Publications by authors named "Marcello Rattazzi"

72 Publications

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies.

Nutrients 2021 Jul 28;13(8). Epub 2021 Jul 28.

Department of Medicine-DIMED, University of Padova, 35122 Padua, Italy.

Cardiovascular calcification is the ectopic deposition of calcium-phosphate crystals within the arterial wall and the aortic valve leaflets. This pathological process leads to increased vascular stiffness, reduced arterial elasticity, and aortic valve stenosis, increasing the risk of cardiovascular diseases. Although cardiovascular calcification is an increasing health care burden, to date no medical therapies have been approved for treating or preventing it. Considering the current lack of therapeutic strategies and the increasing prevalence of cardiovascular calcification, the investigation of some nutraceuticals to prevent this pathological condition has become prevalent in recent years. Recent preclinical and clinical studies evaluated the potential anti-calcific role of nutraceuticals (including magnesium, zinc, iron, vitamin K, and phytate) in the progression of vascular calcification, providing evidence for their dietary supplementation, especially in high-risk populations. The present review summarizes the current knowledge and latest advances for nutraceuticals with the most relevant preclinical and clinical data, including magnesium, zinc, iron, vitamin K, and phytate. Their supplementation might be recommended as a cost-effective strategy to avoid nutritional deficiency and to prevent or treat cardiovascular calcification. However, the optimal dose of nutraceuticals has not been identified and large interventional trials are warranted to support their protective effects on cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13082603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401694PMC
July 2021

Carotid elasticity is impaired in stage 1 hypertensive patients with well-controlled blood pressure levels.

J Hum Hypertens 2021 Aug 5. Epub 2021 Aug 5.

Medicine Unit, Mirano Town Hospital, Mirano, Venezia, Italy.

Whether impaired arterial elasticity in stage 1 hypertension can be brought back to normal by antihypertensive treatment is unknown. Aim of this study was to evaluate the impact of long-term well-controlled blood pressure (BP) on carotid artery elasticity and endothelial function in stage 1 hypertensive patients. We studied 40 middle-age hypertensives (mean age 49.7 years) whose BP had been kept at target by pharmacological treatment and/or lifestyle modifications for a mean of 7.5 years. Carotid compliance coefficient (CC) and distensibility coefficient (DC) were measured by B-mode ultrasound system. Measurement of carotid intima-media thickness (IMT) was performed in each carotid artery segment, bilaterally. Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD). Forty normotensive subjects matched for age and sex served as controls. In the hypertensive subjects, BP levels were well controlled throughout the study period (mean office BP 133.7 ± 9.0/81.27 ± 7.0 mmHg). However, compared to controls, significantly higher office BP levels and waist circumference were present. Compared to normotensives, carotid elasticity (DC 24.5 ± 9.0 vs 37.0 ± 8.5 10/kPa, and CC 0.92 ± 0.34 vs 1.28 ± 0.36 mm/kPa, p < 0.0005 for both) as well as endothelial function (FMD 5.7 ± 2.4% vs 9.2 ± 2.9%, p < 0.0005) were significantly impaired in hypertensives. In a logistic regression, hypertensive patients had increased risk of impaired carotid vascular stiffness (odds ratio, 95% CI: 13.04 (2.27-74.96), p = 0.004). Despite the "pseudo-normalization" of BP levels, hypertensive patients with long-term well-controlled BP according to current standards exhibited increased local arterial stiffness and endothelial dysfunction suggesting that lower BP targets should be sought.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41371-021-00584-7DOI Listing
August 2021

GSK-3 Inhibition Modulates Metalloproteases in a Model of Lung Inflammation and Fibrosis.

Front Mol Biosci 2021 21;8:633054. Epub 2021 Jun 21.

Hematology Unit, Department of Medicine, University of Padova, Padova, Italy.

Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix deposition, consequent to epithelial lung injury and myofibroblast activation, and inflammatory response. Glycogen synthase kinase 3 (GSK-3) is a serine-threonine kinase involved in several pathways, and its inhibition has been already suggested as a therapeutic strategy for IPF patients. There is evidence that GSK-3 is able to induce matrix metalloproteinase (MMP) expression and that its inhibition modulates MMP expression in the tissues. The aim of our study was to investigate the role of GSK-3 and its inhibition in the modulation of MMP-9 and -2 in an mouse model of lung fibrosis and using different cell lines exposed to pro-inflammatory or pro-fibrotic stimuli. We found that GSK-3 inhibition down-modulates gene expression and protein levels of MMP-9, MMP-2, and their inhibitors TIMP-1 and TIMP-2 in inflammatory cells harvested from bronchoalveolar lavage fluid (BALF) of mice treated with bleomycin as well as in interstitial alveolar macrophages and cuboidalized epithelial alveolar cells. To the same extent, GSK-3 inhibition blunted the increased MMP-9 and MMP-2 activity induced by pro-fibrotic stimuli in a human lung fibroblast cell line. Moreover, the αSMA protein level, a marker of fibroblast-to-myofibroblast transition involved in fibrosis, was decreased in primary fibroblasts treated with TGFβ following GSK-3 inhibition. Our results confirm the implication of GSK-3 in lung inflammation and fibrosis, suggesting that it might play its role by modulating MMP expression and activity but also pushing fibroblasts toward a myofibroblast phenotype and therefore enhancing extracellular matrix deposition. Thus, its inhibition could represent a possible therapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.633054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255387PMC
June 2021

Vaccination in PADs.

Vaccines (Basel) 2021 Jun 9;9(6). Epub 2021 Jun 9.

Department of Medicine, University of Padua, 35122 Padua, Italy.

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines9060626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230118PMC
June 2021

Lipid Profile and Vascular Remodelling in Young Dyslipidemic Subjects Treated with Nutraceuticals Derived from Red Yeast Rice.

Cardiovasc Ther 2021 22;2021:5546800. Epub 2021 Apr 22.

Department of Medicine (DIMED), University of Padova, Italy.

Background And Aims: A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease.

Methods And Results: We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, < 0.001), LDL-c (from 150 to 130 mg/dl, = 0.001), triglycerides (from 121 to 109 mg/dl, = 0.013), non-HDL-cholesterol (from 168 to 141 mg/dl, < 0.001), hs-CRP (from 1.74 to 1.20 mg/l, = 0.015), and osteoprotegerin (from 1488 to 1328 pg/ml, = 0.045). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, = 0.022) and M-MAX (from 0.79 to 0.73 mm, = 0.002), and an improvement in carotid elasticity (DC from 22.4 to 24.3 × 10/kPa, = 0.006 and CC from 0.77 to 0.85 mm/kPa, = 0.019).

Conclusions: A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5546800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087481PMC
June 2021

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers.

Front Immunol 2021 10;12:627423. Epub 2021 Mar 10.

Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.

Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis. In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD. In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97). we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.627423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987811PMC
September 2021

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.

J Nephrol 2021 Mar 23. Epub 2021 Mar 23.

Department of Medicine, University of Padua, Padua, Italy.

Background: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database.

Methods: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol.

Results: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m2with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides.

Conclusions: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-021-00985-4DOI Listing
March 2021

Subcutaneous immunoglobulins replacement therapy in secondary antibody deficiencies: Real life evidence as compared to primary antibody deficiencies.

PLoS One 2021 4;16(3):e0247717. Epub 2021 Mar 4.

Department of Medicine-DIMED, University of Padua, Padua, Italy.

Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found to work irrespective of the underlying disease. Especially in Non-Hodgkin Lymphoma patients, whose indication to IgRT is still not included in all guidelines and for whom evidence-based data are still lacking, SCIG were as effective as in Chronic Lymphocytic Leukemia or Multiple Myeloma patients, and SCIG discontinuation, without evidence of B cell recovery, led to IgG decline and relapsed infections. Finally, treatment tolerance in SAD patients was comparable to the PAD cohort. Globally, our data suggest that SCIG, as already appreciated in PAD, represent a valuable option in SAD patients, independent on the disease leading to antibody deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932095PMC
September 2021

The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk.

Clin Res Cardiol 2021 Jul 18;110(7):1073-1082. Epub 2021 Feb 18.

Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS S. Luca Hospital, Lucca, Italy.

Introduction: Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis.

Aim: We assessed the prognostic role of SUA in patients with and without MS.

Methods: We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure.

Results: A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15-2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001).

Conclusion: Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-021-01815-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238697PMC
July 2021

High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.

Eur J Prev Cardiol 2021 Feb 14. Epub 2021 Feb 14.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.

Aims : Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR).

Methods And Results : Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P < 0.0001) over a multivariable model. However, the risk of CVM related to high UA (≥5.5 mg/dL, top tertile) was much lower in the subjects with HR
Conclusion : This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurjpc/zwab023DOI Listing
February 2021

Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.

J Hypertens 2021 02;39(2):333-340

Medicina Interna I, Ca' Foncello University Hospital, Treviso.

Objective: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events.

Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes.

Results: Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group.

Conclusion: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002600DOI Listing
February 2021

Venom immunotherapy during COVID-19 pandemic: Experience from a University Allergy Center in Northern Italy.

World Allergy Organ J 2020 Dec 13;13(12):100489. Epub 2020 Nov 13.

Allergy and Clinical Immunology Center, University of Padua, Department of Internal Medicine, Internal Medicine I Unit, Ca' Foncello Hospital, Treviso, Italy.

During the ongoing pandemic of Coronavirus Disease 2019 (COVID-19) allergic patients need to continue their constant and proper treatment, including allergen-specific immunotherapy. These patients are expected to be at a higher risk for exacerbation of lung inflammation during viral infection. We investigated the putative interplay existing between allergen-specific immunotherapy and COVID-19 infection in a Hymenoptera venom-allergic population. We evaluated the frequency and severity of COVID-19 infection in a cohort of 211 subjects referring to our center for the regular administration of venom immunotherapy (VIT). Our result showed that the median age of our cohort is similar to the one that in our region has been associated with a high incidence of COVID-19 infection, increased hospitalization, and mortality rates. We reported only an isolated positivity of COVID-19 in the overall group; whereas none suffered from upper airway symptoms associated with COVID-19 (fever, cough, dyspnoea, sore throat, anosmia, and/or ageusia). Even though the demographic characteristics pose a substantial risk for such a population, we suggest that a regular administration of VIT may help in the development of an immunological milieu able to down modulate the Th1/Th17 environment that has been linked to inflammatory manifestations of COVID-19. To the best of our knowledge, this is the first description of the incidence of COVID-19 infection in Hymenoptera venom allergic patients treated with VIT, suggesting indirectly that venom immune tolerance-inducing treatment may be capable of reducing the aberrant inflammatory response induced by the virus in this specific population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2020.100489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664475PMC
December 2020

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis.

Int J Mol Sci 2020 Nov 4;21(21). Epub 2020 Nov 4.

Department of Medicine-DIMED, University of Padova, 35122 Padova, Italy.

Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21218263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663524PMC
November 2020

Serum uric acid levels and the risk of recurrent venous thromboembolism.

J Thromb Haemost 2021 01 18;19(1):194-201. Epub 2020 Nov 18.

Medicina Generale I^, Ca' Foncello University Hospital, Treviso, Italy.

Essentials Increase in serum uric acid (SUA) levels has been widely associated with higher risk of cardiovascular disease. We investigated the link between SUA levels and the risk of venous thromboembolism (VTE) recurrence. Patients with SUA levels ≥ 4.38 mg/dL showed a three-fold increase in the risk of VTE recurrence. Elevated SUA levels are associated with increased risk of recurrent VTE independently from traditional risk factors. ABSTRACT: Background The link between serum uric acid (SUA) and the risk of cardiovascular disease is well established. However, the impact of SUA levels on the risk of venous thromboembolism (VTE) recurrence is unknown. Objectives To investigate the association between SUA and the risk of VTE recurrence. Patients and Methods We performed a monocenter, prospective study on 280 patients with a previous episode of VTE that completed the oral anticoagulant period. SUA levels at enrollment were correlated with the risk of VTE recurrence (mean follow-up 71.1 ± 29.2 months). Results Patients were stratified according to SUA tertiles distribution at baseline (tertiles cut-off: I ≤ 4.37 mg/dL, II 4.38--5.54 mg/dL, III ≥ 5.55 mg/dL). Fifty episodes of VTE recurrence occurred during the follow-up and Kaplan-Meier survival analysis showed that subjects in the lower tertile of SUA distribution had significantly lower risk of future VTE recurrence (P = .003). No differences were seen among patients belonging to the second and the third tertile of SUA distribution. A multivariate Cox regression analysis showed that higher tertiles of SUA distribution had about three-fold increase in the risk of VTE recurrence as compared to subjects with SUA ≤ 4.37, independently from potential confounders (hazard ratio [HR] 3.04, 95% confidence interval [CI] 1.15--8.05 P = .025). Moreover, we observed that the adjusted hazard of VTE recurrence increased by 30% for each additional unit of SUA (mg/dL; HR 1.30, 95% CI 1.01--1.22, P = .040). Conclusion Elevated SUA levels are associated with increased risk of future VTE recurrence independently from traditional risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15139DOI Listing
January 2021

Developing an instrument for an early prediction model of long-term functional outcomes in people with acquired injuries of the central nervous system: protocol and methodological aspects.

Neurol Sci 2021 Jun 19;42(6):2441-2446. Epub 2020 Oct 19.

Department of Neuroscience, Section of Rehabilitation & NEUROMOVE-Rehab Lab, University of Padova, Via Giustiniani n. 3, 35128, Padova, Italy.

Severe acquired brain injury (ABI) is a major cause of long-term disability and is the main determinant of health and societal costs. Early identification of favourable long-term recovery would allow personalized rehabilitative programs and better health care resources allocation. In light of the higher survival rate from intensive care units (ICU) in recent years, there is a growing need for early prognostication markers of functional recovery; to date, these data have been mainly collected at rehabilitation unit admission and not during the acute phase. We present the protocol and methodology to develop prediction models in people with severe acquired brain injury (GCS at admission to ICU < 8) for the functional and cognitive outcome at 12 months from the event. Predictors will be collected during the acute stage. Participants will be recruited within the first 72 h from the event in the ICUs of two teaching hospitals (Padova and Treviso). Participants will be followed up at discharge from ICU, admission and discharge from Neurorehabilitation and after 12 months from the event. Clinical and functional scales, electroencephalography, evoked potentials, magnetic resonance imaging and serological markers will be entered into a digital registry. Survival will be estimated using the Cox proportional hazard model. A multivariate prediction model will be developed for each of the functional and cognitive outcomes at 12 months from the event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04821-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159777PMC
June 2021

Short-Term but not Long-Term Blood Pressure Variability Is a Predictor of Adverse Cardiovascular Outcomes in Young Untreated Hypertensives.

Am J Hypertens 2020 11;33(11):1030-1037

Department of Medicine, University of Padova, Padova, Italy.

Background: Whether blood pressure variability (BPV) measured with ambulatory monitoring (short-term BPV) or computed from office visits (long-term BPV) are related to each other and carry similar prognostic information is not well known. We investigated the independent determinants of short-term and long-term BPVs and their predictive capacity for the development of major adverse cardiovascular and renal events (MACEs) in a cohort of young hypertensive participants.

Methods: Long-term BPV was calculated as visit-to-visit SD and average real variability from office blood pressure (BP) measured during 7 visits, within 1 year. Short-term BPV was calculated as weighted 24-hour SD and coefficient of variation. Hazard ratios (HRs) for risk of MACE were computed from multivariable Cox regressions.

Results: 1,167 participants were examined; mean age was 33.1 ± 8.5 years. Variables independently associated with 24-hour systolic SD were 24-hour systolic BP, low physical activity, smoking, baseline office pulse pressure, systolic BP dipping, and diastolic white coat effect, while those associated with long-term BPV were mean systolic BP, age, female gender, and baseline office heart rate. During a median follow-up of 17.4 years 75 MACEs occurred. In Cox analysis only short-term BPV resulted a significant predictor of MACE (HR, 1.31 (1.07-1.59); P = 0.0086), while no index of long-term BPV was independently associated with outcome.

Conclusions: In young hypertensive subjects only short-term BPV resulted a significant predictor of MACE on top of traditional ambulatory BP monitoring parameters. Whether reduction of short-term BPV with therapy may reduce the cardiovascular risk independently from the effects on 24-hour BP is a matter for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajh/hpaa121DOI Listing
November 2020

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

J Hypertens 2021 01;39(1):62-69

Hospital S. Maria della Misericordia, Perugia, Italy.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension.

Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.

Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively.

Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002589DOI Listing
January 2021

Introduction to the review series on atherosclerotic calcification.

Atherosclerosis 2020 08 10;306:57-58. Epub 2020 Jun 10.

Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.016DOI Listing
August 2020

Use of RAAS Inhibitors and Risk of Clinical Deterioration in COVID-19: Results From an Italian Cohort of 133 Hypertensives.

Am J Hypertens 2020 10;33(10):944-948

Department of Medicine-DIMED, Medicina Generale I^, Ca' Foncello Hospital, Treviso, University of Padova, Padua, Italy.

Background: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients.

Methods: A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020.

Results: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09-0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17-1.83, P = 0.341).

Conclusions: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajh/hpaa096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314218PMC
October 2020

Subclinical atherosclerosis evolution during 5 years of anti-TNF-alpha treatment in psoriatic arthritis patients.

Clin Exp Rheumatol 2021 Jan-Feb;39(1):158-161. Epub 2020 May 20.

Clinica Medica 3, Department of Medicine DIMED, University of Padova; and Dipartimento di Medicina, Ospedaledi Mirano, Venezia, Italy.

Objectives: Our aim was to evaluate subclinical atherosclerosis progression during 5 years of anti-tumour necrosis factor (TNF)-α treatment in psoriatic arthritis (PsA) patients.

Methods: Thirty-two consecutive PsA patients starting TNF-α inhibitors were enrolled and evaluated at baseline (T0), 2 years (FU1) and 5 years (FU2) of treatment. Arterial structural properties were evaluated by B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each segment (common, bulb, internal), bilaterally. Endothelial function was assessed by post-occlusion flow-mediated dilation (FMD) of the brachial artery using high-sensitivity ultrasonography. Treatment response was studied through DAS28 (disease activity score) and inflammatory biomarkers (C-reactive protein, TNF-α, osteoprotegerin). Metrologic and metabolic data were collected.

Results: At T1, a significant decrease of DAS28 (4.2±0.7 vs. 2.3±0.8, p<0.001) and CRP (11.25±9.16 vs. 2.91±1.72, p<0.01) was observed. Efficacy was preserved at FU2 (DAS28 2.4±0.9, CRP 2.73±2.51; p=ns vs. FU1). Systolic blood pressure and BMI remained stable throughout the follow-up, while diastolic blood pressure decreased significantly from FU1 to FU2 (80±10 vs. 74±7 mmHg, p=0.001). From T0 to FU1 there was an increase of IMT-mean and M-MAX (0.7±0.1 vs. 0.9±0.4 and 0.9±0.2 vs. 1.1±0.4, p<0.01). At FU2, IMT-mean and M-max did not change significantly (0.9±0.3 and 1.1±0.3, p=ns vs. FU1). No significant variation in FMD values was observed during the study period.

Conclusions: A slight progression of subclinical atherosclerosis in PsA was observed in the first 2 years of anti-TNF-α treatment. This process seemed to decelerate in follow-up extension to 5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

l-Arginine prevents inflammatory and pro-calcific differentiation of interstitial aortic valve cells.

Atherosclerosis 2020 04 5;298:27-35. Epub 2020 Mar 5.

Department of Biomedical Sciences, University of Padova, Italy; Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, Italy.

Background And Aims: Reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of calcific aortic stenosis. Herein, we investigated the effects of l-Arginine, the main precursor of NO, on the osteogenic differentiation of aortic interstitial valve cells (VICs).

Methods: We isolated a clonal population of bovine VICs that expresses osteogenic markers and induces calcification of collagen matrix after stimulation with endotoxin (LPS 500 ng/mL). VICs were treated in vitro with different combinations of LPS ± l-Arginine (50 or 100 mM) and cell extracts were collected to perform proteomic (iTRAQ) and gene expression (RT-PCR) analysis.

Results: l-Arginine prevents the over-expression of alkaline phosphatase (ALP, p < 0.001) and reduces matrix calcification (p < 0.05) in VICs treated with LPS. l-Arginine also reduces the over-expression of inflammatory molecules induced by LPS (TNF-alpha, IL-6 and IL-1beta, p < 0.001). The proteomic analysis allowed to identify 49 proteins with an altered expression profile after stimulation with LPS and significantly modified by l-Arginine. These include proteins involved in the redox homeostasis of the cells (i.e. Xanthine Oxidase, Catalase, Aldehyde Oxidase), remodeling of the extracellular matrix (i.e. ADAMTSL4, Basigin, COL3A1) and cellular signaling (i.e. Fibrillin-1, Legumain, S100A13). The RT-PCR analysis confirmed the modifications of Fibrillin-1, ADAMTSL4, Basigin and Xanthine Oxidase, whose expression levels increase after stimulation with LPS and are reduced by l-Arginine (p < 0.05).

Conclusions: l-Arginine prevents osteogenic differentiation of VICs and reduces matrix calcification. This effect is achieved through the modulation of proteins involved in the cellular redox system, remodeling of extracellular matrix and inflammatory activation of VICs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.02.024DOI Listing
April 2020

Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line.

Nutrients 2020 Feb 9;12(2). Epub 2020 Feb 9.

Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, 35131, Padova, Italy.

Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris, containing MK-7, magnesium carbonate, and Sucrosomial Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (-18.9% in supplemental uremic . uremic diet; < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (-38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12020436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071245PMC
February 2020

Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years.

Hypertension 2020 02 9;75(2):302-308. Epub 2019 Dec 9.

Studium Patavinum, Department of Medicine (E.C., P.P.), University of Padua, Italy.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; <0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13643DOI Listing
February 2020

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.

J Hypertens 2020 03;38(3):412-419

Department of Clinical and Experimental Sciences, University of Brescia, Brescia.

Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.

Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.

Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men.

Conclusion: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012356PMC
March 2020

Blood Pressure Variability and Therapeutic Implications in Hypertension and Cardiovascular Diseases.

High Blood Press Cardiovasc Prev 2019 Oct 26;26(5):353-359. Epub 2019 Sep 26.

O.R.A.S. SpA, Ospedale Riabilitativo di Alta Specializzazione, Motta Di Livenza, Italy.

Blood pressure (BP) is characterized by continuous dynamic and spontaneous oscillations occurring over lifetime and defining the so-called blood pressure variability (BPV). BPV has been associated with target organ damage, cardiovascular (CV) risk and death, suggesting the use of BPV as a new target in hypertension management in addition to mean BP values lowering. The purpose of the review is to focus on the therapeutic implications of BPV and summarize the effects of different drug classes on various types of BPV. Despite most first-line antihypertensive medications contribute to reduce both short and long term BPV, calcium channel blockers (CCBs) as monotherapy or fixed-combination therapy appear to be the most effective on BPV control. Further randomized interventional trials are needed to investigate which drug combinations are most appropriate according to patient CV risk stratification, in order to improve their CV outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40292-019-00339-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825020PMC
October 2019

The broad spectrum of lung diseases in primary antibody deficiencies.

Eur Respir Rev 2018 Sep 29;27(149). Epub 2018 Aug 29.

Dept of Medicine - DIMED, University of Padova, Padova, Italy.

Human primary immunodeficiency diseases (PIDs) represent a heterogeneous group of more than 350 disorders. They are rare diseases, but their global incidence is more relevant than generally thought. The underlying defect may involve different branches of the innate and/or adaptive immune response. Thus, the clinical picture may range from severe phenotypes characterised by a broad spectrum of infections to milder infectious phenotypes due to more selective (and frequent) immune defects. Moreover, infections may not be the main clinical features in some PIDs that might present with autoimmunity, auto-inflammation and/or cancer. Primary antibody deficiencies (PADs) represent a small percentage of the known PIDs but they are the most frequently diagnosed, particularly in adulthood. Common variable immunodeficiency (CVID) is the most prevalent symptomatic PAD.PAD patients share a significant susceptibility to respiratory diseases that represent a relevant cause of morbidity and mortality. Pulmonary complications include acute and chronic infection-related diseases, such as pneumonia and bronchiectasis. They also include immune-mediated interstitial lung diseases, such as granulomatous-lymphocytic interstitial lung disease (GLILD) and cancer. Herein we will discuss the main pulmonary manifestations of PADs, the associated functional and imaging findings, and the relevant role of pulmonologists and chest radiologists in diagnosis and surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/16000617.0019-2018DOI Listing
September 2018

Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE-/- mice.

Cardiovasc Ther 2018 Aug 28;36(4):e12438. Epub 2018 Jun 28.

ORAS Rehabilitation Hospital, Motta di Livenza, Treviso, Italy.

Introduction: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.

Aims: To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice.

Results: 42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over-expression of COX-2 induced by inflammatory mediators.

Conclusion: We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1755-5922.12438DOI Listing
August 2018

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

J Cardiovasc Transl Res 2018 08 17;11(4):329-338. Epub 2018 May 17.

ORAS, Rehabilitation Hospital, Motta di Livenza, Italy.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12265-018-9804-2DOI Listing
August 2018

The multifaceted role of macrophages in cardiovascular calcification.

Atherosclerosis 2018 03 1;270:193-195. Epub 2018 Feb 1.

Department of Pathology, University of Washington, Seattle, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2018.01.046DOI Listing
March 2018

Chronic kidney disease is associated with increased risk of venous thromboembolism recurrence.

Thromb Res 2017 Dec 16;160:32-37. Epub 2017 Oct 16.

Department of Medicine - DIMED, University of Padova, Italy; Medicina Interna I^, Cà Foncello University Hospital, Treviso, Italy.

Introduction: It is currently unclear whether chronic kidney disease (CKD) and the decrease in renal function can influence the risk of venous thromboembolism (VTE) recurrence.

Materials And Methods: We performed an ambispective observational study on 409 patients with a previous episode of VTE. All the patients were included in the retrospective analysis whereas a subgroup of 260 individuals, without history of recurrence and that stopped oral anticoagulation, were then followed-up for a mean of 52.3±20.7months.

Results: At the enrollment, subjects with history of recurrent VTE were prevalently male with higher blood pressure and lower eGFR. Prevalence of CKD (defined as eGFR<60ml/min/1.73m) was higher in patients with previous VTE recurrence with an adjusted OR of 5.69 (IC95% 2.17-14.90, p<0.001) compared to patients with normal eGFR. Similar findings were obtained from the prospective study where an adjusted 5.32 HR for VTE recurrence was seen in patients with CKD compared to subjects with normal renal function (IC95% 1.49-18.95, p=0.010). An increase in the risk of recurrent VTE was also observed in patients with mild decrease in renal function (eGFR 60-90 vs ≥90ml/min/1.73m adjusted HR 2.84, IC95% 1.13-7.11, p=0.025). Moreover, a multivariate Cox regression analysis including eGFR as continuous variable showed that renal function decrease was independently associated with the risk of VTE recurrence (p=0.001).

Conclusions: CKD and mild decrease in renal function are associated with a significant increase in the risk of recurrent VTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2017.10.011DOI Listing
December 2017
-->