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We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.

Although the important contribution of nutrition and physical activity to people's health is known, it is equally well known that there are many barriers to adherence to healthy habits (i.e., of an organizational, economic, and/or psychological nature) experienced by the general population, as well as by people with non-communicable diseases. Knowledge of these barriers seems essential to the implementation of the activities and strategies needed to overcome them. Here, we aim to highlight the most frequent barriers to nutrition and exercise improvement that patients with chronic-degenerative diseases experience. Drawing from the Pubmed database, our analysis includes quantitative or mixed descriptive studies published within the last 10 years, involving adult participants with non-communicable diseases. Barriers of an organizational nature, as well as those of an environmental, economic, or psychological nature, are reported. The study of patients' barriers enables healthcare and non-health professionals, stakeholders, and policymakers to propose truly effective solutions that can help both the general population and those with chronic pathologies to adhere to a healthy lifestyle.

Objective: Children and adolescents with adiposity excess are at increased risk of future cardiovascular (CV) disease. Fat accumulation promotes the development of elevated blood pressure (BP) and arterial stiffness, two main determinants of CV risk which are strongly inter-related. We aimed at investigating whether the association between overweight and arterial stiffness, taken at different arterial segments, is mediated by increased BP or is BP-independent., Methods: Three hundred and twenty-two Italian healthy adolescents (mean age 16.9±1.4 years, 12% with overweight) attending the "G. Donatelli" High School in Terni, Italy, underwent measurement of arterial stiffness by arterial tonometry (aortic stiffness) and semiautomatical detection of pressure-volume ratio of the common carotid (carotid stiffness). The mediator effect of BP was tested for each anthropometric or biochemical measure of fat excess related to arterial stiffness., Results: Both carotid and aortic stiffness showed positive correlations with body mass index, waist, hip, and neck circumferences (NC). Only carotid stiffness, but not aortic stiffness, was associated with serum markers of fat accumulation and metabolic impairment such as insulin, homeostatic model of insulin resistance (HOMA-IR), serum gamma-glutamyl transferase (sGGT) and uric acid. The association with NC was stronger for carotid than for aortic stiffness (Fisher z -to- R 2.07, P  = 0.04), and independent from BP., Conclusions: In healthy adolescents, fat accumulation is associated with arterial stiffness. The degree of this association differs by arterial segments, since carotid stiffness is more strongly associated to adipose tissue excess than aortic stiffness and shows a BP-independent association with NC whereas aortic stiffness does not., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The effectiveness of vaccination against SARS-CoV-2 in preventing COVID-19 or in reducing severe illness in subjects hospitalized for COVID-19 despite vaccination has been unequivocally shown. However, no studies so far have assessed if subjects who get COVID-19 despite vaccination are protected from SARS-CoV-2-induced platelet, neutrophil and endothelial activation, biomarkers associated with thrombosis and worse outcome. In this pilot study, we show that previous vaccination blunts COVID-19-associated platelet activation, assessed by circulating platelet-derived microvesicles and soluble P-selectin, and neutrophil activation, assessed by circulating neutrophil extracellular trap (NET) biomarkers and matrix metalloproteinase-9, and reduces COVID-19-associated thrombotic events, hospitalization in intensive-care units and death., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Highly stressful situations, such as the current COVID-19 pandemic, induce constant changes in the mental state of people who experience them. In the present study, we analyzed the prevalence of some psychological symptoms and their determinants in four different categories of healthcare workers during the second year of the pandemic. A total of 265 physicians, 176 nurses, 184 other healthcare professionals, and 48 administrative employees, working in different Italian healthcare contexts, answered a questionnaire including variables about their mental status and experience with the pandemic. The mean scores for anxiety and depressive symptoms measured more than one year after the onset of the pandemic did not reach the pathological threshold. In contrast, post-traumatic and burnout symptoms tended toward the critical threshold, especially in physicians. The main determinant of psychological distress was perceived stress, followed by job satisfaction, the impact of COVID-19 on daily work, and a lack of recreational activities. These results increase the knowledge of which determinants of mental distress would be important to act on when particularly stressful conditions exist in the workplace that persist over time. If well-implemented, specific interventions focused on these determinants could lead to an improvement in employee well-being and in the quality of care provided., Competing Interests: The authors declare no conflict of interest.

Background: Mid- and long-term sequelae of COVID-19 on cardiorespiratory fitness are unknown. Aim of the study was to assess the mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) in élite athletes., Methods: 13 elite cross-country skiers with previous mild-moderate COVID-19 symptoms underwent CPET before resuming seasonal training (COVID athletes). 13 élite detrained cross-country skiers, matched for principal confounding factors, were taken as controls (control group). Resting peripheral oxygen saturation, pulmonary function test, echocardiography, bioelectrical impedance analysis and CPET (modified XELG2, Woodway, USA) were performed in all participants., Results: Median recovery time in COVID athletes was 34 days (IQR 33-38 days). COVID athletes reached earlier the onset of the aerobic threshold (4'48" vs. 6'28", R 2 =0.15, F=4.37, P<0.05) than controls, whereas the time to anaerobic threshold and maximal efforts did not significantly differ between groups. Oxygen consumption was lower at the aerobic threshold in COVID athletes than controls (VO2/kg 28.6 mL/min vs. 38.9 mL/min, R 2 =0.39, F=15.34, P<0.01), whereas no significant difference between groups was found both at the aerobic threshold and at peak exercise (all P<0.05). Findings from resting echocardiography and pulmonary function test were similar between the two groups., Conclusions: Élite cross-country athletes, previously affected by mild-moderate COVID-19, reached earlier the aerobic threshold than controls, whereas the remaining CPET parameters did not differ between groups. Such changes were not associated with any detectable difference in resting pulmonary and cardiac examination. Subjects affected by mild-moderate COVID-19 may require a longer time course of re-adaptation to aerobic exercise.

Handgrip strength (HGS), a simple tool for the evaluation of muscular strength, is independently associated with negative prognosis in many diseases. It is unknown whether HGS is prognostically relevant in COVID-19. We evaluated the ability of HGS to predict clinical outcomes in people with COVID-19-related pneumonia. 118 patients (66% men, 63 ± 12 years), consecutively hospitalized to the "Santa Maria" Terni University Hospital for COVID-19-related pneumonia and respiratory failure, underwent HGS measurement (Jamar hand-dynamometer) at ward admission. HGS was normalized to weight 2/3 (nHGS) The main end-point was the first occurrence of death and/or endotracheal intubation at 14 days. Twenty-two patients reached the main end-point. In the Kaplan-Meyer analysis, the Log rank test showed significant differences between subjects with lower than mean HGS normalized to weight 2/3 (nHGS) (< 1.32 kg/Kg 2/3 ) vs subjects with higher than mean nHGS. (p = 0.03). In a Cox-proportional hazard model, nHGS inversely predicted the main end-point (hazard ratio, HR = 1.99 each 0.5 kg/Kg 2/3 decrease, p = 0.03), independently from age, sex, body mass index, ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO 2 /FiO 2 ratio), hypertension, diabetes, estimated glomerular filtration rate and history of previous cardiovascular cardiovascular disease. These two latter also showed independent association with the main end-point (HR 1.30, p = 0.03 and 3.89, p < 0.01, respectively). In conclusion, nHGS measured at hospital admission, independently and inversely predicts the risk of poor outcomes in people with COVID-19-related pneumonia. The evaluation of HGS may be useful in early stratifying the risk of adverse prognosis in COVID-19., (© 2022. The Author(s).)

Isolated systolic hypertension (ISH), defined as brachial systolic blood pressure (bSBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg, is highly prevalent among young subjects and in the elderly. The prognostic significance of ISH in young individuals remains the object of large debate which might be solved, at least in part, if considering the prognostic role of central BP. For any given value of pBP, the cardiovascular (CV) risk is better defined by central BP (cBP). Young individuals with ISH have long been considered at low CV risk, given the assumption that a "spurious hypertension" phenotype characterized by elevated peripheral (brachial) BP (pBP), normal cBP, and elevated BP amplification was often found in this population. However, this remains to be proven, because many other studies found no differences in BP amplification between ISH and sisto-diastolic hypertension. Despite numerous attempts, methodologies for cBP assessment by non-invasive devices are currently not standardized. As a result, different devices could provide different cBP values despite using the same biological signals. Devices providing accurate estimates of BP amplification as a dimensionless ratio between amplitudes of central and peripheral arterial waveforms might be well suited for clinical purposes in young individuals with ISH. There is urgent need of well-designed prospective studies aiming at longitudinally evaluating the amount of CV risk associated with elevated cBP in young subjects with ISH and their related incremental prognostic value.

Chicken meat is becoming the most consumed in the world for both economic and nutritional reasons; regarding the latter, the lipid profile may play positive or negative roles in the prevention and treatment of diseases. In this study, we define the state of the art of lipid-based nutritional indexes and used the lipid content and fatty acid profile (both qualitative and quantitative) of breast meat of two poultry genotypes with different growth rates and meat traits. Further, we summarize and review the definitions, implications, and applications of nutritional indexes used in recent years and others of our own design to provide a useful tool to researchers working in the field of meat quality (not only in poultry) to select the most appropriate index for their own scientific purposes. All indexes show advantages and disadvantages; hence, a rational choice should be applied to consider the nutritional effect of meat on human health and for a possible assessment of the most suitable rearing systems (genotype, feeding, farming system or postmortem handling).

Competing Interests: The authors declare no conflict of interest.

Atrial fibrillation (AF), the commonest sustained cardiac arrhythmia affecting the adult population, is often casually discovered among hospitalized people. AF onset is indeed triggered by several clinical conditions such as acute inflammatory states, infections, and electrolyte disturbance, frequently occurring during the hospitalization. We aimed to evaluate whether systematic AF screening, performed through an automated oscillometric blood pressure (BP) device (Microlife WatchBP Office AFIB, Microlife AG, Switzerland), is effective for detecting AF episodes in subjects admitted to an Internal Medicine ward. 163 patients consecutively hospitalized at the Unit of Internal Medicine of the "Santa Maria" Terni University Hospital between November 2019 and January 2020 (mean age ± standard deviation: 77 ± 14 years, men proportion: 40%) were examined. Simultaneously with BP measurement and AF screening, a standard 12-lead electrocardiogram (ECG) was performed in all subjects. AF was diagnosed by ECG in 29 patients (18%). AF screening showed overall 86% sensitivity and 96% specificity. False negatives (n = 4) had RR-interval coefficient of variation lower than true positives (n = 25, p < 0.01), suggesting a regular ventricular rhythm during AF. The repeated evaluation substantially confirmed the same level of agreement. AF screening was positive in all patients with new-onset AF (n = 6, 100%). Systematic AF screening in patients admitted to Internal Medicine wards, performed using the Microlife WatchBP Office AFIB, is feasible and effective. The opportunity to implement such technology in daily routine clinical practice to prevent undiagnosed AF episodes in hospitalized patients should be the subject of further research., (© 2021. The Author(s).)

Background and Aims: Ideal Cardiovascular Health (ICH), defined as optimal levels of cardiovascular (CV) health factors and behaviors, has been reported to be very low in adults and children, with consequent several negative health outcomes and higher CV risk. The present study investigated the burden of ICH among Italian adolescents and its association with carotid-femoral pulse wave velocity (cf-PWV)., Methods and Results: 387 healthy adolescents (mean age 17.1 ± 1.4 years) attending the "G. Donatelli" High School in Terni, Italy, were evaluated. ICH was assessed through clinical evaluation, laboratory measures and interviewer-administered questionnaires. Cf-PWV was measured by arterial tonometry (SphygmoCor). For each ICH metric, a score of 2 was assigned for ideal levels, 1 for intermediate, and 0 for poor. All subjects showed at least one ICH metric, whereas none showed all ICH 7 metrics. The average number of ICH metrics was 4.3 ± 1.1. The highest rates were observed for fasting blood glucose (98%), whereas an ideal healthy diet was achieved only by 8% of subjects. The Cf-PWV was inversely and linearly associated with the sum of ICH metrics (p = 0.03) and the ICH score (p < 0.01). At the multivariate analysis, the association between ICH score and cf-PWV remained significant after adjustment for age, sex, heart rate, mean arterial pressure and other confounders (p = 0.04)., Conclusion: ICH is relatively uncommon among Italian adolescents and inversely related to cf-PWV. Our results showed a detrimental association between CV unhealthy factors and behaviors with increased aortic stiffness, which starts developing at an early stage of the lifespan., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: During the lockdown for COVID-19, a massive decrease in hospital admissions for acute coronary syndrome (ACS) and a drop in air pollution were both detected in Italy. Our aim was to investigate the possible association between these two events at the Province of Terni, one of the most polluted urban and industrial area in Central Italy. Methods: We analyzed data of daily 24-h urban air concentrations of particulate matter (PM)10 and PM2.5 from fixed station monitoring network located in the main city centers of the Terni province, and accesses for ACS at the catheterization laboratory of the Cardiological Hub Center of the Terni University Hospital during lockdown. A comparison was made with data corresponding to the same lockdown time period of years 2019, 2018, and 2017. Results: Invasive procedures for ACS decreased in 2020 ( n = 49) as compared with previous years ( n = 93 in 2019, n = 109 in 2018, and n = 89 in 2017, p < 0.001). Conversely, reductions in average PM10 (20.7 μg/m 3 ) and PM2.5 (14.7 μg/m 3 ) in 2020 were consistent with a long-term decreasing trend, being comparable to those recorded in 2019 and 2018 (all p > 0.05) and slightly lower than 2017 ( p < 0.05). The Granger-causality test demonstrated the lack of association between time-varying changes in air pollution and the number of procedures for ACS. Conclusions: Our results did not support the hypothesis that reduction in invasive procedures for ACS during lockdown was linked to an air cleaning effect. Reasons other than reduced air pollution should be sought to explain the observed decrease in ACS procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Arrivi, Dominici, Bier, Truglio, Vaudo and Pucci.)

Left atrial enlargement (LAe) is a subclinical marker of hypertensive-mediated organ damage, which is important to identify in cardiovascular risk stratification. Recently, LA indexing for height was suggested as a more accurate marker of defining LAe. Our aim was to test the difference in LAe prevalence using body surface area (BSA) and height 2 definitions in an essential hypertensive population. A total of 441 essential hypertensive patients underwent complete clinical and echocardiographic evaluation. Left atrial volume (LAV), left ventricular morphology, and systolic-diastolic function were evaluated. LAe was twice as prevalent when defined using height 2 (LAe h2 ) indexation rather than BSA (LAe BSA ) (51% vs. 23%, p < 0.001). LAe h2 , but not LAe BSA , was more prevalent in females (p < 0.001). Males and females also differed in left ventricular hypertrophy (p = 0.046) and left ventricular diastolic dysfunction (LVDD) indexes (septal Em/Etdi: p = 0.009; lateral Em/Etdi: p = 0.003; mean Em/Etdi: p < 0.002). All patients presenting LAe BSA also met the criteria for LAe h2 . According to the presence/absence of LAe, we created three groups (Norm = BSA-/h 2 -; DilH = BSA-/h 2 +; DilHB = BSA+/h 2 +). The female sex prevalence in the DilH group was higher than that in the other two groups (Norm: p < 0.001; DilHB: p = 0.036). LVH and mean and septal Em/Etdi increased from the Norm to the DilH group and from the DilH to the DilHB group (p < 0.05 for all comparisons). These results show that LAe h2 identified twice as many patients as comparing LAe to LAe BSA , but that both LAe h2 and LAe BSA definitions were associated with LVH and LVDD. In female patients, the LAe h2 definition and its sex-specific threshold seem to be more sensitive than LAe BSA in identifying chamber enlargement.

Serum myostatin (sMSTN) is a proteic compound that regulates skeletal muscle growth, adipogenesis, and production of extracellular matrix. Its relationship with functional and structural properties of the arterial wall is still understudied. We aimed at evaluating the association between sMSTN and carotid-femoral pulse wave velocity (cf-PWV), a measure of aortic stiffness, in a cohort of healthy male adolescents. Fifteen healthy male adolescents were recruited among the participants of the Metabolic And Cardiovascular Investigation at School, TErni (MACISTE) study, a cross-sectional survey conducted at the "Renato Donatelli" High School in Terni, Italy. sMSTN was measured through enzyme-linked immunosorbent assay. cf-PWV was measured through high-fidelity applanation tonometry. Muscle strength and body composition were measured through handgrip and bioimpedentiometry, respectively. sMSTN levels showed a skewed distribution (median: 6.0 ng/mL, interquartile range: 2.2-69.2 ng/mL). Subjects with sMSTN above median value showed higher values of brachial diastolic blood pressure and increased cf-PWV (6.1 ± 1.1 m/s vs. 4.6 ± 0.7 m/s, P < 0.01) values, compared with their counterparts. Such difference remained significant after controlling for age, mean BP, heart rate, body mass index z -score, waist-to-height ratio, body mass/lean mass ratio, and amount of physical activity ( P = 0.02). The association between log-transformed sMSTN and cf-PWV was direct and linear, and independent from the effect of confounders at the multivariate analysis ( P = 0.02). In this preliminary report, sMSTN was independently associated with cf-PWV, a measure of aortic stiffness, in healthy male adolescents. Our results shed lights on the potential role of myokines in the pathogenesis of systemic hypertension and atherosclerosis. NEW & NOTEWORTHY Serum myostatin, a proteic compound known to regulate skeletal muscle growth and production of extracellular matrix, is independently associated with increased aortic stiffness in healthy male adolescents. This result sheds lights on the potential novel role of myokines in the early development of systemic hypertension and early vascular aging, as well as on their inhibition as a hypothetical therapeutic strategy to counteract vascular aging at an early stage of physical development.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE., Methods: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied., Results: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole., Conclusions: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The frequent finding of thrombocytopenia in patients with severe SARS-CoV-2 infection (COVID-19) and previous evidence that several viruses enter platelets suggest that SARS-CoV-2 might be internalized by platelets of COVID-19. Aim of our study was to assess the presence of SARS-CoV-2 RNA in platelets from hospitalized patients with aconfirmed diagnosis of COVID-19. RNA was extracted from platelets, leukocytes and serum from 24 COVID-19 patients and 3 healthy controls, real-time PCR and ddPCR for viral genes were carried out. SARS-CoV-2 RNA was not detected in any of the samples analyzed nor in healthy controls, by either RT-PCR or ddPCR, while RNA samples from nasopharyngeal swabs of COVID-19 patients were correctly identified. Viral RNA was not detected independently of viral load, of positive nasopharyngeal swabs, or viremia, the last detected in only one patient (4.1%). SARS-CoV-2 entry in platelets is not acommon phenomenon in COVID-19 patients, differently from other viral infections.

Among the different effects of bariatric surgery, here we focus on bone-derived inflammatory molecules, and in particular, sclerostin; an osteocyte product potentially associated with cardio-metabolic diseases. In 94 morbidly obese patients undergoing laparoscopic sleeve gastrectomy (SG), over-time changes in anthropometric and biochemical measures-including insulin resistance (IR) indexes-were correlated with serum sclerostin levels. Sclerostin was positively associated with anthropometric indexes of obesity, and inversely with IR, namely homeostatic model assessment for peripheral insulin sensitivity (HOMA2%S) (r = -0.218; p = 0.045). Sclerostin emerged as the only significant predictor of HOMA2-%S normalization, independently of demographic and anthropometric variables (OR 1.01 (95% CI 1.00-1.02); p = 0.024). We also identified two distinct patterns of serum sclerostin change: the higher/lower sclerostin levels at baseline, the greater their post-surgical reduction/increase ( p < 0.001 for all subgroups). Among those two patterns, especially the post-surgery increase in serum sclerostin was associated with lean mass reduction, without any association with IR indexes. Although counterintuitive, this change was likely dependent on the post-surgical increase in bone turnover. In conclusion, baseline serum levels of sclerostin correlate with anthropometric measures of obesity and IR, and the ability to predict glycemic improvements after SG. Specifically, serum sclerostin was closely associated with peripheral insulin sensitivity (HOMA2-%S), thus supporting the role of skeletal muscle/bone interactions in metabolic diseases.

Background: Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age., Methods: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP., Results: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04)., Conclusions: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Matrix metalloproteinases (MMPs) are important extracellular enzymes involved in many physiological and pathological processes. Changes in the activity and concentration of specific MMPs, as well as the unbalance with their inhibitors (tissue inhibitors of metalloproteinases - TIMPs), have been described as a part of the pathogenic cascade promoted by arterial hypertension. MMPs are able to degrade various protein substrates in the extracellular matrix, to influence endothelial cells function, vascular smooth muscle cells migration, proliferation and contraction, and to stimulate cardiomyocytes changes. All these processes can be activated by chronically elevated blood pressure values. Animal and human studies demonstrated the key function of MMPs in the pathogenesis of hypertension-mediated vascular, cardiac, and renal damage, besides age and blood pressure values. Thus, the role of MMPs as biomarkers of hypertension-mediated organ damage and potential pharmacological treatment targets to prevent further cardiovascular and renal complications in hypertensive population is increasingly supported. In this review, we aimed to describe the main scientific evidence about the behavior of MMPs in the development of vascular, cardiac, and renal damage in hypertensive patients., Competing Interests: There are no relationships with industry. The authors report no conflicts of interest in this work., (© 2020 Bisogni et al.)

Introduction: Hypertension is a major and modifiable risk factor for cardiovascular disease. Its prevalence is rising as the result of population aging. Isolated systolic hypertension mostly occurs in older patients accounting for up to 80% of cases., Areas Covered: The authors systematically review published studies to appraise the scientific and clinical evidence supporting the role of blood pressure control in elderly patients with isolated systolic hypertension, and to assess the influence of different drug treatment regimens on outcomes., Expert Opinion: Antihypertensive treatment of isolated systolic hypertension significantly reduces the risk of morbidity and mortality in elderly patients. Thiazide diuretics and dihydropyridine calcium-channel blockers are the primary compounds used in randomized clinical trials. These drugs can be considered as first-line agents for the management of isolated systolic hypertension. Free or fixed combination therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and calcium-channel blockers or thiazide-like diuretics should also be considered, particularly when compelling indications such as coronary artery disease, chronic kidney disease, diabetes, and congestive heart failure coexist. There is also hot scientific debate on the optimal blood pressure target to be achieved in elderly patients with isolated systolic hypertension, but current recommendations are scarcely supported by evidence.

Cardiac catheterization through radial access is associated with significant ionizing radiation exposure for the operator. We aimed at evaluating whether a removable shield placed upon the patient could impact favorably on annual radiation exposure for the operator. We designed a pre-post study comparing radiation exposure in a total of five operators under standard protection procedures (first period) and after applying a removable shield (second period). Each period included all the procedures performed in 1 year. Radiation exposure was measured through three dosimeters on each operator. A total of 1610 procedures were performed during the first period, and 1670 during the second period. For each operator, Fluoroscopy Time (FT) per exam did not differ between the two periods (13.1 ± 1 vs 12.9 ± 2 min/exam, p = 0.73), whereas Dose-Area Product (DAP) per procedure was slightly higher in the second period (5.247 ± 651 vs 6.374 ± 967 mGy/cm 2 , p < 0.01). The use of a removable shield significantly reduced operators' radiation dose at the left bracelet (64.3 ± 13.3 μSv/exam vs 23.8 ± 6.0 μSv/exam, p = 0.003). This remained significant even after adjustment for DAP per procedure (p = 0.015) and number of operators participating to each procedure (p = 0.013), whereas no significant difference was observed for card (5.6 ± 10.5 μSv/exam vs 0.9 ± 0.3 μSv/exam, p = 0.36) and neck bands (3.3 ± 4.5 μSv/exam vs 2.0 ± 2.0 μSv/exam, p = 0.36) dosimeters. The use of a removable shield during cardiac catheterization reduces radiation exposure at the level of the operator's upper limb, whereas no difference was found for other body parts. This may help in reducing radiation exposure of operator's hand. DAP increase merits further investigation.

Very low-carbohydrate ketogenic diets (VLCKDs) are an emerging nutritional treatment for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD). Little is known about the effect of sex differences on weight loss induced by following a VLCKD. The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Forty-two females and 28 males with severe obesity underwent a 25-day VLCKD. Anthropometric parameters, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL) and a greater reduction in γ-glutamyl transferase (γGT) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL and γGT. No significant difference between groups was observed for improvement in the Edmonton stage or in the degree of steatosis. We conclude that the efficacy of following a VLCKD in severe obesity is affected by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences are attenuated after menopause, probably because of changes in hormonal profile and body composition.

Blood pressure (BP) measurement at the forearm (FA) has been proposed as alternative site to upper arm (UA) in people with morbid obesity (MO). We compared nocturnal BP readings simultaneously taken at FA and UA by ambulatory blood pressure monitoring (ABPM). Fourteen individuals with MO and seven normal-weight controls underwent nocturnal ABPM with two devices placed at the UA and contralateral FA, respectively. Agreement between FA-UA BP, diagnosis of nocturnal hypertension, and potential determinants of BP differences were evaluated. BP at the FA was significantly higher than UA in both people with MO and controls. FA-UA differences in systolic and diastolic BP were similar in people with MO and controls. Nocturnal hypertension was diagnosed in 10 subjects (48%) according to UA BP and in 13 subjects (62%) according to FA BP (concordance 76%, moderate agreement). ΔFA-UA systolic BP was associated with ratio between FA/UA circumferences (R = 0.45, P < .05) and with cuff-UA slant angle difference (R = 0.44, P < .05). In conclusions, in people with MO, the agreement between FA and UA nighttime BP measured by ABPM is sub-optimal. Our results raise uncertainty in using ABPM at the FA as an alternative to UA placement in people with MO for the diagnosis of nocturnal hypertension., (©2020 Wiley Periodicals LLC.)

Background: Obesity is a risk factor for vitamin D deficiency and hyperparathyroidism. Hyperparathyroidism could exert a negative effect on glucose metabolism and vascular function. The aim of this study was to identify the determinants of hyperparathyroidism beyond vitamin D deficiency, whether hyperparathyroidism could have a negative impact on individual health and whether laparoscopic sleeve gastrectomy (LSG) negatively affects the levels of intact parathyroid hormone (iPTH) and 25(OH) vitamin D (25(OH)D)., Methods: We evaluated the levels of iPTH, 25(OH)D, and leptin, together with markers of insulin sensitivity and early cardiovascular disease, in a cohort of 160 patients with severe obesity before and after an LSG intervention., Results: Ninety-seven percent of subjects had vitamin D deficiency, and 72% of them had hyperparathyroidism. After correcting for possible confounders, we found a correlation between iPTH levels and carotid intima-media thickness, as well as with the HOMA index. After the LSG, 25(OH)D levels were significantly increased, while iPTH levels were significantly reduced. The reduction of iPTH was significantly correlated with the reduction of BMI, diastolic blood pressure, and leptin, which was the independent predictor of iPTH reduction., Conclusions: Our results suggest that vitamin D deficiency is not the sole determinant of hyperparathyroidism in severe obesity because visceral fat deposition and leptin could both play a role. Obesity-related hyperparathyroidism is associated with insulin resistance and atherosclerosis, although the results from previous studies were conflicting. Finally, LSG intervention does not negatively affect vitamin D status and improves hyperparathyroidism.

Superiority trials are conducted to test the hypothesis that a treatment or strategy A is superior to (i.e., better than) treatment strategy B in reducing the impact of disease. However, A may be considerably safer, more convenient, or cheaper than B. These features may make A more attractive than B even if the burden of disease is reduced comparably by the two treatments, or even a bit worse by A over B. In this context, non-inferiority trials have become increasingly popular to test the hypothesis that a new treatment is not 'unacceptably worse' than an active comparator by more than a predefined non-inferiority margin. Non-inferiority trials have unique design features and methodology and require a different analysis than traditional superiority trials. The main aim of this overview is to analyze the role of non-inferiority trials in the development of new treatments, involving some scientific, statistical, and practical considerations. We elucidate some aspects of non-inferiority trials that contribute to the validity of the results. The unique design features and methodology of non-inferiority trials are summarized and key findings to consider when evaluating a non-inferiority trial are illustrated.

Background & Aims: Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH)., Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM > 48 g/m 2.7 in men and > 44 g/m 2.7 in women), were randomized 1:1 to receive AP or placebo for 24 weeks. Reduction of LVM, regression of LVH, and changes in lipids were analysed., Results: One-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p < 0.0001), and compared to placebo (-4.1%, p < 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile., Conclusions: 24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aims: Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG)., Methods: Fifty-six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima-media thickness (cIMT). Fifty-four subjects were evaluated 1 year after the intervention., Results: Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima-media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut-off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG., Conclusion: Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: HF patients typically show effort intolerance due to a reduction in peak exercise oxygen (peak VO2) consumption, which is related to inability to adapt systolic function to increased demand. Left ventricular ejection fraction (EF) is a surrogate marker of cardiac contractility and a powerful predictor of adverse prognosis in chronic heart failure (HF). The aim of the study was to explore the relationship between EF and other echocardiographic findings with peak VO2 in a population of HF individuals undergoing cardiopulmonary exercise testing (CPX)., Methods: We evaluated 101 patients (61% hypertensives, 74% with documented coronary artery disease) undergoing both resting echocardiography and symptom-limited CPX., Results: Mean age was 58±13 years, 83% were males. Mean EF was 55±12%; 20% of the patients showed EF<40%. Mean test duration was 9.4±2.2 min. Average peak VO2 was 21±6 mL/kg/min. Peak VO2 showed a robust positive correlation with EF (R=0.42, P<0.001). Other independent predictors of peak VO2 were age, male sex, height and tricuspidal anular plane systolic excursion (TAPSE), this latter reflecting right ventricular dysfunction. When subjects were dichotomized according to predicted peak VO2values, those with higher-than-predicted peak VO2 showed significantly lower VE/VCO2 slope, and higher values of both oxygen pulse and VO2/WR slope., Conclusions: EF and TAPSE are associated with peak VO2 in HF patients independently from age, sex and height. The evaluation of potentially relevant mechanisms affecting exercise capacity in HF patients requires further investigation.

Competing Interests: Declaration of Competing Interest The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.

Introduction: Treatment with biological agents interfering with mechanisms of angiogenesis, such as vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors, was associated with an enhanced risk of acute and severe blood pressure (BP) increase and development of hypertensive emergencies. Areas covered: The present article will review the scientific literature reporting hypertensive emergencies as a complication of biological treatment with VSP inhibitors. Hypertensive emergency is a life-threatening condition characterized by very high BP values (>180/110 mmHg) associated with acute organ damage. The exact mechanism of action is still incompletely clarified. Endothelial dysfunction following reduced bioavailability of nitric oxide has been hypothesized to play an important role in promoting hypertension and the occurrence of acute organ damage. Expert opinion: Prevention, prompt recognition and treatment of hypertensive emergencies associated with treatment with VSP-inhibitors are essential to reduce the risk of adverse events. Not infrequently, the occurrence of hypertensive emergency led to VSP treatment discontinuation, with potential negative consequences on patient overall survival. The present review aims at providing detailed knowledge for the clinician regarding this specific issue, which could be of high impact in usual clinical practice, given the increasing burden of indications to treatment with biological agents targeted to the VEGF pathway.

Aims: Microvascular dysfunction is a potential factor explaining the association of obesity, insulin resistance, and vascular damage in morbidly obese subjects. The purpose of the study was to evaluate possible determinants of microcirculatory improvement 1 year after laparoscopic sleeve gastrectomy (LSG) intervention., Methods: Thirty-seven morbidly obese subjects eligible for bariatric surgery were included in the study. Post-occlusive reactive hyperemia (PORH) of the forearm skin was measured as area of hyperemia (AH) by laser-Doppler flowmetry before LSG and after a 1-year follow-up., Results: After intervention, we observed a significant reduction in BMI, HOMA index, HbA1c, and a significant increase of AH in all patients after surgery; this variation was significant only in those patients having insulin resistance or prediabetes/diabetes. Although significant correlation between the increase of AH and the reduction of both BMI, HOMA index, and HbA1c was observed, BMI was the only independent predictor of AH variation after LSG at the linear regression analysis., Conclusions: Our study shows that LSG intervention is correlated with a significant improvement in the microvascular function of morbidly obese subjects; this improvement seems to be related to the baseline degree of insulin-resistance and to the retrieval of insulin-sensitivity post-intervention.

Background & Aims: Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females., Methods and Results: In 110 morbidly obese patients undergoing laparoscopic sleeve gastrectomy, hs-CRP as well as anthropometric assessment of adiposity, completed by electric bioimpedance and ultrasonography quantification of visceral fat area (VFA), were measured before and one year after surgery. As compared to males, obese female showed less severe overweight and prevalent subcutaneous fat deposition, but higher circulating hs-CRP. In obese females, hs-CRP was associated with VFA at baseline, independently of body mass index (BMI) and visceral adiposity index (OR 1.022 [95% CI 1.001-1.044]; p = 0.039). Based on decreases and increases in hs-CRP levels after surgery, two distinct subgroups of females were identified. Post-surgery decreases in hs-CRP was predominantly observed in patients with higher baseline levels of hs-CRP and associated with greater reduction of weight, BMI, fat and lean mass, VFA and visceral to subcutaneous fat ratio. Finally, we observed that high baseline values of hs-CRP were able to predict VFA reduction one-year after surgery, independently of BMI and visceral adiposity index (VAI) loss (OR 1.031 [95% CI 1.009-1.053]; p = 0.005)., Conclusion: In obese females, hs-CRP levels might be a promising biomarker of visceral fat amount and dysfunction, in addition to predict the effectiveness of bariatric surgery in terms of loss of VFA one-year after surgery., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the vasoprotective effects of HDL isolated from carriers of LCAT deficiency, which are characterized by a selective depletion of LpA-I:A-II particles and predominance of preβ migrating HDL. HDLs were isolated from LCAT-deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in cultured endothelial cells. HDLs from carriers were more effective than control HDLs in promoting eNOS activation with a gene-dose-dependent effect ( P Trend = 0.048). As a consequence, NO production induced by HDL from carriers was significantly higher than that promoted by control HDL (1.63 ± 0.24-fold vs. 1.34 ± 0.07-fold, P = 0.031). HDLs from carriers were also more effective than control HDLs in inhibiting the expression of VCAM-1 (homozygotes, 65.0 ± 8.6%; heterozygotes, 53.1 ± 7.2%; controls, 44.4 ± 4.1%; P Trend = 0.0003). The increased efficiency of carrier HDL was likely due to the depletion in LpA-I:A-II particles. The in vitro findings might explain why carriers of LCAT deficiency showed flow-mediated vasodilation and plasma-soluble cell adhesion molecule concentrations comparable to controls, despite low HDL-cholesterol levels. These results indicate that selective depletion of apoA-II-containing HDL, as observed in carriers of LCAT deficiency, leads to an increased capacity of HDL to stimulate endothelial NO production, suggesting that changes in HDL apolipoprotein composition may be the target of therapeutic interventions designed to improve HDL functionality., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1β, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1β, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1β showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1β. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1β, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1β could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Non-alcoholic fatty liver disease (NAFLD) is strongly related with enhanced morbidity and mortality from cardiovascular disease. In obese patients with both NAFLD and features of the metabolic syndrome, the cardiovascular risk is further increased., Aim: The aim of this study is to investigate the relationship between severity of liver fibrosis evaluated by NAFLD fibrosis score (NAFLD-FS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), other obesity-related markers and preclinical atherosclerosis in morbidly obese patients with previously diagnosed NAFLD., Methods: Laboratory parameters, visceral fat area (VFA), flow-mediated dilatation (FMD), intima-media thickness (IMT), HOMA-IR and NAFLD-FS were determined in 196 morbidly obese patients., Results: Patients with higher NAFLD-FS or HOMA-IR show higher left max-IMT and lower FMD (p<0.001). VFA and NAFLD-FS, but not HOMA-IR, were independent predictors of reduced FMD (respectively β -0.268, p=0.001 and β -0.165, p=0.039, p of the model<0.001) and increased left max-IMT (respectively β 0.165, p=0.031 and β 0.301, p<0.001, p of the model<0.001)., Conclusions: In morbidly obese patients, NAFLD-FS correlates with markers of early vascular damage. NAFLD-FS, easier to obtain than VFA, seems to be a better score than HOMA-IR to categorize such subjects who are potentially at risk of future cardiovascular events., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Systemic inflammation and imbalance between endothelial injury and repair, the latter referred to as vascular incompetence, are associated with atherosclerosis and cardiovascular risk. Psoriasis, an inflammatory disease of the skin, has been associated with atherosclerosis. We investigated whether, in psoriasis, inflammation and vascular incompetence are associated with carotid intima-media thickness (cIMT) irrespective of metabolic syndrome and other established cardiovascular risk factors., Methods: High sensitivity C-reactive protein (hsCRP), the ratio between endothelial microparticles (EMPs) and progenitors (EPCs), a marker of vascular incompetence, and cIMT were measured in 84 patients with psoriasis and 90 healthy controls, balanced for age, gender and the prevalence of metabolic syndrome., Results: Patients with psoriasis had higher hsCRP, EMP/EPC ratio and cIMT than controls. Patients with both psoriasis and metabolic syndrome had the highest hsCRP levels, psoriasis and metabolic syndrome being associated with a 3.1- and 2.6-fold increased risk of having high hsCRP levels, respectively. Logarithm transformed hsCRP and EMP/EPC ratio were predictors of high cIMT (odds ratio 3.8; 95% confidence interval 1.3-11.4; p = 0.02 and odds ratio 8.7; 95% confidence interval 2.7-27.5; p < 0.001, respectively) regardless of confounders. Patients with high hsCRP and EMP/EPC ratio had higher cIMT than those with none or at least one of risk variable., Conclusions: Patients with psoriasis have an increased burden of cardiovascular risk, including inflammation, vascular incompetence and early atherosclerosis. Increased hsCRP levels, possibly sustained by the inflammatory nature of psoriasis and metabolic syndrome, and vascular incompetence are associated with early carotid atherosclerosis, regardless of metabolic syndrome and other established cardiovascular risk factors., (© The European Society of Cardiology 2014.)

Oxidative stress is linked to several human diseases, including nonalcoholic steatohepatitis (NASH). In this study, lymphocytes were used as a model to study this disease. These cells offer several advantages for cellular and molecular studies such as easy accessibility, and they are easily accessible and constitute a "time-persistent" system capable of reflecting the condition of the whole organism. Lymphocytes from patients with NASH display oxidative stress features. Among the possible causes for the overproduction of reactive oxygen species in NASH lymphocytes, there might be alterations of enzymatic pathways, auto-oxidation of glucose and mitochondrial superoxide production, which, in turn, would lead to protein oxidative damage. Increased oxidative stress in lymphocytes from patients with NASH may result in a pro-oxidative environment, which, in turn, could modify the pathway of the enzymatic activities. The data confirm that an imbalance between pro-oxidant and antioxidant defense mechanisms may be an important factor in NASH.

Aims: Statin therapy is followed by reductions in carotid intima-media thickness (CIMT) and C-reactive protein (CRP) levels, but a significant number of treated patients still have increased CIMT. We investigated whether on-treatment levels of CRP are associated with CIMT in hypercholesterolemic patients receiving statin therapy. The influence of blood pressure and anti-hypertensive therapy on the association between CRP and CIMT was evaluated., Main Methods: The assessment of cardiovascular risk factors, CRP and CIMT, was performed in a cross-sectional study of 240 hypercholesterolemic patients at intermediate cardiovascular risk under statin therapy; 125 patients received only a statin (statin group) and 115 also anti-hypertensive therapy (combined therapy group)., Key Findings: Logarithmically transformed CRP (β=0.17, p=0.01) and HDL cholesterol levels (β=-0.27, p<0.001) were correlates of CIMT, irrespective of confounders. High CRP levels (>3mg/L) were associated with a 2.7-fold increased risk of having high CIMT (>1.25mm). High CIMT was present in a high percentage of patients not at target for cholesterol and blood pressure levels (61%). Patients in the statin group had lower Framingham risk and CIMT than those in the combined therapy group. In the statin group, logarithmically transformed CRP (β=0.28, p=0.004) and HDL cholesterol (β=-0.21, p=0.03) were associated with CIMT. In the combined therapy group, HDL cholesterol was the only significant CIMT correlate (β=-0.33, p=0.001)., Significance: On-treatment CRP and HDL cholesterol levels are associated with CIMT among hypercholesterolemic patients under statin therapy. In patients receiving both statin and anti-hypertensive therapy, HDL cholesterol remains the main covariate of CIMT., (© 2013.)

Aim: Several factors contribute to the development of atherogenesis in patients with obesity. The aim of our study was to evaluate the different roles of insulin resistance, strictly correlated to visceral adiposity, and the body mass index (BMI), an estimate of overall adiposity, on early vascular impairment in patients with morbid obesity., Methods: We enrolled 65 morbidly obese subjects (BMI 44.6 ± 7 kg/m(2)) who were free of previous cardiovascular events and 28 nonobese subjects (control group) in a cross-sectional study. The presence of glycemia and insulinemia, the levels of lipids and liver parameter and the ultrasonographic assessment of the flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) and visceral fat area (VFA) were evaluated in all subjects., Results: In the obese patients with a median HOMA value of ≥ 3.5, the FMD was significantly lower (p < .05) and the left carotid maximum-IMT was significantly higher (p < .05) than those observed in the group with lower HOMA values. No vascular differences were found between the two groups that were subdivided according to the BMI median value. Both the left max-IMT and FMD exhibited a significant correlation with HOMA-IR ("ρ" .292, p=0.02 , "ρ"-.292, p=0.02 respectively) but not with BMI. According to a multivariate analysis, the VFA was an independent predictor of a reduced FMD (β - .541, p.002; p of the model .002), while age (β .611 p < .0001) and HOMA-IR (β .399 p < .001) were independent predictors of the left max-IMT (p of the model .002)., Conclusions: The HOMA-IR, which is strictly related to visceral fat and is an index of metabolic impairment, and not BMI, which reflects of global adiposity, can be used to identify early vascular impairment in patients with morbid obesity.

Background: Peripheral arterial disease (PAD) is frequently underdiagnosed in the clinical practice, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI) represents a noninvasive, objective tool to diagnose PAD and to predict adverse outcome., Methods: ABI was determined by means of Doppler velocimetry, in 707 patients, aged 50 years or older, consecutively hospitalized in an internal medicine ward, who were followed-up for at least 12 months in order to assess all-cause and CV mortality., Results: Symptomatic PAD affected 8% of the population while the prevalence of PAD, defined as ABI <0.90, was 29%; high ABI (>1.40) was found in 8% of the patients. After a mean follow-up period of 1.6 years, both low and high ABI were independently associated with CV mortality with a hazard ratio of 1.99 (p=0.016) for low and 2.13 (p=0.04) for high ABI, compared with normal ABI (0.90-1.40). High ABI also independently predicted all-cause mortality with a hazard ratio of 1.77 (p=0.04)., Discussion: ABI measurement reveals a large number of individuals with asymptomatic PAD among those hospitalized in an internal medicine department. An increased mortality was observed in patients with both low and high ABI. Hospital admission for any reason may serve as an opportunity to detect PAD and start appropriate preventive actions., (Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: Primary Sjögren's syndrome (SS) shares clinical and serologic features with rheumatoid arthritis and systemic lupus erythematosus, 2 diseases characterized by acceleration of atherosclerosis. Signs of precocious atherosclerosis have also been shown in SS, although the pathogenic basis of early arterial damage is unclear. The arterial wall was functionally evaluated in SS subjects with analysis of the role played by disease-related factors., Methods: Endothelium-dependent flow-mediated vasodilation (FMV) and endothelium-independent nitrate-mediated vasodilation (NMV) were evaluated in 45 women with SS and 59 age-matched female controls. In addition, serum soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (VCAM-1), and nitrotyrosine were detected., Results: Although patient FMV values did not differ from those of control subjects (mean +/- SD 7.4 +/- 3.6 versus 7.7 +/- 1.9; not significant), NMV was lower in SS patients than in controls (mean +/- SD 8.1 +/- 3.5 versus 10.3 +/- 2.1; P