After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidencebased guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guideThe prevalence of hypertension in children is 1%-2% in Canada and is closely associated with childhood obesity and sedentary activity patterns in youth. 1,2 Fortunately, there are encouraging data suggesting that the prevalence of obesity is stabilizing and that the prevalence of elevated blood pressure (BP) in children is decreasing, especially in overweight or obese adolescents in the United States. 3 These findings underscore the importance of a continued and evidence-based approach toward improving the cardiovascular health of Canadian children. Health behaviour modification lies at the foundation of hypertension prevention and management in children. The use of pharmacotherapy in hypertensive children has been increasingly studied over the past 2 decades, and more evidence is currently available to inform therapeutic#
Apres la publication, en 2016, des lignes directrices concernant la mesure, le diagnostic et l' evaluation de l'hypertension chez l'enfant, nous vous pr esentons maintenant les lignes directrices fond ees sur des donn ees probantes portant sur la pr evention et le traitement de l'hypertension chez l'enfant. Ces lignes directrices ont et e elabor ees par le sous-groupe de m edecine p ediatrique du comit e des lignes directrices d'Hypertension Canada apres une revue d etaill ee de la litt erature m edicale publi ee a ce sujet. On retrouve 10 lignes directrices traitant des saines habitudes de vie, des indications de pharmacoth erapie chez l'enfant atteint d'hypertension, du choix du traitement chez l'enfant atteint d'hypertension primaire et des objectifs th erapeutiques pour ce groupe de patients. Bien que la litt erature m edicale concernant les enfants comporte des limites inh erentes au faible nombre d' etudes disponibles, au peu de participants prenant part decision-making in pediatric populations. However, there are important limitations, compromising the quality of this evidence, including: small numbers of participants, short followup, the use of surrogate outcomes (ie, BP change), industry funding, and absence of traditional placebo control.
In 2016, Hypertension Canada's Guidelines Committee (GC) published their first pediatric guidelines for BP measurement, diagnosis, and investigation of pediatric hypertension. 4 Having provided guidance on identification of hypertension in children, the next crucial step is to provide guidance for management of hypertension. Following the highly structured Hypertension Canada's guideline process, the pediatric subgroup systematically evaluated existing literature to construct guidelines for the prevention and treatment of pediatric hypertension. Specifically, guidelines were developed for health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension.
Together these guidelines aim to guide primary care practitioners and pediatricians to identify, investigate, and manage hypertension in children and adolescents and also provide recommendations on when referral to experts in pediatric hypertension is appropriate. Health behaviour modification might be beneficial to hypertensive children of all ages. Medications need to be dosed on a milligram per kilogram basis in children and dosing ranges might differ from those for adults so familiarity with the drugs is important for treating physicians. Our guidelines for pharmacologic treatment of pediatric hypertension by primary care practitioners apply to children 12 years of age and older with primary hypertension. As is standard practice with Hypertension Canada guidelines, diagnostic and therapeutic algorithm tools will be developed and guidelines will continue to be reviewed annually and updated as new evidence becomes available.
Hypertension Canada's GC is a multidisciplinary panel of content and methodological experts comprised of 1 Chair, 1 Chair of the Central Review Committee (CRC), a CRC, and 15 subgroups. Each subgroup addresses a distinct content area (Supplemental Appendix S1 presents the current GC membership list). Members of the Canadian Task Force on Preventive Health Care, the Canadian Diabetes Association GC, the Canadian Society of Nephrology, the Canadian Stroke Network, the Canadian Cardiovascular Society, and the Canadian Cardiovascular Harmonized National Guideline Endeavour Initiative regularly collaborate with Hypertension Canada members to facilitate harmonization of hypertensionrelated guidelines across organizations. In many cases, Hypertension Canada GC members serve as volunteers for multiple organizations.
A systematic literature search of MedLine/PubMed from January 2004 to December 2015 was performed by a highly trained research librarian. Search terms included hypertension and BP; these were combined with relevant topic-specific terms and age limited to children (birth to 18 years). References of identified articles were also reviewed to identify additional works. Details of search strategies and retrieved articles are available on request.
The pediatric subgroup reviewed the search results. Study characteristics and quality were assessed using prespecified standardized algorithms developed by Hypertension Canada's GC for the critical appraisal of studies. 5 Recommendations were graded according to the strength of their underlying evidence (details in Supplemental Table S1) from grade A (strongest evidence, on the basis of high-quality studies) to grade D (weakest evidence, on the basis of low-powered imprecise studies or expert opinion). Although Hypertension Canada's GC does not use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendation scheme (www.gradeworkinggroup.org), it should be noted that all GC guidelines are considered to be "strong" in nature.
Pediatric subgroup members are hypertension specialists in pediatric nephrology, pediatric cardiology, pharmacology, and nursing. The pediatric subgroup was responsible for reviewing abstracts, critically appraising the literature, and drafting the guidelines. An independent CRC consisting of methodological experts with no industry affiliations independently reviewed, graded, and refined the proposed guidelines, which were then presented at a consensus conference of the GC in Montreal, Quebec, Canada on October 19, 2016. Present at the meeting were the Chair of the Hypertension Canada's current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence. aux etudes et a l'importante p eriode de latence entre le diagnostic et l'apparition de problemes vasculaires, notre rapport s'appuie sur les plus r ecentes et les meilleures donn ees probantes actuellement disponibles pour offrir aux intervenants de premiere ligne des indications sur la prise en charge de l'hypertension chez l'enfant. Diverses etudes sur la modification du mode de vie a des fins th erapeutiques chez l'enfant permettent d esormais de guider les intervenants a ce chapitre et nous disposons egalement d'information sur un plus grand nombre d'antihypertenseurs ayant et e etudi es chez l'enfant a la suite de l'adoption de la Food and Drug Administration Modernization Act aux Etats-Unis. Conform ement a la politique sur les lignes directrices d'Hypertension Canada, nous elaborerons des algorithmes de diagnostic et de traitement de l'hypertension chez l'enfant et nous reverrons annuellement les lignes directrices en fonction des donn ees probantes emergentes.
GC, the CRC Chair, the CRC, and members of all subgroups. Further revisions to proposed guidelines were on the basis of these discussions. Members with potential conflicts of interest recused themselves from voting on specific guidelines (a list of conflicts is available in Supplemental Appendix S2). After the consensus meeting, the guidelines that were supported by the majority of the consensus conference attendees were finalized and submitted electronically to all 81 voting members of the Hypertension Canada GC for final approval. Guidelines receiving > 70% approval passed. The Hypertension Canada guidelines process is in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II guidelines and has been externally reviewed. 6 A summary of how the Hypertension Canada guidelines process aligns with AGREE II can be found online at . hypertension.ca/about/overview-process. Materials to assist with patient and public education on the basis of these guidelines are available at .  S3; Grade D).

# II. Criteria for diagnosis of hypertension in children
Background. There are no changes to these guidelines 4 for 2017.
- Using office BP measurements, children can be diagnosed as hypertensive if systolic BP (SBP) or diastolic BP (DBP) is at the 95th percentile or greater for age, sex, and height, measured on at least 3 separate occasions (Grade C). 2. If the BP is at the 95th percentile or greater, BP should be staged. Stage 1 is defined by BP between the 95th and 99th percentiles plus 5 mm Hg. Stage 2 is defined by BP > the 99th percentile plus 5 mm Hg (Grade D). i. If BP is stage 1, BP measurements should be repeated on 2 more occasions within 1 month; if hypertension is confirmed, evaluation (as described in section IV. Routine Laboratory Tests for the Investigation of Children
With Hypertension) or appropriate referral should be initiated within 1 month, or both (Grade D). ii. If BP is stage 2, prompt referral should be made for evaluation and therapy (Grade C).

# All children with suspected or confirmed hypertension
should undergo a hypertension-focused history and physical evaluation (Supplemental Table S4; Grade C).

# III. Assessment of overall cardiovascular risk in hypertensive children
Background. There are no changes to these guidelines 4 for 2017.
- Cardiovascular risk factors should be assessed in hypertensive children (Grade C).

# IV. Routine laboratory tests for the investigation of children with hypertension
Background. There are no changes to these guidelines 4 for 2017.
- Routine tests that should be performed for the investigation of all children with hypertension include: i. Blood chemistry (sodium, potassium, chloride, total CO 2 and creatinine; Grade D); ii. Urinalysis (Grade D); iii. Renal ultrasonography (Grade D). 2. Routine laboratory tests that should be performed for the assessment of cardiovascular risk in all children with hypertension include the following: i. Fasting blood glucose (Grade C); ii. Serum total cholesterol and high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels (Grade C). 3. Routine tests that should be performed for the assessment of target organ damage in all children with hypertension include the following: i. Echocardiography (Grade C); ii. Retinal examination (Grade C); iii. Albumin-to-creatinine ratio (first-morning determination; Grade D).

# V. Ambulatory BP monitoring in children
Background. There are no changes to these guidelines 4 for 2017. With the reported associations between childhood BP and BMI, 1,2,7 diet,  and physical activity, 1,10 recent intervention studies to modify these risk factors have shown some improvements in markers of cardiovascular health.  One randomized controlled trial of exercise intervention including 60 minutes of physical activity 3 times a week for 3 months compared with no intervention showed reduction in office and ambulatory BP in the physical activity group. 11 In the no intervention group, the BPs increased so that the exercise intervention BP difference was 7 mm Hg for clinic SBP and DBP, and 11 mm Hg for 24-hour ambulatory SBP. They also showed improvements in carotid intima-media thickness and arterial stiffness in the intervention group at 6 months. A systematic review and meta-analysis of exercise intervention trials in children with obesity showed a small but significant pooled effect estimate for reduction in BP. 12 The analysis was likely affected by the heterogeneity in trial design with differences in duration of study intervention, frequency of intervention, length of time of activity during session, and total exercise time. These limitations make it challenging to offer specific evidence-based recommendations for amount and frequency of physical activity, and an individualized and patient-centred approach is likely to be the most successful.
Evidence for dietary improvements in reducing BP in children is increasing. Most children consume high amounts of salt and a meta-analysis of 10 controlled trials of salt reduction in children by 42% found a small but significant reduction in systolic (A1.2 to A2.5 mmHg) as well as diastolic (A1.3 mm Hg) BPs. 13 In a longitudinal study of young girls followed for 10 years it was reported that a higher intake of potassium (! 2400 mg/d) was related to lower BP. 14 Higher potassium foods are generally fruits and vegetables, as well as dairy products. The Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits, vegetables, grains, low fat dairy, and low in fat, sugar, and sodium has shown some benefits in adult as well as pediatric populations. Specifically, in a randomized cross-over trial of DASH diet vs usual dietary advice in children with metabolic syndrome a reduction in the prevalence of elevated BP with the DASH diet was reported. 15 The combination of dietary improvements as well as increased physical activity seems to amplify the beneficial effects. A systematic review and meta-analysis of 23 studies of obesity prevention programs in children found that combined diet and physical activity interventions led to a significantly greater reduction in SBPs and DBPs than either alone. 16 Although healthy eating and physical activity is taught in most school systems, children with hypertension, obesity, or those at risk for either might benefit from specific advice from health care practitioners or allied health team members to improve these healthy behaviours. A patient-and familycentred approach to promote changes to the entire family diet and lifestyle might increase the probability of long-term beneficial change. 17
- Height and weight should be measured and body mass index (BMI) calculated for all children at routine health visits (Grade D). 2. Achieving a healthy body weight (BMI < 85th percentile) is recommended for nonhypertensive individuals to prevent hypertension and for hypertensive children to reduce BP (Grade C). 3. A comprehensive approach should include dietary education and increased physical activity (Grade C).

# II. Indications for drug therapy for children with hypertension
Background. The decision to initiate drug treatment of pediatric hypertension depends on many factors including the presence of symptoms of hypertension, level of BP elevation, presence of end-organ damage, response to nonpharmacologic therapy, and presence of comorbid conditions that confer increased cardiovascular risks. Symptoms of hypertension might include irritability, fatigue, dizziness, chest pain, abdominal pain, and headache. End-organ damage might be detected on echocardiogram as left ventricular hypertrophy (LVH), on fundoscopy as hypertensive retinopathy, or on urine analysis as albuminuria. These factors are not entirely exclusive because children with more severe hypertension might also have greater LVMI and albuminuria than those with less significant hypertension and albuminuria has been correlated with LVMI. 18,19 In a retrospective cohort study, Kupferman et al. compared children treated with antihypertensive medications with untreated patients. 20 The indications for drug treatment included hypertensive symptoms, severe hypertension, risk factors such as chronic kidney disease, and target organ damage. They reported that 33% of treated patients with LVH had resolution of the cardiac anomaly by follow-up echocardiogram after more than 6 months of treatment. 20 Of untreated patients, 28% developed LVH by follow-up. The change in LVMI correlated with the change in SBP. 20 Additional evidence for pharmacologic intervention comes from the Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. They showed that treatment of BP reduced LVMI in all treated and more so in those with LVH. 21 The prevalence of LVH decreased from 38% to 25% after 1-2 years of treatment. In addition, intensified BP control reduced systolic dysfunction. Many factors, including side effects, need to be considered for initiation of pharmacologic management of hypertension in children but with treatment, cardiac target organ damage can be reduced.

# III. Choice of therapy for children with primary hypertension
Background. There are an increasing number of antihypertensive drugs approved for use in children since passage of the Food and Drug Administration Modernization Act in 1997. However, trials have primarily been limited to the newer medications, mostly ACE inhibitors and ARBs. Most of the drugs are approved for use only in children older than 6 years of age because of limited trials in the younger age groups.
In children, medications need to be dosed on a milligram per kilogram basis and dosing ranges might differ from those in adults because of differences in drug metabolism and body composition. 22,23 Younger children usually prefer suspension formulations if they are palatable. Targeting drug therapy to an underlying cause of hypertension should be directed by an expert in pediatric hypertension. The younger the child, the more likely they are to have a secondary cause identified for the hypertension. For these reasons, we strongly recommend that the guidelines for pharmacologic treatment of pediatric hypertension by primary care practitioners should apply only to children 12 years of age or older. Younger children and those suspected of having a secondary cause for their hypertension should be referred to and managed by experts in pediatric hypertension. The pharmacologic guidelines apply to children with systolic and/ or diastolic hypertension. There are 3 good-quality randomized controlled trials of ACE inhibitors in children with hypertension. The drugs studied include enalapril, lisinopril, and fosinopril and each showed a good BP response to the medication (A6 to A16 mm Hg) and difference from placebo in the withdrawal phase (4-6 mm Hg).  Meta-analysis of all ACE inhibitor trials in children submitted to the Food and Drug Administration showed that black patients experienced less BP reduction than other races with these drugs. 27 Side effects are uncommon but are similar to those in adult patients with the potential for hypotension, increased serum creatinine, acute kidney injury, hyperkalemia, and angioedema. 23,28 Cough seems to be less common in children with ACE inhibitors and not different than placebo in trials. 29 Interval monitoring of kidney function and electrolytes should be practiced and caution should be used when considering these drugs in children prone to dehydration. Counselling on risks of teratogenicity should be done in female patients of child-bearing age.
Several randomized controlled trials of ARBs in children with hypertension have shown a good BP response to the medication (A6 to A13 mm Hg) and a difference from placebo (3-7.5 mm Hg).  Good-quality trials have been completed with losartan, candesartan, olmesartan, and valsartan. Most of the studies report a lesser BP response in black patients. Side effects are not common and potentially might include hypotension, hyperkalemia, and acute kidney injury. 23 Similar to ACE inhibitors, caution should be used with these medications in children prone to dehydration; kidney function and electrolytes should be monitored, and counselling on risks of teratogenicity should be done in female patients of child-bearing age. One comparison trial, in which hypertensive children were randomized to either ARB (valsartan) or ACE inhibitor (enalapril) reported similar significant reductions in BP in both groups. 34 b-Blockers are less well studied in children. Only 1 trial in the literature has been completed using extended-release metoprolol showing a BP reduction significantly different from placebo. 35 With potential for bronchospasm, b-blockers are not recommended in children with asthma. 23 They also cause bradycardia because of their mechanism of action, and are therefore not preferred in high-performance athletes and b-blockers might mask symptoms of hypoglycemia in children with diabetes mellitus. 23 More recent studies in adults suggest an increased risk of insulin resistance and new diabetes onset with b-blockers making them a less desirable choice in children with or at risk for diabetes mellitus. 28,36 Other medications studied for pediatric hypertension have had less consistent results. Trials of the long-acting dihydropyridine calcium channel blockers amlodipine and felodipine have shown modest differences from placebo in BP response but the trials were confounded by lack of adjustment for body weight, low drug dosing, and inadequate time during the dose titration phase. 37,38 Benefits of calcium channel blockers include good tolerance of the drug with uncommon side effects including edema and gingival hyperplasia, and no need for bloodwork monitoring. 28 Only a single trial of a combination antihypertensive drug has been completed in children with a b-blocker/thiazide combination but the BP reduction was not significantly different from placebo. 39 Unlike in adult populations, diuretics alone have not been systematically studied in children for hypertension. In practice, diuretics are used in combination with other antihypertensive agents but caution must be taken because of the potential for electrolyte disturbances or dehydration with minor illness in children. 23,28 The lack of trials of singlepill combination drugs and diuretics limits our ability to provide guidance regarding the efficacy of these medications for the treatment of pediatric hypertension.
A recent Cochrane systematic review of randomized placebo controlled trials of antihypertensive drugs in children found a limited number of positive trials with most trials of very low-quality evidence by their strict criteria. 40 Simonetti et al. completed a systematic analysis of data from 27 antihypertensive drug trials in children and reported that all drug classes (ACE inhibitors, ARBs, and calcium channel blockers) reduced BP by a similar amount with a mean of just > 10 mm Hg. 41 Our recommendations are on the basis of the best available evidence for practitioners who are comfortable in prescribing antihypertensive medications to children and adolescents. Referral to an expert in pediatric hypertension for BP management is always an acceptable alternative. ii. An alternate option is a b-blocker (Grade D) although they are less preferable because of the side effect profile in children. iii. If there are adverse effects, another drug from this group should be substituted. 2. If BP goals are not achieved with standard-dose monotherapy for ! 6 months, children should be referred to an expert in pediatric hypertension (Grade D). 3. ACE inhibitors (Grade C) and ARBs (Grade D) are not recommended as first-line agents in black patients and bblockers are not recommended as first-line agents in children with asthma, diabetes (type 1 or type 2), or in highperformance athletes (Grade D).

# IV. Goals of therapy for children with hypertension
Background. The overall goals of therapy for children with hypertension are to achieve a BP level that reduces the risk of target organ damage in childhood, and ultimately reduces the risk of hypertension and cardiovascular disease in adulthood. The International Childhood Cardiovascular Cohort Consortium has shown that adult carotid intima-media thickness is significantly higher in adults who had elevated BP during childhood that persisted to adulthood compared with those whose BP normalized in adulthood. 42 In addition, several longitudinal studies provide evidence that elevated BP in childhood increases the risk up to 5-fold for developing adulthood hypertension and metabolic syndrome.  Limited evidence exists on assessment of goals of pharmacologic treatment of pediatric hypertension to guide hypertension management. In a prospective controlled trial of 12-month antihypertensive treatment of children with hypertension, 80% were able to achieve the goal clinic BP of less than the 95th percentile at 1 year. 19 With treatment, LVMI decreased by 32% and albuminuria decreased by 45%. A study of pharmacologic treatment of pediatric hypertension to an ABPM goal BP less than the 95th percentile or BP load < 25% showed that the prevalence of LVH was lower in children with controlled hypertension than in those with uncontrolled hypertension (13% vs 46%, respectively). 46 In other ABPM studies, treatment of pediatric hypertension was able to reduce BP to less than the 95th percentile in 53%-74% of children, and LVH reduced from 42%-46% at baseline to 11%-28% at 6-12 months. 18,47 Although these studies show that targeting a BP less than the 95th percentile reduces LVH, achievement of the goal does not seem to eliminate the end-organ damage in all. Therefore, it seems reasonable to target less than the 90th percentile clinic or ambulatory BP in children with current target organ damage or concurrent cardiovascular risk factors including diabetes mellitus type 1 and 2, chronic kidney disease, or a structural or functional cardiac anomaly. This is in keeping with current practice of most pediatric nephrologists in North America. 48 Guidelines 1. The treatment goal is office BP (systolic and diastolic) less than the 95th percentile (Grade D). The goal for ABPM is BP (systolic and diastolic) less than the 95th percentile (Grade D). 2. For patients with risk factors or target organ damage the goal is BP (systolic and diastolic) less than the 90th percentile (Grade D).

# Summary/Future Directions
These evidence-based guidelines represent the second report of Hypertension Canada's GC pediatric subgroup. Building on the previous guidelines for BP measurement, diagnosis and investigation of hypertension, the current guidelines on prevention and treatment of pediatric hypertension aim to guide primary care practitioners in providing initial evidence-based care to children and adolescents with hypertension. Although the etiology, implications, and management considerations of hypertension in children might differ from that in adults, we appreciate that primary care practitioners might be evaluating and managing patients of most age groups. We have therefore provided a table that highlights the major guideline recommendations for BP assessment and management from the pediatric as well as adult guidelines for comparison (Table 1). 49 Diagnostic and therapeutic algorithm tools to complement the Pediatric Guidelines will be developed by Hypertension Canada's Implementation Task Force in collaboration with the pediatric subgroup. We will continue to systematically review the literature annually and update guidelines as new evidence emerges.   For adults with diastolic with or without systolic hypertension, without compelling indications for specific agents.
We sincerely thank Ms Susan Carter for her technical assistance with the manuscript and administrative support of the process and committee.

# Funding Sources
The Hypertension Canada GC is operated and funded by Hypertension Canada. The members of the GC are unpaid volunteers who contribute their time and expertise to the annual development and dissemination of the guidelines. To maintain professional credibility of the content, the process for the development of the guidelines is fully independent and free from external influence. External partners assist with the dissemination of the approved guidelines.
A complete list of author disclosures is available in Supplemental Appendix S2.