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In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin- converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin- angiotensin-aldosterone system (RAAS). It’s dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to- renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result.

The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March–April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May–June 2020 (LL: −8.40%; AD: −12.09%; AH: −10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January–February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies.

Purpose Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. Patients and Methods This study was a non‐interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End‐Results (SEER)‐Medicare database. The association between AH drug utilization on AJCC stage I–III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. Results The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer‐specific mortality (HR: 0.79, 95% CI: 0.75–0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80–0.87), beta‐blockers (HR: 0.87, 95% CI: 0.84–0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80–0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer‐specific mortality (HR: 0.94, 95% CI: 0.90–0.98). Conclusion Further research needs to be performed, but AH medications may present a promising, low‐cost pathway to supporting CRC treatment for stage I–III cancers., The use of antihypertensive agents following colorectal cancer diagnosis is associated with lower mortality (both all‐cause and cancer‐specific) in elderly Medicare patients. Among the studied classes of antihypertensives, ACE inhibitors and beta‐blockers seem to be associated with protective associations.

Purpose: To compare ocular redness score calculated automatically between glaucoma patients and healthy controls, and to assess the associations between this score and both demographical and clinical characteristics. Methods: Glaucoma patients under different topical medications and matched controls were enrolled in this observational cross-sectional study. The Keratograph 5M (Oculus Optikgeräte GmbH) was used to automatically measure 5 redness scores: global; nasal bulbar; temporal bulbar; nasal limbal; temporal limbal. The Student t and ANOVA tests were used to compare continuous variables between groups. A multiple linear regression analysis was performed to evaluate the associations between redness scores and the use of different active principles. Results: One hundred two glaucoma patients and 32 controls were included. Ocular redness scores were significantly higher in glaucoma patients compared to controls (always p Conclusion: Ocular redness was significantly higher in patients with glaucoma compared to control subjects. The number of active principles and the use of PAs, CAIs and AAAs were associated with higher redness scores.

Background: Resistant hypertension is defined when the blood pressure remains elevated above the therapeutic target levels despite the use of three antihypertensive agents including calcium channel blocker (CCB), renin-angiotensin system (RAS) blocker and a diuretic. These drugs should be used at maximally tolerated doses and white coat effect and non-adherence should also be excluded. In this article, by describing a case of resistant hypertension, we discuss a diagnostic and therapeutic approach to resistant hypertension. Case Presentation: A 59 years old man, known case of diabetic nephropathy with a serum creatinine level of 1.2 mg/dL and proteinuria of about 3300 mg in 24 hours referred to Hypertension Clinic of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, for evaluation of resistant hypertension. The patient was under treatment by losar-H, diltiazem, and furosemide, which are not appropriate combinations of antihypertensive agents. The ambulatory blood pressure monitoring (ABPM) of the patient revealed daytime and nighttime hypertension and also the non-dipping status of blood pressure. Dihydropyridine CCB was prescribed in combination with RAS blocker (Exforge 50 mg/ 160 mg) and the diuretic was changed to thiazide-like agents. In the next step, spironolactone and carvedilol were added for better control of blood pressure. The patient referred to the sleep clinic for polysomnography and evaluation of obstructive sleep apnea. Following three months prescription of these medications, ABPM revealed relatively appropriate control of blood pressure, so the average 24-hour blood pressure decreased from 157/91 mm Hg to 136/83 mm Hg. Conclusion: The complications and mortality of hypertension would be increased dramatically in patients with resistant hypertension. So, an appropriate diagnostic and therapeutic approaches should be considered for these patients. Choosing appropriate diuretic agents would be important in the management of resistant hypertension.

Blood pressure control, which can induce a slight decrease in the glomerular filtration rate (GFR), plays a nephron- and cardioprotective role. However, the more important early decline in GFR associated with antihypertensive therapy and strict blood pressure targets is still of concern. Since few data are available from trials and observational studies, and the phenomenon is relatively rare, we performed a meta-analysis of available studies. We conclude that major reductions in the glomerular filtration rate occurring soon after starting angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or under intensive blood pressure control predict end-stage kidney disease.

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.

Objectives: Some patients with deep intracerebral hemorrhage (ICH) have a transient hypertensive response and they may be erroneously classified as secondary to hypertension. We investigated frequency, risk factors, and outcomes for patients with deep ICH without hypertension. Materials and methods: We consecutively recruited patients with spontaneous ICH attending two Spanish stroke centers (January 2015-June 2019). Excluded were patients with lobar/infratentorial ICH and patients who died during hospitalization. We defined deep ICH without hypertension when the bleeding was in a deep structure, no requirement for antihypertensive agents during follow-up and no evident chronic hypertension markers evaluated by transthoracic echocardiography, 24 h ambulatory blood pressure monitoring and/or electrocardiography. We compared clinical, radiological, and 3-month functional outcome data for deep-ICH patients with hypertension versus those without hypertension. Results: Of 759 patients with ICH, 219 (mean age 69.6 ± 15.4 years, 54.8% men) met the inclusion criteria and 36 (16.4%) did not have hypertension. Of these 36 patients, 19 (52.7%) had a transient hypertensive response. Independent predictors of deep ICH without hypertension were age (adjusted OR:0.94;95%CI:0.91–0.96) and dyslipidemia (adjusted OR:0.27;95% CI:0.08–0.85). One third of deep ICH without hypertension were secondary to vascular malformations. Favorable outcomes (modified Rankin Scale 0–2) were more frequent in patients with deep ICH without hypertension compared to those with hypertension (70.9% vs 33.8%; p < 0.001). Conclusion: Of patients with deep ICH, 16.4% were unrelated with hypertension, around half showed hypertensive response, and around a third had vascular malformations. We suggest studying hypertension markers and performing a follow-up brain MRI in those patients with deep ICH without prior hypertension. © 2021 Elsevier Inc.

It is a known fact that diabetes can mostly be prevented or delayed with health-promoting and protective lifestyle changes in people at high risk of diabetes. In addition, awareness of the risk of diabetes in the relatives of individuals with diabetes may also contribute to the prevention of the disease. This study was carried out to determine the relationship between perceived and actual diabetes risk level with promotive and protective health behaviors in relatives of individuals with type 2 diabetes. This cross-sectional study included 596 individuals. Of the participants, 62.7% stated that they perceive their risk of developing diabetes at a high-very high level in the next 10 years. The participants had promotive and protective health behaviors at a moderate level. No significant difference was found between the perceived diabetes risk level and promotive and protective health behaviors. Health professionals should take more responsibility for risk identification and risk management. © 2022 by Author/s and Licensed by Modestum.

It has long been known that blood pressure (BP) is characterized by marked short‐term fluctuations occurring within a 24‐h period and also by long‐term oscillations occurring over more prolonged periods of time. An increased short‐term blood pressure variability (BPV) appears to importantly contribute to target organ damage and to the enhanced cardiovascular risk of hypertensive patients, over and above the effect of an increase in mean BP levels. Reducing 24‐h mean BP is the main aim of antihypertensive therapy, but initial data are available that additional cardiovascular protection can be achieved by reducing BPV. However, to definitively prove the prognostic role of short‐term BPV and the need for its control by treatment, evidence is still needed from intervention trials aimed at demonstrating that by reducing BPV through administration of antihypertensive drugs, a reduction in organ damage and in the rate of cardiovascular events can be obtained.

Summary Background A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. Methods The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov , number NCT01271985 . Findings Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. Interpretation Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. Funding Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Introduction: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy. Aims: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals. Methods: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors (“Abbasso la Pressione!”) in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits. Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication. Hypertension prevalence was defined as systolic BP ≥140 and/or diastolic BP ≥90 mmHg. A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied. Results: Diabetic individuals (N=5695, 12%) had higher rates of hypertension prevalence (80% vs. 54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs. 76.7%, p < 0.001), but lower hypertension control rates (36.1% vs. 39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics. Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001). Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age. Conclusions: Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world. Concomitant unfavorable metabolic features and unhealthy lifestyle habits might contribute to this observation.

Aim This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their management by non-specialists in the field. This document by the Italian Society of Hypertension summarizes the updated evidence linking sleep disorders to hypertension and cardiovascular diseases, the major underlying mechanisms, and the possible management strategies. A simplified, evidence-based diagnostic and therapeutic algorithm for comorbid hypertension and common sleep disorders, namely obstructive sleep apnoea and insomnia, is proposed.

The purpose of this work was to reach the consensus of a multidisciplinary and multistakeholder Italian panel on the value of polypill in cardiovascular disease, with respect to the clinical, technological, economic and organizational dimension. A three-step modified Delphi method was used to establish consensus. Eleven experts in the area of cardiology, pharmaceutical technology, general practice, hospital pharmacy, pharmacology, and health economics participated in the expert panel. To identify existing evidence concerning the value of polypill in the prevention of patients with cardiovascular disease, a systematic literature review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines. In the first round, 22 statements were distributed to the panel. Panel members were asked to mark 'agree' or 'disagree' for each statement and provide any comments. The same voting method was again used for the second round. In the first round nine statements met consensus. In the second round, 10 statements reached consensus. Overall, consensus was reached for 19 statements representing five value polypill domains: clinical, technological, economic and organizational. During a final web meeting with all panel members consensus document open points were discussed. Panel members agreed to recognize polypill as effective in reducing cardiovascular events, blood pressure and lipids, cardiovascular risk and the weight of therapy, in therapeutic adherence improvement, in the absence of differences in bioavailability between drugs administered in fixed or free combinations and the better cost-effectiveness profile compared with standard care. This document represents a knowledge framework to inform decision makers of the value of polypill in cardiovascular prevention.

Aim: Quantitative comparison of the effects of intensive (IPT) or conventional (CPT) periodontal treatment on arterial blood pressure, endothelial function and inflammatory/metabolic biomarkers. Materials and methods: A systematic search was conducted to identify randomized controlled trials (RCT) of IPT (supra and subgingival instrumentation). Eight RCTs were included in the meta-analysis. Difference in change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after IPT or CPT were the primary outcomes. The secondary outcomes included: endothelial function and selected inflammatory/anti-inflammatory (CRP, IL-6, IL-10, IFN-γ) and metabolic biomarkers (HDL, LDL, TGs). Results: The overall effect estimates (pooled Weighted Mean Difference (WMD)) of the primary outcome for SBP and DBP was −4.3 mmHg [95%CI: −9.10–0.48], p = 0.08 and −3.16 mmHg [95%CI: −6.51–0.19], p = 0.06 respectively. These studies were characterized by high heterogeneity. Therefore, random effects model for meta-analysis was performed. Sub-group analyses confirmed statistically significant reduction in SBP [WMD = −11.41 mmHg (95%CI: −13.66, −9.15) P < 0.00001] and DBP [WMD = −8.43 mmHg (95%CI: −10.96,−5.91)P < 0.00001] after IPT vs CPT among prehypertensive/hypertensive patients, while this was not observed in normotensive individuals. The meta-analyses showed significant reductions in CRP and improvement of endothelial function following IPT at all analysed timepoints. Conclusions: IPT leads to improvement of the cardiovascular health in hypertensive and prehypertensive individuals.

Animal models, human observational and genetic studies have shown that immune and inflammatory mechanisms play a key role in hypertension and its complications. We review the effects of immunomodulatory interventions on blood pressure, target organ damage and cardiovascular risk in humans. In experimental and small clinical studies both non-specific immunomodulatory approaches, such as mycophenolate mofetil and methotrexate, and medications targeting T and B lymphocytes, such as tacrolimus, cyclosporine, everolimus, rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin (isoLG) scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (secukinumab, tocilizumab, canakinumab, TNF-α inhibitors). In many studies, trial designs have been complicated by a lack of blood pressure related endpoints, inclusion of largely normotensive study populations, polypharmacy, and established comorbidities. Among a wide range of interventions reviewed, TNF-α inhibitors have provided the most robust evidence of blood pressure lowering. Treatment of periodontitis also appears to deliver non-pharmacological antihypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are discussed. Animal model, observational studies, and trial data in humans support the therapeutic potential of immune targeted therapies in blood pressure lowering and in hypertension-mediated organ damage. Targeted studies are now needed to address their effects on blood pressure in hypertensive individuals.

Digital, Objective Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. Methods We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Results Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (pheterogeneity, Ciencias Médicas y de la Salud

Background: Antihypertensive drugs play a crucial role in reducing cardiovascular morbidity and mortality. Variability in prescribing patterns constitutes a major challenge for current healthcare systems. This study aimed to compare patterns of use of antihypertensives in general practice in two southern European populations. Methods: Observational study. Data on antihypertensive drugs consumption in primary care setting (2016) were obtained from pharmacy refill records in Campania (Italy) and Aragon (Spain). Prescribing rates and the number of defined daily doses [DDD/1, 000 inhabitants/day (DID)] were calculated, and the Drug Utilization 90% (DU90%) approach used to reveal differences in prescribing patterns in both regions. Results: Antihypertensive prescribing rates in Campania and Aragon were 250.8 (95%CI: 250.2–251.3) and 201.7 (95%CI: 200.9–202.5) users/1, 000 inhabitants/year. Overall consumption was of 310.1 and 256.8 DID, respectively. Spanish users, especially women and the elderly, consumed a greater volume of diuretics. Conversely, other therapeutic subgroups were more consumed in Campania. However, the most prescribed subgroups accounted for comparable proportions of the total consumption in each region. Conclusions: Both prescribing rates and intensity of antihypertensive use were higher in Campania. Pharmacy refill records in cross-country comparisons allow to know the factors influencing variability in prescribing habits with a view to improving prescribing quality.

Background: Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome. Methods: Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II–III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline. Results: Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P =0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group). Conclusions: Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01743001.

A major paradigm in nephrology states that the loss of filtration function over a long time is driven by a persistent hyperfiltration state of surviving nephrons. This hyperfiltration may derive from circulating immunological factors. However, some clue about the hemodynamic effects of these factors derives from the effects of so-called nephroprotective drugs. Thirty years after the introduction of Renin-Angiotensin-system inhibitors (RASi) into clinical practice, two new families of nephroprotective drugs have been identified: the sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the vasopressin receptor antagonists (VRA). Even though the molecular targets of the three-drug classes are very different, they share the reduction in the glomerular filtration rate (GFR) at the beginning of the therapy, which is usually considered an adverse effect. Therefore, we hypothesize that acute GFR decline is a prerequisite to obtaining nephroprotection with all these drugs. In this study, we reanalyze evidence that RASi, SGLT2i, and VRA reduce the eGFR at the onset of therapy. Afterward, we evaluate whether the extent of eGFR reduction correlates with their long-term efficacy. The results suggest that the extent of initial eGFR decline predicts the nephroprotective efficacy in the long run. Therefore, we propose that RASi, SGLT2i, and VRA delay kidney disease progression by controlling maladaptive glomerular hyperfiltration resulting from circulating immunological factors. Further studies are needed to verify their combined effects.

BACKGROUND AND OBJECTIVES Claudin-16 and -19 are proteins forming pores for the paracellular reabsorption of divalent cations in the ascending limb of Henle loop; conversely, claudin-14 decreases ion permeability of these pores. Single-nucleotide polymorphisms in gene coding for claudin-14 were associated with kidney stones and calcium excretion. This study aimed to explore the association of claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms with calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective observational study of 393 patients with hypertension who were naive to antihypertensive drugs, in whom we measured 24-hour urine calcium excretion; history of kidney stones was ascertained by interview; 370 of these patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours) to evaluate the response of calcium excretion in three different 2-hour urine samples collected before, during, and after saline infusion. Genotypes of claudin-14, claudin-16, and claudin-19 were obtained from data of a previous genome-wide association study in the same patients. RESULTS Thirty-one single-nucleotide polymorphisms of the 3' region of the claudin-14 gene were significantly associated with 24-hour calcium excretion and calcium excretion after saline infusion. The most significant associated single-nucleotide polymorphism was rs219755 (24-hour calcium excretion in GG, 225±124 mg/24 hours; 24-hour calcium excretion in GA, 194±100 mg/24 hours; 24-hour calcium excretion in AA, 124±73 mg/24 hours; P

One of the oldest questions in acute stroke management, and perhaps the most challenging since it has yet to be solved after more than half a century of published research, is how to manage high blood pressure (BP). The problem might be summed up as follows: > To treat , or not to treat : that is the question: > > Whether ’tis nobler in the mind to suffer > > The slings and arrows of outrageous pressure , > > Or to take drugs against a sea of blood , > > And by opposing end them? To live : to walk ; > > —With apologies to Shakespeare , Hamlet Act III, Scene I To treat, or not to treat, high BP was debated >30 years ago in 1985,1–3 and yet there is no definitive answer here in 2018. Part of the debate is driven by opposing arguments based on epidemiology and pathophysiology and part by the failure of every large trial to provide a definitive answer. There is considerable evidence that high BP is associated independently with a poor outcome after ischemic stroke (IS) whether defined by early recurrence or death, or late death and dependency.4,5 Similarly, high BP is related to hematoma expansion6 and functional outcome after intracerebral hemorrhage (ICH).7 A straightforward conclusion of this epidemiological evidence is that high BP should be lowered. In contrast, pathophysiological concerns are based on the presence of dysfunctional cerebral autoregulation during acute stroke, and so lowering BP will reduce tissue perfusion, increase lesion size, and thereby worsen outcome.8 There are many causes of high BP in acute stroke, including prior hypertension, acute neuroendocrine stimulation (via the renin-angiotensin-aldosterone system [RAAS], sympathetic autonomic nervous, and corticotrophin-cortisol systems), the Cushing reflex (due to raised intracranial pressure), and stress associated with admission to hospital and …

Background Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the pre-dialysis period has not been fully examined. Methods We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study to identify factors that are associated with increased LVMI in patients with stage 3–5 CKD. Results We analyzed the baseline characteristics in 1088 participants (male 63.8%, female 36.2%). Diabetes mellitus was the underlying disease in 41.7% of the patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 23.4% of the patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease [odds ratio (OR) 2.364; 95% confidence interval ([CI) 1.463–3.822; P = 0.0004], body mass index (OR 1.108; 95% CI 1.046–1.173; P = 0.0005), systolic blood pressure (OR 1.173; 95% CI 1.005–1.369; P = 0.0433), urinary albumin (OR 1.425; 95% CI 1.028–1.974; P = 0.0333), and serum total cholesterol level (OR 0.994; 95% CI 0.989–0.999; P = 0.0174). Conclusion The cross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients.

Combination therapy is now regarded as the standard of care in pulmonary arterial hypertension (PAH) and is becoming widely used in clinical practice. Given the inherent complexities of combining medications, there is a need for practical advice on implementing this treatment strategy in the clinic. Drawing on our experience and expertise, within this review, we discuss some of the challenges associated with administration of combination therapy in PAH and how these can be addressed in the clinic. Despite their differing modes of action, all of the currently available classes of PAH therapy induce systemic vasodilation. In initial combination therapy regimens in particular, this may lead to additive side effects and reduced tolerability compared with monotherapy. However, approaches such as staggered treatment initiation and careful up-titration may reduce the risk of additive side effects and have been used successfully in clinical practice, as well as in clinical trials and registry studies. When combination therapy regimens are initiated, it is important that patients are monitored regularly for the presence of any side effects and that these are then managed promptly and appropriately. For patients to attain the best outcomes, the treatment regimen must be tailored to the individual's specific needs, including consideration of PAH etiology, the presence of comorbidities and concomitant medications beyond PAH therapy, and patient lifestyle and preference. It is also vital that individuals are managed at expert care centers, where multidisciplinary teams have a wealth of specialist experience in treating PAH patients. Adherence to therapy can be a concern in a chronic disease such as PAH, and as treatment regimens become increasingly complex, maintaining good treatment adherence may become more challenging. It is essential that patients are educated on the importance of treatment adherence, and this is a key role for the PAH nurse specialist. For patients who are managed carefully in expert centers with combination therapy regimens that are tailored to their specific needs, a favorable benefit-risk ratio can be achieved. With individual and carefully managed approaches, the excellent results observed with combination therapy in clinical trials can be obtained by patients in a real-world setting.

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P P

Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the 'high normal blood pressure' or 'stage 1 hypertension', so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.

Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndrome (CMS)—and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, or sea microorganisms displayed important biological activities to treat hypertensive patients. Here, we reviewed the anti-hypertensive activities of bioactive molecules isolated/extracted from marine organisms and discussed the associated molecular mechanisms involved. We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.

AimsThis retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs).Methods and resultsAll adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (AOR: 1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease.ConclusionNo association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.

*Kemeriz, Funda ( Aksaray, Yazar ) *Kilitçi, Asuman ( Aksaray, Yazar ), LETTERLichen planus actinicus treated successfully with topicaltacrolimus 0.1%: A report of six casesDear Editor,Lichen planus actinicus (LPA) is a photodistributed variant of lichenplanus (LP) that frequently occurs individuals with dark complexionson sun-exposed areas.1,2All of the cases admitted to our clinics forasymptomatic discoloration and rash on different parts of the faces.Five of six cases were male and one of them was female. Lesions ofthree male patients were on the forehead; one of these was in torm of an annular brown-violaceous plaque and two of these were inthe form of hyperpigmented patch lesion (case-1, 3, 6). Other two ofthem had hyperpigmented patch lesions on the neck (case-2, 5).Hyperpigmented patch lesions of female patient were on perioralregion (case-4). Detailed demographic and clinical features of thecases were presented in Table 1, and clinical images of the cases wereshown in Figure 1. Histopathology results of all patients revealed

Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms areactually occurring in the present COVID-19 outbreak. Here we present the reasoned statement of the Italian Society of Hypertension to maintain ongoing antihypertensive treatments. Furthermore, the Italian Society of Hypertension presents its own initiative to investigate the issue using an online questionnaire to collect relevant data in human disease.

Resume L’anesthesie d’un patient hypertendu traite est une situation frequente et a risque de complications cardiovasculaires. Une evaluation cardiovasculaire doit etre faite avant intervention chez ces patients. L’instabilite hemodynamique per-anesthesie est particulierement deletere dans ce contexte. Les traitements betabloquants doivent etre poursuivis en perioperatoire, mais il n’y a pas d’argument en faveur de leur introduction. Les recommandations europeennes, mais pas nord-americaines sont d’arreter les IEC et les ARA2 avant l’anesthesie sauf en cas d’insuffisance cardiaque. Les inhibiteurs calciques ne necessitent pas un arret. Les diuretiques sont arretes le jour de l’intervention et leurs consequences sur l’equilibre ionique doivent etre verifiees. L’introduction de la clonidine avant l’anesthesie n’est pas justifiee.

Background Observational studies demonstrate that communities of low socioeconomic status have higher blood pressure and worse cardiovascular outcomes. Yet, whether the clinical outcomes resulting from antihypertensive therapy vary by socioeconomic context in a randomized clinical trial, in which participants are treated under a standard protocol, is unknown. Methods and Results We used data from ALLHAT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial) to study the effect of socioeconomic context, defined as the county‐level median household income, of study sites. We stratified sites into income quintiles and compared characteristics, blood pressure control, and cardiovascular outcomes among ALLHAT participants in the lowest‐ and highest‐income quintiles. Among 27 862 qualifying participants, 2169 (7.8%) received care in the lowest‐income sites (quintile 1) and 10 458 (37.6%) received care in the highest‐income sites (quintile 5). Participants in quintile 1 were more likely to be women, to be black, to be Hispanic, to have fewer years of education, to live in the South, and to have fewer cardiovascular risk factors. After adjusting for baseline demographic and clinical characteristics, quintile 1 participants were less likely to achieve blood pressure control (, See Editorial Mehta and Anstey et al

Arterial hypertension (AH) is a chronic degenerative disease of multifactorial etiology responsible for thousands of deaths each year. One of the main pathophysiological processes in AH is endothelial dysfunction, which is caused primarily by a decrease in the bioavailability of nitric oxide (NO). NO is an important molecule responsible for the maintenance of vascular homeostasis. The use of compounds that increase NO bioavailability present as a therapeutic strategy in the treatment of AH. Thus, the aim of the present study was to characterize the 1,3-bis (hexyloxy) propane-2-yl nitrate (NDHP) as a novel NO donor and to evaluate its effects on the cardiovascular system of normotensive and hypertensive rats. All results were considered significant when p

Background Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results Four hundred seventy‐seven patients with mild‐to‐moderate Alzheimer disease were randomized to the calcium‐channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH‐related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow‐up visits. Mean age of the study population was 72.2±8.2 years and mean Mini‐Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by −7.8/−3.9 mm Hg for nilvadipine and by −0.4/−0.8 mm Hg for placebo ( P< 0.001). Across the 78‐week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8–1.5], P =0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH‐related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild‐to‐moderate Alzheimer disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02017340.

Background Hypertension is a known risk factor for heart failure (HF), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (LVH). We studied the extent to which blood pressure (BP) change and evolving LVH contribute to the effect that lisinopril, doxazosin, and amlodipine have on HF compared with chlorthalidone. Methods and Results We conducted causal mediation analysis of ALLHAT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial) data (1994‐2002; in‐trial follow‐up). ALLHAT participants with available serial ECGs and BP measurements were included (n=29 892; mean age 67±4 years; 32% black; 56% men): 11 008 were randomized to chlorthalidone, 5967 to doxazosin, 6593 to amlodipine, and 6324 to lisinopril. Evolving ECG LVH and BP lowering served as mediators. Incident symptomatic HF was the primary outcome. Linear regression (for mediator) and logistic regression (for outcome) models were adjusted for mediator‐outcome confounders (demographic and clinical characteristics known to be associated both with both LVH/hypertension and HF). A large majority of participants (96%) had ECG LVH status unchanged, but 4% developed evolving ECG LVH. On average, BP decreased by 11/7 mm Hg. In adjusted Cox regression analyses, progressing ECG LVH (hazard ratio [HR] 1.78 [95% CI 1.43‐2.22]), resolving ECG LVH (HR 1.33 [95% CI 1.03‐1.70]), and baseline ECG LVH (1.17 [95% CI 1.04‐1.31]) carried risk of incident HF. After full adjustment, evolving ECG LVH mediated 4% of the effect of doxazosin on HF. Systolic BP lowering mediated 12% of the effect of doxazosin, and diastolic BP lowering mediated 10% of the effect of doxazosin, 7% of the effect of amlodipine, and borderline 9% of the effect of lisinopril on HF. Conclusions Evolving ECG LVH and BP change account for 4% to 13% of the mechanism by which antihypertensive medications prevent HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542., See Editorial Ferdinand and Maraboto

Supplemental Digital Content is available in the text, Background: The response to antihypertensive drugs is predictable. The absence of precise prescription recommendations to treat arterial hypertension (HT) lead to use drugs unable to reduce blood pressure (BP) to target values. We published ATOM study, in which we found significant differences in the ability to reduce BP between the different drugs. The objective of the study was to determine the expected decrease in blood pressure with the use of commercialized doses of the drugs commonly used in the treatment of HT in clinical practice, to avoid the use of drugs or combinations that even with the best response, are unable to obtain the necessary BP decrease to reach the goal. Methods: The analysis was based on the results of the ATOM study. To convert the mean doses of the different drugs and combinations in commercialized doses, the conclusions of the study by Law et al have been applied. Results: Based on the results, two tables were drawn, one for systolic BP and the other for diastolic BP, where the doses of the different drugs and combinations are classified according to the BP decrease that can be expected from them. In order to favor the use of the tables in clinical practice, the different drugs have been grouped in intervals of 10 millimeters of mercury (mmHg) for the decrease of the systolic BP and of 5 mmHg for the diastolic BP. Conclusions: Recommendations for the use of antihypertensive treatments should not be limited to pharmacological families. They should also consider differences between drugs or specific combinations. From the data of the ATOM study we have implemented tables that express the effect of the drugs commonly used in clinical practice and that should allow the clinicians to choose with care the treatment to use.

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p &lt, 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6, flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.

While there have been advances in the field of pulmonary arterial hypertension (PAH), disease management remains suboptimal for many patients. The development of novel treatments and strategies can provide opportunities to target other mechanisms that play a role in the complex pathobiology of PAH outside of the three main pathophysiological pathways. In this review, we highlight some of the potential PAH therapies or techniques that are being, or have been, investigated in phase II clinical trials. This review also discusses potential points for consideration in the development of novel therapies that target putative disease mediators or modifiers.

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of

Introduction: The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH). Methods: 124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated. Results: 122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (−25.8 ± 12 vs −21.2 ± 14 mm Hg, P

Introduction: Limited data are available on the impact of hypertension in the different regions or urban areas in Italy. Aim: To evaluate hypertension prevalence and control among adult outpatients followed by general practitioners (GPs) in different regions and macro-areas in our Country. Methods: We retrospectively analysed data extracted in 2013 from the national GP Health Search-CSD database and stratified into three groups, depending on their own regions (North, Center and South). Hypertension prevalence was estimated within the overall population sample of adult individuals, whereas control was assessed in hypertensive outpatients. Hypertension diagnosis was defined according to International Classification of Diseases 9. Clinic blood pressure (BP) levels were measured according to European guidelines. BP control was defined as BP

Although blood pressure control is considered the main mechanism for preventing the progression of chronic kidney disease (CKD), angiotensin-converting enzyme inhibitors and angiotensin receptors blockers have an additional organ-protective role. The effects of calcium channel blockers (CCBs) in renal disease are not so clearly defined. CCBs have pleiotropic effects that might contribute to protection of the kidney, such as attenuating the mesangial entrapment of macromolecules, countervailing the mitogenic effect of platelet-derived growth factors and platelet-activating factors and suppressing mesangial cell proliferation. Some evidence has accumulated in recent years demonstrating that the new dihydropyridinic CCBs (such as lercanidipine or efonidipine) may affect both postglomerular and preglomerular vessels, resulting in a decreased filtration fraction and nephroprotective effect. Increasing clinical and experimental evidence supports this view and the use of CCBs in CKD hypertensive patients.

Two years after the publication of the 2013 guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC),1 the ESH and the European Union Geriatric Medicine Society have created a common working group to examine the management of hypertensive subjects aged >80 years. The general term hypertension in the elderly is not sufficiently accurate because it mixes younger old patients (60–70 years) with the oldest old. Our group believes that the management of hypertension in individuals aged ≥80 years should be specifically addressed. Although arbitrary, this cutoff value identifies a population that is expanding faster than any other age group with a 50% increase of life expectancy during the past 50 years2,3; furthermore, the incidence and prevalence of comorbidities, frailty, and loss of autonomy greatly increases after the age of 80 years4; finally, although there is limited evidence on the management of hypertension in this age group, the latest clinical studies indicate that in these patients, treatment may not be the same as in patients in the lower age strata. The aim of this Working Group was to discuss more in-depth treatment aspects of hypertensive patients aged ≥80 years or older, with special focus on the difficulties and uncertainties posed by very old frail individuals. We focused, in particular, on the following points of the 2013 ESH/ESC guidelines: The 2013 ESH/ESC guidelines1 reported the results of the Hypertension in the Very Elderly Double Blind Trial (HYVET). This showed that in hypertensive patients aged ≥80 years, the administration of the thiazide-like diuretic indapamide supplemented, if necessary, by the angiotensin-converting enzyme inhibitor perindopril led to a significant reduction in the …

Background: Hypertension is considered as a major health problem in Indonesia, especially in older adult population because of its prevalence increases by age. Treatment strategy and control management of hypertension in Public Health Center (Pusat Kesehatan Masyarakat, Puskesmas) as primary health care should be enhanced to overcome this issue. This study aimed to describe the pattern of antihypertensive agent in older adults. Methods: This was a descriptive study with total sampling method for data collection. Data were collected from medical record of older adult patients with diagnosis of hypertension at Puskesmas Tanjung Sari from January to December 2013. The variables observed were gender, number of visits, the degree of hypertension, types of antihypertensive drug, combinations of antihypertensive drugs, and blood pressure control. Results: The number of older adults with hypertension was 180 people. Some of which, 120 women (66.7%) participated, 152 (84.4%) had hypertension stage 2, 100 (55.6%) had just one visit, and 80 (44.4%) had more than one visit. Among 80 participants with more than one visit, 8 had achieved target blood pressure. There were 166 participants (92.2%) who received single antihypertensive agent (captopril was given the most), and 14 participants (7.8%) who received the combination of two antihypertensive agent (combination of captopril and HCT (hydrochlorothiazide)) were given the most). Conclusions: More than 75% of older adult with hypertension have stage 2 hypertension and are treated by single antihypertensive agent. Ninety percent of the patient have uncontrolled blood pressure.

DISTINCT was an 8‐week, double‐blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to

Background We have demonstrated that the antihypertensive effect of the angiotensin‐converting enzyme inhibitor, captopril ( CAP ), is associated with beneficial effects on gut pathology. Coupled with the evidence that CAP exerts prolonged reduction in blood pressure ( BP ) after discontinuation of treatment, we investigate whether persistent beneficial actions of CAP are linked to alterations of gut microbiota and improvement of hypertension‐induced gut pathology. Methods and Results Spontaneously hypertensive rats ( SHR ) and Wistar Kyoto rats were treated with CAP (250 mg/kg/day) for 4 weeks followed by withdrawal for 16 weeks. Gut microbiota, gut pathology, BP, and brain neuronal activity were assessed. CAP resulted in a ≈60 mm Hg decrease in systolic BP after 3 weeks of treatment in SHR , and the decrease remained significant at least 5 weeks after CAP withdrawal. In contrast, CAP caused modest decrease in systolic BP in Wistar Kyoto. 16S rRNA gene‐sequencing–based gut microbial analyses in SHR showed sustained alteration of gut microbiota and increase in Allobaculum after CAP withdrawal. Phylogenetic investigation of communities by reconstruction of unobserved states analysis revealed significant increase in bacterial sporulation upon CAP treatment in SHR . These were associated with persistent improvement in gut pathology and permeability. Furthermore, manganese‐enhanced magnetic resonance imaging showed significantly decreased neuronal activity in the posterior pituitary of SHR 4 weeks after withdrawal. Conclusions Decreased BP , altered gut microbiota, improved gut pathology and permeability, and dampened posterior pituitary neuronal activity were maintained after CAP withdrawal in the SHR . They suggest that CAP influences the brain‐gut axis to maintain the sustained antihypertensive effect of CAP after withdrawal.