Hypertension Is Difficult to Control in Children, Too

See the Original Article by Seeman and Gilik on page 939. Although debate about the optimal blood pressure (BP) target in adults persists, it is well established that hypertension should be controlled to reduce the incidence of cardiovascular events such as heart attack and stroke and also to prevent the development of end-stage renal disease. Efforts to improve control of hypertension in adults are beginning to achieve positive results: the percentage of hypertensive adults with controlled hypertension has increased from about 27% in the period from 1988 to 1994 to 50% in the period from 2007 to 2008.1 Data from numerous clinical trials conducted in hypertensive adults have demonstrated that achievement of goal BP typically requires multiple-drug regimens; in fact, combination therapy is often recommended at the outset of treatment, as combinations of drugs with different mechanisms of actions may be more effective than reliance upon a single agent.2 Effective control of hypertension also requires frequent follow-up appointments for dose titration, home BP measurement, and screening for adverse effects of medications and barriers to achieving goal BP. No data exist, however, on rates of control of hypertension in children and adolescents or on how best to achieve BP control in the young. Clinical practice recommendations for management of childhood hypertension typically advocate a stepped-care approach starting with a single agent and early referral to a specialist if BP control is not achieved with 1 or 2 antihypertensive agents.3,4 The optimal goal BP for children with hypertension has yet to be established, and there are differing recommendations in the currently available pediatric guidelines (Table 1). The goals for lower pediatric BP advocated by the European Society of Hypertension (ESH)4 have not been subjected to extensive clinical evaluation, except in children with renal disease, in whom lower BP appears to convey a significant renoprotective benefit.5 Finally, there is uncertainty in pediatrics as to whether detection and treatment of high BP in the young has any beneficial effect at all in terms of reducing cardiovascular morbidity in adulthood.6 Comparison of currently recommended pediatric blood pressure goals a Based upon casual/office blood pressure measurement. b Based upon ambulatory blood pressure measurement. Comparison of currently recommended pediatric blood pressure goals a Based upon casual/office blood pressure measurement. b Based upon ambulatory blood pressure measurement. With the preceding background in mind, the study by Seeman and Gilik7 (this issue) raises a number of intriguing questions. They examined their success in treating a small group of hypertensive children, most of whom had underlying renal disease. Therapy in all cases was initiated with the angiotensin-converting enzyme inhibitor ramipril, and annual ambulatory BP monitoring [ABPM] was performed to assess BP control. No information was provided regarding the implementation of nonpharmacologic measures such as dietary sodium restriction or exercise. Achievement of the BP targets recommended in the ESH pediatric guidelines occurred in just one-third of the patients studied. Of note, just one-third of all subjects in the study received combination therapy, and there was no difference in the number of antihypertensive drugs used in controlled vs. uncontrolled patients. Finally, the prevalence of obesity did not change over the study period, and there was no difference in obesity prevalence between children with controlled and uncontrolled hypertension.7 There are some obvious potential explanations for the failure to achieve better BP control in this study, some of which the authors acknowledge. First and foremost would have to be the low utilization of combination antihypertensive therapy. The pathophysiology of hypertension is complex and may involve multiple mechanisms in a single patient, even in patients with “uncomplicated” primary hypertension. Thus, there is ample rationale for widespread use of multiple agents with different mechanisms of action and even for use of combination agents as initial therapy.2 Yet in pediatrics, there seems to be a reluctance to use combination therapy, particularly in patients with primary hypertension. This is illustrated by a recent analysis of antihypertensive prescribing patterns among hypertensive adolescents in the state of Michigan.8 In that study, most of the 25% or so of patients who received multiple agents were under the care of adult primary-care providers, not pediatricians. Even pediatric subspecialists were much less likely to prescribe multiple agents than adult providers.8 Why is this? Both current pediatric guidelines explicitly endorse the use of a second or even third agent when BP goals are not met.3,4 Yet the data presented by Seeman and Gilik7 seem to suggest that these guidelines do not appear to be “hard-wired” into the day-to-day care of hypertensive children. Perhaps the lack of pediatric labeling data for antihypertensive medications is playing a role here: many commonly used antihypertensives have not been studied in children and still lack pediatric labeling and approval by regulatory agencies. This is especially true for combination antihypertensives, none of which are currently labeled for use in children and adolescents. On the other hand, recent data suggest that many antihypertensive medications that lack pediatric labeling or regulatory approval are, in fact, commonly prescribed to children.9 So practitioners appear to be comfortable with off-label use of antihypertensive medications in the young but do not appear to be comfortable combining multiple agents. A potential issue with achievement of BP control that is unique to pediatrics is the complexity of the normative data itself. Unlike in adults where a single BP value is used to define hypertension, in children and adolescents, complex charts of normative BP values must be consulted to determine if a patient’s BP value is normal or elevated.3 These charts are time consuming and cumbersome to use, and have been blamed for underdiagnosis of hypertension by primary-care providers, especially among younger children.10 If the charts are to blame for underrecognition of elevated BP values, it follows that they must also complicate the treatment of hypertension—what busy provider has the time to consult these charts when determining whether a patient’s BP is below the 90th or 75th or 50th percentile? The variability in the ESH recommendations for children with renal hypertension (Table 1) add a further layer of complexity to the office visit at which BP control is assessed. An additional factor that might have been at play in the study by Seeman and Gilik is that patients were probably assessed relatively frequently using casual (office) BP measurements but only once annually using ABPM.7 Resting BP values are typically lower than ambulatory BP values, so it is possible that patients might have seemed controlled by causal BP but were then uncontrolled when studied by ABPM (i.e., they had masked ambulatory hypertension). Because we do not yet have data on whether casual or ambulatory BP values are more predictive of long-term cardiovascular outcome in children, perhaps reliance on ABPM-based targets as recommended by the ESH needs to be reexamined. One final issue that deserves mention is the role of nonpharmacologic measures in hypertensive pediatric patients who fulfill criteria for drug therapy. Seeman and Gilik briefly mention in their discussion the potential role of dietary sodium restriction,7 but they provide no information on whether they used this or other nonpharmacologic measures in their population. Indeed, the number of obese children in their small study increased from 6 at baseline to 7 at last follow-up (numbers calculated from tables 1 and 2 in Seeman and Gilik7). Obesity and high sodium intake are common features of patients with “resistant” hyper tension.2 Weight loss, dietary modification, and increased exercise need to be implemented and sustained regardless of whether patients are prescribed anti hypertensive medications.2–4 Thus, as in adults, it appears that control of hypertension is difficult to achieve in pediatric patients. Pediatricians who care for such patients need to overcome their reluctance to intensify therapy, particularly the use of multiple antihypertensive agents. Nonpharmacologic measures should not be overlooked just because a prescription has been written. And current pediatric treatment guidelines need to be reexamined and perhaps simplified, optimally after better long-term evidence has been generated. The author declared no conflict of interest.