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Introduction: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. Aim: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. Methods: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD – endothelial function) and Pulse Wave Velocity (PWV—arterial stiffness) Results: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. Conclusions: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects. [ABSTRACT FROM AUTHOR]

Introduction: Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs. Aim. Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. Aim: Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. Methods: We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers. Conclusions: Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement. [ABSTRACT FROM AUTHOR]

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)—Lp(a)—lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years. [ABSTRACT FROM AUTHOR]

Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio‐Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest β for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non‐HDL, P < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cutoff displays highest OR as compared to the URRAH one. In conclusions, newly reported URRAH cutoff for hyperuricemia better relate to atherogenic lipoprotein (LDL and non‐HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut‐off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED. [ABSTRACT FROM AUTHOR]

Introduction: A possible alternative to pharmacological antihypertensive therapies in grade 1 low risk hypertensive patients or in those experienced drugs adverse effects could be acupuncture. Aim: we focused on its possible effects on BP both as Office BP (OBP) and as Ambulatory BP Monitoring (ABPM) evaluating it before starting a 6 weeks twice weekly (total 12 session) acupuncture cycle and after 2 months from its completion. Methods: in this prospective study we treated with acupuncture 45 patients: 24 of them presents high-normal BP values and low cardiovascular risk while 21 patients were on anti-hypertensive drug with slightly uncontrolled BP values (from 140 to 145 mmHg for Systolic BP—SBP—and/or from 90 to 95 mmHg for Diastolic BP—DBP). Results: regarding SBP, a significant reduction have been observed for office values (from 134.2 ± 15.7 to 125.1 ± 12.2, p = 0.03), and for ABPM 24 h (from 131.1 ± 10.7 to 126.0 ± 10.1, p = 0.01) and day-time values (from 134.7 ± 10.5 to 127.1 ± 18.4, p = 0.02). For DBP, only ABPM 24 h and day-time values showed significant changes (from 85.3 ± 9.1 to 82.1 ± 7.5, p = 0.03; and from 88.5 ± 9.3 to 85.7 ± 7.8, p = 0.02). Within session SBP decrease was − 5.8 mmHg (-3.75%) during the first session while it falls to – 2.1 mmHg (– 1.25%) and stands firmly under 2 mmHg for all the next session. At the last session SBP reduction was − 1.9 mmHg (– 1.6%). Conclusions: we found a significant reduction in office, 24 h and day-time ABPM SBP determined by a 6-weeks twice weekly acupuncture cycle that lasts at least for the first two months after its completion. [ABSTRACT FROM AUTHOR]

The relationship between HyperUricemia (HU) and Metabolic Sindrome (MS) and if Uric Acid (UA) should be inserted into MS definitions is a matter of debate. Aim of our study was to evaluate the correlation between UA and HU with Insulin Resistance (IR) and MS in a population of hypertensive patients. HU was defined with two cut-offs (the classic one of ≥6 mg/dL for women and ≥ 7 for men; the newly proposed URRAH one with ≥5.6 mg/dL for both sexes). We enrolled 473 Hypertensive patients followed by the Hypertension Unit of San Gerardo Hospital (Monza, Italy). IR was defined through TG/HDL ratio and NCEP-ATP-III criteria were used for MS diagnosis. MS was found in 33.6 % while HU affected 14.8 % of subjects according to the traditional cut-off and 35.9 % with the URRAH cut-off. 9.7 % (traditional cut-off) and 17.3 % (URRAH's threshold) of the subjects had both HU and MS. UA level was significantly higher in MS group (5.7 vs 4.9 mg/dL, p < 0.0001) as well as for HU (29.0 vs 7.6 % and 51.6 vs 28.0 %, for classic and URRAH cut-off respectively, p < 0.0001 for both comparison). Logistic multivariable regression models showed that UA is related to MS diagnosis (OR = 1.608 for each 1 mg/dL), as well as HU with both cut-off (OR = 5.532 and OR = 3.379, p < 0.0001 for all comparison, for the classic cut-off and the URRAH one respectively). The main finding of our study is that UA and HU significantly relate to IR and MS. The higher the values of UA and the higher the cut-off used, the higher the strength of the relationship. • If uric acid should be inserted into Metabolic Syndrome definition or not is still a matter of debate. • Uric acid and hyperuricemia (classic and CV cut-off) were related to metabolic syndrome. • The higher the hyperuricemia cut-off the higher the strength of the relationship. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Image 1 • The ankle-brachial index (ABI) is a simple and cheap measurement of atherosclerosis disease. • It could help to correctly reclassify cardiovascular risk prediction when added to Framingham risk score (FRS). • Addition of ABI evaluation to FRS is a cost-effective examination in women at low and intermediate risk. [ABSTRACT FROM AUTHOR]

• The relationship between baseline levels of SUA and cardiovascular diseases is not fully elucidated. • The levels of SUA were significantly higher in male compared to women, in the elderly (>75 years old), in patients with diabetes, with hypertension, with CKD, with NSTE-ACS, with AKIN during hospitalization and in patients who died. • The rates of AKIN, implantation of IABP and NIV use were significantly higher in patients in high levels of SUA. • High admission levels of SUA are positively and independently associated with in-hospital adverse outcomes and mortality. • The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality. To assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score). The data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed. 1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60–78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33–2.22, p < 0.0001) and GRACE score (OR 1.04 95%CI 1.02–1.06, p < 0.0001) were significantly associated with an increased risk of in-hospital death at the multivariate analysis. Admission values of SUA were stratified in four quartiles. Rates of acute kidney injury, implantation of intra-aortic balloon pump and non-invasive ventilation use were significantly higher in the last quartile compared to Q1, Q2 and Q3 (p < 0.01). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89–0.93, p < 0.0001) and 0.79 (95% CI 0.76–0.81, p < 0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93–0.95). High admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population. [ABSTRACT FROM AUTHOR]

• Radiation Induced Heart Disease represents a late effect of chest irradiation. • Chest irradiation represents a strong cardiovascular risk factor. • More studies are needed in order to assess which non-invasive screening tests should be used. Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5–10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group. A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group. The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p < 0.001) and presents a lower percentage of males when compared with the control group. In this latter group 25.9% of subjects has diabetes, 62.9% dyslipidaemia, 67.4% hypertension and 19.2% actively smoke. Despite this important differences regarding classic cardiovascular risk factors, no significant differences were found in the number of positive exercise stress electrocardiography (10.4 vs 5.9%, p = ns). Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease. Aim: Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test—6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR. Methods: We collected data from 249 patients (age 66.79 ± 11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the Δ between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR. Results: Patients were divided accordingly to their pre-rehab LVEF (≥ 55% vs < 55%). With superimposable age and baseline 6MWT distance covered (434.58 vs 405.12 m, p = 0.08), the latter group presented higher Δ meter values at 6MWT (167.93 vs 193.97 m, p = 0.018). However, no statistically significant positive correlation between Δ meters and Δ LVEF was found. Moreover, linear regression analyses found that nor baseline LVEF nor Δ LVEF were significant determinants of Δ meters when considering the whole group, with age, basal 6MWT and peak CK-MB as additional covariates in the model. Conclusion: Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population. [ABSTRACT FROM AUTHOR]

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis. [ABSTRACT FROM AUTHOR]

The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P < 0.001) with mean ΔPWV of+ 0.5 ± 2.2 m/s. A total of 61 patients were hyperuricemic (14.4%), and they present higher PWV baseline (9.0 ± 2.5 vs 8.5 ± 1.8 m/s, P = 0.03) without significant differences in ΔPWV. Hyperuricemic female (6.2%, 11 patients) presents higher baseline PWV without significant differences in ΔPWV. No differences were found in arterial stiffness in hyperuricemic males (20.4%, 50 patients). UA showed association with baseline and ΔPWV in the whole population but it loses statistical significance at the linear regression model. Same figures were also for sex analysis. Our findings provide evidence that baseline UA levels are not determinants of PWV progression over a median follow-up of 3.8 years' in hypertensive patients. [ABSTRACT FROM AUTHOR]

Structural and functional arterial properties commonly impair with aging process. These effects on vasculature could act at many levels from microcirculation to large vessels. Above normal aging process classic cardio-vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, etc.) accelerate the physiological process leading to premature structural and functional alterations that has also been termed early vascular aging. Target organ damage evaluation could be clinically important since these alterations precede by many years' cardiovascular events and so their assessment can predict the onset of more serious and costly events giving the opportunity to prevent CV events by earlier therapeutic intervention. This review will focus on large artery functional properties and particularly on the role of inflammation on the aortic stiffening process. [ABSTRACT FROM AUTHOR]

Purpose: Only few studies evaluated biomarkers useful for defining the cardiovascular risk of a subject in a pre-clinical condition (i.e. healthy subjects). In this context we sought to determine the relationships of Plasminogen activator inhibitor type 1 (PAI‐1), P-Selectin, Tissue Inhibitors Metalloproteinases type 1 (TIMP-1) and Cystatin-C with subclinical Target Organ Damage (TOD) in normotensive and normoglycemic subjects without known cardiovascular and kidney diseases. Materials and Methods: 480 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Hypertrophy (LVH) and Intima Media Thickness (IMT) and carotid plaque presence) grouped together under carotid TOD. Results: 3.1% of the subjects showed a PWV higher than 10 m/sec with those subjects exerting significantly lower values of P-Selectine (0.068 ± 0.015 vs 0.08 ± 0.036 mg/L, p = .014). 8.8% of the subjects showed carotid TOD that was associated with higher Cystatin-C values (0.67 ± 0.17 vs 0.63 ± 0.14 mg/L, p = .045). Finally 23.8% of the subjects showed LVH with no significant differences regarding biomarkers. Despite some significant correlations between biomarkers and TOD, at the multivariate analysis none came out to be as significant predictor of the assessed TOD. Conclusions: in normotensive and normoglycemic healthy subjects, the evaluated biomarkers of atherosclerotic process didn’t show any significant association with cardiac, carotid and vascular TOD while age and BP are its principal predictors. [ABSTRACT FROM AUTHOR]

Hypertensive urgencies-emergencies are important and common events. They are defined as a severe elevation in BP, higher than 180/120 mmHg, associated or not with the evidence of new or worsening organ damage for emergencies and urgencies respectively. Anamnestic information, physical examination and instrumental evaluation determine the following management that could need oral (for urgencies) or intravenous (for emergencies) anti-hypertensives drugs. The choice of the specific drugs depend on the underlying causes of the crisis, patient’s demographics, cardiovascular risk and comorbidities. For emergencies a maximum BP reduction of 20-25% within the first hour and then to 160/110-100 over next 2-6 h, is considered appropriate with a further gradual decrease over the next 24-48 h to reach normal BP levels. In the case of hypertensive urgencies, a gradual lowering of BP over 24-48 h with an oral medication is the best approach and an aggressive BP lowering should be avoided. Subsequent management with particular attention on chronic BP values control is important as the right treatment of the acute phase. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) represents a risk of non-fatal and cardiovascular events. The aim of the present study was to evaluate simultaneously left and right atrial and ventricular function, as well as arterial stiffness, in RA patients.Methods: This cross-sectional study included 55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood pressure and arterial stiffness were assessed in all participants, who also underwent a complete echocardiographic examination.Results: RA patients were treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy (54.5%). Disease activity score revealed low average RA activity. Augmentation index was significantly higher in RA patients (32.2 ± 8.6 vs. 28.4 ± 8.9%, P = 0.02). Left atrial volume was also higher among RA patients (23.1 ± 8.2 vs. 20.1 ± 7.1 ml/m2, P = 0.04), whereas mitral and tricuspid E/A ratios were significantly lower in RA individuals (0.90 ± 0.24 vs. 1.03 ± 0.35, P = 0.02; 1.07 ± 0.31 vs. 1.27 ± 0.35, P = 0.003, respectively). Tissue Doppler systolic and diastolic velocities were similar between the observed groups. Arterial stiffness index showed significant correlation with disease duration (r = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity (A′) showed significant correlation with index of disease activity in the RA patients.Conclusions: Our results showed that left and right ventricular diastolic function and arterial stiffness were significantly deteriorated in the RA patients comparing with controls. The assessment of left and right ventricular diastolic function, as well as vascular function, should be an essential part of clinical evaluation in the RA patients. [ABSTRACT FROM AUTHOR]

Objective:The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects. Materials and Methods:We enrolled 333 consecutive hypertensive outpatients 18–80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75 ± 0.53 years. Results:At baseline the mean age was 54.5 ± 12.6 years, SBP and DBP were 141.3 ± 18.6 and 86.4 ± 10.4 mmHg and PWV was 8.56 ± 1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (ΔPWV 0.87 ± 3.05 m/s). PWV and ΔPWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ΔPWV showed a greater increase as compared to patients with controlled BP (1.46 ± 3.67 vs 0.62 ± 2.61 m/s,p < .05). The independent predictors of ΔPWV were age, baseline PWV, baseline SBP/MBP and ΔSBP/MBP. Conclusions:the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies. [ABSTRACT FROM PUBLISHER]

Heterogeneous results have been obtained in the relationship between serum uric acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD were assessed in 762 consecutive patients with hypertension. Hyperuricemia was defined as an SUA >7.0 in men and >6.0 mg/dL in women. Men with hyperuricemia compared with those with normal SUA showed lower estimated glomerular filtration rates and E/A ratios and a higher prevalence of carotid plaques. Women with hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios and a higher intima-media thickness. Except for pulse wave velocity, all TODs significantly correlated with SUA. However, at multivariate analysis, only estimated glomerular filtration rate was significantly determined by SUA. Our data provide evidence on the role of SUA in the development of TOD only in the case of renal alteration. It is likely that SUA may indirectly act on the other TODs through the increase in blood pressure and the decrease in glomerular filtration rate. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. Aim: We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. Methods: In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls. Results: The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P < 0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3 ± 8 to 157.1 ± 9 mg/dl, P < 0.05, from 7.9 ± 0.1 to 6.9 ± 0.2%, P < 0.001 and from 3.6 ± 0.3 to 7.4 ± 0.8%, respectively P < 0.05). No significant difference was detected in the other parameters, including blood pressure. Conclusions: Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process. [ABSTRACT FROM AUTHOR]

Introduction: Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS. Aim: We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI). Methods: 30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated. Results: On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: −42.9 ± 17.2 vs −27.9 ± 10.1, peak: −68.7 ± 29.2 vs −42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup. Conclusions: In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn. [ABSTRACT FROM AUTHOR]

Early vascular aging is a process characterized by a reduction in arterial elastin with an increase in collagen that has been related to cardiovascular risk factor and can determine an increased arterial stiffness and central blood pressure. It can be measured by several non invasive methods and in different arterial segment. The present paper will focus on functional (local stiffness parameter) and structural (intima media thickness) carotid arteries alterations typically evaluated by ultrasound methods. Methodological, research and clinical issue has been reviewed. [ABSTRACT FROM AUTHOR]

Objective Scanty data are available on the accuracy of NT-proBNP in the diagnosis of HF and effects of comorbidities in very elderly patients. Methods Symptoms, signs, NT-proBNP, eGFR, Ht, CRP and the presence of cardiomegaly and pleuric effusion were assessed in 895 consecutive patients aged 86 ± 4.3 years admitted to Emergency Department and used to define the diagnosis of HF according to Framingham criteria. Receiver operating characteristic curves (ROC) were used to calculate diagnostic performance and cutoff of NT-proBNP. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were computed for all NT-proBNP cutoffs. Results Satisfactory diagnostic performance was obtained with a lower threshold of 980 pg/mL (Sn 0.95; NPV 0.90) and a higher threshold of 5340 (Sp 0.85; PPV 0.76) but with 42.4% of patients in the uncertainty area. We determined a second couple of cutoffs (1470–4200) that reduced the gray-area to 27.4%, maintaining an acceptable diagnostic performance compared to commonly used cutoffs (300–1800). Ht, CRP and eGFR all correlated with NT-proBNP in groups with and without HF but none affected diagnostic performance. Conclusion NT-proBNP performs satisfactorily for the diagnosis of HF in very elderly patients. Proposed threshold couple, compared with the most used cutoffs, showed a gain in Sp and PPV with a slightly lower performance in Sn and NPV and with a decrease in the gray-area with the second one. Our data do not support the use of different NT-proBNP cutoffs depending on eGFR, Ht and CRP. [ABSTRACT FROM AUTHOR]

Background & Aims: Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension. Methods: Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension. Results: At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006). Conclusions: In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness. [ABSTRACT FROM AUTHOR]

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = β = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (β = −0.64 per g/dL, 95% CI −1.19; −0.09, p = 0.023) and severe disease (β = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease. [ABSTRACT FROM AUTHOR]

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events. [ABSTRACT FROM AUTHOR]

Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements. The survey included 30 different items on how to perform the HBPM. It was developed by the 'Young Investigators' group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021. A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque. Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients. [ABSTRACT FROM AUTHOR]

Introduction: The role of uric acid (UA) and Hyper Uricemia (HU) in cardiac rehabilitation (CR) patients have been very little studied. Aim: To evaluate the prevalence of HU and if it is associated to the functional improvement obtained or the left ventricular Ejection Fraction (EF) in CR patients after Acute or Chronic Coronary Syndrome (ACS and CCS respectively). Methods: We enrol 411 patients (62.4 ± 10.2 years; males 79.8%) enrolled in the CR program at Niguarda Hospital (Milan) from January 2012 to May 2023. HU was defined both as the classic cut-off (> 6 for females, > 7 mg/dL for males) and with the newly identified one by the URRAH study (> 5.1 for females, > 5.6 mg/dL for males). All patients performed a 6MWT and an echocardiography at the beginning and at the end of CR program. Results: Mean UA values were within the normal range (5.6 ± 1.4 mg/dL) with 19.5% (classic cut-off) HU patients with an increase to 47.4% with the newer one. Linear regression analysis showed no role for UA in determining functional improvement, while UA and hyperuricemia (classic cut-off) were associated to admission and discharge EF. The same was not with the URRAH cut-off. Conclusions: HU is as frequent in CR patients as in those with ACS and CCS. UA didn't correlate with functional recovery while it is associated with admission and discharge EF as also is for HU (classic cut-off). Whit the URRAH cut-off HU prevalence increases significantly, however, it doesn't show any significant association with EF. [ABSTRACT FROM AUTHOR]

Few certainties exist regarding optimal management of Blood Pressure (BP) in the very first hours after an ischemic stroke and many questions remain still unanswered. Our work aimed to evaluate the role of BP and its trend as possible determinants of in-hospital mortality (primary outcome), discharge disabilities and hospitalization length (secondary outcomes) in ischemic stroke patients presented with Hypertensive Emergencies (HE). We retrospectively evaluated patients presented to Niguarda Hospital, Emergency Department (ED), from 2015 to 2017 with a neurological ischemic HE. BP at ED presentation (T0), its management in ED (T1) and its values at the stroke unit admission (T2) were evaluated. 267 patients were included (0.13 % of all ED accesses and 17.9 % of all ischemic strokes). In the whole population, BP values were not associated with in-hospital mortality while T0 and T2 SBP result were associated to discharge disability and hospitalization length. In pre-specified subgroup analysis these associations were confirmed only in untreated subjects (not anti-hypertensive nor thrombolysis). In fact, no significant relationship can be found between BP values and any secondary outcome in thrombolysis and anti-hypertensive treated patients. BP values and its management can not be related to in-hospital mortality in stroke patients, presented with HE, while they are associated to discharge disability and hospitalization length. In subgroup analysis, results were confirmed only in untreated (not anti-hypertensive therapies nor thrombolytic). [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Background: This study explored both the evolution of the information needs and the perceived relevance of different health information sources in patients with essential hypertension. It also investigated the relationships between information needs and the perceived relevance of information sources with socio-demographic and clinical variables.Methods: Two hundred and two patients with essential arterial hypertension were enrolled in the study and evaluated at baseline and during three follow-ups at 6, 12 and 24 months after baseline. Patients had a mean age of 54.3 years [range 21-78; SD = 10.4], and 43% were women. Repeated measures ANOVA, Bonferroni post hoc tests, and Cochran's Q Test were performed to test differences in variables of interest over time.Results: It was observed a significant reduction in all the domains of information needs related to disease management except for pharmacological treatment and risks and complications. At baseline, patients reported receiving health information primarily from specialists, general practitioners, relatives, and television, but the use of these sources decreased over time, even if the decrease was significant only for relatives. Multiple patterns of relationships were found between information needs and the perceived relevance of sources of information and socio-demographics and clinical variables, both at baseline and over time.Conclusions: The findings showed a general decrease in both the desire for information and the perceived relevance of different information sources. Hypertensive patients appeared to show little interest in health communication topics as their disease progressed. Understanding patients' information needs and the perceived relevance of different information sources is the first step in implementing tailored communication strategies that can promote patients' self-management skills and optimal clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data. Methods: In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2–5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14. Results: Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40–3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30–2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions). Conclusion: A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile. [ABSTRACT FROM AUTHOR]

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug–drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios. [ABSTRACT FROM AUTHOR]

• A relationship between serum uric acid and cardiovascular events has been documented in the Uric Acid Right for Heart Health (URRAH) study. • In this analysis serum uric acid was independently associated with left ventricular mass index in both men and women. • A significantly higher incidence of CV death was observed in men with hyperuricemia without left ventricular hypertrophy (LVH), LVH without hyperuricemia and their combination as compared with those with normal serum uric acid and normal cardiac mass. A poorer survival rate was reported in women with LVH alone and the combination of hyperuricemia and LVH but not with hyperuricemia alone. • The combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women. A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P < 0.001 and women: beta 0,069, F 4.36, P <0.001. During follow-up 319 CV deaths occurred. Kaplan–Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P <0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women. [ABSTRACT FROM AUTHOR]

Background: Psychoactive substances have toxic effects resulting different cardiovascular and non-cardiovascular organ damage. Through a variety of mechanisms, they can trigger the onset of various forms of cardiovascular disease: acute or chronic, transient or permanent, subclinical or symptomatic. Hence, a thorough knowledge of the patient's drug habits is essential for a more complete clinical-etiopathogenetic diagnosis and consequent therapeutic, preventive, and rehabilitative management. Summary: The prime reason for taking a psychoactive substance use history in the cardiovascular context is to identify those people who use substances (whether habitual or occasional users, symptomatic or not) and adequately assess their overall cardiovascular risk profile in terms of "user status" and type of substance(s) used. A psychoactive substance history could also alert the physician to suspect, and eventually diagnose, cardiovascular disease related to the intake of psychoactive substances, so optimizing the medical management of users. This anamnesis could finally assess the likelihood of patients persisting in the habit as a user or relapse, while maintaining high their cardiovascular risk profile. Taking such a history should be mandatory when a causal connection is suspected between intake of psychoactive substances and the observed symptoms or pathology, regardless of whether the individual is a declared user or not. Key Messages: The purpose of this article was to provide practical information on when, how, and why to perform a psychoactive substance use history. [ABSTRACT FROM AUTHOR]

Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. 798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy. [Display omitted] • PCSK9i have been proven to reduce cardiovascular events in hypercholesterolemia patients. • Few studies are available in a real-world setting on the use and effects of PCSK9i. • AT-TARGET-IT is the first Italian nation-wide registry on PCSK9i. • PCSK9i were very effective, leading to high adherence and persistence to therapy. • LDL-C target was reached in most patients, especially when used in combined therapy. [ABSTRACT FROM AUTHOR]

Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p < 0.004) and the sizes of cuffs available were different according to the setting. Cardiologists more frequently defined epistaxis (55.2% p = 0.012) and conjunctival hemorrhages (70.7%, p < 0.0001) as possible presentation of HE, and rarely considered dyspnea (67.2% p = 0.014) or chest pain (72.4%, p = 0.001). Intensive care (IC) unit doctors were more familiar with lung ultrasound (50% p = 0.004). With regard to therapy, cardiologists reported the lowest prescription of i.v. labetalol (39.6%, p = 0.003) and the highest of s.l. nifedipine (43.1% p < 0.001). After discharge, almost all categories of physicians required home BP assessment or referral to a general practitioner, whereas hypertensive center evaluation or ambulatory BP monitoring were less frequently suggested. Conclusion: Management and treatment of HE and HU may be different according to the doctor's specialty. Educational initiatives should be done to standardize treatment protocols and to improve medical knowledge. [ABSTRACT FROM AUTHOR]

• Data on the role of Uric Acid (UA) as a determining factor of Heart Failure related issue in Acute Coronary Syndrome (ACS) patients are scanty. • UA was confirmed to be significantly associated with Acute Heart Failure, Cardiogenic Shock, Non Invasive Ventilation and Ejection Fraction in ACS patients. • Evaluation of UA in ACS patients could help to identify the one with the worst heart failure related outcomes. We focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcomes were acute HF and cardiogenic shock at admission, secondary outcomes were the use of Non Invasive Ventilation (NIV) and the admission Left Ventricular Ejection Fraction (LVEF). We consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Median age was 68 (first-third quartile 59–77) years and males were 970 (76%). All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (UA higher than 6 mg/dL for females and 7 mg/dL for males, n = 292): acute HF 35.8 vs 11.1% (p < 0.0001), cardiogenic shock 10 vs 3.1% (p < 0.0001), NIV 24.1 vs 5.1% (p < 0.0001) and lower admission LVEF (42.9±12.8 vs 49.6±9.9, p < 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following Odds Ratio (OR): acute HF OR = 1.119; 95% CI 1.019;1.229; cardiogenic shock OR = 1.157; 95% CI 1.001;1.337; NIV use OR = 1.208; 95% CI 1.078;1.354; LVEF β = -0.999; 95% CI -1.413;-0.586. We found a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed. [ABSTRACT FROM AUTHOR]

Background: Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.Methods: Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.Results: The multivariate Cox's proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000-1.034; P = 0.049). An angiopoietin-2 concentrations ≥ of 33,418 pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.Conclusions: Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting. [ABSTRACT FROM AUTHOR]

The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory. [ABSTRACT FROM AUTHOR]

Purpose: The association between serum uric acid (SUA) and pulse wave velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. The purpose of this study was to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies. Materials and methods: Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed. Results: Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: −0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association. Conclusion: The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cf- and ba-PWV in hypertensive subjects. [ABSTRACT FROM AUTHOR]

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study. [ABSTRACT FROM AUTHOR]