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Hypertension urgency and emergency represents a challenging condition in which clinicians should determine the assessment and/or treatment of these patients. Whether the elevation of blood pressure (BP) levels is temporary, in need of treatment, or reflects a chronic hypertensive state is not always easy to unravel. Unfortunately, current guidelines provide few recommendations concerning the diagnostic approach and treatment of emergency department patients presenting with severe hypertension. Target organ damage determines: the timeframe in which BP should be lowered, target BP levels as well as the drug of choice to use. It's important to distinguish hypertensive emergency from hypertensive urgency, usually a benign condition that requires more likely an outpatient visit and treatment.

More than 90 % of patients developing heart failure (HF) have hypertension. The most frequent concomitant conditions are type-2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and non-steroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). Subsequently, they have been investigated in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) of mostly hypertensive etiology, and with modest benefits largely assessed on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Patients with HFpEF may have diastolic dysfunction but also systolic dysfunction visualized by lack of longitudinal shortening. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.

Background and aims: Hyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study. Methods and results: We analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P<0.001), the average SUA elevation amounting to of 0.3 ± 1.1 mg/dl 26.7 % of the subjects displayed HU at the follow-up. This was associated at the multivariable analysis with female gender, office, home and 24-h blood pressure, diuretic treatment, serum triglycerides and baseline SUA, as well as the increase in waist circumference and the reduction in renal function. Conclusion: The present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU.

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study. Methods: The study included 239 out of 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP),blood examinations, echocardiography and CAVI measurements. Results: In the whole study sample (age 69+9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with LVM index (p< 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6+2.8 vs 9.2+1.8 m/sec. P<0.001), larger left atrial diameter and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/sec was the best cut-off for prediction of LVH in the whole sample. Conclusions: Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH.

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

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

Recent evidence suggests that an exaggerated blood pressure (BP) response to standing (ERTS) is associated with an increased risk of adverse outcomes, both in young and old individuals. In addition, ERTS has been shown to be an independent predictor of masked hypertension. In the vast majority of studies reporting on the prognostic value of orthostatic hypertension (OHT), the definition was based only on systolic office BP measurements. This consensus statement provides recommendations on the assessment and management of individuals with ERTS and/or OHT. ERTS is defined as an orthostatic increase in SBP at least 20 mmHg and OHT as an ERTS with standing SBP at least 140 mmHg. This statement recommends a standardized methodology to assess ERTS, by considering body and arm position, and the number and timing of BP measurements. ERTS/OHT should be confirmed in a second visit, to account for its limited reproducibility. The second assessment should evaluate BP changes from the supine to the standing posture. Ambulatory BP monitoring is recommended in most individuals with ERTS/OHT, especially if they have high-normal seated office BP. Implementation of lifestyle changes and close follow-up are recommended in individuals with ERTS/OHT and normotensive seated office BP. Whether antihypertensive treatment should be administered in the latter is unknown. Hypertensive patients with ERTS/OHT should be managed as any other hypertensive patient. Standardized standing BP measurement should be implemented in future epidemiological and interventional studies.

Background: Evidence exists that lowering high blood pressure reduces the risk of dementia. However, the generalizability of this evidence to old patients from the general population remains uncertain. Objectives: This study sought to evaluate the effect of antihypertensive drug treatment on the risk of dementia in a heterogeneous group of new users of antihypertensive drugs. Methods: A nested case-control study was carried out by including the cohort of 215,547 patients from Lombardy, Italy, aged ≥65 years, who started taking antihypertensive drugs between 2009 and 2012. Cases were the 13,812 patients (age 77.5 ± 6.6 years; 40% men) who developed dementia or Alzheimer's disease during follow-up (up to 2019). For each case, 5 control subjects were selected to be matched for sex, age, and clinical status. Exposure to drug therapy was measured by the proportion of the follow-up covered by antihypertensive drugs. Conditional logistic regression was used to model the outcome risk associated with exposure to antihypertensive drugs. Results: Exposure to treatment was inversely associated with the risk of dementia. Compared with patients with very low exposure, those with low, intermediate, and high exposure exhibited a 2% (95% CI: −4% to 7%), 12% (95% CI: 6%-17%), and 24% (95% CI: 19%-28%) risk reduction, respectively. This was also the case for very old (aged ≥85 years) and frail patients (ie, those characterized by a high mortality risk at 1 year). Conclusions: In the old fraction of the general population, antihypertensive drug treatment is associated with a lower risk of dementia. This was also the case in very old and frail patients.

Objective:To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension.Methods:A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices.Statement:International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features.Conclusions:These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones.

Objective:To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.Methods:Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.Results:About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32-2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.Conclusions:In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. The first and most important requirement for the diagnosis and management of hypertension is an accurate measurement of office blood pressure that is currently recommended for screening, diagnosis, and management of high blood pressure in children and adolescents. Blood pressure levels should be screened in all children starting from the age of 3 years. In those children with risk factors for high blood pressure, it should be measured at each medical visit and may start before the age of 3 years. Twenty-four-hour ambulatory blood pressure monitoring is increasingly recognized as an important source of information as it can detect alterations in circadian and short-term blood pressure variations and identify specific phenotypes such as nocturnal hypertension or non-dipping pattern, morning blood pressure surge, white coat and masked hypertension with prognostic significance. At present, home BP measurements are generally regarded as useful and complementary to office and 24-h ambulatory blood pressure for the evaluation of the effectiveness and safety of antihypertensive treatment and furthermore remains more accessible in primary care than 24-h ambulatory blood pressure. A grading system of the clinical evidence is included.

Little is known on the effects of respiratory patterns on baroreflex function in heart failure (HF). Patients with HF (n = 30, age 61.6 ± 10 years, mean ± SD) and healthy controls (CNT, n = 10, age 58.9 ± 5.6 years) having their R–R interval (RRI, EKG), systolic arterial blood pressure (SBP, Finapres) and respiratory signal (RSP, Respitrace) monitored, were subjected to three recording sessions: free-breathing, fast- (≥ 12 bpm) and slow- (6 bpm) paced breathing. Baroreflex sensitivity (BRS) and power spectra of RRI, SBP, and RSP signals were calculated. During free-breathing, compared to CNT, HF patients showed a significantly greater modulation of respiratory volumes in the very-low-frequency (< 0.04 Hz) range and their BRS was not significantly different from that of CNT. During fast-paced breathing, when very-low-frequency modulations of respiration were reduced, BRS of HF patients was significantly lower than that of CNT and lower than during free breathing. During slow-paced breathing, BRS became again significantly higher than during fast breathing. In conclusion: (1) in free-breathing HF patients is present a greater modulation of respiratory volumes in the very-low-frequency range; (2) in HF patients modulation of respiration in the very-low and low frequency (around 0.1 Hz) ranges contributes to preserve baroreflex-mediated control of heart rate.

Background: The Global SYMPLICITY Registry DEFINE (Denervation Findings in Real World) investigates radiofrequency renal denervation (RDN) in a broad range of patients with hypertension. We evaluated whether the number or type of antihypertensive medications were associated with increased long-term blood pressure (BP) reductions and cardiovascular outcomes following radiofrequency RDN. Methods: Patients underwent radiofrequency RDN and were categorized by baseline number (0-3 and ≥4) and different combinations of medication classes. BP changes were compared between groups through 36 months. Individual and composite major adverse cardiovascular events were analyzed. Results: Of 2746 evaluable patients, 18% were prescribed 0 to 3 and 82% prescribed ≥4 classes. At 36 months, office systolic BP significantly decreased (P<0.0001) by -19.0±28.3 and -16.2±28.6 mm Hg in the 0 to 3 and ≥4 class groups, respectively. Twenty-four-hour mean systolic BP significantly decreased (P<0.0001) by -10.7±19.7 and -8.9±20.5 mm Hg, respectively. BP reduction was similar between the medication subgroups. Antihypertensive medication classes decreased from 4.6±1.4 to 4.3±1.5 (P<0.0001). Most decreased (31%) or had no changes (47%) to the number of medications, while 22% increased. The number of baseline antihypertensive medication classes was inversely related to the change in prescribed classes at 36 months (P<0.001). Cardiovascular event rates were generally low. More patients in the ≥4 compared with 0 to 3 medication classes had myocardial infarction at 36 months (2.8% versus 0.3%; P=0.009). Conclusions: Radiofrequency RDN reduced BP safely through 36 months, independent of the number and type of baseline antihypertensive medication classes. More patients decreased than increased their number of medications. Radiofrequency RDN is a safe and effective adjunctive therapy regardless of antihypertensive medication regimen. Registration: URL: https://www. Clinicaltrials: gov; Uniqu

Objective:The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs).Method:Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment.Results:The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity (I2= 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%).Conclusion:Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.

Background: Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response. Methods: Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes). Results: During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (P-values for heterogeneity >0.1). There was no significant difference in achieving BP <140/90 mm Hg at follow-up, major cardiovascular events, nor treatment tolerability according to the SBP change during active run-in period (all P-values >0.1). Conclusions: An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control. Registration: U

BACKGROUND: Approximately 40% of people with hypertension have left ventricular hypertrophy (LVH) detected by ECG or echocardiography. Because patients with LVH have poor myocardial microcirculation, they may be too sensitive to lowering systolic blood pressure (SBP) too much due to a lack of myocardial perfusion pressure. We aimed to investigate whether the average achieved SBP <130 mm Hg may cause harm in patients with LVH in the Valsartan Antihypertensive Long-Term Use Evaluation trial (VALUE). METHODS: Of the 15 245 VALUE participants, we identified 13 803 patients without cardiovascular events during the first 6 months after randomization. Of these, 2458 patients had electrocardiographic LVH (ECG-LVH). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other prespecified end points for patients who achieved average SBP 130 to 139 mm Hg (No-LVH group n=4863; ECG-LVH group n=929) and <130 mm Hg (No-LVH group n=2107; ECG-LVH group n=305). Reference groups were patients who achieved average SBP ≥140 mm Hg following the first excluded 6 months (No-LVH group n=4375; ECG-LVH group n=1224). RESULTS: The No-LVH group achieving average SBP <130 mm Hg had a significantly lower incidence of several cardiovascular end points. The ECG-LVH group achieving average SBP <130 mm Hg had higher cardiac mortality (hazard ratio, 1.98 [95% CIs, 1.06-3.70]; P=0.032) and all-cause mortality (hazard ratio, 1.74 [95% CIs, 1.17-2.60]; P=0.007), and SBP <130 mm Hg was not associated with a reduction in any end point. CONCLUSIONS: Our findings may be seen as a signal that caution is warranted when treating middle-aged and older patients with electrocardiographic or echocardiographic LVH to SBP <130 mm Hg.

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. Arterial hypertension is not only the most important risk factor for cardiovascular morbidity and mortality, but also the most important modifiable risk factor. Early hypertension-mediated organ damage may already occur in childhood. The duration of existing hypertension plays an important role in risk assessment, and structural and functional organ changes may still be reversible or postponed with timely treatment. Therefore, appropriate therapy should be initiated in children as soon as the diagnosis of arterial hypertension has been confirmed and the risk factors for hypertension-mediated organ damage have been thoroughly evaluated. Lifestyle measures should be recommended in all hypertensive children and adolescents, including a healthy diet, regular exercise, and weight loss, if appropriate. If lifestyle changes in patients with primary hypertension do not result in normalization of blood pressure within six to twelve months or if secondary or symptomatic hypertension or hypertension-mediated organ damage is already present, pharmacologic therapy is required. Regular follow-up to assess blood pressure control and hypertension-mediated organ damage and to evaluate adherence and side effects of pharmacologic treatment is required. Timely multidisciplinary evaluation is recommended after the first suspicion of hypertension. A grading system of the clinical evidence is included.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown profoundly affected almost all aspects of daily life including health services worldwide. The established risk factors for increased blood pressure (BP) and hypertension may also demonstrate significant changes during the pandemic. This study aims to determine the impact of the COVID-19 pandemic on BP control and BP phenotypes as assessed with 24-hour ambulatory BP monitoring (ABPM). Materials and Methods: This is a multi-centre, observational, retrospective and comparative study involving Excellence Centres of the European Society of Hypertension across Europe. Along with clinical data and office BP, ABPM recordings will be collected in adult patients with treated arterial hypertension. There will be two groups in the study: Group 1 will consist of participants who have undergone two ABPM recordings - the second one occurring during the COVID-19 pandemic, i.e. after March 2020, and the first one 9–15 months prior to the second. Participants in Group 2 will have two repeated ABPM recordings - both performed before the pandemic within a similar 9–15 month interval between the recordings. Within each group, we will analyse and compare BP variables and phenotypes (including averaged daytime and night-time BP, BP variability, dipper and non-dipper status, white-coat and masked hypertension) between the two respective ABPM recordings and compare these changes between the two groups. The target sample size will amount to least 590 participants in each of the study groups, which means a total of at least 2360 ABPM recordings overall. Expected outcomes: As a result, we expect to identify the impact of a COVID-19 pandemic on blood pressure control and the quality of medical care in order to develop the strategy to control cardiovascular risk factors during unpredictable global events.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment.The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

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

Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties. This position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failure. Analogous differences in beta-blocker efficacy is also likely in hypertension. Beta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blocker first choices in clinical practice. Thus, beta-blockers should be regarded as relevant first choices for hypertension in clinical practice, particularly if characterised by a long half-life, highly selective beta-1 blocking activity and no intrinsic agonist properties.SUMMARYBeta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trialsHypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rateBeta-blockers represent a heterogenous class of drug

This review will discuss the limitations of data collected by RCTs in relation to their applicability to daily life clinical management. It will then argue that these limitations are only partially overcome by modifications of RCT design and conduction (e.g. 'pragmatic trials') while being substantially attenuated by real-life-derived research, which can fill many gaps left by trial-collected evidence and have thus an important complementary value. The focus will be on the real-life research approach based on the retrospective analysis of the now widely available healthcare utilization databases (formerly known as administrative databases), which will be discussed in detail for their multiple advantages as well as challenges. Emphasis will be given to the potential of these databases to provide low-cost information over long periods on many different healthcare issues, drug therapies in particular, from the general population to clinically important subgroups, including (i) prognostic aspects of treatments implemented at the medical practice level via hospitalization and fatality data and (ii) medical practice-related phenomena such as low treatment adherence and therapeutic inertia (unsatisfactorily evaluated by RCTs). It will also be mentioned that thanks to the current availability of these data in electronic format, results can be obtained quickly, helping timely decisions under emergencies. The potential shortcomings of this approach (confounding by indication, misclassification, and selection bias) will also be discussed along with their possible minimization by suitable analytic means. Finally, examples of the contributions of studies on hypertension and other cardiovascular risk factors will be offered based on retrospective healthcare utilization databases that have provided information on real-life cardiovascular treatments unavailable via RCTs.

Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hyper-tension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardio-protective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes.

Background and objectives Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear. Design, setting, participants, & measurements Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor–based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to,5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (,3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor–based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median). Results During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor–based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00; P=0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in (P for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new

Background: Information on the relationship between ambulatory blood pressure (ABP) and concurrently office blood pressure (BP) values in youth still suffers from limitations. We provide information on the differences between office BP and ABP, the factors related, and the clinical implications. Methods: Three thousand six hundred ninety matched measurements of office BP and ABP on the same day, from 2390 children, aged 5 to 15 years, of both sexes were eligible. Office BP was measured using an oscillometric device (Omron 705 IT) and 24-hour ABP using oscillometric SpaceLabs 90207. Average of office, 24-hour, daytime, nighttime, systolic, and diastolic BP and heart rate was calculated. BP categories according to the European guidelines and phenotype of mismatch office BP versus ABP were defined. Results: Both daytime systolic and diastolic BP were higher than office BP with a progressive reduction of the differences from 5 to 15 years. The office minus daytime BP differences were the largest in normotensive subjects, less at high-normal, and reversed in hypertensive ones, independently of age and weight status. White coat and masked hypertension covered no more than 13.6% at all ages. Conclusions: In youth, it is inaccurate to obtain reference values for ABP by extrapolating from office BP values. The differences between office BP and ABP are minimal in children with office BP values in the range of hypertension, reinforcing the recommendation to use ABP measurement at the time to confirm hypertension.

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.

Background: The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on tertiary hypertension care. Methods: We conducted an electronic survey regarding 6 key procedures in hypertension care within the Excellence Center network of the European Society of Hypertension. Results: Overall, 54 Excellence Centers from 18 European and 3 non-European countries participated. From 2019 to 2020, there were significant decreases in the median number per centre of ambulatory blood pressure monitorings (ABPM: 544/289 for 2019/2020), duplex ultrasound of renal arteries (Duplex RA: 88.5/55), computed tomographic/magnetic resonance imaging angiography of renal arteries (CT/MRI RA: 66/19.5), percutaneous angioplasties of renal arteries (PTA RA: 5/1), laboratory tests for catecholamines (116/67.5) and for renin/aldosterone (146/83.5) (p < 0.001 for all comparisons, respectively). While reductions in all assessed diagnostic and therapeutic procedures were observed in all annual 3-months periods in the comparisons between 2019 and 2020, the most pronounced reduction occurred between April and June 2020, which was the period of the first wave and the first lockdown in most affected countries. In this period, the median reductions in 2020, as compared to 2019, were 50.7% (ABPM), 47.1% (Duplex RA), 50% (CT/MRI RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41.0% (renin/aldosterone), respectively. Overall differences in reduction between 3-month time intervals were statistically highly significant. Conclusion: Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated.