Publications by authors named "Cristina Giannattasio"

150 Publications

Determinants of Functional Improvement After Cardiac Rehabilitation in Acute Coronary Syndrome.

High Blood Press Cardiovasc Prev 2021 Sep 13. Epub 2021 Sep 13.

Dipartimento A. De Gasperis, Cardiac Rehabilitation, Cardiology 4, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20159, Milan, Italy.

Introduction: Cardiac rehabilitation (CR) is an effective tool for secondary prevention after acute coronary syndrome (ACS).

Aim: Aim of our study was to find the significant determinants of exercise capacity (evaluated with the six-minute walking test-6-MWT) and functional improvement in patients undergoing CR after an ACS.

Methods: The study group included 298 patients (mean age 61.6 ± 10.2 years; males 80.2%) who, after ACS, were enrolled in CR program at Niguarda Hospital in Milan from 2015 to 2018. For all patients, we collected anamnestic, clinical and instrumental cardiological data. All patients performed a 6-MWT at the beginning (6-MWT-1) and at the end (6-MWT-2) of CR program. Δ meters were used to represent functional improvement.

Results: Multiple linear regression models were carried out for 6-MWT-1, 6-MWT-2, Δ meters and % Δ meters. Standardized regression coefficients showed that age (β = - 0.237; p < 0.001), BMI (β = - 0.116; p = 0.006) and heart rate (β = - 0.082; p = 0.040) were determinants of exercise capacity (6MWT-1 and 2), whereas age (β = -.231; p = 0.004), sex (β = - 0.187; p = 0.008) and BMI (β = - 0.164; p = 0.022) were determinants of functional improvement (Δ meters).

Conclusions: Our data showed that functional improvement after CR in ACS patients is mainly related to non-cardiological variables. Instead it is related to intrinsic factors, both modifiable (BMI) and non-modifiable (age, sex).
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http://dx.doi.org/10.1007/s40292-021-00473-7DOI Listing
September 2021

Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.

J Hum Hypertens 2021 Sep 7. Epub 2021 Sep 7.

Cardiology IV, "A.De Gasperis" Department, ASTT GOM Niguarda Ca' Granda, Milan, Italy.

Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.
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http://dx.doi.org/10.1038/s41371-021-00604-6DOI Listing
September 2021

Depression symptoms as longitudinal predictors of the psychological impact of COVID-19 pandemic in hypertensive patients.

Sci Rep 2021 08 13;11(1):16496. Epub 2021 Aug 13.

Department of Psychology, University of Milano-Bicocca, Milan, Italy.

COVID-19 has brought considerable changes and caused critical psychological responses, especially among frail populations. So far, researchers have explored the predictive effect of diverse factors on pandemic-related psychological distress, but none have focused on the impact of prior depression and anxiety symptomatology adopting an extended (10-year) longitudinal design. 105 patients aged over 60, affected by hypertension who participated in a previous longitudinal study were assessed through a follow-up telephone structured interview. The Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale-Revised (IES-R) were used for assessing depression and anxiety symptoms and the psychological impact of COVID-19, respectively. Multiple linear regression analyses were conducted. At the assessment, participants did not report clinically relevant depression, anxiety, and psychological pandemic-related distress symptoms. However, significant mean differences between baseline and current follow-up evaluations for both depression and anxiety were found, reflecting a decrease in symptomatology over time (p < .001). Baseline depression symptoms (β = 1.483, p = .005) significantly predicted the psychological impact of COVID-19 after 10 years. Conversely, their decrease (β = -1.640, p < .001) and living with others (β = -7.274, p = .041) significantly contributed to lower psychological distress scores. Our findings provide insight into the predisposing influence of depressive symptoms on pandemic-related psychological distress ten years later. Preventive interventions and strategies considering these factors are needed to better pre-empt the severe mental consequences of the pandemic.
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http://dx.doi.org/10.1038/s41598-021-96165-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363734PMC
August 2021

Troponin elevation in COVID-19 patients: An important stratification biomarker with still some open questions.

Int J Cardiol 2021 Aug 2. Epub 2021 Aug 2.

Cardiac Rehabilitation, Cardiology 4, ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan, Italy; School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.

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http://dx.doi.org/10.1016/j.ijcard.2021.07.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327562PMC
August 2021

Continuous flow left ventricular assist devices do not worsen endothelial function in subjects with chronic heart failure: a pilot study.

ESC Heart Fail 2021 Jul 31. Epub 2021 Jul 31.

Department of Biomedical Sciences and Human Oncology, Pediatric Section, University "A. Moro" of Bari, Bari, Italy.

Aims: To evaluate endothelial function in subjects with left ventricular assist devices (LVADs), comparing them with subjects with chronic heart failure with reduced ejection fraction on the list for heart transplant (HT) and with HT patients with a normal systolic cardiac function to identify any differences.

Methods: We enrolled 28 subjects with LVAD, 55 subjects with HT, and 42 subjects with heart failure on the transplant list. The subjects underwent a general physical examination, assessment of laboratory blood parameters, and assessment of endothelial function through flow-mediated dilation (FMD) of brachial artery.

Results: The three groups were homogeneous as regards age, gender, smoke abuse, C-reactive protein (CRP) and FMD parameters (P = ns). In LVAD group percentage of FMD change showed an inverse correlation with CRP (rho: -0.5, P: 0.003), a well-known marker of inflammation and tissue damage.

Conclusions: Continuous flow related to LVAD seems to not worsen endothelial function. Endothelial function was not affected by cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, and tobacco habit), by the functional status expressed by New York Heart Association class, by the left ventricular systolic function and by the presence or absence of ischaemic heart disease in all the populations analysed. CRP was the only factor able to influence percentage of FMD change in patient with LVAD, reinforcing the hypothesis that inflammation is the main determinant of endothelial function.
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http://dx.doi.org/10.1002/ehf2.13484DOI Listing
July 2021

Home blood pressure monitoring: methodology, clinical relevance and practical application: a 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension.

J Hypertens 2021 Sep;39(9):1742-1767

Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH.
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http://dx.doi.org/10.1097/HJH.0000000000002922DOI Listing
September 2021

Covid and Cardiovascular Diseases: Direct and Indirect Damages and Future Perspective.

High Blood Press Cardiovasc Prev 2021 Jun 26. Epub 2021 Jun 26.

School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.
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http://dx.doi.org/10.1007/s40292-021-00464-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233573PMC
June 2021

Acute cardiovascular syndrome in the Italian multiethnic society.

J Cardiovasc Med (Hagerstown) 2021 Apr 28. Epub 2021 Apr 28.

Cardiac Intensive Care Unit and De Gasperis Cardio Center Cardiology IV and De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda School of Emergency Medicine School of Medicine and Surgery, Università degli Studi Milano-Bicocca, Milan, Italy.

Background: In multiethnic societies, it has frequently and repeatedly been shown that some minority groups have higher rates of traditional coronary artery disease (CAD) risk factors, different rates of treatment with revascularization procedures, and excess morbidity and mortality from CAD when compared with the white population. In the last two decades, Italy is becoming a diverse society with more than five millions of inhabitants from minority ethnic groups: for this reason, we decided to investigate whether ethnic differences in our metropolitan area are similar compared with the experience of Western countries.

Methods And Results: We performed a retrospective cohort study of 1285 patients with acute coronary syndromes (ACS) hospitalized at Intensive Cardiac Care Unit (ICCU), Heart Center of ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy between 2014 and the end of 2019. Six percent of these patients were South-Asian, North-African, and South-American. Despite the younger age of nonwhite patients, their comorbid conditions and traditional cardiovascular risk factors showed peculiar differences. We did not observe any difference in terms of the number of coronary arteries involved at the enrollment, patients candidate to coronary artery bypass graft and either intra-hospital or at follow-up mortality. Nevertheless, the rate of re-infarction at follow-up was significantly higher in the nonwhite group.

Conclusion: We believe that a better knowledge and understanding of epidemiological changes in Italian society could improve our clinical practice, in particular, in order to better customize treatments and therapies.
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http://dx.doi.org/10.2459/JCM.0000000000001207DOI Listing
April 2021

Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.

Nutr Metab Cardiovasc Dis 2021 05 6;31(5):1501-1508. Epub 2021 Feb 6.

Cardiology IV, "A.De Gasperis" Department, Ospedale Niguarda Ca' Granda, Milan, Italy; School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.

Background And Aims: Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation.

Methods And Results: 231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function.

Conclusions: In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.
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http://dx.doi.org/10.1016/j.numecd.2021.01.023DOI Listing
May 2021

Ankle-Brachial Index Is a Predictor of In-Hospital Functional Status but Not of Complications in Hospitalized Elderly Patients.

Gerontology 2021 Mar 23:1-7. Epub 2021 Mar 23.

School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.

Introduction: Atherosclerosis causes a chronic reduction of vascularization with consequent impairment of the performance of organs, like the brain or muscles, which determines the functional and cognitive decline of the elderly and their ability to respond to acute stressful condition. Therefore, our aim was to evaluate if ankle brachial index (ABI) could effectively be a determinant of in-hospital functional status and complications in elderly hospitalized patients.

Methods: This is a monocentric cross-sectional study of 189 patients aged 65 years or older. The study was undertaken at the Internal Medicine ward of Niguarda Hospital in Milan. ABI (BOSO ABY-System 100) and in-hospital status (activities of daily living, ADL and instrumental activities of daily living, IADL) were collected on the second day of hospitalization. Complications (falls and delirium episodes) were also recorded during the whole hospitalization period.

Results: The average age of patients was 79.3 ± 6.9 years. Among outcomes, only ADL (r = 0.192, p = 0.007) and IADL score (r = 0.200, p = 0.005) showed significant correlation with ABI. Moreover, during the subsequent logistic regression, ABI remained among the statistically significant determinants of both scores (β = 0.231, p = 0.013 and β = 0.314, p = 0.001, respectively).

Conclusions: The main result of our study is the finding of ABI as a significant determinant of acute in-hospital functional impairment (evaluated as ADL and IADL scores). The continuous exposure of the brain and muscles to the reduced perfusions induced by vascular atherosclerosis, probably determined the reduced ability to respond to stressful conditions.
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http://dx.doi.org/10.1159/000514450DOI Listing
March 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.
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http://dx.doi.org/10.1007/s40620-021-00985-4DOI Listing
March 2021

Protein Intake and Physical Activity in Newly Diagnosed Patients with Acute Coronary Syndrome: A 5-Year Longitudinal Study.

Nutrients 2021 Feb 16;13(2). Epub 2021 Feb 16.

Department of Psychology, University of Milano-Bicocca, 20126 Milan, Italy.

Cardiovascular disease is one of the most common causes of hospitalization and is associated with high morbidity and mortality rates. Among the most important modifiable and well-known risk factors are an unhealthy diet and sedentary lifestyle. Nevertheless, adherence to healthy lifestyle regimes is poor. The present study examined longitudinal trajectories (pre-event, 6-, 12-, 24-, 36-, and 60-month follow-ups) of protein intake (fish, legumes, red/processed meat) and physical activity in 275 newly-diagnosed patients with acute coronary syndrome. Hierarchical Generalized Linear Models were performed, controlling for demographic and clinical variables, the season in which each assessment was made, and the presence of anxiety and depressive symptoms. Significant changes in protein intake and physical activity were found from pre-event to the six-month follow-up, suggesting the adoption of healthier behaviors. However, soon after the six-month follow-up, patients experienced significant declines in their healthy behaviors. Both physical activity and red/processed meat intake were modulated by the season in which the assessments took place and by anxiety symptoms over time. The negative long-term trajectory of healthy behaviors suggests that tailored interventions are needed that sustain patients' capabilities to self-regulate their behaviors over time and consider patient preference in function of season.
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http://dx.doi.org/10.3390/nu13020634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919823PMC
February 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.
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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.
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http://dx.doi.org/10.1093/eurjpc/zwab023DOI Listing
February 2021

Emergent Biosensing Technologies Based on Fluorescence Spectroscopy and Surface Plasmon Resonance.

Sensors (Basel) 2021 Jan 29;21(3). Epub 2021 Jan 29.

Institute of Food Science, CNR Italy, 83100 Avellino, Italy.

The purpose of this work is to provide an exhaustive overview of the emerging biosensor technologies for the detection of analytes of interest for food, environment, security, and health. Over the years, biosensors have acquired increasing importance in a wide range of applications due to synergistic studies of various scientific disciplines, determining their great commercial potential and revealing how nanotechnology and biotechnology can be strictly connected. In the present scenario, biosensors have increased their detection limit and sensitivity unthinkable until a few years ago. The most widely used biosensors are optical-based devices such as surface plasmon resonance (SPR)-based biosensors and fluorescence-based biosensors. Here, we will review them by highlighting how the progress in their design and development could impact our daily life.
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http://dx.doi.org/10.3390/s21030906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866296PMC
January 2021

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Front Med (Lausanne) 2020 20;7:607786. Epub 2021 Jan 20.

Central Clinical Hospital of Ministry of the Interior and Administration, Warsaw, Poland.

Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.
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http://dx.doi.org/10.3389/fmed.2020.607786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855590PMC
January 2021

Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects.

Nutr Metab Cardiovasc Dis 2021 04 20;31(4):1044-1052. Epub 2020 Nov 20.

Cardiology IV, "A.De Gasperis" Department, Ospedale Niguarda Ca' Granda, Milan, Italy; Health Science Department, Milano-Bicocca University, Milan, Italy.

Background And Aims: Metabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls.

Methods And Results: We enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p < 0.001) and showed higher PWV (9.0 ± 2.3 vs 8.4 ± 2.1 m/s, p = 0.001) and IMT (0.72 ± 0.22 vs 0.65 ± 0.17 mm, p < 0.001) than those without MS, however at the age-adjusted analysis only the difference in IMT was confirmed (p = 0.007). Regression models showed that MS was an independent determinant of IMT in both controls (β = 0.08, p = 0.03) and hypertensives (β = 0.08, p = 0.01), but not of PWV either in controls (β = 0.006, p = 0.886 and β = 0.04, p = 0.19, respectively).

Conclusions: the main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.
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http://dx.doi.org/10.1016/j.numecd.2020.11.011DOI Listing
April 2021

Left atrial volume indexed for height is a new sensitive marker for subclinical cardiac organ damage in female hypertensive patients.

Hypertens Res 2021 Jun 1;44(6):692-699. Epub 2021 Feb 1.

Department of Medical Sciences, Hypertension Center, AOU Città della Salute e della Scienza di Torino, University of Torino, Turin, Italy.

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 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 (LAe) indexation rather than BSA (LAe) (51% vs. 23%, p < 0.001). LAe, but not LAe, 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 also met the criteria for LAe. According to the presence/absence of LAe, we created three groups (Norm = BSA-/h-; DilH = BSA-/h+; DilHB = BSA+/h+). 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 identified twice as many patients as comparing LAe to LAe, but that both LAe and LAe definitions were associated with LVH and LVDD. In female patients, the LAe definition and its sex-specific threshold seem to be more sensitive than LAe in identifying chamber enlargement.
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http://dx.doi.org/10.1038/s41440-021-00614-4DOI Listing
June 2021

Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

Eur Heart J Cardiovasc Pharmacother 2021 Jan 7. Epub 2021 Jan 7.

Department of Medical and Surgical Sciences, Ospedale Malpighi, University of Bologna, Bologna, Italy.

Aims: Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.

Methods And Results: A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open label trial with blind end-points evaluation. One hundred and ninetyseven adults with gout and SUA levels ≥8 mg/dL were randomised to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomisation and week 36 were respectively 8.69 m/s and 9.00 m/s for subjects randomised to febuxostat and 9.02 m/s and 9.05 m/s for subjects randomised to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs 61.1% at week 36, p = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomised to febuxostat and 63 (62.5%) patients randomised to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.

Conclusions: In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.
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http://dx.doi.org/10.1093/ehjcvp/pvaa144DOI Listing
January 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.
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http://dx.doi.org/10.1097/HJH.0000000000002600DOI Listing
February 2021

Costs and effects of cardiovascular risk reclassification using the ankle-brachial index (ABI) in addition to the Framingham risk scoring in women.

Atherosclerosis 2021 01 10;317:59-66. Epub 2020 Nov 10.

Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy; IRCCS Multimedica, Sesto San Giovanni, Italy.

Background And Aims: Ankle brachial index (ABI) is a simple and cheap parameter to assess the presence of atherosclerosis. It could also help correctly reclassify the cardiovascular risk when added to the Framingham risk score (FRS). Recent evidence has demonstrated improvement in prediction performance of ABI when added to FRS, particularly in women. However, no studies have been published yet evaluating the cost-effectiveness of this approach. This study attempts to fill in this gap by assessing the cost-effectiveness of ABI measurements in primary prevention in women.

Methods: We developed a Markov model to compare two different strategies for assessing the cardiovascular risk (low, intermediate and high) among women in the general population: 1) FRS strategy, and 2) FRS + ABI strategy; and the relative impact associated with interventions for preventing CV events in intermediate and high-risk categories.

Results: In the base-case analysis, FRS + ABI reported an additional cost of € 110 and a gain of 0.0039 QALYs per patient, resulting in an ICER of € 27.986/QALY, when compared to FRS alone. The ICER improved to €1.641/QALY when using a lifetime horizon. The effectiveness of preventive CV disease interventions reported also a significant impact. A 32% reduction of CV events was the minimum value estimated to maintain FRS + ABI as a cost-effective strategy.

Conclusions: The addition of ABI to FRS is a cost-effective approach in women classified at low and intermediate risk with FRS only. This new approach gives the possibility to reclassify and allocate them into the appropriate risk group and treatment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.11.004DOI Listing
January 2021

Determinants of healing among patients with coronavirus disease 2019: the results of the SARS-RAS study of the Italian Society of Hypertension.

J Hypertens 2021 02;39(2):376-380

Department of Advanced Biomedical Sciences, Federico II University, Naples.

Objective: The burst of COVID-19 epidemics in Italy prompted the Italian Society of Hypertension to start an observational study to explore the characteristics of the hospitalized victims of the disease. The current analysis aimed to investigate the predictors of healing among Italian COVID-19 patients. We also assessed the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers on the outcome.

Methods: We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to explore the demographic and clinical characteristics of patients with confirmed COVID-19 infection. We analyzed information from 2446 charts of Italian patients admitted for certified COVID-19 in 27 hospitals. Healing from COVID-19 infection, defined as two consecutive negative swabs, was reported in 544 patients (22.2%), 95% of them were hospitalized.

Results: Age and Charlson Comorbidity Index were significantly lower in healing compared with nonhealing patients (63 ± 15 vs. 69 ± 15 and 2 ± 2 vs. 3 ± 2, both P < 0.05). In multivariable regression model, predictors of healing were younger age (OR: 0.99; 95% CI 0.98-0.99, P = 0.0001), absence of chronic kidney disease (OR: 0.35; 95% CI 0.17-0.70, P = 0.003) or heart failure (OR: 0.44; 95% CI, 0.28-0.70, P = 0.001). In the subgroup of patients suffering from hypertension and/or heart failure (n = 1498), no differences were observed in the use of ACE inhibitors and angiotensin receptor blockers.

Conclusion: Our study demonstrated that younger age and absence of comorbidities play a major role in determining healing in patients with COVID-19. No effects of ACE inhibitors and angiotensin receptor blockers on the outcome was reported.
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http://dx.doi.org/10.1097/HJH.0000000000002666DOI Listing
February 2021

Nutraceuticals in Chronic Coronary Syndromes: Preclinical Data and Translational Experiences.

High Blood Press Cardiovasc Prev 2021 Jan 30;28(1):13-25. Epub 2020 Oct 30.

Cardiologia IV, Dipartimento A. De Gasperis, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20159, Milan, Italy.

Non-pharmacological treatments have always been considered important in the management of Chronic Coronary Syndromes. Nutraceuticals ("Nutrition" + "Pharmaceutical") could fall both under the definition of non-pharmacological treatment and pharmacological one or, probably more correctly, in the middle of these two kinds of therapies. However, the word "nutraceuticals" never appears in the latest guidelines on this issue. This is probably determined by the fact that evidences on this topic are scarce and most of the published articles are based on preclinical data while translational experiences are available only for some molecules. In this review we will focus on nutraceutical strategies that act on the ischemic myocardium itself and not only on the cardiovascular risk factors. As demonstrated by the important number of papers published in recent years, this is an evolving topic and evaluated substances principally act on two mechanisms (cardiac energetics and ischemia-reperfusion damage) that will be also reviewed.
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http://dx.doi.org/10.1007/s40292-020-00416-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864844PMC
January 2021

Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

PLoS One 2020 6;15(10):e0237297. Epub 2020 Oct 6.

Dept. of Clinical & Experimental Sciences, Medicina 2, ASST Spedali Civili Brescia, University of Brescia, Brescia, Italy.

Background: The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.

Methods And Findings: We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 p<0.05). In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05). In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission.

Conclusions: Our study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.

Trial Registration: Clinicaltrials.gov: NCT04331574.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537902PMC
October 2020

Hyperuricemia prevalence in healthy subjects and its relationship with cardiovascular target organ damage.

Nutr Metab Cardiovasc Dis 2021 01 20;31(1):178-185. Epub 2020 Aug 20.

Cardiology IV, "A. De Gasperis" Department, ASTT GOM Niguarda Ca' Granda, Milan, Italy; University of Milano-Bicocca, Milan, Italy.

Background And Aim: Heterogeneous results have been obtained in the relationship between Uric Acid (UA) and Target Organ Damage (TOD). In the present study we sought to assess the prevalence of hyperuricemia in healthy subjects as well as the role of UA in determining TOD. We evaluated vascular, cardiac and renal TODs in the whole population as well as sub-grouped by gender.

Methods And Results: As many as 379 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT). Hyperuricemia was defined with the classic cut-off (>7.0 in men and >6.0 mg/dL in women) but also with a most recently defined one (5.6 mg/dL for both sex). Hyperuricemia was present in 6.3% of the whole population (7.3% males, 2.8% females) considering the classic cut-off, while, with the recently identified one, it was present in 28.2% of the whole population (37.3% males, 4.7% females). Despite all the evaluated TODs significantly correlated with UA, linear multivariate regression analysis showed that none of them, except for GFR, displayed UA as a significant covariate. Similar figures were found also when both correlation and linear regression analyses were repeated in the two genders separately.

Conclusions: Hyperuricemia is an important problem also in healthy subjects and its prevalence could further increase if lower cut-off will be used. In this specific population UA is significantly associated with renal impairment while this was not the case for cardiac and vascular damage.
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http://dx.doi.org/10.1016/j.numecd.2020.08.015DOI Listing
January 2021
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