Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 1. How to correctly measure blood pressure in children and adolescents.

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.

Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 2. How to manage high blood pressure in children and adolescents.

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.

Narrative update of clinical trials with antihypertensive drugs in children and adolescents.

Introduction: To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension. Methods: Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility. Results: In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage. Conclusions: Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as 'n-of-1', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.

Obesity and Eating Disorders in Children and Adolescents: The Bidirectional Link.

Obesity, eating disorders and unhealthy dieting practices among children and adolescents are alarming health concerns due to their high prevalence and adverse effects on physical and psychosocial health. We present the evidence that eating disorders and obesity can be managed or prevented using the same interventions in the pediatric age. In the presence of obesity in the pediatric age, disordered eating behaviors are highly prevalent, increasing the risk of developing eating disorders. The most frequently observed in subjects with obesity are bulimia nervosa and binge-eating disorders, both of which are characterized by abnormal eating or weight-control behaviors. Various are the mechanisms overlying the interaction including environmental and individual ones, and different are the approaches to reduce the consequences. Evidence-based treatments for obesity and eating disorders in childhood include as first line approaches weight loss with nutritional management and lifestyle modification via behavioral psychotherapy, as well as treatment of psychiatric comorbidities if those are not a consequence of the eating disorder. Drugs and bariatric surgery need to be used in extreme cases. Future research is necessary for early detection of risk factors for prevention, more precise elucidation of the mechanisms that underpin these problems and, finally, in the cases requiring therapeutic intervention, to provide tailored and timely treatment. Collective efforts between the fields are crucial for reducing the factors of health disparity and improving public health.

Hypertension and cardiac arrhythmias: a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents.

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Morbidity and mortality risk among patients with screening-detected severe hypertension in the Malmö Preventive Project.

OBJECTIVE: Screening of hypertension has been advocated for early detection and treatment. Severe hypertension (grade 3 hypertension) is a strong predictor for cardiovascular disease. This study aimed to evaluate not only the risk factors for developing severe hypertension, but also the prospective morbidity and mortality risk associated with severe hypertension in a population-based screening and intervention programme. RESEARCH DESIGN AND METHODS: In all, 18,200 individuals from a population-based cohort underwent a baseline examination in 1972-1992 and were re-examined in 2002-2006 in Malmö, Sweden. In total, 300 (1.6%) patients with severe hypertension were identified at re-examination, and predictive risk factors from baseline were calculated. Total and cause-specific morbidity and mortality were followed in national registers in all severe hypertension patients, as well as in age and sex-matched normotensive controls. Cox analyses for hazard ratios were used. RESULTS: Men developing severe hypertension differed from matched controls in baseline variables associated with the metabolic syndrome, as well as paternal history of hypertension (P < 0.001). Women with later severe hypertension were characterized by elevated BMI and a positive maternal history for hypertension at baseline. The risk of mortality, coronary events, stroke and diabetes during follow-up was higher among severe hypertension patients compared to controls. For coronary events, the risk remained elevated adjusted for other risk factors [hazard ratio 2.31, 95% confidence interval (CI) 1.22-4.40, P = 0.011]. CONCLUSION: Family history and variables associated with metabolic syndrome are predictors for severe hypertension after a long-term follow-up. Severe hypertension is associated with increased mortality, cardiovascular morbidity and incident diabetes in spite of treatment. This calls for improved risk factor control in patients with severe hypertension.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

How to estimate left ventricular hypertrophy in hypertensive patients.

Left ventricular hypertrophy (LVH) is a structural remodeling of the heart developing as a response to volume and/or pressure overload. Previous studies have shown that hypertension is not an independent factor in the development of LVH and occurrence does not depend on the length and severity of hypertension, but the role played by other comorbidities such as triglycerides, age, gender, genetics, insulin resistance, obesity, physical inactivity, increased salt intake and chronic stress. LVH develops through three phases: adaptive, compensatory, and pathological phase. Contractile dysfunction is reversible in the first two phases and irreversible in the third. According to the Framingham study, LVH develops in 15-20% of patients with mild arterial hypertension, and in 50% of patients with severe hypertension. The pathophysiology of LVH includes hypertrophy of cardiomyocytes, interstitial and perivascular fibrosis, coronary microangiopathy and macroangiopathy. Individuals with LVH have 2-4 times higher risk of having adverse CV events compared to patients without LVH.

Monitoring treatment adherence in hypertension.

Hypertension is associated with high mortality and morbidity that will increase if hypertension is left untreated. Treatment adherence is crucial in blood pressure control, and monitoring patient adherence is essential to the successful management of hypertension, since nonadherence is associated with poor prognosis. There are both direct and indirect methods to monitor adherence. Direct methods can be defined as assessment of treatment response or level of drug or its metabolite in blood, urine and body fluids without any intermediate or agent. Indirect methods require several instruments, such as questionnaires, reports, devices, and monitors. Certain methods may be advantageous in specific clinical and research settings. Advances in technology (new tools, devices, laboratory methods), and new approaches to reporting will not only help patients control high blood pressure but decrease hypertension-related mortality and morbidity.

Reduction in cardiovascular risk using proactive multifactorial intervention versus usual care in younger (< 65 years) and older (≥ 65 years) patients in the CRUCIAL trial.

OBJECTIVE: To compare the reduction in calculated Framingham 10 year coronary heart disease (CHD) risk after 52 weeks' intervention with a proactive multifactorial intervention (PMI) strategy (based on single-pill amlodipine/atorvastatin [SPAA]) versus continuing usual care (UC) (based on investigators' best clinical judgment) among younger (<65 years) and older (≥ 65 years) patients. RESEARCH DESIGN AND METHODS: Sub-analysis of the Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term risk (CRUCIAL) trial. Eligible patients had hypertension and ≥ 3 cardiovascular risk factors. MAIN OUTCOME MEASURE: Treatment-related reduction in calculated Framingham 10 year CHD risk between baseline and Week 52 in younger and older patients. RESULTS: Nine hundred patients (63.5%) were <65 years (mean age 54.2 years, 57.4% men) and 517 patients (36.5%) were ≥ 65 years (mean age 70.5 years, 42.7% men). Younger patients had lower mean baseline CHD risk versus older patients (17.1% vs. 22.6%). A greater reduction in calculated CHD risk at Week 52 was observed in the PMI versus the UC arm in both younger (-33.2% vs. -2.9%, p < 0.001) and older (-32.7% vs. -5.7%, p < 0.001) patients. Least-squares mean treatment differences (PMI vs. UC) in percentage change from baseline in calculated CHD risk were similar in younger and older patients (-26.3% vs. -25.7%, age interaction p = 0.887). CHD risk reduction was slightly greater among younger men than younger women (-29.3 vs. -23.9, gender interaction p = 0.062). A low proportion of patients discontinued the PMI strategy due to adverse events in both age groups (5.8% vs. 6.1%, respectively). Study limitations included ad-hoc (not pre-specified) sub-group analysis and short duration of follow-up. CONCLUSIONS: The PMI strategy based on the inclusion of SPAA in the treatment regimen is more effective than UC in reducing calculated CHD risk. This strategy may be considered as the treatment of choice in younger and older hypertensive patients with additional cardiovascular risk factors.

Are physicians underestimating the challenges of hypertension management? Results from the Supporting Hypertension Awareness and Research Europe-wide (SHARE) survey.

AIMS: The Supporting Hypertension Awareness and Research Europe-wide (SHARE) survey aimed to qualify the key challenges that physicians face when trying to get patients to recommended blood pressure (BP) goals. METHODS AND RESULTS: The survey was open to physicians involved in the treatment of hypertension, was anonymous, and included 45 questions covering: physicians' demographic information, familiarity with BP treatment guidelines, views on the BP targets recommended by the 2007 European Society of Hypertension and European Society of Cardiology (ESH-ESC) guidelines, and perceptions on the proportion of 'challenging patients' in hypertension management (defined as patients not achieving the BP goal, where the BP goal is at least <140/90 mm Hg, and <130/80 mm Hg for patients with co-morbidities or high CV risk). Physicians significantly underestimated the proportions of their 'challenging patients' with hypertension compared with their perceptions of the proportions achieving 2007 ESH-ESC BP targets (p < 0.0001). The majority of cardiologists (75.5%) and general/family practitioners (GPs) (81.3%) as well as internists (59.3%) (p < 0.05 for cardiologists and GPs vs internists) felt that it was a challenge to get their patients to target BP, stating that only 43.2%, 57.4% and 38.2% of their patients, respectively, achieved these targets in practice (p < 0.05 for GPs vs cardiologists and internists). CONCLUSION: Physicians may underestimate the proportion of 'challenging patients' with hypertension and there is a need to improve their BP control. Increasing physicians' awareness about the risks of uncontrolled BP and improving compliance are two possible ways to improve management of hypertension.

How do compliance, convenience, and tolerability affect blood pressure goal rates?

Uncontrolled hypertension imposes a substantial global health burden, and poor patient compliance with prescribed antihypertensive medication makes a major contribution to the development of suboptimal blood pressure (BP) control. The asymptomatic nature of hypertension, side effects of medication, treatment complexity, and high pill burdens all have a negative impact on patient compliance. It is important to address the issue of poor patient compliance as studies have shown that good compliance is associated with improvement of BP control and positive health outcomes. As the majority of hypertensive patients require treatment with two or more agents to achieve goal BP, treatment guidelines have acknowledged the value of simplifying treatment through the use of fixed-dose combination (FDC) therapy. Triple FDC therapy comprising an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker), calcium channel blocker, and thiazide diuretic is a novel treatment strategy for the improvement of BP control in hard-to-treat patients.

Proactive cardiovascular risk management versus usual care in patients with and without diabetes mellitus: CRUCIAL trial subanalysis.

UNLABELLED: Patients with diabetes mellitus (DM) and additional cardiovascular (CV) risk factors are at very high risk for future CV events. This study investigated the efficacy and safety of a proactive, multifactorial CV risk factor-management strategy based on single-pill amlodipine/atorvastatin (SPAA) versus continuing physicians' usual care (UC) over 52 weeks in patients with and without DM. Patients with hypertension and ≥ 3 additional CV risk factors from the Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-Term-Risk (CRUCIAL) trial--an open-label, cluster-randomized trial conducted in 19 countries--were enrolled and randomized to receive proactive intervention (based on SPAA 5/10 to 10/20 mg) or UC (based on investigators' best clinical judgment). Patients were analyzed according to baseline DM status. Six hundred patients had DM. Patients with DM in the SPAA and UC arms had mean ages of 61.8 and 61.5 years, respectively, and an absolute coronary heart disease (CHD) risk of 25.2% and 21.5%, respectively. Among non-DM patients, mean ages were 58.6 and 59.5 years, respectively, and CHD risk was 16.0% vs 15.7%, respectively. Least-squares mean treatment differences in percentage change from baseline in calculated 10-year Framingham CHD risk were -26.3% vs -27.3% among DM and non-DM patients (adjusted for respective baseline values) (both P < 0.0001). Among DM and non-DM patients, adverse events were reported in 52.8% versus 45.6% in the SPAA and 49.6% versus 41.6% in the UC arms, respectively. This global risk-management approach, simultaneously targeting blood pressure and lipids, was more effective for reducing calculated 10-year Framingham CHD risk than UC in patients with DM. While blood pressure changes were of smaller magnitude among patients with DM, this strategy reduced overall risk to an extent comparable with that observed in non-DM patients. Further studies are thus warranted to study this proactive risk factor intervention on CV or mortality endpoints in patients with and without DM. TRIAL REGISTRATION: www.ClinicalTrials.gov identifier NCT00407537.

Hypertension in women--pathophysiological and clinical aspects.

Hypertension is the most important risk factor, responsible for cardiovascular morbidity and mortality worldwide, both in men and women. Cardiovascular disorders in women are still underestimated, due to lower absolute risk calculations and the underdetection of classical risk factors. In recent years the differences in pathophysiology and the clinical presentation and treatment of cardiac diseases in women have become fields of interest and research. Several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. This article presents current data on differences in prevalence, control and mechanisms of hypertension in women.

Olmesartan/amlodipine: blood pressure lowering and beyond in special populations.

Clinical studies and population-based analyses show that in patients with hypertension, the majority cannot control their blood pressure (BP) by treatment with a single antihypertensive agent. Combining agents from different antihypertensive classes with complementary modes of action significantly increases efficacy and is a treatment strategy recommended by European treatment guidelines, particularly in patients at high cardiovascular risk. The combinations of antihypertensive agents recommended by the European guidelines include an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). The single-pill combination formulation of the ARB olmesartan medoxomil plus the CCB amlodipine is an effective and well-tolerated treatment that provides greater blood pressure lowering and control than the component monotherapies and favours compliance by not increasing pill burden. Importantly, the efficacy and tolerability of olmesartan plus amlodipine is not affected by age, gender, hypertension severity, diabetes status, race or body mass index. Additional blood pressure lowering effects are observed with stepwise uptitration of olmesartan plus amlodipine with or without hydrochlorothiazide, with more patients achieving blood pressure goals. In addition, olmesartan plus amlodipine has demonstrated effects beyond BP lowering by showing beneficial effects on markers of inflammation, endothelial dysfunction and oxidative stress, as well as metabolic improvements and a reduction in new-onset diabetes incidence in hypertensive patients with metabolic syndrome.

Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group 'Hypertension Arrhythmias and Thrombosis' of the European Society of Hypertension.

Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.