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Background Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional‐based Italian cohort. Methods and Results Among 14 189 subjects aged 18 to 95 years followed‐up for 11.2 (5.3–13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high‐density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid‐lowering drugs. During 139 375 person‐years of follow‐up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients’ functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07–6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan–Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

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 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

Abstract 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.

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.

Hyponatremia is associated with adverse outcomes in hospitalized patients. An elevated value of the serum urea-to-creatinine ratio (UCR) has been proposed as a proxy of hypovolemia. The aim of this study was to investigate the relationship between the UCR and in-hospital death in patients hospitalized with COVID-19 and hyponatremia. We studied 258 patients admitted for COVID-19 between January 2020 and May 2021 with serum sodium at < 135 mmol/L. The primary end-point was all-cause mortality. A 5-unit increase in the serum UCR during hospital stays was associated with an 8% increase in the hazard of all-cause death (HR = 1.08, 95% CI: 1.03–1.14, p = 0.001) after adjusting for potential confounders. In patients with a UCR > 40 at baseline, a > 10 mmol/L increase in serum sodium values within the first week of hospitalization was associated with higher odds of in-hospital death (OR = 2.93, 95% CI: 1.03–8.36, p = 0.044) compared to patients who experienced a < 10 mmol/L change. This was not observed in patients with a UCR < 40. Hypovolemia developing during hospital stays in COVID-19 patients with hyponatremia detected at hospital admission bears an adverse prognostic impact. Moreover, in hypovolemic patients, a > 10 mmol/L increase in serum sodium within the first week of hospital stays may further worsen the in-hospital prognosis.

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan–Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12–1.40], p < 0.001) and CVM (1.31 [1.11–1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12–1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02–1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23–1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99–1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels.

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 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.

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.

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and

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.

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.

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.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented.Methods: 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.Findings: 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, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773–0.944, p = 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.Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Background: There is evidence of a closer relation between 24 hour aortic systolic blood pressure (aSBP) and left ventricular mass (LVM) compared with 24 hour brachial SBP. However, sample sizes are relatively small and there is some inconsistency in findings. We sought to address this by pooling data from 16 centers in Asia, Europe and Latin America to determine the relationship between LVM and brachial office, as well as brachial and aortic 24 hour ambulatory SBP. Methods: In all centers, brachial and aortic SBP was measured with the same validated oscillometric device, using a transfer function for aortic pressure, and mean/diastolic pressure calibration. LVM was determined by echocardiography. Results: We studied 2092 participants (972 women) with a mean age of 52 years. Mean brachial office BP was 137/84 mmHg, and mean 24 hour bSBP and aSBP was 126 [118;134] and 131 [120;137] mm Hg, respectively. Mean LVM indexed to body surface area was 88.4 g/m2, and 27.2% of participants had left ventricular hypertrophy (LVH). The correlation coefficients between LVM and brachial office SBP, 24 hour bSBP, and 24 hour aSBP were 0.24, 0.35, and 0.43, respectively (p < 0.001 for differences). The areas under the curve for prediction of LVH were 0.62, 0.67, and 0.70 for brachial office SBP, 24 hour bSBP, and 24 hour aSBP, respectively (p < 0.001 for differences). Conclusion: In this pooled analysis of international data, we demonstrate that aortic ambulatory SBP, measured with an oscillometric cuff, shows a significantly closer association with hypertensive cardiac organ damage (left ventricular mass and hypertrophy) than brachial office/brachial ambulatory systolic blood pressure.

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.

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

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.

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.

The aim of the study was to investigate the role of chronic kidney disease (CKD) on in-hospital mortality and on incident atrial fibrillation (AF) in patients infected with SARS-CoV-2. The incidence of acute kidney injury (AKI) was also investigated. Multivariable regression models were used to assess the association between renal function groups (estimated Glomerular Filtration Rate, eGFR, >60 mL/min, 30–59 mL/min,

Background: Wave reflection parameters predict cardiovascular events, but 24-hour profiles in large samples of healthy adults are unknown. Methods: In 1645 individuals free from antihypertensive drugs from 11 centers in Europe and Asia, 24-hour blood pressure monitoring with a validated oscillometric brachial cuff (Mobilograph, I.E.M., Stolberg; Germany) was performed. Brachial waveforms were acquired and processed with ARCSolver algorithms to derive information relating to wave reflections using pulse waveform analysis (heart-rate corrected augmentation index-AIx75, augmentation pressure-AP) and wave separation analysis (backward wave amplitude-Pb, reflection magnitude-RM). Nighttime/daytime difference (N/D) was nighttime (01.00–06.00) minus daytime (09.00–21.00) values/daytime values. Participants were categorized as young (13–39 years; male/female: 219/112), middle-aged (40–66 years; male/female: 545/553), and old (67–104 years; male/female: 86/130). Results: 24-hour measures of wave reflections increased with increasing age and were significantly lower in men compared to women (AIx75: 18.3 vs 28.0 %, AP: 10.1 vs 14.9 mm Hg, Pb: 18.9 vs 20.0 mm Hg, RM: 63.0 vs 66.2). AIx75 was higher during daytime compared to nighttime (23.3 vs 21.3%), but only in young and middle-aged participants. For all participants, AP (11.6 vs 14.5 mm Hg), Pb (18.5 vs 21.7 mm Hg), and RM (62.9 vs 68.8) were higher during nighttime compared to daytime. N/D varied with age and was more pronounced in younger individuals. Conclusion: 24-hour variability of wave reflection parameters differs according to age and gender. In future, this information could be useful for tailoring individual cardiovascular risk management.

Background: Conventional brachial cuff BP is known to vary according to age and gender, but the influence of these factors on 24-hour ambulatory central BP is unknown. We sought to determine this in a large healthy population from 11 centers in Europe and Asia. Methods: 24-hour ambulatory BP using a validated oscillometric device (Mobilograph, I.E.M, Stolberg, Germany) was performed in 1645 individuals free from antihypertensive drugs. Participants were categorized as young (Y: 13–39 years; M/F:219/112), middle-aged (MA: 40–66 years; M/F:545/553), and older (O: 67–104 years; M/F:86/130). Nighttime/daytime difference (N/D) was defined as nighttime (01.00–06.00) minus daytime (09.00–21.00) values / daytime values. Results: Averaged 24-hour brachial BP was 125/79 (Y), 128/83 (MA), and 127/77 (O) mmHg. N/D for brachial SBP was −10.3% (Y), −6.4% (MA), and −4.7% (O), but was significantly less pronounced for central SBP: −1% (Y), −3.1% (MA), and −1.9% (O). Men, compared to women, had higher brachial and central SBPs, mainly in younger participants. Brachial pulse pressure (PP) displayed limited and age-dependent circadian variations, whereas central PP was substantially higher at nighttime: N/D was 24% (Y), 9% (MA), and 5.9% (O). Brachial and central PPs were higher in men in the younger group, but higher in women in middle-aged and older groups. Conclusion: Both age and gender each have a significant influence on 24-hour variability of central BP, but is different than variability in brachial BP. These data have potential implications for refining hypertension diagnosis and management.

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.

Background: To date no definitive results exist about the relationship of Serum Uric Acid (SUA) and TOD in HT subjects. We sought to determine if such an association exist between SUA and subclinical cardiac, vascular and renal alterations in HT. Methods: We enrolled 632 consecutive outpatients, followed by the Hypertension Unit of S. Gerardo Hospital (Monza, Italy) affected by essential HT. We evaluated anamnestic data, clinical BP and laboratory data as well as TOD with cardiac echocardiography (both as LMVI and diastolic function – E/A), carotid ultrasound (IMT), arterial stiffness (PWV) and renal function analysis (creatinine and microalbumiuria). Results: Age was 53.4±12.7 years, SBP/DBP were 140.5±18.8 and 85.1±13.1 mmHg and SUA was 5.2±1.4 mg/dL. Regarding TOD mean LVMI was 109.6±31.4g/m2, IMT 0.71±0.1 mm, PWV 8.5±2.2 m/s, while creatinine and microalbuminuria were 0.8±0.2 mg/dL and 25.4±126.1 mg/24h respectively. When subjects were divided into high and low SUA group (depending on the median SUA of 5.2 mg/dL), with similar age and BP values the first group showed significantly higher values of metabolic index (BMI, HDL chol, triglycerides and glucose, p < 0.001), LVMI (117.1±32.8 vs 102.1±28.1g/m2, p < 0.01), IMT (0.73±0.1 vs 0.70±0.1mm, p = 0.04), PWV (8.8±2.4 vs 8.3±2.1m/s, p = 0.01) and creatinine (0.9±0.2 vs 0.7±0.1 mg/dL, p < 0.01) and lower E/A (1,0±0.3 vs 1.1±0.3, p < 0.01). SUA showed significant correlation with sex, age, BMI, SBP, HDL chol, triglicerides, glucose, creatinine, IMT, LVMI and E/A. Regarding TOD only creatinine presents SUA as as significant determinant in logistic regression analysis. Conclusion: In HT, SUA values correlate with metabolic derangements and with cardiac, vascular and renal TOD. The most significant correlation is with renal damage.

Objective: Prior studies have suggested that the principal determinants of arterial stiffening are age, BP and others CV risk factors such as dyslipidemia and diabetes. However, scanty data are available on the role of psychological factors on arterial stiffness. The aim of the current cross-sectional study was to evaluate the association between depression, anxiety, perceived stress, Type A personality, and Type D personality and Pulse Wave Velocity (PWV) in a cohort of hypertensive patients, using baseline examination data of the TIPICO project. Methods: A total of 259 outpatients (ages 18–80 years) followed by the Hypertension Unit of S. Gerardo Hospital (Monza, Italy) affected by essential hypertension were recruited. Aortic stiffness was evaluated by c-f PWV. Moreover, anamnestic data, clinical BP, and laboratory data were evaluated. Patients were asked to complete a battery of psychological questionnaires under the guidance of a psychologist. Results: At T0 mean age was 55.9±10.1years, SBP/DBP were 135.6±17.7/82.5±9.1 mmHg and PWV was 8.6±2.1m/s. The multivariate stepwise linear regression analysis showed that age (beta = 0.284, p < 0.001), pulse pressure (beta = 0.369, p < 0.001), dyslipidemia (beta = 0.130, p = 0.012), family history of CV disease (beta = −0.123, p = 0.017), and depression (beta = 0.126, p = 0.014) were significantly and independently associated with PWV. Conclusion: Among psychological factors, higher levels of depression is related to higher PWV, while anxiety, perceived stress, Type-A personality and Type-D personality are not. Depression assessment and target intervention to reduce it should be recommended in hypertensive patients.

Objective: Thoracic Endovascular Aortic Repair (TEVAR) currently represents the gold standard of treatment for Blunt Thoracic Aortic Injury (BTAI). Nevertheless, there is an ongoing debate surrounding its safety and efficacy and its subsequent CV effects. The present study is aimed at assessing heart and aortic structure and function after TEVAR in BTAI patients Method: In 20 patients (18 men, age 41 ± 14 years) treated with TEVAR (11 Gore-CTAG, 9 Medtronic-Valiant) after BTAI, between 2004–2015, after a median follow-up time of 3 years (range 12–1 years; T1) we evaluated BP, cf-PWV (sphygmocor) and Left Ventricular Mass Index (LVMI) on echocardiography. Results: At baseline, all the patients were normotensive; At T1 despite mean normal BP value (131 ± 12/85 ± 10) 11 patients (55%) were hypertensives. Also LVMI (81,84 ± 28,11 g/m2) and PWV (7,58 ± 1,48 m/s) mean values were within the normal range. When patients were divided accordingly to the used graft patients treated with Medtronic-Valiant showed a significantly higher LVMI (97.17 ± 35.78 vs 69.58 ± 11.24 g/m2; p < 0,05) and PWV (7,78 ± 1,74 vs 6,45 ± 1,54 m/s; p < 0,05) compared with those treated with Gore-CTAG. Same figures were founded when patients were divided accordingly to the treating time with those treated more than 3 years before the evaluation that showed higher LVMI (91,16 ± 34,73 vs 70,20 ± 9,44 g/m2; p < 0,01) and PWV (7,50 ± 1,98 vs 6,38 ± 1,04 m/s; p < 0,05). Conclusions: TEVAR for BTAI is associated after some years with the development of hypertension and heart and vascular alterations. The presence of TEVAR modify aortic functional properties and induce in young subject an increase in BP and LVMI probably related to the presence of a rigid aorta.

Background: Increased Left Ventricular Mass Index (LVMI) is a well known risk factor for cardiac morbidity and mortality. Furthermore, it is widely recognized that clinical evolution and progression of established CV diseases are related to a range of psychological characteristics, which may partially explain the spread and recurrence of these diseases. Little is known about LVMI and its association with psychological characteristics in arterial Hypertension (HT) patients. The aim of the current cross- sectional study was to evaluate the association between psychological characteristics and LVMI in a cohort of hypertensive patients. Methods: A total of 244 outpatients (age 18–80 years) followed by the Hypertension Unit of S. Gerardo Hospital (Monza, Italy) affected by essential hypertension were recruited. Anamnestic data, clinical BP, and laboratory data and LVMI were evaluated. Patients were asked to complete a battery of psychological questionnaires under the guidance of a psychologist. Results: At T0 the mean age was 55.9±10.1years, SBP and DBP were 135.6±17.7 and 82.5±9.1 mmHg and PWV was 8.6±2.1m/s. The multivariate stepwise linear regression analysis showed that sex (beta = 0.252, p < 0.001), age (beta = 0.135, p < 0.037), mean BP (beta = 0.178, p = 0.003), family history of CV disease (beta = 0.129, p = 0.027), and Type-A personality (beta = 0.148, p = 0.014) were significantly and independently associated with LVMI. Conclusion: Among psychological factors, higher levels of Type-A personality is related to higher LVMI, while Type-D personality, anxiety, depression and stress are not associated.

The introduction of antiretroviral therapy (ART) has substantially modified the clinical history and epidemiology of HIV infection with an important decline in infective causes of death and an increase in non-infective comorbidities particularly in cardiovascular complications. HIV infection has been related to an increased cardiovascular risk due to the presence of three factors: classic cardiovascular risk factors (shared with the general population), HIV infection itself (indirectly due to the inflammation and directly due to viral molecule) and ART-related chronic metabolic alterations. We describe a peculiar case of metabolic alteration in an HIV infected patient on ART with particular attention to the diagnosis and therapeutic aspects. Giving the higher cardiovascular risk of this specific population it is advisable that the clinician performs a frequent re-assessment of risk factors and cardiovascular organ damage. An early detection of metabolic alteration must lead to an aggressive specific therapy; this must be done by taking care of the HIV-infected subject fragility and the interactions with ART.

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