Search

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70–95%]) than MRA (20% [10–30%]), SGLT2i (30% [20–50%]) or (GLP1-RA (10% [5–15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15–40%) vs 18% [10%–25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5–5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers’ dosage reduction was the usual management.

AbstractBackground Healthcare providers are faced with an increasing number of patients with obesity and arterial hypertension. Preventing obesity-associated hypertension and appropriately managing patients with established disease are both important. Hence, the aim of our study was to evaluate the clinical care of patients with obesity and hypertension among ESH Excellence Centres (ECs).Methods We conducted a cross-sectional, international 30-item survey through e-mails.Results In total, 70 representatives of ECs participated (78% men) with 66% of them practicing medicine for more than 30 years and working in well-equipped clinics. Most were internists (41%) and cardiologists (37%) and 73% reported training on the management of obese patients with hypertension. A majority weigh their patients (77%) and evaluate patients for sleep disorders (93%). However, only 47% spend more than 5min to advise for lifestyle modification in general, 59% for weight loss, 56% for salt intake and 64% for exercise. Finally, a minority of participants ask patients if they like their body (6%) or about previous attempts to lose weight (28%), evaluate 24h urinary sodium excretion rate (22%) and provide written (15%) or personalized (10%) dietary advices. If the patient suffers also from type 2 diabetes mellitus, 66% switch treatment to GLP1 receptor agonists and 60% to SGLT2 inhibitors.Conclusion Most clinicians in ESH ECs are well educated regarding obesity-associated hypertension, and clinics are sufficiently equipped to manage these patients, as well. However, several deficits were reported regarding efforts to address and implement obesity specific aspects and interventions to improve care in patients with obesity and hypertension.

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

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

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

Abstract 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 2nd evaluation performed 10 years later. Δ (delta) LVM, Δ LVMI, and Δ EKG parameters values were calculated from 2nd 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 2nd evaluation was threefold increased compared to baseline (29.3% and 33.7% for LVM indexed to BSA and height2.7, 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.

Purpose To describe the history of the Excellence Centre (EC) programme of the European Society of Hypertension (ESH) since the beginning in 2006, its achievements, and its future developments. Materials and Methods We list the number of ECs per country, the research projects performed so far, and the organisational steps needed to reshape the EC programme for the future. Results In August 2023, the ESH EC programme includes 118 registered ECs in 21 European and 7 non-European countries. Updates about the formal steps for application, re-application, transfer of EC and retirement of EC heads are given. Conclusions The EC programme of the ESH has been a success from the beginning. Further refinements will make it fit for the next decades.

The 2023 hypertension guidelines of the European Society of Hypertension (ESH) have been published in the December issue of the official Journal of the Society (Journal of Hypertension),1 where they are freely available online. Compared to the guidelines published 5 years ago,2 the new guidelines address issues never or only marginally addressed before, including a large number of comorbidities to hypertension that may change the approach to antihypertensive management. [...]

Abstract Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio‐Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest β for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non‐HDL, P

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

Abstract 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/m2), 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.

Abstract We examined in 11 young subjects (age 29.7±3.6 years, mean±SEM) whether carotid baroreceptor stimulation via the neck chamber device may affect central venous pressure (CVP), thus potentially involving other reflexogenic areas in the examined responses. Application of progressively greater neck chamber subatmospheric pressures caused a progressive lengthening in RR interval, which reached a peak at the maximal value of negative neck chamber pressure applied. This was accompanied by significant and progressively greater reduction in CVP values when the data were calculated considering the early changes occurring within the first 2 seconds of the stimulus. There was a weak correlation between the early changes in CVP and the RR interval responses when all stimuli were pooled together (r = 0.32, P

Purpose The aim of this study was to examine myocardial performance using pressure-strain loops in hypertensive patients with different level of blood pressure control. Material and methods This cross-sectional study included 204 subjects (45 controls, 70 patients with well-controlled hypertension, 58 patients with uncontrolled hypertension and 31 patients with resistant hypertension) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine global myocardial work, constructive work, wasted work and work efficiency in all study participants. Results Left ventricular (LV) longitudinal strain gradually reduced from controls throughout well-controlled hypertensive patients, to patients with uncontrolled and resistant hypertension. Global myocardial work was higher in patients with uncontrolled and resistant hypertension than in controls and well-controlled hypertension. Constructive work was also higher in all hypertensive patients than in controls. Global wasted work and work efficiency were similar between different groups. Global myocardial work index was associated with peak oxygen consumption independently of sex, age, body mass index (BMI), LV structural and functional parameters in all hypertensive participants. Conclusions Myocardial work was significantly deteriorated in patients with uncontrolled and resistant arterial hypertension compared to controls and well-controlled hypertensive patients. Global myocardial work was associated with functional capacity independent of clinical and echocardiographic parameters.

To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19–97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in ∼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (

Vascular and sympathetic abnormalities characterize chronic heart failure (CHF). Alterations include (1) a reduction in arterial distensibility, (2) endothelial dysfunction, (3) a decrease in arterial compliance and a parallel increase in arterial stiffness, and (4) sympathetic cardiovascular activation. Altogether, these alterations represent important targets in therapeutic interventions, because they display an independent negative impact on the disease prognosis, favouring disease progression and the development of cardiovascular complications with direct and indirect mechanisms. The present review will examine the effects of the different therapeutic interventions targeting the vascular/sympathetic alterations detected in CHF. Non-pharmacological, pharmacological and device-based treatments will be discussed in detail, highlighting the possible mechanisms responsible for the vascular/sympathetic effects of each intervention. Finally, the unmet goals in treatment in relation to endothelial and adrenergic targets will be also discussed.

Aim: Whether exaggerated blood pressure response (EBPR) to exercise represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. We investigated this issue through a review and a meta-analysis of studies providing data on this association in normotensive individuals undergone both to dynamic or static exercise and to 24 h blood pressure monitoring (ABPM). Design: A systematic search was performed using Pub-Med, OVID, EMBASE, and Cochrane library databases from inception up to 31 December 2022. Studies were identified by using the following search terms: “masked hypertension”, “out-of-office hypertension”, “exercise blood pressure”, “exaggerated blood pressure exercise”, “exercise hypertension”. Results: Nine studies including a total of 387 participants with MH and 406 true normotensive controls were considered. Systolic BP (SBP) and diastolic BP (DBP) at rest were significantly higher in MH individuals than in sustained normotensives: 126.4 ± 1.4/78.5 ± 1.8 versus 124.0 ± 1.4/76.3 ± 1.3 mmHg (SMD: 0.21 ± 0.08, CI: 0.06–0.37, p = 0.007 for SBP; 0.24 ± 0.07, CI: 0.08–0.39, p = 0.002 for DBP). The same was true for BP values at peak exercise: 190.0 ± 9.5/96.8 ± 3.7 versus 173.3 ± 11.0/88.5 ± 1.8 mmHg (SMD 1.02 ± 0.32, CI: 0.39–1.65, p = 0.002 for SBP and 0.97 ± 0.25, CI: 0.47–1.96, p < 0.0001 for DBP). The likelihood of having an EBPR was significantly greater in MH than in their normotensive counterparts (OR: 3.33, CI: 1.83–6.03, p < 0.0001). Conclusions: Our meta-analysis suggests that EBPR reflects an increased risk of MH and that BP measurement during physical exercise aimed to assess cardiovascular health may unmask the presence of MH. This underscores the importance of BP measured in the medical setting at rest and in dynamic conditions in order to identify individuals at high cardiovascular risk due to unrecognized hypertension.

The hypertensive response to exercise testing, defined as exaggerated blood pressure response (EBPR), has been documented to be independently associated with unhealthy conditions, carrying an increased risk of future hypertension, cardiovascular (CV) morbidity and mortality. In treated hypertensives, EBPR is a marker of uncontrolled hypertension, a condition previously undetected by office blood pressure (BP) measurements at rest; EBPR may also detect masked hypertension, a phenotype characterized by normal BP values in the medical environment but elevated home or ambulatory BP monitoring (ABPM). The aim of the present review is to provide a comprehensive and up-dated information on the clinical importance of EBPR targeting the following issues: (I) definition and prevalence; (II) underlying mechanisms; (III) clinical correlates and association with subclinical organ damage; (IV) predictive value; (V) clinical decision making.

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

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

Background: Childhood obesity, including overweight, continues increasing worldwide affecting health expectancy, quality of life and healthcare expenditure. These subjects have higher probability of suffering or developing cardio metabolic risk factors. Recent studies have revealed cardiorespiratory fitness (CRF) as a valuable clinical parameter to identify these subjects and have even suggested cut-off values. However, evaluating CRF in overweight and obese youth can be difficult to implement, unfriendly and expensive. Objective: Develop a screening tool to identify high-risk subjects in a representative population of those attending overweight/obesity assessment programmes without prior intervention. It will be based on heart rate variability parameters, which has strong association with CRF and cardio metabolic risk factors. Methods: Sixty-three subjects, overweight and obese, between 9 and 17 years of age, and of both sexes were enrolled. None of them had secondary obesity syndromes and/or suffered from acute or chronic disease. Anthropometric parameters, electrocardiogram signal recording under resting conditions and cardiorespiratory fitness – evaluated by oxygen consumption and time elapsed of cardiopulmonary exercise test – were measured. Results: Significant differences in the sympathetic nervous system activity – assessed by heart rate variability analysis – are observed when grouping by overweight and obesity degree as well as by CRF (poor/normal). Body mass index, puberty and sympathetic nervous system activity are the significant variables of a logistic regression model develop to identify poor CRF individuals. Its accuracy reaches 92%. Conclusions: A screening tool based on heart rate variability and anthropometric parameters was developed to identify subjects with higher probability of suffering or developing cardio metabolic risk factors.

The endothelium is composed of a monolayer of endothelial cells (ECs) covering the inner side of arterial, venous and lymphatic vessels [...]

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

Objective: Altered coagulation parameters in COVID-19 patients is associated with a poor prognosis. We tested whether COVID-19 patients on chronic oral anticoagulants (cOACs) for thromboembolism prophylaxis could receive protection from developing more severe phenotypes of the disease.Approach and Results: We searched the database of the SARS-RAS study (Clinicaltrials.gov: NCT04331574), a cross-sectional observational multicenter nationwide survey in Italy designed by the Italian Society of Hypertension. The database counts 2,377 charts of Italian COVID-19 patients in 26 hospitals. We calculated the Charlson comorbidity index (CCI), which is associated with death in COVID-19 patients. In our population (n = 2,377, age 68.2 ± 0.4 years, CCI: 3.04 ± 0.04), we confirm that CCI is associated with increased mortality [OR: 1.756 (1.628-1.894)], admission to intensive care units [ICU; OR: 1.074 (1.017-1.134)], and combined hard events [CHE; OR: 1.277 (1.215-1.342)]. One hundred twenty-five patients were on cOACs (age: 79.3 ± 0.9 years, CCI: 4.35 ± 0.13); despite the higher CCI, cOACs patients presented with a lower risk of admissions to the ICU [OR 0.469 (0.250-0.880)] but not of death [OR: 1.306 (0.78-2.188)] or CHE [OR: 0.843 (0.541-1.312)]. In multivariable logistic regression, cOACs confirmed their protective effect on ICU admission and CHE. The CCI remains the most important risk factor for ICU admission, death, and CHE.Conclusions: Our data support a mechanism for the continuation of cOAC therapy after hospital admission for those patients who are on chronic treatment. Our preliminary results suggest the prophylactic use of direct cOACs in patients with elevated CCI score at the time of the COVID-19 pandemic even in absence of other risks of thromboembolism.

Abstract Background Cytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported. Case presentation We report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient’s clinical history. Conclusion Different risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.

Abstract Background Vitamin B12 deficiency-induced thrombotic microangiopathy, known as pseudothrombotic microangiopathy, is a rare condition which resembles the clinical features of thrombotic thrombocytopenic purpura but requires a markedly different treatment. Most cases of vitamin B12 deficiency have only mild hematological findings, but in approximately 10% of patients life-threatening conditions have been reported. Case presentation We report a case of a 46-year-old Moroccan man presenting with severe hemolytic anemia, thrombocytopenia, and renal failure in absence of macrocytosis, thus mimicking a genuine thrombotic thrombocytopenic purpura. Rapid improvement of renal function observed with only hydration and transfusions of packed red blood cells and the presence of pancytopenia suggested a bone marrow deficiency associated to a hemolytic component of unclear origin. Detection of low levels of vitamin B12 and rapid restitutio ad integrum with its replacement supported the diagnosis of pseudothrombotic thrombocytopenic purpura caused by vitamin B12 deficiency. Conclusions Diagnosis of pseudothrombotic thrombocytopenic purpura caused by vitamin B12 deficiency might be difficult. Awareness of clinicians toward this differential diagnosis might spare patients from unnecessary therapeutic plasma exchange that is burdened by morbidity and mortality.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic responsible for millions of deaths around the world. Hypertension has been identified as one of the most common comorbidities and risk factors for severity and adverse outcome in these patients. Recent investigations have raised the question whether hypertension represents a predictor of outcome in COVID-19 patients independently of other common comorbidities such as diabetes, obesity, other cardiovascular diseases, chronic kidney, liver, and pulmonary diseases. However, the impact of chronic and newly diagnosed hypertension in COVID-19 patients has been insufficiently investigated. The same is true for the relationship between blood pressure levels and outcomes in COVID-19 patients. It seems that the long discussion about the impact of angiotensin-converting enzyme inhibitors (ACEI) and blockers of angiotensin I receptors (ARB) on severity and outcome in COVID-19 is approaching an end because the large number of original studies and meta-analyses discarded the initial findings about higher prevalence of ACEI/ARB use in patients with unfavorable outcomes. Nevertheless, there are many controversies in the relationship between hypertension and COVID-19. The aim of this review article is to provide a clinical overview of the currently available evidence regarding the predictive value of hypertension, the effect of blood pressure levels, the impact of previously known and newly diagnosed hypertension, and the effect of antihypertensive therapy on the severity and outcomes in COVID-19 patients.

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Background and aim: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. Methods: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. Results: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. Conclusions: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.

BackgroundThe global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.Methods and findingsWe designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 pConclusionsOur study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.Trial registrationClinicaltrials.gov: NCT04331574.

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

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

The endothelium is considered the largest organ of the body, composed of a monolayer of endothelial cells (ECs) lining the interior surface of blood and lymphatic vessels [...]

The sympathetic nervous system is known to play a pivotal role in the short- and long-term regulation of different cardiovascular functions. In recent decades, increasing evidence has demonstrated that sympathetic neural influences are involved not only in the vasomotor modulation of small resistance arteries but also in the control of large arteries. Sympathetic activity and vascular function, which are key factors in the pathophysiology and prognosis of cardiovascular disease, are linked by a close relationship. Evidence from experimental studies indicates that the sympathetic nervous system is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, namely nitric oxide, reactive oxygen species and endothelin. Additionally, there is evidence of a reciprocal influence between endothelial function and sympathetic mechanisms. This paper will provide an overview of the relationships between endothelial function and the sympathetic nervous system characterizing physiological states. It will also briefly mention the alterations described in cardiovascular disease, with particular emphasis on essential hypertension and congestive heart failure, i.e., the two pathological states in which endothelial dysfunction and neuroadrenergic activation appear to be relevant factors for determining cardiovascular prognosis.

Studies show that patients with elevated triglycerides and well-controlled LDL levels under statin therapy still have a significant residual risk of cardiovascular (CV) events. Despite many attempts to reduce triglycerides with different hypolipidemic drugs, no therapeutic option has given satisfactory results so far. The initial enthusiasm that omega-3 fatty acids can effectively reduce triglycerides and CV risk was replaced with skepticism when the first large clinical trials failed to show any benefit in primary or secondary prevention. However, the latest studies succeeded in showing a positive effect of omega-3 fatty acids on CV outcome in patients with hypertriglyceridemia. The largest benefit was reported in secondary but not primary prevention. Interestingly, the reduction in triglycerides in some of these studies was disproportionately low to the relatively high CV risk reduction, which could indicate some other effects of omega-3 fatty acids that go well beyond hypotriglyceridemic action. This includes blood pressure reduction, antithrombotic effect, improvement of inflammatory status, endothelial function, and insulin resistance. Investigations also reported a significant and positive influence of omega-3 fatty acids on the composition and stabilization of coronary atherosclerotic plaques in patients with and without previous CV events. In addition to insufficiently known mechanisms of action and conflicting results about the effectiveness of omega-3 fatty acids, the safety problems, which include increased prevalence of atrial fibrillation and hemorrhage, were also reported. The aim of this clinical review was to summarize the current knowledge regarding the use of omega-3 fatty acids in CV patients, particularly those with coronary artery disease, and to present an overview of key clinical trial data.

Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability.

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

Aim: We examined the reduced blood pressure (BP) nocturnal fall in patients with obstructive sleep apnea (OSA) by a meta-analysis including studies that provided data on prevalence rates of non-dipping (ND) pattern during 24-h ambulatory blood pressure monitoring (ABPM). Design: The PubMed, OVID-MEDLINE, and Cochrane CENTRAL literature databases were searched for appropriate articles without temporal restriction up to April 2019 through focused and sensitive search methods. Studies were identified by crossing the search terms as follows: “obstructive sleep apnea”, “sleep quality”, “non dipping”, “reduced nocturnal BP fall”, “circadian BP variation”, “night-time BP”, and “ambulatory blood pressure monitoring”. Results: Meta-analysis included 1562 patients with OSA from different clinical settings and 957 non-OSA controls from 14 studies. ND pattern prevalence in patients with OSA widely varied among studies (36.0−90.0%). This was also the case for non-OSA controls (33.0% to 69.0%). Overall, the ND pattern, assessed as an event rate in the pooled OSA population, was 59.1% (confidence interval (CI): 52.0−65.0%). Meta-analysis of the seven studies comparing the prevalence of ND pattern in participants with OSA and controls showed that OSA entails a significantly increased risk of ND (Odds ratio (OR) = 1.47, CI: 1.07−1.89, p < 0.01). After the exclusion of patients with mild OSA, OR increased to 1.67 (CI: 1.21−2.28, p < 0.001). Conclusions: The present meta-analysis, extending previous information on the relationship between OSA and impaired BP dipping, based on single studies, suggests that this condition increases by approximately 1.5 times the likelihood of ND, which is a pattern associated with a greater cardiovascular risk than normal BP dipping.

Introduction: Cardiovascular risk factors, such as hypertension, hypercholesterolemia, and diabetes mellitus, often cluster together and can also be seen with other pathophysiological conditions that greatly increase an individual’s risk for cardiovascular morbidity and death. Aim of the study: This article emphasizes the importance of assessing and managing the total cardiovascular risk in an individual patient. Materials and methods: Suggestions and recommendations from the most current hypertension management guidelines have been integrated with results from the major clinical trials published in the last decade. Results: Based on a review of the epidemiological data on cardiovascular disease, this paper expands the concept of stratification of hypertensive patients according to the approximate added risk of major cardiovascular events in the next 10 years and stresses the importance of subclinical target-organ damage. Conclusions: Although common in clinical practice, high-risk patients are often undiagnosed. Intensive hypertensive therapy is recommended for high-risk patients, and this treatment strategy will require combination therapy to control or reverse subclinical organ damage and prevent the progression of cardiovascular risk in subjects at low risk or medium risk.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.