outcome was change in CIMT and circulating inflammatory markers at 12 months. Morning BP decreased more among patients in the carvedilol group (P < .001), whereas clinic BP showed a similar decrease in both groups. The CIMT (P < .001), IL-6 (P < .001), IL-18 (P < .001), and CRP (P < .001) decreased more in the carvedilol group than in the metoprolol group. The CIMT regression was observed in 49% of patients in the carvedilol group and 18% of patients in the metoprolol group (P < .01). Reduction in CIMT was directly associated with changes in morning BP., Conclusions: Higher CIMT and circulating inflammatory markers coexist in hypertensive patients with morning BP peak, and might contribute to their increased cardiovascular risk. Carotid atherosclerosis can be prevented by control of morning BP.

To define the degree of heart derangement in recent myocardial infarction (MI) occurring in different wall locations of myocardium, we echocardiographically evaluated left ventricular volumes, ejection fraction, wall-motion score index, isovolumetric contraction and relaxation time, ejection time, and index of myocardial performance in 74 patients with MI. Participants were chosen among the patients with MI of comparable extent and interesting unlike zones of myocardial walls. Mean values of evaluated left ventricular end-diastolic and end-systolic volumes and ejection fraction were nearly alike in all patients, whereas wall-motion score index and index of myocardial performance were cleary prolonged in those with anterior MI in comparison with the values recorded in patients with lateral or inferior MI. The mean values of isovolumetric contraction and relaxation time suggest that a prevalent systolic dysfunction is present in the early phase of MI. In addition, the different index of myocardial performance prolongation in MI otherwise located suggests evidence that MI located in the anterior wall has more serious effect than lateral or inferior MI.

Objective: Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss., Research Design and Methods: Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women., Results: Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-alpha, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity., Conclusions: In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.

Objective: Stress hyperglycemia has been associated with increased mortality in patients with myocardial infarction (MI). We examined the association between plasma glucose levels, circulating inflammatory markers, T-cell activation, and functional cardiac outcome in patients with first MI., Research Design and Methods: Echocardiographic parameters, circulating levels of interleukin-18 (IL-18), C-reactive protein (CPR), and the percent of CD16-CD56, CD4/CD8, CD152, and HLA-DR expression were investigated in 108 patients with acute MI on admission to the emergency ward., Results: Our review found that 31 new hyperglycemic patients (glycemia >or=7 mmol/l) had higher infarct segment length (P < 0.05) and myocardial performance index (P < 0.02) and reduced transmitral Doppler flow (P < 0.05), pulmonary flow analysis (P < 0.02), and ejection fraction (P < 0.05) compared with 36 hyperglycemic diabetic patients and 41 normoglycemic patients. Plasma IL-18 and CRP were higher in the hyperglycemic than in the normoglycemic patients (P < 0.005), with the highest values in patients with new hyperglycemia (P < 0.05). Hyperglycemic patients had a higher percent of CD16+/CD56+ cells and CD4/CD8 ratio (P < 0.01), whereas they had lower CD152 expression (which has a negative regulatory function in T-cell activation) compared with normoglycemic patients (P < 0.001)., Conclusions: During MI, hyperglycemia is associated with increased levels of inflammatory markers, enhanced expression of cytotoxic T-cells, and reduced expression of T-cells, which are implicated in limiting the immune process. An increased inflammatory immune process seems a likely mechanism linking acute hyperglycemia to poor cardiac outcome in MI patients.