The clinical value of ß-blockers in patients with stable angina.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

Assessment and management of exaggerated blood pressure response to standing and orthostatic hypertension: consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability.

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.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

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

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

Instability of Healthy Overweight and Obesity Phenotypes over the Long Term in Young Participants in the HARVEST Study: Influence of Sex.

BACKGROUND: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term. METHODS: We examined 970 individuals of 18 to 45 years of age. The participants' mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy (p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight (p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants (p = 0.073). CONCLUSION: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Accuracy of the KOROT P3 Accurate automated auscultatory blood pressure measuring device for professional use in people with extra-large arms.

OBJECTIVE: To determine the accuracy of the KOROT P3 Accurate (previously InBody BPBIO480KV) monitor, an automated auscultatory blood pressure (BP) measuring device developed for professional use, in people with extra-large arms according to the ISO81060-2 2018 protocol. METHODS: The KOROT P3 Accurate was tested in 37 subjects with upper-arm circumference ranging from >42 to 53 cm using a mercury sphygmomanometer coupled to a 20 × 40 cm tronco-conical cuff as the reference standard. RESULTS: The mean BP difference between the device and the observers' reference measurements was 1.2 ±â€…2.0 mmHg for systolic BP and 1.0 ±â€…2.0 mmHg for diastolic BP. These data were in agreement with criterion 1 of the protocol standard requirements (≤5 ±â€…8 mmHg). Also criterion 2 was satisfied being the standard deviations ± 1.7 mmHg for systolic BP and ± 1.6 for diastolic BP, well below the maximum values required by the protocol (±6.84/6.87 mmHg). Scatterplots of device-reference systolic and diastolic BP differences showed similar accuracy across the range of participants' BP, arm circumference and upper-arm slant angle. CONCLUSIONS: These data show that the KOROT P3 Accurate monitor satisfied the ISO 81060-2:2018 standard requirements in a special population of people with extra-large arms ranging from >42 to 53 cm.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Healthy overweight and obesity in the young: Prevalence and risk of major adverse cardiovascular events.

AIMS: To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE). METHODS AND RESULTS: The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53). CONCLUSION: The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

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

Orthostatic Hypertension: A Newcomer Among the Hypertension Phenotypes.

The prognostic role and the clinical significance of orthostatic hypertension (OHT) remained undefined for long because data were sparse and often inconsistent. In recent years, evidence has been accumulating that OHT is associated with an increased risk of masked and sustained hypertension, hypertension-mediated organ damage, cardiovascular disease, and mortality. Most evidence came from studies in which OHT was defined using systolic blood pressure (BP) whereas the clinical relevance of diastolic OHT is still unclear. Recently, the American Autonomic Society and the Japanese Society of Hypertension defined OHT as an orthostatic systolic BP increase ≥20 mm Hg associated with a systolic BP of at least 140 mm Hg while standing. However, also smaller orthostatic BP increases have shown clinical relevance especially in people ≤45 years of age. A possible limitation of the BP response to standing is poor reproducibility. OHT concordance is better when the between-assessment interval is shorter, when OHT is evaluated using a larger number of BP readings, and if home BP measurement is used. The pathogenetic mechanisms leading to OHT are still controversial and may vary according to age. Excessive neurohumoral activation seems to be the main determinant in younger adults whereas vascular stiffness plays a more important role in older individuals. Conditions associated with higher activity of the sympathetic nervous system and/or baroreflex dysregulation, such as diabetes, essential hypertension, and aging have been found to be often associated with OHT. Measurement of orthostatic BP should be included in routine clinical practice especially in people with high-normal BP.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA).

DOCUMENT REVIEWERS: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

European Society of Hypertension recommendations for the validation of cuffless blood pressure measuring devices: European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability.

BACKGROUND: There is intense effort to develop cuffless blood pressure (BP) measuring devices, and several are already on the market claiming that they provide accurate measurements. These devices are heterogeneous in measurement principle, intended use, functions, and calibration, and have special accuracy issues requiring different validation than classic cuff BP monitors. To date, there are no generally accepted protocols for their validation to ensure adequate accuracy for clinical use. OBJECTIVE: This statement by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability recommends procedures for validating intermittent cuffless BP devices (providing measurements every >30 sec and usually 30-60 min, or upon user initiation), which are most common. VALIDATION PROCEDURES: Six validation tests are defined for evaluating different aspects of intermittent cuffless devices: static test (absolute BP accuracy); device position test (hydrostatic pressure effect robustness); treatment test (BP decrease accuracy); awake/asleep test (BP change accuracy); exercise test (BP increase accuracy); and recalibration test (cuff calibration stability over time). Not all these tests are required for a given device. The necessary tests depend on whether the device requires individual user calibration, measures automatically or manually, and takes measurements in more than one position. CONCLUSION: The validation of cuffless BP devices is complex and needs to be tailored according to their functions and calibration. These ESH recommendations present specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices to ensure that only accurate devices will be used in the evaluation and management of hypertension.

Requirements for design and function of blood pressure measuring devices used for the management of hypertension: Consensus Statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and STRIDE BP.

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.