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Purpose of Review: To examine published and unpublished data collected in the context of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study on the relationships between serum uric acid (SUA), office and out-of-office blood pressure (BP), and organ damage., Recent Findings: SUA values were directly and significantly related to a large number of covariates that participate at cardiovascular risk determination, such as blood glucose, total serum cholesterol, serum triglycerides, body mass index, and serum creatinine. Additional variables included echocardiographically-determined left ventricular mass index and BP values, the latter not just when measured in the office but also when evaluated at home or over the 24-h period. White-coat hypertension and masked hypertension were characterized, as sustained hypertension, by a significant increase in SUA levels, which were also directly related to different indices of 24-h BP variability. No substantial difference in SUA levels was found when data were analyzed according to the dipping or non-dipping nocturnal BP profile. Data collected in the frame of the PAMELA study document the presence of a close relationship between SUA levels and BP values independently on the hypertensive phenotype patterns of BP increase (office, 24 h, or both) and nighttime BP profile. They also document the increase in SUA as a potential factor favoring the occurrence of new hypertension and new left ventricular hypertrophy., (© 2022. The Author(s).)

Background: Scarce and non-homogeneous data are available on the prognostic value of clinic heart rate (HR) in coronavirus disease 2019 (COVID-19)., Methods: The present study evaluated in 389 patients hospitalized for COVID-19 the in-hospital prognostic value of resting HR, assessed over different time periods, i.e., at hospital admission, during initial 3 days and 7 days of hospitalization., Results: Results show that assessment of this hemodynamic variable during hospitalization provides information on the clinical outcome of the patients, greater HR values being associated with a worse inhospital prognosis. The prognostic value of elevated HR during COVID-19: 1) was independent on other confounders such as age, gender, comorbidities and fever, 2) appeared to be strengthened by repeated measurements of HR during the initial 3/7 days of hospitalization, and 3) was detectable in patients in which the therapeutic intervention did not include drugs, such as beta-blockers, calcium antagonists, digoxin, ivabradine and antiarrhythmic compounds known to interfere with HR., Conclusions: Heart rate may represent an important marker of a patient's outcome in COVID-19.

Few issues of modern cardiovascular medicine have been as controversial as the relationship between white-coat hypertension (WCH), that is, a common condition in which office blood pressure is elevated while out-of-office blood pressure (ambulatory blood pressure or home blood pressure) is normal. While earlier studies showed no increased risk of cardiovascular events in WCH compared with the normotensive state, more recent studies have changed this conclusion by showing that an increased cardiovascular risk represents a trait of this hypertensive phenotype. The present article will review a number of issues related to WCH, that is, its definition, pathophysiological background, clinical alterations, and prognostic significance. This will be done by considering the available evidence published during the last decades, with special focus on the data collected in PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni)-a research project performed with a cross-sectional and longitudinal design, which has provided a series of novel clinical information on WCH throughout the years. The final part of the article will discuss the therapeutic implications of the abovementioned evidence, as well as some controversial or still undefined issues related to WCH, whose investigation will be an important goal to pursue by future research.

Objective: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course., Design: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed., Results: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170)., Conclusions: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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Aim: Findings regarding the extent of persistence over time of normal left ventricular (LV) geometry, a reference healthy echocardiographic phenotype, in the community are scanty. We sought to assess this issue in members of the general population enrolled in the Pressioni Arteriose Monitorate e Loro Associazioni study., Methods: The study included 433 participants who attended the second and third survey of the Pressioni Arteriose Monitorate e Loro Associazioni study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure, routine blood examinations and echocardiography., Results: During 25-year follow-up 167 participants showed persistently normal LV mass (LVM) and LV geometry pattern, whereas 266 participants exhibited LV hypertrophy or LV concentric remodelling at any point during study. Compared with participants developing, maintaining or regressing from LV hypertrophy and LV concentric remodelling those with a persistently normal LVM index and geometry were younger (-8 years) and more frequently female (63 vs. 45%), exhibited baseline (and follow-up) lower office and out-of-office blood pressure, BMI, serum creatinine, fasting blood glucose total serum cholesterol and rate of antihypertensive treatment. In multivariate regression analysis age [odds ratio (OR): 0.93, confidence interval (CI): 0.91-0.96, P < 0.0001] BMI (OR: 0.90, CI: 0.83-0.97, P = 0.008), office SBP (OR: 0.97, CI: 0.95-0.99, P = 0.005) and fasting blood glucose (OR: 0.96, CI: 0.93-0.99, P = 0.007) were independently associated with persistent normal LVM index and geometry., Conclusion: The current long-term longitudinal study suggests that persistence of normal LV geometry is associated with normal/optimal SBP, BMI and blood glucose. Thus, a closer control of these risk factors in midlife may increase the likelihood of maintaining normal ventricular geometry and, in turn, reduce the burden of subclinical cardiac organ damage and related complications in advanced age., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events., Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes., Results: Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group., Conclusion: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Home and 24-hour blood pressure (BP Home and BP 24h ) are believed to improve the prognostic value of office BP (BP Office ) alone, but the evidence has limitations such as that (1) these 3 BPs are characterized by multicollinearity and (2) the procedures adopted do not allow quantification of the prognostic advantage. One thousand eight hundred thirty-three individuals belonging to the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) were followed for 16 years. Prediction of cardiovascular and all-cause mortality was determined via the goodness of fit of individual data (Cox model), the area underlying the receiving operator curves and the net reclassification improvement of cardiovascular and all-cause mortality risk. Calculations were made for BP Office alone and after addition of BP Home , BP 24h , or both, limited to their residual portion which was found to be unexplained by, and thus independent on, BP Office . With all methods addition of residual out-of-office systolic or diastolic BP to BP Office significantly improved cardiovascular and all-cause mortality prediction. The improvement was more consistent when BP Home rather than BP 24h was added to BP Office and, compared with BP Office plus BP Home , no better prediction was found when addition was extended to BP 24h . With all additions, however, the improvement was quantitatively modest, which was the case also when data were separately analyzed in younger and older individuals or in dippers and nondippers. Thus, addition of out-of-office to BP Office improves prediction of cardiovascular risk, even when data analysis avoids previous limitations. The improvement appears to be limited, however, which raises the question of the advantage to recommend their extended use in clinical practice.

Aims: There is conflicting evidence on whether in treated hypertensive patients the risk of renal outcomes is associated with visit-to-visit SBP variability. Furthermore, limited evidence is available on how important is SBP variability for prediction of renal outcomes compared with on-treatment mean SBP. We addressed these issues in 28 790 participants of the Ongoing Treatment Alone and in combination with Ramipril Global End point Trial and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant Subjects with Cardiovascular Disease trials., Methods and Results: SBP variability was expressed as the coefficient of variation of the mean with which it showed no relationship. SBP variability and mean values were obtained from five visits during the first 2 years of treatment after the end of the titration phase. Incidence of several renal outcomes (end-stage renal disease, doubling of serum creatinine, new microalbuminuria, new macroalbuminuria and their composite) was calculated from the third year of treatment onward. Patients were divided in quintiles of SBP-coefficient of variation (SBP-CV) or mean SBP, which exhibited superimposable mean blood pressure and SBP-CV values, respectively. A progressive increase of SBP-CV was not accompanied by a parallel increase in a widely adjusted (baseline and on-treatment confounders) risk of most renal outcomes (end-stage renal disease, new macroalbuminuria, new microalbuminuria and their composite) in the subsequent on-treatment years. In contrast, the adjusted risk of most renal outcomes increased progressively from the lowest to the highest quintile of on-treatment mean SBP. Progression from lowest to highest mean on-treatment SBP, but not SBP-CV, was also associated with a less frequent return to normoalbuminuria in patients with initial micro or macroalbuminuria. Renal outcome prediction was slightly improved by the combined use of SBP-CV and mean SBP quintiles., Conclusion: Visit-to-visit SBP variability had no major predictive value for the risk of renal outcomes, which, in contrast, was sensitively predicted by mean on-treatment SBP. A further slight increase in prediction of renal outcomes was seen by combining on-treatment mean SBP and variability.

Findings regarding long-terms variations in blood pressure (BP) taken in different setting (ie, office, home, and ambulatory BP) in the community are scanty. We sought to assess this issue in members of the general population enrolled in the PAMELA (Pressioni Monitorate E Loro Associazioni) study. The study included 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory BP, and standard blood examinations. Office, home, and 24-hour systolic BP over the 25-year interval between the first and third survey increased in a parallel way (ie, 12%, 10%, and 15.5%). The increments in office, home, and 24-hour diastolic BP were lower than the systolic BP ones (ie, 3.3%, 5.6%, and 6.1%). Thus, the combined changes in systolic BP and diastolic BP from the first to the third data collection resulted in a marked increase in pulse pressure (ie, 29%, 19%, and 30%). The prevalence of hypertension assessed at office visits and out-of-office either by self-BP measurements at home and ambulatory blood pressure monitoring increased ≈3 to 4× (3.1 office, 3.3 home, 3.9 ABPM, respectively). This trend was associated with adiposity indexes and worsening of the glucose profile. This community-based longitudinal study suggests that the progressive and marked increase in hypertension with age, consistently documented with different BP measurement methods, represents an epochal challenge for the prevention of cardiovascular diseases, due to the rapid growth the elderly population worldwide.

The recent European Society of Cardiology/European Society of Hypertension hypertension guidelines identify resting heart rate (HR) values >80 bpm as predictors of cardiovascular risk, with the unproven assumption that this might reflect the presence of a sympathetic overdrive. In the present study, we tested this hypothesis throughout the use of direct and indirect sympathetic markers. In 193 untreated moderate essential hypertensives aged 50.4±0.6 years (mean±SEM), we measured clinic and ambulatory blood pressure and corresponding HR, venous plasma norepinephrine (high performance liquid chromatography), and muscle sympathetic nerve traffic (microneurography). We then subdivided the study population into 2 groups according to HR < or >80 bpm. Eighty-four patients displayed resting HR >80 bpm, which was this cutoff value in the remaining 109 patients, the 2 groups showing superimposable age, and sex distribution. Clinic and ambulatory blood pressure were similar in the 2 groups, whereas left ventricular mass index was significantly greater in the group with HR >80 bpm. Muscle sympathetic nerve traffic values were also significantly greater in this latter group (72.77±0.9 versus vs 36.83±1.3 bursts/min, P <0.0001); this being the case also for norepinephrine (293.0±8.7 versus 254.1±8.9 pg/mL, P <0.002). In the whole population, there was a significant direct relationship between muscle sympathetic nerve traffic, norepinephrine, left ventricular mass index, and HR values. Similar results were obtained when 24-hour HR values were analyzed. Thus patients with hypertension displaying HR >80 bpm are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are used. This finding suggests that cardiac and peripheral sympathetic activation are involved in the increased cardiovascular risk detected in this group of patients.

Aim: Information regarding the association of hypertension-mediated organ damage (HMOD) with extreme dipping pattern is scanty and not univocal. We sought to assess the clinical correlates of this blood pressure (BP) phenotype and its relationship with cardiac HMOD in the general population belonging to Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study., Methods: The present analysis included all participants with good-quality ABPM recordings with reliable echocardiography at entry., Results: A total of 792 out of 1597 patients (49.6%) exhibited an extreme dipping pattern (155 had a night-time reduction in both SBP and DBP at least 20% compared with daytime values and 637 a night-time reduction in DBP at least 20%); 34.2% were dippers and 16.2% nondippers. Left ventricular mass (LVM) indexed to height and LV hypertrophy (LVH) prevalence rates increased progressively from diastolic extreme dipping (14%), dipper (17%), systolic/diastolic extreme dipping (21%) to nondipper group (27%). However, after adjusting for confounders, statistical differences in both LVMI and LVH rates among the four groups disappeared. Similar results were obtained for LVM indexed to body surface area and absolute/indexed left atrial diameter., Conclusion: Extreme dipping pattern is a BP phenotype highly frequent in the general population largely consisting of middle-aged individuals without prevalent cardiovascular disease. In this population, the extreme dipping pattern is not associated with an increased risk of cardiac HMOD, which suggests that the mechanisms invoked for the potential adverse cardiovascular effects of this condition (i.e. nocturnal hypoxemia, low-grade myocardial inflammation, coronary hypoperfusion, sympathetic activation at early morning, etc.) are not operative.

Aims: To evaluate the long-term reproducibility of masked (MUCH) and white-coat uncontrolled hypertension (WUCH), an information crucial for determining the long-term prognostic impact of these conditions., Methods and Results: Reproducibility of MUCH and WUCH was assessed in 1664 hypertensive patients recruited for the European Lacidipine Study on Atherosclerosis and treated with atenolol or lacidipine (±additional drugs) during a 4-year period. Office and 24 h blood pressure (BP) was measured at baseline and every year during treatment, allowing repeated classification of either condition. After 1 year of treatment 21.1% and 17.8% of the patients were classified as MUCH and WUCH, respectively. For both conditions the prevalence was similar in the following years, although with a large change in patients composition because only about 1/3 of patients classified as MUCH or WUCH at one set of office and ambulatory BP measurements maintained the same classification at a subsequent set of measurements. In only 4.5% and 6.2% MUCH and WUCH persisted throughout the treatment period. MUCH and WUCH reproducibility was worse than that of patients showing control or lack of control of both office and ambulatory BP, i.e. controlled and uncontrolled hypertension, respectively., Conclusion: Both MUCH and WUCH display poor reproducibility over time. This should be taken into account in studies assessing the long-term prognostic value of these conditions based on only one set of BP measurements., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Sleep disorders are highly prevalent among university students. In particular, the symptoms of sleep disorders are more prevalent among healthcare students., Aims: To assess the prevalence of risk factors of insomnia and sleep disorders and to examine the correlations between them among nursing and medical students. We also compared the effects of shift work during internship., Methods: The sample was 417 healthcare students; 202 of them were nursing students, and the remaining 215 were medical students. We used a self-administered questionnaire to assess the risk factors for insomnia (i.e. age, BMI, tobacco consumption, physical activity and perceived stress, using the General Health Questionnaire-12). We also used the Sleep and Daytime Habits Questionnaire and Epworth Sleepiness Scale to assess the prevalence of sleep disorders and daytime sleepiness., Results: A higher percentage of nursing students than medical students were aged 25 years or older, engaged in inadequate levels of physical activity and consumed tobacco. With the exception of tobacco consumption among nursing students, high scores on the GHQ-12 were the only risk factor associated with daytime and nighttime symptoms and poor sleep quality. There was no significant association between the symptoms of sleep disorders and shift work including night shifts., Conclusions: Since sleep disorders are highly prevalent among healthcare students, early detection and management is recommended. This will decrease the risk of harm to students and patients, due to medical mistakes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

Masked hypertension (MH) is defined as normal office blood pressure (BP) and elevated ambulatory BP (ABP) or home BP or both. This study assessed the association of MH (ie, isolated home, isolated ABP and dual MH) with echocardiographic left ventricular hypertrophy (LVH). The present analysis of the PAMELA study included 1087 untreated and treated participants with normal office BP and a measurable LV mass (LVM). A total of 193 individuals (17.7%) had any MH (ie, normal office BP, elevated ABP or home BP or both), 48 had dual MH (25%), 62 isolated ambulatory MH (32%), and 83 isolated home MH (43%). Average LVM indexed to body surface area was superimposable in the three MH phenotypes (being the largest difference between groups <3 g/m 2 ) and significantly higher than in true normotensives. This was also for the LVH prevalence that varied across the MH subgroups in a narrow range (from 8.3% to 10.8%). In conclusion, individuals from the general population with isolated MH, in which either home or ABP was elevated, exhibited an increased risk of LVH similar to that entailed by dual MH. Our findings add the notion both home and ABP measurements are useful to more accurately assess the risk of LVH associated with MH in the community., (© 2020 Wiley Periodicals, Inc.)

Aim: Findings regarding the association of left ventricular mass (LVM) and new-onset hypertension are based on blood pressure measured in the office. We sought to assess the value of LVM in predicting in-office and out-of-office incident hypertension in members of the general population enrolled in the Pressioni Monitorate E Loro Associazioni study., Methods: The study included participants with normal office (n = 792), home (n = 714) and 24-h (n = 825) ambulatory blood pressure (ABP) at baseline evaluation who had a readable echocardiogram at entry and at the end of follow-up. Each normotensive group was divided into quartiles of LVM indexed (LVMI) to height., Results: Over a follow-up of 148 months cumulative incidence of new office, home and 24-h ABP hypertension were 35.9, 30.7 and 36.1%, respectively. In fully adjusted models (including age, sex, BMI change during follow-up, baseline serum glucose, creatinine, total cholesterol office, home and 24-h SBP and DBP). higher LVMI values (i.e. the highest vs. the lowest quartile) were independently associated with an increased risk of home [odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.21-3.77, P = 0.008] and 24-h ABP hypertension (OR = 1.70, 95% CI 1.05-2.76, P = 0.03). This was not the case for new-onset office hypertension (OR = 1.61, 95% CI 0.94-2.74, P = 0.07)., Conclusion: Our study provides the first evidence that in normotensive individuals the magnitude of LVMI is independently associated with the risk of incident out-of-office hypertension.

Background: Twenty-four-hour blood pressure variability (BPV) is independently related to cardiovascular outcomes, but limited and conflicting evidence is available on the relative prognostic importance of systolic and diastolic BPV. The aim of this study was to verify the hypothesis that the association of systolic and diastolic blood pressure variability over 24 h with cardiovascular mortality in untreated subjects is affected by age., Design and Methods: The study included 9154 untreated individuals assessed for hypertension between 1982 and 2002 in the frame of the Dublin Outcome Study, in which 24 h ambulatory blood pressure monitoring was obtained (age 54.1 ± 14.3 years, 47% males). The association of short-term systolic and diastolic blood pressure variability with cardiovascular and all-cause mortality in the entire sample and separately in younger and older age subgroups was assessed over a median follow-up period of 6.3 years., Results: Diastolic BPV was directly and independently related to cardiovascular mortality (adjusted hazard ratio (adjHR) for daytime standard deviation 1.16 (95% confidence interval 1.08-1.26)) with no significant differences among age groups. Conversely, systolic BPV was independently associated with cardiovascular mortality only in younger (<50 years) subjects (adjHR for daytime standard deviation 1.72 (95% confidence interval 1.33-2.23)), superseding the predictive value of diastolic BPV in this group., Conclusions: Diastolic short-term BPV independently predicts cardiovascular mortality in hypertensive subjects at all ages, while systolic BPV seems a particularly strong predictor in young adults. If confirmed, these findings might improve the understanding of the prognostic value of BPV, with new perspectives for its possible clinical application.

Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18% ± 9.6 vs. 44.59% ± 12.67 respectively; p-value < 0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.

Aim: The association between prehypertension (pre-HTN) and abnormal left ventricular (LV) geometric patterns is unclear. We performed a meta-analysis of echocardiographic studies aimed to provide a new piece of information on LV geometric alterations in untreated pre-HTN individuals., Design: Studies were identified by crossing the following search terms: 'prehypertension,' 'high normal blood pressure,' 'heart,' 'LV hypertrophy' (LVH), 'LV geometry,' 'LV mass,' and 'echocardiography.', Results: A total 60 949 participants (38 536 normotensive, 14 453 pre-HTN, and 7960 HTN individuals) were included in six studies. LV concentric remodelling was the most common abnormal pattern in pre-HTN participants followed by eccentric and concentric LVH. Compared with normotensive group, pre-HTN exhibited a higher risk of LV concentric remodelling (OR 1.89, CI 1.70-2.10, P < 0.001), eccentric LVH (OR 1.65, CI 1.40-1.90, P < 0.001) and concentric LVH (OR 2.09, CI 1.50-3.00, P < 0.001). The likelihood of having abnormal LV patterns in HTN was significantly higher (P < 0.001 for all) than in pre-HTN participants., Conclusion: Our meta-analysis shows that alterations in LV geometry in pre-HTN individuals are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN is associated to early changes in LV structure and geometry, and preventive strategies may have a protective impact on development of subclinical cardiac damage in this setting.

In the PAMELA study (Pressioni Arteriose Monitorate e Loro Associazioni), clinical variables, an echocardiogram, as well as office and ambulatory blood pressure (ABP) were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of masked hypertension (MH) as a predictor of new-onset left ventricular hypertrophy (LVH). The present analysis included 803 participants without LVH at baseline (left ventricular mass index <115 g/m 2 in men and <100 g/m 2 in women). Based on office and 24-hour mean ABP values, subjects were divided into 3 groups: normal subjects (normotensive, office blood pressure [BP] <140/90 mm Hg and 24-hour mean ABP <130/80 mm Hg), MH (office BP, normal, and 24-hour mean ABP, elevated), and sustained hypertension (office and 24-hour BP, both elevated). At entry, 57 of 803 subjects fulfilled diagnostic criteria for MH (7.1%); 182 participants developed LVH (22.6%). Compared with subjects with normal in-office and out-of-office BP, the risk of new-onset LVH was greater in MH (odds ratio, 2.22; CI, 1.11-4.46, P=0.0250) after adjustment for potential confounders. This was also the case for the absolute increase of left ventricular mass index. Our study provides a new piece of evidence that MH, identified by office and ABP values, is associated with an increased risk of new-onset LVH. Moreover, our findings convey the notion that office BP may inaccurately estimate the risk of incident LVH in the general population.

Background: Vascular structural (intima-media thickness) and functional (carotid pulse wave velocity, cPWV) alterations are related to different patterns of left ventricular (LV) geometry in general population samples and in hypertensive patients. The relationship between vascular damage, evaluated by both echotracking ultrasound and coronary angiography, and LV geometry has not been prospectively analyzed., Methods: In eight Italian centers, 399 consecutive patients, without history of prior coronary artery disease and with clinical indication to coronary angiography, prospectively underwent cardiac standard ultrasound examination for the evaluation of LV mass, indexed by height to 2.7 power (LVMi g/m) and relative wall thickness (RWT), the measurement of Doppler flow in the left anterior descending artery (LAD) and the echocardiographic calcium score (eCS). In all patients measurement of common carotid intima-media thickness (cIMT) and cPWV by carotid ultrasound, with the realtime echotracking system was performed. The noninvasive evaluations were performed blindly to clinical information, before coronary angiography., Results: cIMT and cPWV were higher in patients with concentric LV hypertrophy (LVH) (LVMi ≥ 49 g/m in men and ≥47 g/m in women and RWT ≥ 0.42) as compared with those with normal LVMi and geometry (N: LVMi < 49 g/m in men and <47 g/m in women and RWT < 0.42) and to those with concentric remodeling (normal LVMi and RWT ≥ 0.42). Distal LAD velocity and eCS were greater in patients with concentric LVH than in others groups. At coronary angiography the prevalence of coronary stenosis (>50%) was greater in patients with concentric LVH and concentric remodeling, as compared with N. Patients with both concentric LVH and concentric remodeling showed higher values of cIMT and cPWV and distal LAD velocity and a greater prevalence of coronary stenosis (>50%) than patients with RWT less than 0.42., Conclusion: Our results further reinforced the observation that in patients undergoing elective coronary angiography, concentric geometry is associated with structural and functional carotid alterations, with higher distal LAD flow velocity and eCS. In this large group of patients, concentric geometry is associated with a greater prevalence of coronary stenosis, as assessed by coronary angiography. These results might contribute to explain the greater cardiovascular risk associated with concentric remodeling and LVH.

Background: Risk behaviors are frequent among young adults and they are particularly relevant when considering healthcare students., Objectives: The study is aimed to examine the prevalence of smoking, binge drinking, physical inactivity, and excessive bodyweight in a population of healthcare students attending an Italian university., Methods: Healthcare students filled an anonymous multiple-choice questionnaire on the occasion of the occupational health visit that preceded their hospital internship. The questionnaire covered socio-demographic characteristics (including student's working status and cohabitation) and risk behaviors. We evaluated the prevalence of risk behaviors and their association with socio-demographic characteristics., Results: The sample consisted of 494 students (65% women): 23.2% were smokers, 7.9% had excessive bodyweight, 35% did not practice any physical activity and 50% reported binge drinking at least once in the last 12 months. We found associations of male sex (30.5%) and being nursing students (29.9%) with smoking habit. The frequency of binge drinking was higher in men (38.4%), working students (53.9%), and among those who lived without family (50%). Physical inactivity was associated with female sex (44.2%) and living without family (57.1%). Finally, the co-presence of 2 risk behaviors or more was higher in men (36.8%), in nursing students (39.6%) and in working students (44.7%)., Conclusions: Our findings regarding the prevalence of risk behaviors and their potential association with socio-demographic factors may be a clue to the definition of targeted strategies aimed at reducing of risk behaviors among healthcare students.

Aim: Whether increased serum uric acid (SUA) favours resistance to antihypertensive drugs is not clear., Methods: The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind, multicenter trial comparing the effects of a 4-year treatment with either lacidipine or atenolol on progression of carotid atherosclerosis in patients with moderate hypertension. SUA was assessed at randomization and at the study end, office blood pressure (BP) was measured at each titration visit and every 6 months thereafter, ambulatory BP was measured at randomization and every year thereafter., Results: No difference was found in office and ambulatory BP reduction achieved after 1 and 4 years of treatment in baseline SUA tertiles. This was the case for both treatments. The percentage of patients with controlled office BP (<140/90 mmHg) after 1 year (36.5, 34.2 and 33.8%, P = 0.56) and 4 years (39.9, 39.4 and 38%, P = 0.82) was not different in SUA tertiles. Similar results were obtained basing the analysis on the control of ambulatory BP (<130/80 mmHg) or when data were analyzed taking into account SUA extreme values (≥7 and <3.5 mg/dl). The average and percentage changes of SUA (baseline-study end) were not different between patients who achieved or did not achieve office BP control (5.31 ± 1.26 vs. 5.4 ± 1.29 mg/dl, P = 0.22 e 0.13 ± 0.33 vs. 0.13 ± 0.68, P = 0.87, respectively). This was the case also for control of ambulatory BP., Conclusion: In the ELSA study, SUA levels do not affect the responsiveness to antihypertensive treatment.

Cross-sectional and longitudinal data analysis of the PAMELA (Pressioni Monitorate E Loro Associazioni) population was performed to assess the association between prehypertension and left ventricular hypertrophy (LVH) at entry and the risk of new-onset LVH associated to this condition in the subset of participants with normal LV mass index (LVMI). A total of untreated 1397 participants with measurable echocardiographic parameters at baseline were considered in the cross-sectional analysis. The longitudinal analysis included 880 participants without LVH at baseline and with measurable LVMI at follow-up examination performed 10 years later. At entry, after adjustment for major confounders LVH prevalence rates (LVM/body surface area) showed a significant, progressive increase from the normotensive (2.1%), to prehypertension (6.7%), and hypertension group (18.3%). The incidence of LVH increased progressively from the normotensive to prehypertension and hypertension group (9.0%, 23.2%, and 36.5%, respectively). The risk of new LVH was significantly greater in prehypertension who progressed to sustained hypertension (odds ratio, 4.21; CI, 1.64-10.83; P=0.003) than in those with persistent prehypertension (odds ratio, 1.89; CI, 0.77-5.11; P=0.21) compared with persistent normotensive participants after adjustment for age, sex, baseline LVMI, obesity, glucose, creatinine, total cholesterol and the use of antihypertensive drugs at follow-up. Further adjustments for changes in body mass index, metabolic variables, and creatinine during the follow-up did not modify the strength of association between prehypertension and new-onset LVH. Our findings offer a new piece of evidence on the association of prehypertension with LVH and support the view that preventive actions for this condition affecting a large fraction of the general population should be intensified.

Objective: Hyperuricemia has been associated with high blood pressure (BP) values, diabetes mellitus, metabolic syndrome and chronic kidney disease (CKD). In the present study, we assessed the gender-related relationships between serum uric acid (SUA) and cardionephrometabolic variables in central and east European hypertensive patients., Methods: A total of 3206 treated hypertensive patients with available SUA levels from the BP-CARE study was analyzed. Correlations among SUA, BP values, BP control, diabetes mellitus, metabolic syndrome and CKD were performed according to gender., Results: Twenty-five percent of the whole population showed hyperuricemia (28% in women and 23% in men). These patients were older and showed a greater burden of cardiovascular risk factors (high BP, BMI, glucose, total cholesterol and triglyceridemia). They also showed a greater prevalence of metabolic syndrome, diabetes mellitus, rate of uncontrolled BP, more than high cardiovascular risk and CKD. Prevalence of metabolic syndrome and uncontrolled BP was similar in normouricemic and hyperuricemic women, the latter displaying a higher prevalence of diabetes mellitus, high cardiovascular risk and CKD. Hyperuricemic men were characterized by a greater prevalence of metabolic syndrome, diabetes mellitus, high cardiovascular risk, rate of uncontrolled BP and CKD but not polytherapy. Logistic regression analysis showed that none of the evaluated variables, except CKD, displayed SUA as significant covariate., Conclusion: Our findings provide evidence that a high prevalence of hyperuricemia occurs in hypertensive patients from central and east Europe. The data also show that gender-related differences in the association between SUA and cardionephrometabolic variables exist. This is also the case for the relationships between SUA and CKD.

Aim: Although abnormalities in reflex sympathetic neural function represent a hallmark of heart failure, no information is available on the neuroadrenergic and baroreflex function in heart failure with preserved, midrange and reduced ejection fraction. The current study was designed to assess muscle sympathetic nerve traffic (MSNA) and baroreflex function in the clinical classes of heart failure defined by the new European Society of Cardiology/American College of Cardiology Foundation/American Heart Association guidelines., Methods: In 32 treated heart failure patients aged 69.3 ± 1.1 (mean ± SEM) classified according to new heart failure guidelines, we measured MSNA (microneurography), spontaneous baroreflex sensitivity and venous plasma norepinephrine (HPLC). Fourteen age-matched healthy individuals represented the control group., Results: MSNA was progressively and significantly increased from controls to heart failure conditions characterized by preserved, midrange and reduced ejection fraction (40.4 ± 2.5, 55.6 ± 2.1, 70.4 ± 3 and 78.6 ± 2.6 bursts/100 heart beats, P < 0.01). In contrast, plasma norepinephrine was significantly increased in heart failure with reduced ejection fraction only. Baroreflex sensitivity was significantly reduced in the latter two clinical conditions and almost unaltered in heart failure with preserved ejection fraction. There was an inverse relationship between different markers of adrenergic activity (MSNA, heart rate and plasma norepinephrine), left ventricular ejection fraction and baroreflex function. Brain natriuretic peptides were directly and significantly related to MSNA and plasma norepinephrine., Conclusion: Thus clinical categories of heart failure patients defined by the new European Society of Cardiology/American College of Cardiology Foundation/American Heart Association classification share as a common pathophysiological link the marked overactivity of the sympathetic nervous system, whose magnitude is significantly and strongly related to the impairment of the left ventricular ejection fraction. A baroreflex dysfunction accompanies in the more severe heart failure state the neuroadrenergic activation.

The present study was aimed at assessing the relationships between absolute and individual residual blood pressure (BP) variability and cognitive function in a general population. This cross-sectional study evaluated cognitive function using minimental state evaluation (MMSE) in 471 subjects enrolled in the PAMELA study. MMSE was calculated 10 years after initial enrollment of the subjects in the PAMELA study. Measurements included office, home, and 24-hour ambulatory BP monitoring. BP variability was obtained by calculating: (a) 24-hour standard deviation (SD) for systolic and diastolic BP and (b) individual residual BP variability. Mean age (±SD) of the subjects enrolled was 63 ± 5.7 years at the initial evaluation, with a 10-year increase when MMSE was performed. There was no significant difference in BP or heart rate values measured at office, home, or during 24-h BP monitoring between subjects with MMSE < 24 and those with ≥24. BP variability measured by SBP and DBP SD was also similar between these two groups. However, individual residual BP variability was significantly greater in subjects with lower MMSE and this difference became more pronounced when the study population was divided in three groups according to MMSE score (10-20, 21-23, 24-30). Individual residual SBP and DBP variability gradually decreased with the increase in MMSE score. Our data show that a sensitive parameter for the development of cognitive impairment is not BP or absolute BP variability but rather its short-term erratic component, which has been previously shown to be an important prognostic marker for organ damage, cardiovascular, and all-cause mortality., (©2018 Wiley Periodicals, Inc.)

Backgrounds & Aims: Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting., Methods: One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up., Results: Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%)., Conclusions: Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs., Methods: This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017)., Results: Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807)., Conclusions: In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe., Lay Summary: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Aim: In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, clinical and metabolic variables as well as office, home and ambulatory blood pressure (BP) values were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of selective and combined elevation of different BP phenotypes in predicting new-onset metabolic syndrome (MetS)., Methods: The present analysis included 1182 participants without MetS at baseline, as defined by the APT III criteria. On the basis of office, 24-h ambulatory BP and home values, participants were divided into four groups: normal, white-coat hypertension (WCH), masked hypertension and sustained hypertension., Results: Compared with participants with in-office and out-of-office normal BP, a greater incidence of new-onset age-adjusted and sex-adjusted MetS was observed in WCH (OR = 1.75, CI 1.01-3.04, P = 0.0046), masked hypertension (OR = 2.58, CI 1.26-5.30; P = 0.009) and sustained hypertension (OR = 2.14, CI 1.20-3.79, P = 0.009)) when out-of-office BP was defined by ambulatory criteria. This was not the case when out-of-office BP was defined by home criteria, as only the WCH group showed a greater risk (OR 2.16, CI 1.28-3.63, P = 0.003). Similar findings were obtained for single components of the MetS such as abdominal obesity and hyperglycemia., Conclusion: Our study provides evidence that either isolated or combined BP elevations identified by office/ambulatory measurements, carry an increased risk of new-onset MetS, whereas, only WCH is associated with a greater risk of incident MetS whenever BP phenotypes are identified by office/home measurements. In a clinical perspective, a comprehensive evaluation of BP status based on office/ambulatory measurements may improve diagnosis of new-onset MetS and activate measures for its prevention.

Purpose of Review: The paper examines the patterns of BP control achieved in two large scale observational studies, i.e., the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study and the Blood Pressure control rate and CArdiovascular Risk profilE (BP-CARE), carried out in the general population and in treated hypertensive patients, respectively., Recent Findings: It is well known that only a minor fraction among the treated hypertensive patients exhibits a good blood pressure control. However, few study investigated blood pressure control on the basis not only of office, but also home and ambulatory blood pressure measurement, examining its impact on organ damage. In the whole sample of the PAMELA study, only in about 21.1% of cases treated hypertensive subjects exhibit a well-controlled office BP. Control of systolic blood pressure was rarer than the diastolic one. Control of home and, even more, ambulatory blood pressure was more frequent. Left ventricular mass was not normalized even when blood pressure was adequately controlled. Most subjects of BP-CARE study show high or very high cardiovascular risk, due to concomitant risk factors and organ damage. The percentage of well-treated hypertensive patients is lower when CV risk is higher.

Background: Although several data suggest that serum uric acid (SUA) predicts future development of metabolic abnormalities, the evidence is not conclusive in Mediterranean populations., Methods: A total of 3200 individuals were randomly selected from the residents of Monza (North Italy) to be representative of its general population for sex and age (25-74 years). The participation rate was 64%. At baseline and 10 years later, we measured waist circumference, office blood pressure, fasting blood glucose, serum triglycerides, serum HDL cholesterol and SUA., Results: The analysis was carried out in individuals without metabolic syndrome at baseline (N = 1192) when looking for incidence of metabolic syndrome, without impaired fasting glucose (IFG) at baseline (N = 1320) when looking for incidence of IFG and without diabetes mellitus at baseline (N = 1352) when looking for incidence of diabetes mellitus. Adjusting for confounders, a 1-SD increase of baseline SUA was not associated with and increased risk of new-onset metabolic syndrome, but with new-onset IFG [relative risk (RR) = 1.26, confidence interval (CI) 1.06-1.5, P = 0.01]. It was associated with a 29% increased risk of new-onset diabetes mellitus, that was more than twice in the highest as compared with the lowest quartile of baseline SUA (RR = 1.29, CI 0.98-1.7, P = 0.07, and RR = 2.16, CI 0.95-4.88, P = 0.07). Focusing the analysis on the individuals with age above the median value, SUA increase was significantly associated with an increased risk of new-onset metabolic syndrome, IFG and diabetes mellitus., Conclusion: SUA increase is associated with an increased risk of developing IFG and, in the population fraction with age above the median value, also metabolic syndrome and diabetes mellitus.

Different strategies of DAAs treatment are currently possible both pre- and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately investigated; this study aims at assessing their cost-effectiveness. A decision analytical model was created to simulate the progression of HCV-infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12-week course of DAAs prior to transplantation (PRE-LT), (ii) a 4-week course of DAAs starting at the time of transplantation (PERI-LT) and (iii) a 12-week course of DAAs administered at disease recurrence (POST-LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE-LT treatment strategy was dominant for DCC patients with MELD<16 and cost-effective for those with MELD16-20, while POST-LT strategy emerged as cost-effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE-LT as the cost-effective strategy for patients with MELD≤20. In conclusion, PRE-LT treatment is cost-effective for patients with MELD≤20 without HCC, while treatments after LT are cost-effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant-related factors., (© 2018 John Wiley & Sons Ltd.)

The aim of the present study is to investigate the predictive value of pulse pressure (PP) on cardiovascular events in the general population and in both sexes, separately. The study involved 2045 participants from the PAMELA study who underwent 24-hour ambulatory blood pressure (BP) monitoring. The participants were followed from the initial medical visit for a time interval of 137 ± 23 months. It was found that office, home, and 24-hour blood pressures were significantly higher in the individuals who experienced cardiovascular (CV) events. Office, 24-hour, and daytime PP were independent predictors of CV events after adjustment for main demographic and clinical parameters in the whole study population. Nighttime PP was an additional independent predictor in men. In conclusion, PP represents an important predictor of cardiovascular events in the general population, particularly among men. Daytime and 24-hour PP have greater predictive importance than nighttime PP in the general population., (©2018 Wiley Periodicals, Inc.)

Aim: Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We evaluated this issue in individuals enrolled in the Pressioni Monitorate E Loro Associazioni study., Methods: At entry, 2021 individuals underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure (BP) monitoring and echocardiography. Participants were followed from the initial medical visit for a time interval of 148 ± 27 months. To explore the association of circadian HR rhythm and outcomes, participants were classified in the primary analysis according to quartiles of nocturnal HR decrease. In secondary analyses, the population was also classified according nondipping nocturnal HR (defined as a drop in average HR at night lower than 10% compared with day-time values) and next in four categories: first, BP/HR dipper, second, BP/HR nondipper, third, HR dipper/BP nondipper, fourth, HR nondipper/BP dipper)., Results: A flattened circadian HR rhythm (i.e. lowest quartile of night-time HR dip) was independently associated with left atrial enlargement, but not to left ventricular hypertrophy; moreover, it was predictive of fatal and nonfatal cardiovascular events, independently of several confounders (hazard ratio 1.8, confidence interval: 1.13-2.86, P < 0.01 vs. highest quartile)., Conclusion: A blunted dipping of nocturnal HR is associated with preclinical cardiac damage in terms of left atrial enlargement and is predictive cardiovascular morbidity and mortality in the general population.

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.

Aim: We sought to assess the long-term changes in left ventricular (LV) mass in a population-based sample, focusing on new onset, persistence, regression and severity of LV hypertrophy (LVH), as well as on the demographic and clinical variables independently related to this dynamic process., Methods: A total of 1113 participants with measurable echocardiographic parameters at baseline and after a 10-year follow-up were included in the analysis. Cut points for LVH were derived from current echocardiographic guidelines., Results: LVH prevalence significantly increased from 13 to 33% as a result of LVH new onset in 254 and LVH regression in 31 cases. Severe LVH prevalence increased by 4.3 times from baseline, a trend mainly related to transition from mild-moderate-to-severe LVH in patients with preexisting cardiac hypertrophy. Variables such as age, female sex, baseline SBP, as well as delta follow-up-baseline SBP, BMI, metabolic syndrome and use of antihypertensive drugs were independently related either to new-onset or to persistent LVH., Conclusion: Long-term LV mass changes in a general population are associated with a marked increase in the prevalence and severity of LVH, and this unfavourable trend was more frequent in women. As blood pressure, metabolic variables and BMI emerged as key correlates of this adverse process, our findings suggest that interventions aimed to modify such risk factors may have a role in preventing new onset and progression LVH, as well as a marked worsening of cardiovascular risk profile at the community level.

Aim: Scanty information is available about the association of isolated daytime hypertension (IDH) and isolated night-time hypertension (INH) with subclinical cardiac damage in the general population. We examined this issue in patients enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study., Methods: The analysis included 2021 participants with valid ambulatory blood pressure (BP) monitoring at baseline evaluation. IDH and INH were defined according to current guidelines. Subclinical organ damage was assessed by validated electrocardiographic and echocardiographic criteria., Results: A total of 1258 patients (62.3%) had daytime/night-time normotension, 376 (18.6%) daytime/night-time hypertension, 231 (11.4%) INH and 156 (7.7%) IDH, respectively. Participants with hypertension, compared with their normotensive counterparts were older, included a higher fraction of men, had higher BMI, LDL cholesterol, triglyceride and glucose levels and exhibited a greater subclinical cardiac involvement. Furthermore, INH and IDH patients showed a similar degree of cardiac damage (i.e. left ventricular mass index: 89 ± 18 vs 90 ± 20 g/m), intermediate between normotensive (82 ± 19 g/m) and day-night hypertensive patients (99 ± 24 g/m)., Conclusion: The present study shows that IDH and INH exert similar detrimental effects on cardiac structure. In a practical perspective, appropriate antihypertensive chrono-therapeutic approaches in these opposite ambulatory hypertensive subtypes may have important implications in cardiovascular prevention.

Background: The association between serum uric acid (SUA) and left ventricular hypertrophy (LVH) is controversial and the ability of SUA in predicting incident LVH remains unsettled. Thus, we evaluated the relationship of SUA with new-onset echocardiographic LVH over a 10-year period in subjects of the general population enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study., Methods: The study included 960 subjects with normal LV mass index (LVMI) at baseline echocardiographic evaluation and a readable echocardiogram at the end of follow-up. Cut-points for LVH were derived from reference values of the healthy fraction of the PAMELA population., Results: Over a 10-year period, 258 participants (26.9%) progressed to LVH. The incidence of new-onset LVH increased from the lowest (23%) to intermediate (25%) and the highest baseline SUA tertile (32%). After adjusting for confounders (not including body mass index (BMI)), each 1 mg/dl increase in SUA entailed a 26% higher risk of incident LVH. Adjusted odd ratio of LVH risk in the highest SUA tertile was 96% higher than in the lowest tertile (odds ratio (OR) = 1.966, 95% CI = 1.158-3.339, P = 0.0123). Correction for BMI reduced the magnitude and statistical significance of ORs., Conclusions: The study shows that SUA is a predictor of long-term echocardiographic changes from normal LVMI to LVH in a community sample. Thus, life-style and pharmacologic measures aimed to reduce SUA levels may concur to preventing LVH development in the general population., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Aims: The aim of the present study was to assess the association of the presence and amount of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) with cardiovascular adverse events in patients with orthotopic heart transplantation (HTx)., Methods and Results: We enrolled 48 patients (mean age, 54.7 ± 14.6 years; 37 men) at various stages after HTx. All patients underwent standard CMR at 1.5 T, to characterize both cardiac anatomy and LGE. Late gadolinium enhancement was detected in 26 patients (54%). All-cause and cardiovascular mortalities, and a composite of major adverse cardiovascular events (MACE) recurrence were evaluated during the follow-up period for a median of 5.16 years. Ten patients (21%) died and 26 (54%) were readmitted because of MACE. Multivariate Cox analysis identified as independent predictors of MACE a diagnosis of cardiac allograft vasculopathy (CAV) (HR 3.63; 1.5-8.7 95% CI; P = 0.0039), left ventricular end systolic volume index (HR 1.04; 95% CI 1.01-1.079; P = 0.008), LGE mass (HR 1.04; 1.01-1.06 95% CI; P = 0.0007), LGE % of left ventricular mass (HR 1.083; 1.03-1.13 95% CI; P = 0.0002). Independent predictors of all-cause death were CAV (HR 6.33; 95% CI 1.33-30.03; P = 0.0201), LGE mass (HR 1.04; 1.01-1.07 95% CI; P = 0.005), LGE % of left ventricular mass (HR 1.075; 1.02-1.13 95% CI; P = 0.007). Patients with CAV had a risk of MACE by 5 years of 67% (95% CI 0.309-0.851%); the addition of 7.9 LGE % to the risk model increased the predicted risk to 88% (95% CI 0.572-0.967%)., Conclusions: The current study demonstrated that the presence of CAV and the total amount of LGE have a significant independent association with MACE and mortality in HTx patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: Annexin A5 (AnxA5) has been previously linked to the presence of carotid and cardiac target organ damage (TOD) in the context of heart failure and rheumatologic patients. However, information is scant in the context of hypertension. Aim of our study was to evaluate AnxA5 in treated hypertension patients compared with normotensive controls and to determine whether it is associated with vascular and heart TOD evaluated as arterial stiffness, carotid plaque and left ventricular hypertrophy., Methods: We enrolled 123 consecutive treated hypertension and 124 normotensive controls. TOD was evaluated as pulse wave velocity (PWV, complior), left ventricular hypertrophy (echocardiography) and intima-media thickness and carotid plaque presence (ecographic methods). AnxA5 levels was dosed and compared in patients with and without hypertension and with and without TOD., Results: With similar age hypertension patients showed higher SBP, DBP and AnxA5 levels (13.9 ± 11.1 vs 10.1 ± 8.4 ng/ml, P < 0.001) compared with controls. Regarding TOD hypertension showed higher PWV (8.5 ± 1.8 vs 7.6 ± 1.5 m/s, P < 0.001) and LVMI (121.7 ± 29.3 vs 113.5 ± 21.1 g/m, P < 0.05), whereas carotid intima-media thickness was superimposable. AnxA5 correlates with PWV (r = 0.13, P < 0.05) and DBP (r = 0.15, P < 0.01), whereas it has never been found as a significant independent predictor of TOD in linear regression analysis., Conclusion: Our data have shown that AnxA5 levels are increased in treated hypertension patients. In this condition, it is probably released in the plasma as a defensive mechanism through its anti-inflammatory and anticoagulants effects. We found a significant association with arterial stiffness, but AnxA5 was not found to be a significant predictor of TOD.

Aims: According to recent data, more accurate selection of patients undergoing coronary angiography for suspected coronary artery disease (CAD) is needed. From the Active PREvention Study multicentre prospective study, we further analyse whether carotid intima-media thickness (cIMT), carotid plaques (cPL), and echocardiographic cardiac calcium score (eCS) have incremental discriminatory and reclassification predictive value for CAD over clinical risk score in subjects undergoing coronary angiography, specifically depending on their low, intermediate, or high class of clinical risk., Methods and Results: In eight centres, 445 subjects without history of prior CAD but with chest pain of recent onset and/or a positive/inconclusive stress test for ischaemia prospectively underwent clinically indicated elective coronary angiography after cardiac and carotid ultrasound assessments with measurements of cIMT, cPL, and eCS. The study population was divided into subjects at low (10%), intermediate (10-20%), and high (>20%) Framingham risk score (FRS). Ultrasound parameters were tested for their incremental value to predict CAD over FRS, in each pre-test risk category. No significant difference could be appreciated between the discrimination value of FRS and Diagnostic Imaging for Coronary Artery Disease score for the presence of CAD. eCS or cPL demonstrated significant incremental prediction over FRS, consistently in the three FRS categories (P < 0.01); this applied to both discrimination and reclassification, with the exception of high-risk subjects, in whom cPL was apparently not incremental over FRS, and eCS was only of borderline significance for better discrimination., Conclusions: Ultrasound eCS and cPL assessments were significant predictors of angiographic CAD in patients without prior CAD but with signs or symptoms suspect for CAD, independently and incrementally to FRS, across all pre-test risk probability strata, although in high-risk subjects, only eCS maintained an incremental value. The use of cIMT was not significantly incrementally useful in any FRS risk category., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background & Aims: All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting., Methods: 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015., Results: The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p<0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p<0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16-20: HR=0.120; p=0.0005, MELD >20:HR=0.042; p<0.0001), delta MELD (HR=1.349; p<0.0001) and delta albumin (HR=0.307; p=0.0069) both assessed after 12weeks of DAA therapy., Conclusions: This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained., Lay Summary: The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: EKG Tpeak-Tend (Tp-Te) interval, an index of transmural dispersion of myocardial repolarization, is gaining interest as possible cardiovascular prognostic variable. Evidence that this is the case in the general population is scanty, however. This was tested in the Pressioni Arteriose Monitorate E Loro Associazioni population., Methods and Results: EKG, echocardiographic, office, home and ambulatory (24-h) blood pressure (BP), metabolic and laboratory data were assessed. Cardiovascular and all-cause mortality were evaluated over a mean follow-up of 16 years. Repetition of all measurements after 10 years allowed to evaluate also the risk of developing office and out-of-office hypertension and echocardiographic left ventricular hypertrophy. At baseline, Tp-Te adjusted for confounders (c) showed a significant correlation with office, home and 24-h blood pressure but not with left ventricular mass. The cTp-Te value predicted the risk of cardiovascular and all-cause mortality before and after adjustment for demographic and clinical variables, the increase being 31 and 13% for 1-SD cTp-Te increase, respectively (P < 0.0001 and P < 0.002). This was the case also in hypertensive patients in which the corresponding increase in risk with 1-SD increase of Tp-Te was 47 and 25% (P < 0.05). cTp-Te did not predict the 10-year risk of developing office, home, ambulatory hypertension and left ventricular hypertrophy., Conclusion: Tp-Te interval retains an independent prognostic value both in the general population and in its hypertensive fraction. This easily and cheaply obtainable variable may be employed for improving cardiovascular-risk stratification, representing a useful measure to add to the recommended screening in hypertension.

Aim: Increased left atrium diameter (LAD) is associated with elevated risk of cardiovascular morbidity and mortality. We evaluated new-onset left atrium enlargement (LAE) and their correlates over a 10-year period in participants of the general population enrolled in the Pressioni Monitorate e Loro Associazioni study., Methods: The study included 1045 participants with normal LAD at baseline evaluation having a readable echocardiogram at the end of follow-up. Cut-points for abnormal LAD were derived from reference values recommended by American Society of Echocardiography., Results: Over a 10-year period, 123 participants (11.8%) progressed to LAE. The incidence of new-onset LAE increased significantly from the lowest to the highest tertile of baseline office, home and 24-h blood pressure (BP); BMI; fasting blood glucose and left ventricular mass index (LVMI). In multivariate analysis, baseline LAD [odds ratio (OR) 3.18, confidence interval (CI) 2.26-4.47, P < 0.001], female sex (OR 3.68, CI 2.20-6.18, P < 0.001), office SBP (OR 1.36, CI 1.08-1.70, P = 0.008), BMI (OR 1.35, CI 1.07-1.69, P = 0.01 and LVMI (OR 1.29, CI 1.01-1.64, P = 0.04) emerged as key correlates of new-onset LAE., Conclusion: The study shows that in the population, long-term changes from normal LAD to LAE are independently driven by several risk factors such as the female sex and an increased baseline LAD, BMI, LVMI and BP, with no predictive superiority of home and ambulatory versus office values. Preventing BP elevations, overweight/obesity and left ventricular hypertrophy may thus all be important for LAE prevention.

The authors estimated the risk of cardiovascular mortality associated with echocardiographic (ECHO) left ventricular hypertrophy (LVH) and subtypes of this phenotype in patients with and without electrocardiographic (ECG) LVH. A total of 1691 representatives of the general population were included in the analysis. During a follow-up of 211 months, 89 cardiovascular deaths were recorded. Compared with individuals with neither ECHO LVH nor ECG LVH, fully adjusted risk of cardiovascular mortality increased (hazard ratio [HR], 3.36; 95% confidence interval [CI], 1.51-7.47; P=.003) in patients with both ECHO-LVH and ECG-LVH, whereas the risk entailed by ECHO-LVH alone was of borderline statistical significance (P=.04). Combined concentric nondilated LVH and ECG-LVH, but not concentric nondilated LVH alone, predicted cardiovascular death (HR, 3.79; 95% CI, 1.25-11.38; P=.01). Similar findings were observed for eccentric nondilated LVH (HR, 3.37; 95% CI, 1.05-10.78; P=.04.). The present analysis underlines the value of combining ECG and ECHO in the assessment of cardiovascular prognosis related to abnormal left ventricular geometric patterns., (© 2016 Wiley Periodicals, Inc.)