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

Introduction

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 grading system of the clinical evidence reads as follows:

A Recommendations are based on randomized trials (or systematic reviews of trials) with high levels of internal validity and statistical precision, provided that the trial results can be directly applied to the patients because of similar clinical characteristics and outcomes have clinical relevance.

B Recommendations are based on randomized trials, systematic reviews, or prespecified subgroup analyses that have lower levels of precision, or need to extrapolate from studies in different populations or using validated intermediate/surrogate outcomes.

C Recommendations are based on trials that have lower levels of internal validity and/or precision, trials for which non validated surrogate outcomes were used, or results from observational studies.

D Recommendations are based on expert opinion alone.

Arterial hypertension (HTN) is the most important risk factor for cardiovascular (CV) morbidity and mortality. The duration of existing HTN also plays a role in risk assessment.

Therefore, just as in adults, appropriate therapy should be initiated in children after the diagnosis of arterial HTN is confirmed and risk factors for hypertension-mediated organ damage (HMOD) are thoroughly assessed.

In all hypertensive children and adolescents, lifestyle interventions incorporating a healthy diet, regular exercise, and weight reduction, if necessary, should be recommended. If this does not lead to normalization of blood pressure (BP) within 6 to 12 months in patients with primary HTN, or if secondary or symptomatic HTN, or HMOD is already present, pharmacological therapy is required. The choice of medication should take into account the cause of HTN. In most cases, blockade of the renin-angiotensin system is recommended as first-line therapy. Combination therapy may be required to optimize BP control, especially in patients with secondary HTN.

Regular follow-up to evaluate BP control and HMOD, and to assess adherence to therapy and side effects of the pharmacological treatment is required.

Early referral to a childhood HTN center, ideally following initial suspicion of HTN, is encouraged to facilitate timely multidisciplinary input including cardiological and nephrological evaluation. The age of transfer to adult care services should be flexible upon patient readiness and specific needs.

Initial work-up of the hypertensive child

Patient history

Assessment of patient history should include pre- and postnatal history and a thorough assessment of patient family history including potential risk factors for hypertension, cardiovascular and cerebrovascular disease (1).

In the following materials we present assessment of patient and family history for hypertension and cardiovascular risk factors (Table 1).

TABLE 1

Table 1. Assessment of patient and family history for hypertension and cardiovascular risk factors.

Physical examination

Routine pediatric examination with special attention to anthropometric parameters is necessary (1) (Table 2).

TABLE 2

Table 2. Physical examination of hypertensive children and adolescents for underlying diseases and additional cardiovascular risk factors.

Laboratory evaluation and ultrasound

Laboratory tests should focus on kidney function and CV risk factors (Table 3).

TABLE 3

Table 3. Recommended evaluation in children and adolescents with hypertension.

Other imaging studies are usually performed in children in whom despite first step work-up, etiology of arterial HTN remains unestablished and/or in whom secondary HTN is suspected and done in referential centers (1).

When and how to assess the presence of hypertension-mediated organ damage

The main marker of HMOD is left ventricular hypertrophy (LVH) assessed by echocardiography (ECHO) (Table 4). In children up to 16 years left ventricular mass index (LVMI) should be indexed to height^2.7 in meters (5).

TABLE 4

Table 4. Definitions of left ventricular hypertrophy (LVH) by age and sex.

In Table 5 we present recommendation when and how to assess the presence of hypertension-mediated organ damage.

TABLE 5

Table 5. Recommendation when and how to assess the presence of hypertension-mediated organ damage.

Treatment

Lifestyle changes

Lifestyle interventions incorporating a dietary component along with exercise or behavioural therapy can lead to improvements in both weight and cardiometabolic factors, including BP in overweight and obese children (1) (Box 1, Table 6).

BOX 1

BOX 1. Lifestyle interventions for blood pressure reduction.

TABLE 6

Table 6. Lifestyle recommendations to reduce high blood pressure values: goals.

There is a consensus in the literature that non-pharmacological treatment of adolescent HTN is important because lifestyle modification leads to a reduction in BP (26). However, the results of several trials confirmed that a single factor is rarely capable of controlling an elevated BP and that combined lifestyle interventions (dietary component, physical activity and behavioral therapy) accomplish the most effective reduction in BP. A personalized approach may increase the overall moderate success rate of lifestyle changes.

Pharmacological treatment

When to start

The decision to start pharmacological antihypertensive treatment in a child should not be based on BP level alone but also on the symptoms and comorbidities of the child, the etiology and duration of HTN and the presence of HMOD (Table 7).

TABLE 7

Table 7. Indications for initiation of pharmacological treatment.

It should be made clear that, unlike in adults, these recommendations are not based on randomized controlled trials showing that treatment-induced reduction in BP is associated with decreased cardiovascular morbidity and mortality. There are no mortality studies in pediatrics and they will never be performed because cardiovascular mortality in the pediatric population is negligible. However, several uncontrolled studies have shown that antihypertensive drug therapy in children is associated with a reduction in HMOD, such as left ventricular hypertrophy or microalbuminuria.

Choice of antihypertensive drugs

In contrast to adults, there are no large comparative studies on different classes of antihypertensive drugs in children. One exception is a small short-term study comparing the angiotensin receptor blocker (ARB) valsartan with the angiotensin converting enzyme -inhibitor (ACEi) enalapril, which demonstrated similar antihypertensive efficacy and adverse effects of these two agents blocking the renin-angiotensin-aldosterone system (RAAS) (27). A Cochrane review found 21 randomized controlled trials, usually of short duration and without placebo control groups. Most studies showed BP lowering effects of antihypertensive drugs without severe adverse effects (Grade B) (28). However, no pediatric randomized controlled trials have investigated the efficacy of any antihypertensive drug on the prevention or regression of HMOD.

In the absence of high-quality randomized controlled trials comparing different antihypertensive agents in children, several antihypertensive agents may be considered as first-line drugs [ACEis, ARBs, calcium-channel-blockers (CCBs), ß-blockers, and diuretics] based on the evidence available on HTN in adulthood. An exception is that of children with chronic kidney disease (renoparenchymal HTN) who have been shown to benefit from the antiproteinuric and renoprotective properties of ACE-inhibitors and ARBs.

In addition, certain classes of drugs may be favorable or contraindicated in specific clinical conditions (1) (Table 8). For example, in children with obesity-related HTN, the negative metabolic adverse effects of diuretics and beta-blockers on glucose and lipid metabolism make the metabolic neutral classes of ACE-inhibitors and ARBs potentially preferable.

TABLE 8

Table 8. Therapeutic approaches.

However, in females of childbearing age, RAAS inhibitors should be prescribed only under strict contraceptive measures due a potential teratogenic effect of these drugs.

Therapeutic approaches in special conditions

Combination therapy

Whenever a single agent, prescribed at the maximum recommended or tolerated dose, does not achieve target BP the use of antihypertensive combination therapy is recommended. Combinations of different drug classes with complementary modes of action should be prescribed, taking into account the underlying diseases and comorbidities of the individual patient (Tables 9, 10, Box 2). (Table 8).

BOX 2

BOX 2. Goals to achieve in the general hypertensive pediatric population and in diabetic and renal disease.

TABLE 9

Table 9. Exemplary step scheme for combining antihypertensive drug classes.

TABLE 10

Table 10. Principles of antihypertensive therapy in children with diabetes mellitus type 1 or 2 (grade C).

Motivation strategies for patients and caregivers

Essential information

As in many other chronic diseases (32), patient adherence, the degree to which patients follow the recommendations of their health professionals, is a salient outcome of the process of care and, treatment nonadherence is a major problem in the management of hypertension. Therefore, it is important to introduce motivation strategies for patients and caregivers to increase adherence to treatment (33).

Motivation to change

Motivation to change includes the constructs that must arise from the person him/herself and that are not imposed by third parties. It is an internal state, which fluctuates according to external factors. It has a series of phases, through which the person may undergo, ranging from the decision not to change (by considering only the positive/gratifying aspects of the harmful behavior), to a complete and stable change of habits in favor of a healthier lifestyle such as an adequate diet, physical exercise, giving up tobacco, alcohol, or even increasing adherence to pharmacological treatment (34).

Motivational style

A motivational style has to be followed, on the part of the family and/or physician, by asking openly these types of questions: asking to know how the person feels (with unhealthy habits), what worries he/she has, what doubts he/she has regarding the new habits to change, why do they think it might be important to change his/her new habits, asking about his/her opinion about potential positive consequences of doing so, helping him/her to explore his/her ambivalences and discrepancies. The most important tool to achieve this motivational style is empathy, although others may be active and reflective listening (showing genuine and sincere interest in understanding their concerns and doubts in relation to the change), honesty, not judging or criticizing, being willing to go at the individual's pace, promoting self-efficacy (see Boxs 3, 4 and Table 11) (35, 36).

BOX 3

BOX 3. Motivational Interview.

BOX 4

BOX 4. Identifications of resistances by the patient/family member.

TABLE 11

Table 11. Motivation style and recommendations .

Suggested schedule for follow-up examinations

Follow-up of hypertensive individuals is based on the underlying etiology of the high BP condition, presence of co-morbidities, severity of HTN, presence of HMOD and patient's knowledge and understanding of the rationale of the HTN management (Table 12) (1).

TABLE 12

Table 12. Follow-up evaluation for HMOD in children with hypertension.

In the majority of patients with primary HTN, especially those advised non-pharmacological lifestyle changes, infrequent but regular, follow-up is advisable. In contrast, in those whose management includes both pharmacological treatment and lifestyle changes, a more frequent regular follow-up is needed. Home BP monitoring can facilitate the management of HTN. Telemedicine could additionally be helpful. Ideally, in those with chronic kidney disease or diabetes annual ABPM should be recommended to rule out BP control limited to office BP a condition that in adults is termed MUCH (masked uncontrolled HTN). Accessibility to appropriate resources to facilitate this is a key factor.

Patients with well-controlled HTN and no HMOD should be monitored in regular intervals to rule out de novo HMOD, and to assess adherence to therapy and side effects of the pharmacological treatment (1).

Optimal BP control over a prolonged period of time may justify a reduction of the number and dose of antihypertensive drugs. Healthy lifestyle changes should be maintained, the reduction of pharmacological therapy should be made gradually and the patient should frequently be monitored (at 3 to 6 months intervals) because of the risk of re-emergence of HTN (1).

Long-Term consequences of childhood hypertension

Hypertension remains the main modifiable risk factor for the risk of cardiovascular disease and death, and cardiac and vascular damage by an elevated BP begins in childhood.

Early organ damage occurs in the form of left ventricular hypertrophy, thickening and stiffening of the vascular wall, albuminuria, and cognitive dysfunction. HTN and other cardiometabolic factors cause endothelial dysfunction and are responsible for the accelerated process of atherosclerosis. At this stage, organ structural and functional changes may still be reversible or postponed with appropriate treatment.

In recent years, studies have shown both tracking of high BP into adulthood and increased cardiovascular risk in young adults with childhood onset of HTN. High normal BP and hypertensive trajectory groups have worse cardiovascular outcomes by early midlife. Higher body mass index and cigarette smoking are associated with increased BP values across trajectories, particularly in the higher BP groups that in childhood predict adult cardiovascular risk (37).

In a prospective cohort study, childhood risk factors (higher body-mass index, systolic BP, total cholesterol level, triglyceride level, and youth smoking) and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife (38).

The goal of antihypertensive treatment is to reduce the global risk of cardiovascular events. Recognition of risk factors and early cardiovascular damage, at a time when these processes are still reversible, and development of prevention strategies are key factors for the reduction of cardiovascular morbidity and mortality in the general population (39). Long-term follow-up multicenter studies are necessary to assess cardiovascular risk stratification in children and adolescents with HTN and to develop standards for diagnostic and treatment procedures (1, 37–39).

Criteria to refer patients to pediatric specialists

Pediatric specialists for arterial HTN, usually pediatric nephrologists or cardiologists, should be involved in the management of a persistently elevated office BP in an asymptomatic healthy child, i.e., elevated BP values over at least three separate visits (Table 13) (1).

TABLE 13

Table 13. Recommended responsibility for hypertension work-up and management in children and adolescents.

Patients should be referred to specialist management earlier (after one or two visits with a BP elevation) if stage 2 HTN is present or HTN is symptomatic. Intervals between visits should be judged on a clinical basis (1).

We encourage early referral to a childhood HTN center, ideally following initial suspicion of HTN, to facilitate timely multidisciplinary input including cardiological and nephrological evaluation. This should encourage Children's Hospitals in Europe to organize expert HTN services which will provide an opportunity for specialist care to work together with family physicians, pediatricians, the hypertensive child and their family, with a greater chance for optimal HTN management.

Reaching the age for transition to adult units. How to proceed

Essential information

Transition refers to the process of moving from pediatric to adult care services beginning in adolescence and continuing into early adulthood (Box 5). This should be done according to preplanned strategies, with the overarching goals to develop patient's readiness, increase the young people' s level of responsibility for their own health care management, engage and enhance the understanding of the conditions they are living with, and build the skills needed to navigate the adult care system. Family support and both patient and family willingness to transfer are also key elements to be considered during transition (40, 41).

BOX 5

BOX 5. Indications for the transition from pediatric to adult care services.

In pediatric patients with early onset of HTN the transition process may start at the age of 12–14 years, gradually introducing an individualized transition plan during adolescence (40–42) based also on the presence of HMOD and/or comorbidities. The adoption of adult thresholds for the diagnosis of HTN in adolescents ≥16 years old by the ESH 2016 guidelines (1), enable smooth transition to adult health care.

Present challenges

• Little guidance is provided in the literature, with low evidence on the effectiveness of any specific intervention on transition to improve transfer to adult health care (43).

• Involving primary care practitioners in transition. Very little is known about the impact and role of primary health providers in supporting the transition of youth with health care needs. Community services and primary care teams tend to provide holistic care and are effective for integrating social determinants of health.

Conclusions

Arterial hypertension is the most important modifiable risk factor for cardiovascular morbidity and mortality. Therefore, appropriate antihypertensive therapy including lifestyle measures and pharmacologic treatment should be initiated in children as soon as the diagnosis of arterial hypertension has been confirmed and the risk factors for hypertension-induced organ damage have been thoroughly evaluated. Early referral to a pediatric hypertension center, ideally after the first suspicion of hypertension, is recommended to allow timely multidisciplinary evaluation, including workup by pediatric cardiologists and nephrologists, and initiation of antihypertensive treatment.

Author contributions

All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication. All authors contributed to the article and approved the submitted version.

Acknowledgments

Chapter 1 “How to correctly measure blood pressure in children and adolescents” and Chapter 2 “How to manage high blood pressure in children and adolescents” of the JOINT STATEMENT FOR ASSESSING AND MANAGING HIGH BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS are based upon the work of the COST Action HyperChildNET (CA19115), with the support of COST (European Cooperation in Science and Technology).

Conflict of interest

JC was employed by Analog Devices Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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