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Background Left atrial (LA) enlargement (LAE) is associated to an increased risk of cardiovascular complications, and in particular of atrial fibrillation. The 2018 ESH/ESC Hypertension guidelines suggested the use of LA volume instead of linear dimensions, and for the first time proposed the indexation to height2 (h2) The aim of our study was to assess the prevalence of left atrial dilatation in a large sample of patients undergoing an echocardiogram for cardiovascular risk stratification at an ESH excellence centre in Italy. Design and methods 3872 subjects undergoing a diagnostic work-up for arterial hypertension (known or suspect) were analysed. The mean age was 56±15 years, BMI 26±5 kg/m, 44% normal weight, 39% overweight, 17% obese, 53% males. Left atrial volume was measured by the area-length method using the apical 4-chamber and 2-chamber views. Results The prevalence of left ventricular hypertrophy (LVH) was 11% when indexing for BSA and 12% when indexing for height2.7. LAE was observed in 30% of subjects when indexing for h2 and in 9% when indexing for BSA. In obese or overweight subjects the prevalence of LAE was 38% of subjects when indexing for h2 and in 11% when indexing for BSA. The different prevalence of LAE was particularly evident in extremely obese patients. LAE was very common in patients with LVH: 62% and 26% when indexing for h2 and for BSA, respectively. Interestingly, it was frequent also in patients without LVH, in particular when the indexation for h2 was used (25% as compared to 7% when indexing for BSA). Conclusions In a large sample of subjects undergoing a diagnostic work-up for arterial hypertension LAE was frequently observed, particularly when the new indexation proposed by the 2018 ESH/ESC hypertension guidelines was used. Even in the absence of clear-cut LVH, LAE was observed in one quarter of subjects. The indexation to BSA leads to an under-recognition of LAE, in particular in patients with overweight and/or obesity

Objective:Left atrial (LA) enlargement (LAE) is associated to an increased risk of cardiovascular complications, and in particular of atrial fibrillation. The 2018 ESH/ESC Hypertension guidelines suggested the use of LA volume instead of linear dimensions, and for the first time proposed the indexat

Objectives This study sought to derive age-, sex-, and ethnic-appropriate adult reference values for left atrial (LA) and left ventricular (LV) dimensions and volumes, LV mass, fractional shortening, and ejection fraction (EF) derived from geographically diverse population studies. Background The current recommended reference values for measurements from echocardiography may not be suitable to the diverse world population to which they are now applied. Methods Population-based datasets of echocardiographic measurements from 22,404 adults without clinical cardiovascular or renal disease, hypertension, or diabetes were combined in an individual person data meta-analysis. Quantile regression was used to derive reference values at the 95th percentile (upper reference value [URV]) and fifth percentile (lower reference value [LRV]) of each measurement against age (treated as linear), separately within sex and ethnic groups. Results The URVs for left ventricular end-diastolic volume (LVEDV), LV end-systolic volume, and LV stroke volume (SV) were highest in Europeans and lowest in South Asians. Important sex and ethnic differences remained after indexation by body surface area or height for these measurements, as well as for the LRV for SV. LVEDV and SV decreased with increasing age for all groups. Importantly, the LRV for EF differed by ethnicity; there was a clear apparent difference between Europeans and Asians. The URVs for LV end-diastolic diameter and LV end-systolic diameter were higher for Europeans than those for East Asian, South Asian, and African people, particularly among men. Similarly, the URVs for LA diameter and volume were highest for Europeans. Conclusions Sex- and/or ethnic-appropriate echocardiographic reference values are indicated for many measurements of LA and LV size, LV mass, and EF. Reference values for LV volumes and mass also differ across the age range.

Chronic kidney disease (CKD) is well established risk factor for atrial fibrillation (AFib). The aim of the study was to analyze association of CKD and AFib in the consecutive sample of patients with AFib who were admitted to the UHC Zagreb Cardiology Clinic, part of the ESH Excellence centre of hypertension. This cohort is part of the ESH –FA project.

Objective:It has been suggested that measurement of “unattended” or “automated oscillatory(AOBP)” blood pressure values may provide advantages over conventional BP measurement and some hypertension guidelines now suggest this approach as the preferred one for measuring office BP. Data on the strengt

This article discusses the results of clinical and experimental studies that examine the association of hyperuricemia and gout with cardiovascular (CV) disease.Key papers for inclusion were identified by a PubMed search, and articles were selected for their relevance to the topic, according to the authors' judgment.Significant progress has been made in confirming an association, possibly causal, between hyperuricemia and CV outcomes. Xantine-oxidase (XO) inhibitors appear to be the most promising agents for prevention and treatment of CV consequences associated with hyperuricemia. Several small and medium sized studies have examined the effect of these agents on CV function in a variety of patient populations. Improvements in measures of endothelial function, oxidative stress, cardiac function, hemodynamics, and certain inflammatory indices have been demonstrated. Compounds for XO inhibition with more specific clinical effects and fewer side effects than allopurinol may be promising options to further explore the therapeutic potential in patients with CV disease. It is too early to make clinical recommendations with regard to the benefits of using XO inhibitor allopurinol or the novel febuxostat in patients with asymptomatic increased UA levels and high CV risk because only a small number of studies have shown that they may be beneficial in terms of CV outcomes. More studies are therefore needed to determine the potential of these drugs for reducing the risk of developing CV disease.

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18-24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (-0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines.

Better BP control and anticoagulation with more frequent use of NOACs is needed. Physicians must be aware of high prevalence of CKD in AFib patients and consequent drug dose adjustments.

Aims To briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. Data synthesis The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries' smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, while in some secondary forms of hypertension, hypertrophic remodeling may be detected. Moreover, in non-insulin-dependent diabetes mellitus hypertrophic remodeling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effects on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations to the small resistance arteries with drugs blocking the renin-angiotensin system (ACE inhibitors, angiotensin II receptor blockers) was demonstrated. Conclusion Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing and/or regressing alterations in the microvascular structure.

Background: In patients with Systemic lupus erythematosus (SLE) a greater prevalence of structural and functional cardiovascular (CV) alterations has been described, possibly explaining the higher incidence of CV events, as compared to subjects matched for age and sex. Aim of this study was to analyze the presence of target organ damage in premenopausal women with SLE and in controls matched not only for demographic characteristics but also for other cardiovascular risk factors. Subjects and methods: 4 patients with SLE clinically stable(SLEDAI Score 2.5±1.5)(age 32±7years, range 19-44)and 34 controls matched for sex, age, BMI, clinic blood pressure(BP) and antihypertensive treatment(if present), underwent:24 hours BP monitoring, echocardiography with tissue Doppler analysis(TDI) for the evaluation of left ventricular(LV)structure and of systolic and diastolic function, carotid ultrasound for intima-media thickness(IMT), carotid distensibility measurement, and pulse wave velocity measurement(PWV). Results: By definition no difference was observed for age, sex, BMI and clinic BP values and a similar Framingham risk score was observed between SLE and controls(1.3±2.7 vs 1.5±2.3%, p=ns). No significant differences were observed for all echocardiographic parameters except LV longitudinal systolic function(Sm), an early index of LV systolic dysfunction(see Table). Carotid IMT and distensibility, as well as PWV and the prevalence of an abnormal aortic stiffness were both similar in the two groups. At the logistic analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients. Conclusions: In patients with SLE and low activity index of the disease we did not observe significant vascular alterations as compare to controls with similar cardiovascular risk. The early LV systolic impairment observed in this group of patients needs confirmation in larger cohorts.

Background: Parathyroid cysts (PC) are a rare entity, representing only 0.5–1% of all parathyroid lesions and

Objective: The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension.

The SILVER (Study of Irbesartan in Left VEntricular hypertrophy Regression) trial is designed to test the hypothesis that the newly developed angiontensin-II receptor antagonist, irbesartan, will produce a greater reduction in left ventricular (LV) mass than felodipine ER, in a population of hypertensive patients defined by seated diastolic blood pressure (SeDBP) in the range 95-115 mmHg or seated systolic blood pressure (SeSBP) in the range 160-200 mm Hg. A population of 360 men and women of non-childbearing potential, >18 years of age, with hypertension, newly diagnosed or after a 3-week washout from previous anti-hypertensive or vasodilator therapies, will be randomised at approximately 80-90 European sites. Add-on therapy with hydrochlorothiazide and atenolol will be allowed for blood pressure control. Patients will be studied by two-dimensional and M-mode echocardiography at baseline (central validation of LV hypertrophy), on randomisation day, and after 6 and 12 months randomised therapy. Blinded analysis of echocardiograms will be performed at a central laboratory, which will provide measurements of the LV mass index (LVMI), determined by M-mode readings according to Devereux formula and using the Penn convention. The primary end-point of the study will be the change in LVMI from baseline to 12 months. The study power is 90% to detect differences between groups from baseline of approximately 8 g/m2.

The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes.A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi)60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P0.0001). These associations were stronger in patients without diabetes and with normal renal function.Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.

Background. The anticontractile effect of perivascular adipose tissue(PVAT) is lost in obese patients due to adipocyte hypertrophy, leading to hypoxia, inflammation, and oxidative stress(Circulation 2009; 119(12):1661–1670).We recently demonstrated that the property of PVAT, partially maintained in an animal model of genetic obesity, seems to be related to the activity of BKCA channels, since is selectively blocked by iberiotoxin. We aimed to investigate functional responses of small mesenteric arteries in an animal model of genetic obesity after chronic treatment with melatonin, an endogenous hormone with antioxidant and vasculoprotective properties. Methods. Obese mice (n = 9) (B6.V-Lep ob/OlaHsd, Harlan Laboratories S.r.l.) (ob/ob) and control lean mice (n = 8) (CLM) were treated with melatonin (MEL)100 mg/kg per day for 8 weeks (from the5th to the 13th week of age).Data were compared from untreated ob/ob (n = 15) and CLM (n = 10) animals. Mesenteric small resistance arteries were dissected and mounted on a wire myograph. Concentration-response to norepinephrine was evaluated in vessels with intact PVAT (WF) and in vessels in which PVAT was removed (NoF) under normoxic and hypoxic (30’95% N2/5%CO2) conditions. Norepinephrine concentration-response curve was repeated with iberiotoxin(30’preincubation 100 nm/L). Results. MEL significantly reduced the contractile response in NoF ob/ob and CLM vessels (ANOVA P = 0.014 and P = 0.049 respectively).The improvement after MEL was also seen in CLM NoF vessels during hypoxia(ANOVA p < 0.05) and following preincubation with iberiotoxin(P < 0.05), with no significant improvements in ob/ob. Increases in contractility following hypoxia and iberiotoxin treatment were restored byMEL in Ob/Ob WF vessels (P = 0.013 and P = 0.036 respectively),whereas MEL only rescued the effects of hypoxia(P = 0.045) in CLM WF arteries. In conclusion, MEL exerts a protective effect in small vessels with and without PVAT from both ob/ob and CLM, counteracting the adverse effect of hypoxia and iberiotoxin in vessels with PVAT and in CLM vessels whitout PVAT. However, in Ob/Ob animals MEL rescues the effects only in the presence of PVAT indicating the importance of PVAT oxidative stress in vascular dysfunction observed in Ob/Ob animals.

The primary aim of antihypertensive therapy is to reduce blood pressure. Whatever their mechanisms of action, almost all the antihypertensive drugs currently available can be considered to achieve this goal. However, the most common complications of hypertension (myocardial infarction, thrombolytic stroke and sudden cardiac death) are related to structural cardiovascular changes rather than being directly related to blood pressure elevation. Thus, it would appear logical that an optimum antihypertensive drug should also prevent and reverse the cardiovascular abnormalities associated with hypertension before irreversible damage occurs. The different classes of antihypertensive drug are in fact largely successful in preventing or reversing these target abnormalities, in particular cardiac and vascular abnormalities. In hypertensive patients, angiotensin-converting enzyme (ACE) inhibitors appear to be particularly effective in achieving this goal, probably because they alter vascular wall and cardiac structure, irrespective to some extent of the haemodynamic changes they produce. ACE inhibitors may have particularly beneficial effects on left ventricular mass because of their favourable interference with growth factors; an increased production of bradykinin, and hence of nitric oxide, may add further benefit. ACE inhibitors also prevent and/or reduce reactive perivascular and interstitial growth, as well as fetalisation of cardiac myocytes. Furthermore, in common with calcium channel antagonists and nitrates, ACE inhibitors improve arterial compliance, and thus decrease cardiac load. Indirect evidence suggests that a reduction in left ventricular hypertrophy during antihypertensive therapy reverses the pathological consequences of an increased left ventricular mass, although further studies are needed to assess the true clinical impact of these treatment-induced changes in the morbidity and mortality of hypertensive patients.

Objective: It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th17 lymphocytes may contribute to the progression of hypertension and microvascular damage while TREG lymphocytes seem to be protective. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed. Methods: We have investigated 32 severely obese patients undergoing bariatric surgery, 24 normotensive lean subjects and 11 hypertensive lean subjects undergoing an election surgical intervention. No sign of local or systemic inflammation was present in any subject or patient. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry after 5 hour in vitro activation in order to assess T-effector and T-regulatory (TREG) lymphocytes. Subsets of TREGS were defined as follows: −TREGS recent thymic emigrants (RTE), directly derived from thymus: CD31+; −TREGS naïve: CCR7+CD45RA+; −TREGS central memory (CM): CCR7+CD45RA−; −TREGS effector memory (EM): CCR7−CD45RA−; −TREGS terminal differentiated effector memory (TDEM): CCR7−CD45RA+. Results: The results are summarized in the Table (*p < 0.05, **p < 0.01, ***p < 0.001 vs. lean normotensives; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. lean hypertensives). A marked reduction of several TREG subpopulations was observed in obese patients compared with controls, together with an increased in some T-effector cells. Lean normotensives Lean hypertensives Obese patients TREGs (%) 4.11 ± 1.60 4.64 ± 1.66 2.69 ± 1.81**## TREGs (abs number) 45.4 ± 24.3 45.4 ± 23.8 27.3 ± 21.1**# TREGs naíve (%) 22.1 ± 10.1 18.1 ± 13.1 13.34 ± 12.9** TREGs naíve (abs number) 10.6 ± 7.75 9.71 ± 8.87 3.87 ± 5.28***## TREG CM (%) 32.3 ± 13.8 32.8 ± 17.8 22.7 ± 15.2*# TREGs CM (abs number) 14.7 ± 10.2 14.2 ± 9.08 6.10 ± 8.08***## CD4+ EM (%) 24.4 ± 9.96 26.8 ± 12.5 34.1 ± 13.3** CD161+CD28+ (%) 86.2 ± 28.5 94.9 ± 5.63 97.2 ± 5.39* Conclusion: TREG lymphocytes are clearly reduced in severely obese patients, possibly contributing to the development of marked microvascular alterations previously observed in such a population.

Resume Preserver la perfusion tissulaire des organes essentiels devrait etre, en definitive, le veritable but de tout antihypertenseur. Des decouvertes majeures permettent aujourd’hui de mieux comprendre pourquoi tous les organes essentiels souffrent tres precocement, lors de l’hypertension, d’une ischemie tissulaire et pourquoi, face a ces alterations, les traitements antihypertenseurs obtiennent des benefices si inegaux. La maladie hypertensive entraine chez tous les hypertendus, des alterations vasculaires avec, au niveau de la microcirculation, une rarefaction arteriolocapillaire. Ces decouvertes ont des consequences capitales puisqu’il est etabli que la microcirculation regule non seulement la majorite des resistances peripheriques, mais surtout conditionne la qualite de perfusion de tous les organes essentiels. Il est essentiel d’evaluer les differentes strategies antihypertensives non seulement sur un plan tensionnel mais aussi sur leur impact vasculaire et leur capacite a preserver le reseau microvasculaire des atteintes liees a l’hypertension.

Only 20-30% out of the treated hypertensive patients in Europe are achieving blood pressure (BP) control. Among other recognized factors, these poor results could be attributable to the fact that for many doctors it is very difficult to detect which is the predominant hemodynamic cause of the hypertension (hypervolemia, hyperinotropy or vasoconstriction). The aim of the study was to use non-invasive thoracic electrical bioimpedance (TEB) to evaluate hemodynamic modulators and subsequent hemodynamic status in uncontrolled hypertensive patients, receiving at least two antihypertensive drugs. A number of 134 uncontrolled hypertensive patients with essential hypertension were evaluated in nine European Hypertension Excellence centers by means of TEB (the HOTMAN(®) System). Baseline office systolic and diastolic BP averaged 156/92 mmHg. Hemodynamic measurements show that almost all patients (98.5%) presented at least one altered hemodynamic modulator: intravascular hypervolemia (96.4%) and/or hypoinotropy (42.5%) and/or vasoconstriction (49.3%). Eleven combinations of hemodynamic modulators were present in the study population, the most common being concomitant hypervolemia, hypoinotropy and vasoconstriction in 51(38%) patients. Six different hemodynamic states (pairs of mean arterial pressure and stroke index) were found. Data suggest that there is a strong relation between hypertension and abnormal hemodynamic modulators. This method might be helpful for treatment individualization of hypertensive patients.

Objective Background:Epistaxis and hypertension are frequent diseases in the adult population. A relationship between the increase of the blood pressure (BP) and the prevalence and incidence of epistaxis has been suggested (Kikidis et al, 2013).Design and method:Aim of our study was to analyze blood

Objective: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves’ hyperthyroidism (GD), in whom an increased oxidative stress was observed. Design and methods: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, tumor necrosis facotr-α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzyme-linked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. Results: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p

Surgery is the treatment of choice for symptomatic primary hyperparathyroidism; unlikely few patients do not meet established surgical criteria or have comorbid conditions that prohibit surgery. In these subjects, medical therapy alone offers little hope for a sustained long normocalcemic period. However percutaneous ethanol injection (PEI) may represent an alternative therapeutic procedure. It is currently in use for the treatment of secondary or tertiary hyperparathyroidism, however, few studies or case reports suggest it for the treatment of primary hyperparathyroidism. Moreover, little information is available about the long-term follow-up, where incomplete necrosis or the spreading of ethanol in the surrounding tissues is often reported. We believe that many of the side effects could be correlated to procedure itself. Taking these experiences into account, we have reasoned that in order to limit these side effects, we had to modify the standard PEI procedure. We reported this preliminary experience describing our modified PEI procedure.

Background Papillary thyroid carcinoma (PTC) represents 70%–75% of well-differentiated thyroid cancers. Although most reports have shown that papillary thyroid microcarcinomas (PMC) follow an indolent course, a few series have demonstrated that a significant number of them are associated with extrathyroidal extension and nodal or distant metastases. Methods Four hundred eighty-four patients with papillary thyroid cancer (102, PMC; 382, PTC) were enrolled in this study. The median follow-up was 102 months. Results No difference between PTC and PMC patients was observed for age, gender, multifocality, extrathyroidal extension, and lymph nodes metastasis. The prevalence of nodal involvement developing during the follow-up period was significantly higher in PMC than PTC (58.8% vs. 38.5%, P = 0.002). An unfavorable clinical course occurred in 96 subjects (21.8%). Logistic analysis showed that the strongest association with the worst prognosis was found for age and TNM stage III (P