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Background: Vascular structural(intima-media thickness, IMT) and functional(carotid stiffness, cPWV)alterations are related to different pattern of left ventricular (LV) geometry in general populations and in hypertensives. The relationship between vascular damage and LV geometry has not been analyzed prospectively in patients undergoing coronary angiography. Methods: 399 consecutive patients with clinical indication to coronary angiography, prospectively underwent standard ultrasound examination for the evaluation of LV mass index(LVMi g/m2.7), relative wall thickness(RWT), distal anterior descending coronary artery flow velocity(LADd_vel), carotid ultrasound with real time echotracking system for measurement of central blood pressure(cSBP, cDBP), common carotid intima media thickness(cIMT) and carotid pulse wave velocity(cPWV) (Esaote MyLab 70). The noninvasive evaluations were performed blindly to clinical information, before coronary angiography. Results: cIMT and cPWV were higher in patients with concentric LVH(LVMI≥49 g/h2.7 in men and ≥47 g/h2.7 in women and RWT≥ 0.42) as compared to N (normal LV mass and geometry) and CR (concentric remodeling, normal LVMi and RWT>0.42). LADd_vel was greater in patients with concentric LVH than in others groups. The prevalence of coronary stenosis(>50%) was greater in patients with concentric LVH and CR as compared to N. Patients with concentric geometry (RWT≥0.42) showed higher values of cIMT(773±169 vs 729±162, p50%)than patients with RWT

Background: Evidence on the association of arterial stiffness and left ventricular (LV) concentric remodelling/LVH assessed by echocardiography, with abnormal blood pressure (BP) phenotypes, defined by office and ambulatory BP monitoring (ABPM) in the community is scanty. Thus, we investigated this issue in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The present study included 491 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, blood examinations, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements., Results: In the whole study sample (age 66+10 years, 50% males), the prevalence rates of sustained normotension (NT), white coat hypertension (WCH), masked hypertension (MH), sustained hypertension (SH) and non-dipping (ND) were 31.2, 10.0, 24.2, 34.6, and 35.8% and respectively. The likelihood of having SH, the BP phenotype carrying the greatest CV risk, was four times higher (OR= 4.31, CI:2.39-7.76, p<0.0001) in participants with increased CAVI and LV remodelling/LVH compared to their counterparts without organ damage. This association showed an incremental value in discriminating SH compared to both isolated markers of organ damage (OR=1.92,p=0.03 for increased CAVI and OR= 2.02, p=0.02 for LV remodelling/LVH). The presence of isolated but also combined organ damage was unrelated to ND., Conclusions: Our study provides new evidence of the incremental value of looking for both vascular and cardiac target organ damage to optimize the identification and clinical management of SH in the general population., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: In the absence of outcome-based ambulatory blood pressure (BP) data hypertension guidelines provide 24-hour mean BP values corresponding to trial-validated office BP values. Data are shown for untreated and treated patients together, but whether corresponding ambulatory values are similar in untreated and treated hypertensives and reproducible at yearly measurements during treatment is undefined., Methods: In 2397 patients of the ELSA (European Lacidipine Study on Atherosclerosis) and PHYLLIS (Plaque Hypertension Lipid-Lowering Italian Study) trials, we calculated the office and 24-hour BP relationship according to the linear regression model, with office systolic BP as the independent variable, at baseline and yearly during a 3-year treatment. Twenty-four hour BP values corresponding to clinically important office BP values (hypertension grades and treatment thresholds and targets) were calculated and compared with those provided by guidelines., Results: Office/24-hour systolic BP or diastolic BP always exhibited a significant linear relationship, with, however, limited Pearson correlation coefficients (never >0.44).The slopes of the relationship were superimposable between different years of treatment but always significantly less steep than the slope seen in untreated individuals. Compared with the guideline-provided corresponding values, 24-hour BP showed qualitative and quantitative differences; for example, it was considerably lower and higher than the guideline-corresponding values when office BP was in the high hypertension and low treatment target ranges, respectively., Conclusions: In treated patients with hypertension the slope of the office/24-hour BP linear regression is reproducible over time. However, the slopes are steeper in untreated individuals, indicating that information on ambulatory BP values corresponding to office BP values can be more accurate if separately estimated in these 2 conditions.

Background: We evaluated whether chronic coffee consumption affects arterial stiffness, assessed by cardio-ankle vascular index (CAVI)., Methods: In 514 subjects, aged 66.6 ± 9.9 years (mean ± SD), recruited in the 3rd follow-up of the PAMELA study, subdivided into 3 groups according to the daily intake of regular coffee (0, 1-2, and ≥3 cups/day), we measured CAVI and clinic, ambulatory blood pressure (BP), and other variables., Results: The 3 groups displayed similar age, gender, metabolic, and renal profile. Clinic and ambulatory BPs were similar in the 3 groups, this being the case for CAVI (0 cup: 9.1 ± 1.8, 1-2 cups: 9.5 ± 2.3, and ≥3 cups: 9.2 ± 2.1 m/s, P = NS). No significant gender difference in CAVI and in participants under antihypertensive treatment was detected., Conclusions: Our data show that chronic coffee consumption leaves unaffected arterial stiffness in the general population, this being the case in subgroups. The neutral vascular impact of coffee may favor the absence of any significant BP effect of habitual coffee intake., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and the extent of nocturnal blood pressure (BP) fall in the general population are scanty. We sought to investigate this issue in the participants enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The study included 491 participants who attended the second and third surveys of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure BP monitoring (ABPM), blood examinations, echocardiography, and CAVI measurements., Results: In the whole study, both CAVI and left ventricular mass index (LVMI) were inversely correlated with nocturnal SBP fall, expressed as day-night percent change (r =  - 0.152, p = 0.0007, and r =  - 0.213, p < 0.0001, respectively). However, after adjustment for sex and age, the correlation remained significant only for LVMI (r =  - 0.124, p = 0.006). Non-dipper participants exhibited significantly higher sex-age adjusted LVMI (91 ± 22 vs 82 ± 18 g/m 2 (p < 0.0001)), but not of CAVI (9.07 ± 2.0 and 9.57 ± 2.2 m/s, p = ns). Similar results were found when classifying participants into quartiles of nocturnal SBP drop. Finally, both sex-age adjusted CAVI and LVMI were positively correlated with mean nocturnal SBP (r = 0.181, p < 0.001, and r = 0.240, p < 0.0001)., Conclusions: Although arterial stiffness assessed by CAVI, unlike LVMI, is unrelated with the degree of nocturnal BP drop, this marker is useful in identifying nocturnal hypertension and optimizing cardiovascular risk stratification in the community., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Heterogeneous are the results of the published studies aimed at determining the long-term effects of habitual coffee consumption on blood pressure (BP). Specifically, no data are available on the longitudinal association between habitual coffee consumption and office, home and 24 h BP profile and variability., Methods: In 1408 subjects recruited in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, followed for a 10 year follow-up period and classified as coffee consumers and nonconsumers (self-reporting), we prospectically investigated the association between habitual coffee consumption and office, home and 24-h ambulatory BP; 24-h BP variability; and development of a new hypertensive state. Data were also analysed according to gender., Results: When data were adjusted for confounders habitual coffee nonconsumers and consumers displayed similar long-term BP changes during the follow-up in office, home, and ambulatory BP. No difference was found between heavy and moderate coffee consumers. Furthermore, also new-onset hypertension and patterns of BP variability were superimposable in coffee nonconsumers and consumers, independently on confounders including gender, number, and characteristics of the antihypertensive drug treatment., Conclusion: The present study, which is the first longitudinal investigation never performed examining in a prospective fashion the long-term (10 year) effects of coffee consumption on office, home, and ambulatory BP, provides conclusive evidence that habitual coffee consumption is associated with neutral effects on in-office and out-of-office BP values and related variabilities. This is the also the case for the new-onset hypertensive state., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The study included 239 out of 562 participants who attended the second and third surveys of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP), blood examinations, echocardiography, and CAVI measurements., Results: In the whole study sample (age 69 ± 9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index, and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with the LVM index (P < 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6 ± 2.8 vs. 9.2 ± 1.8 m/s P < 0.001), larger left atrial diameter, and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/s was the best cut-off for prediction of LVH in the whole sample., Conclusions: Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Backgroud: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies., Aim: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy., Methods: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020., Results: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication., Conclusion: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Objectives: In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV., Methods: In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared., Results: Twenty-four-hour SBP-CV was about 20% less than office SBP-CV ( P  < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P  < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values., Conclusion: Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Hyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study., Methods and Results: We analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P<0.001), the average SUA elevation amounting to of 0.3 ± 1.1 mg/dl 26.7 % of the subjects displayed HU at the follow-up. This was associated at the multivariable analysis with female gender, office, home and 24-h blood pressure, diuretic treatment, serum triglycerides and baseline SUA, as well as the increase in waist circumference and the reduction in renal function., Conclusion: The present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Aortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We investigated the incidence of new-onset aortic root (AR) dilatation and its principal correlates among middle-aged adults over a 25-year time period., Methods: A total of 471 participants with measurable echocardiographic parameters at baseline and after a 25-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from healthy normotensive PAMELA participants., Results: New AR dilatation occurred in 7.4% (AR/BSA), 9.1% (AR/height) and 14.6% (absolute AR), respectively. According to the AR/height index, the risk of new dilation was similar in men and women. As for echocardiographic parameters, baseline AR diameter emerged as a key predictor of AR dilation, regardless of the diagnostic criteria and the 10-year change in LVMI was positively associated to new AR/height dilatation. No significant relationship was observed between baseline office and ambulatory systolic/diastolic blood pressure or their changes over time with incident AR dilatation. Baseline and the 25-year change in 24-h pulse pressure were negatively related to new AR dilatation., Conclusions: The incidence of AR dilatation from mid to late adulthood occurs in a small but clinically relevant fraction of participants and is unaffected by both office and out-office BP. It is significant related to baseline AR diameter and to the 25-year change in LVMI. Our data suggest that echocardiography performed in middle-aged individuals of both sexes may identify those at increased risk of future AR dilatation; moreover, preventing LVH may reduce the risk of progressive AR enlargement., (© 2022. The Author(s).)

The present study was designed to provide information on the ability of several different anthropometric markers to reflect the renal impairment associated with body weight increase and to predict the development of renal alterations linked to overweight and obesity. In 574 subjects representative of the general population of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, with an age range between 57 and 73 years, we investigated the association between different anthropometric markers of body fat, as alternative to body mass index, and renal failure, to obtain information useful for determining their potential predictive value. Renal dysfunction was significantly associated with almost all anthropometric markers of adiposity related to body weight and body shape. After adjustment for confounders, such as age, sex, office blood pressure, serum glucose, antihypertensive drugs and smoking habit, association remained significant only for waist-to-hip ratio (WHR), lipid accumulation product (LAP) and visceral adiposity index (VAI). These 3 markers also displayed at the receiver operating curves (ROC) analysis the best ability to detect subjects with or without kidney dysfunction. The results of the present study provide evidence that WHR, LAP and VAI represent the best markers of renal dysfunction associated with visceral body fat accumulation., (© 2023. The Author(s).)

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project., (© 2023. The Author(s).)

Background and Aims: Chronic coffee consuption has been reported to be associated with a modest but significant increase in blood pressure (BP), although some recent studies have shown the opposite. These data, however, largely refer to clinic BP and virtually no study evaluated cross-sectionally the association between chronic coffee consuption, out-of-office BP and BP variability., Methods and Results: In 2045 subjects belonging to the population of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we analyzed cross-sectionally the association between clinic, 24-hour, home BP and BP variability and level of chronic coffee consumption. Results show that when adjusted for confounders (age, gender, body mass index, cigarette smoking, physical activity and alcohol drinking) chronic coffee consumption does not appear to have any major lowering effect on BP values, particulary when they are assessed via 24-hour ambulatory (0 Cup/day: 118.5 ± 0.7/72.8 ± 0.4 mmHg vs 3 cups/day: 120.2 ± 0.4/74.8 ± 0.3 mmHg, PNS) or home BP monitoring (0 cup/day: 124.1 ± 1.2/75.4 ± 0.7 mmHg vs 3 cups/day: 123.3 ± 0.6/76.4 ± 0.36 mmHg, PNS). However, daytime BP was significantly higher in coffee consumers (about 2 mmHg), suggesting some pressor effects of coffee which vanish during nighttime. Both BP and HR 24-hour HR variability were unaffected., Conclusion: Thus chronic coffee consumption does not appear to have any major lowering effect either on absolute BP values, particulary when they are assessed via 24-hour ambulatory or home BP monitoring, or on 24-hour BP variability., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular events, and evidence has been obtained that an increase of a normal left ventricular mass (LVM) or new-onset LVH over time augments cardiovascular outcomes., Methods: We addressed this issue in a sample of a general population at relatively low cardiovascular risk. We analyzed subjects with normal echocardiographic LVM enrolled in the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study to follow the increase of LVM over time and assess the prognostic impact of this change on the incidence of cardiovascular events (mean follow-up 18.5 years)., Results: In 990 subjects with no LVH at baseline, there was a significant average increase of LVM (21.2%), LVMI BSA (18.9%), and LVMI HT (22.3%) more than 10 years later. About a quarter developed LVH. The LVMI BSA change exhibited an association with the cardiovascular risk mortality during the following 18.5 years, and the association remained significant after adjustment for confounders (hazard ratio, 1.2 [1.0-1.5]). Similar findings were obtained for LVM in absolute values or indexed for height. The association was seen in both genders, but the link with the cardiovascular risk was statistically significant in males only., Conclusions: Thus, although over 10 years, the LVM increase does not reach a LVH status, it is associated with an augmented cardiovascular mortality risk. This suggests that it might be important to consider periodical LVM assessment, even when LVM is within the normal range, to timely detect its increase and cope with the need of cardiovascular risk restratification., Competing Interests: Disclosures None.

We assessed the value of 3 electrocardiographic (EKG) voltage criteria in detecting variations of left ventricular mass (LVM) over time, taking echocardiographic (ECHO) LVM as reference, in the Pressioni Arteriose Monitorate E Loro Associazioni study. In 927 subjects (age 47 ± 13 years on entry, 49.9% men) an ECHO evaluation of LVM and EKG suitable for measurement of EKG-LVH criteria (Sokolow-Lyon voltage, Cornell voltage and R-wave voltage in aVL) were available at baseline and at a 2 nd evaluation performed 10 years later. Δ (delta) LVM, Δ LVMI, and Δ EKG parameters values were calculated from 2 nd evaluation to baseline. The sensitivity of the EKG criteria in the diagnosis of LVH, poor at baseline, becomes even worse after 10 years, reaching very low values. Only the sensitivity of R-wave amplitude exhibited slight increase over time but with unsatisfactory absolute values. Despite the prevalence of ECHO-LVH at the 2 nd evaluation was threefold increased compared to baseline (29.3% and 33.7% for LVM indexed to BSA and height 2.7 , respectively), the prevalence of EKG-LVH was unchanged when evaluated by Sokolow-Lyon criteria, significantly reduced when assessed by Cornell voltage index, while significantly increased using R-wave voltage in aVL criteria. Despite an ECHO-LVM increase over the time, mean EKG changes were of opposite sign, except for R-wave amplitude in aVL. Our study highlights the discrepancy between ECHO and EKG in monitoring LVM changes over the time, especially for Sokolow-Lyon and Cornell voltage. Thus, EKG is an unsuitable method for the longitudinal evaluation of LVM variations., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Surveillance costs and appropriateness of surgery of "low-risk" BD-IPMNs are relevant issues. In this study we evaluated the rate of correct indication for pancreatectomy defined as high grade dysplasia (HGD) at histology in 961 patients who underwent surveillance for a median of 5.1 years. Undertreatment and overtreatment were defined as invasive cancer and low grade dysplasia (LGD) at histology, respectively. Of the 66 patients (6.9%) who were operated, only 16 (23.8%) had a HGD while 40 (59.7%) had a LGD and 10 (14.9%) an invasive cancer, without differences regarding timing of surgery. The mean surveillance cost was € 194.9 ± 107.6 per patient-year, with a median cost of € 277.1 ± 148.2 in the correct surgery group compared with € 222.7 ± 111.6 and € 197 ± 102.7 in the overtreatment and undertreatment groups. The surveillance mean cost from diagnosis to surgery was € 854.8. Rate of appropriate surgery in BD-IPMNs under surveillance is low., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Results of recent clinical trials have shown that in heart failure (HF) heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk. No information is available on whether the sympathetic nervous system is differently activated in HF patients displaying resting HR values above or below this cutoff., Methods: In 103 HF patients aged 62.7 ± 0.9 (mean ± SEM) years and in 62 heathy controls of similar age we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the subjects in different groups according to their resting clinic and 24-h HR values., Results: In HF progressively greater values of clinic or 24-h HR were associated with a progressive increase in both MSNA and NE. HR cutoff values adopted in large scale clinical trials for determining cardiovascular risk, i.e., 70 beats/minute, were associated with MSNA values significantly greater than the ones detected in patients with lower HR, this being the case also for NE. In HF both MSNA and NE were significantly related to clinic (r = 0.92, P < 0.0001 and r = 0.81, P < 0.0001, respectively) and 24-h (r = 0.91, P < 0.0001 and r = 0.79, P < 0.0001, respectively) HR. The behavior of sympathetic markers described in HF was specific for this clinical condition, being not observed in healthy controls., Conclusions: Both clinic and 24-h HR values greater than 70 beats/minute are associated with an increased sympathetic activation, which parallels for magnitude the HR elevations. These findings support the relevance of using in the therapeutic approach to HF drugs exerting sympathomoderating properties., (© 2022. The Author(s).)

Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest β for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, P < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cutoff displays highest OR as compared to the URRAH one. In conclusions, newly reported URRAH cutoff for hyperuricemia better relate to atherogenic lipoprotein (LDL and non-HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut-off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

We evaluated the relationships between Berlin questionnaire (BQ) scores, hypertension and other metabolic variables in 598 subjects (age: 65.8 ± 10 years, mean ± SD) enrolled in the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study representative of the general population, treated or untreated with antihypertensive drugs. Two hundred and eleven subjects (35%) had a positive BQ with two or more positive categories of the inquiry. Compared to those without sleep disorders these subjects showed a greater male prevalence (55.9%), worse serum cholesterol, triglycerides and glucose profile, greater body mass index (BMI) (28.9 ± 4.9 vs. 24.9 ± 3.4 kg/m 2 ), higher office (and to a lesser extent 24-h) BP and HR values, higher serum creatinine values and greater rate of echocardiographic left ventricular (LV) hypertrophy (25% vs. 13%). These differences were not detected when the data analysis was restricted to treated hypertensive patients. Thus, BQ scores allow to identify among subjects belonging to a general population those with elevated BP, organ damage and altered metabolic. When antihypertensive drug treatment is present, however, the approach fails to detect differences between groups with low or high BQ index., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background and Aim: The present study was aimed at determining whether and to what extent a specific heart rate (HR) cutoff value allows to identify in obeses a more pronounced level of adrenergic overdrive., Methods and Results: In 86 obese subjects aged 44.7 ± 0.9 (mean ± SEM) years and in 45 heathy lean controls of similar age we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the subjects in 3 different groups according to their resting clinic and 24-h HR values (<70, 70-79 and 80-89 beats/minute). MSNA and plasma NE values detected in the three obese groups were almost superimposable each other, no significant difference between groups being observed. A similar behavior was observed when HR values were assessed during the 24-h Holter monitoring. In the group as a whole no significant relationship was detected between MSNA, plasma NE and clinic HR, this being the case also when 24-h HR replaced clinic HR in the correlation analysis. In contrast lean controls displayed a progressive significant increase in MSNA values form the group with clinic (and 24 Holter) values below 70 beats/minute to the ones with HR values between 70 and 79 and above 80 beats/minute., Conclusions: In the obese state measurement of resting HR may allow to provide some general information on the functional status of the adrenergic cardiovascular drive. When the information required, however, are more subtle the sensitivity of the approach appears to be reduced and HR cannot be regarded as a faithful sympathetic biomarker., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Previous studies have shown that white-coat and masked uncontrolled hypertension (WUCH and MUCH, respectively) are clinical conditions with very poor reproducibility over time. This is also the case for the different nighttime blood pressure (BP) patterns (dipping, nondipping, reverse dipping or extreme dipping). Whether and to what extent the phenomenon might depend on the type of antihypertensive treatment is unknown. In the present study, we addressed this issue by analyzing the data collected in the Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS), in which office and ambulatory BP were measured three times during an almost 3-year treatment period. The results showed that a limited number of WUCH or MUCH patients at an initial office measurement and 24-h systolic (S) BP measurement maintained the same status at a second set of measurements one or more years later. This was also the case for all dipping patterns, and only a minimal number of patients exhibited the same phenotype throughout all on-treatment SBP measurements. The results were similar for treatment with a thiazide diuretic or an ACE inhibitor and are in line with those of the European Lacidipine Study on Atherosclerosis (ELSA) trial, i.e., the only other available trial with multiple on-treatment office and ambulatory BP measurements, in which patients were treated with a calcium channel blocker or a beta-blocker. All the BP patterns identified in hypertensive patients treated by joint office and ambulatory BP measurements display poor reproducibility, and this is unrelated to the type of antihypertensive treatment used., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aim: Little evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection might be indirectly inferred, however, from the blood pressure (BP) effects of treatment as in trials BP reduction is linearly related to outcome reduction. We analyzed the effect of antihypertensive treatment on office and ambulatory BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS)., Methods: : Office and ambulatory blood pressure were measured in 470 hypertensive patients randomized to fosinopril or hydrochlorothiazide alone or combined with a statin before treatment and at 6 month or yearly intervals during 2.6 years of follow-up. Patients were divided into two groups according to whether before randomization to treatment office and 24-h mean BP were elevated (sustained hypertension) or office BP was elevated but 24-h BP values were normal (WCH)., Results: : In both sustained hypertension and WCH antihypertensive treatment was associated with an early marked office BP reduction, which persisted virtually unchanged throughout the treatment period. In contrast, 24-h (and day and night) BP showed a marked and persistent treatment-related fall in sustained hypertension but no change in WCH. The results were similar when data were separately analyzed in patients under fosinopril or diuretic, with or without statin treatment., Conclusion: : In WCH, antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline. This appears to be unrelated to the type of treatment employed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: According to some guidelines, white-coat hypertension (WCH) carries little or no increase of cardiovascular risk in the absence of organ damage (OD), but no data are available on this issue., Methods: Using the population data from PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni), we evaluated cardiovascular and total mortality over a median follow-up of 29 years in WCH (elevated office and normal 24-hour or home blood pressure [BP]) and normotensive controls (normal in- and out-of-office blood pressure) with no echocardiographic left ventricular hypertrophy and no reduction of estimated glomerular filtration rate. Patients with sustained hypertension (SH, in- and out-of-office blood pressure elevation) and normotensive, WCH, and SH with cardiac and renal OD served as controls., Results: In the 1423 subjects analyzed, there were 165 cardiovascular and 526 all-cause deaths. After adjustment for confounders, no-OD WCH exhibited a risk of fatal cardiovascular events lower than that of no-OD SH but greater than that of no-ODN (hazard ratio, 2.0 [95% CI, 1.1-3.6], P =0.02), this being the case also for all-cause mortality. Compared with no-OD normotensive, no-OD WCH also exhibited a greater 10-year adjusted risk to develop new SH or OD. Similar findings were obtained in normotensive, WCH, and SH with OD., Conclusions: The present study provides the first evidence that WCH with no OD is accompanied by a noticeable increase in long-term risk of mortality, new hypertension, and new OD, thereby differing from normotension.

Aim: We sought to assess the long-term changes in aortic root diameter in a population-based sample, focusing on new-onset aortic root dilatation, as well as on the demographic and clinical variables independently related to this dynamic process., Methods: A total of 1122 participants with measurable echocardiographic parameters at baseline and after a 10-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute aortic root diameter, aortic root diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants., Results: Over the 10-year follow-up, new aortic root dilatation occurred in 3.4% (aortic root /BSA), 4.4% (aortic root /height) and 7.3% (absolute aortic root), respectively. No substantial relationship was observed between baseline office and ambulatory blood pressure (BP) or their changes over time and incident aortic root /BSA and aortic root /height dilatation. Baseline aortic root diameter and left ventricular mass index (LVMI) emerged as important predictors of aortic root dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between nonhemodynamic variables and new-onset aortic root dilatation was variable, depending on the definition of the aortic phenotype., Conclusion: The incidence of aortic root dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of aortic root dilatation in the community., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Haemophilia management and patients' quality of life significantly improved. However, data on current patients', caregivers' and clinicians' satisfaction and limitations of treatments and haemophilia management are limited., Aim: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians., Methods: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020., Results: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department., Conclusions: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options., (© 2022 John Wiley & Sons Ltd.)