Editorial
Controversy about hypertension screening in children: a public health perspective Arnaud Chiolero a, Pascal Bovet a, and Gilles Paradis b
I
n 2013, the US Preventive Services Task Force (USPSTF) updated its recommendations about screening for elevated blood pressure in children and adolescents [1]. On the basis of a thorough review of the evidence [2], it concluded that ‘current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease (CVD)’ [1]. These recommendations have raised an important controversy [3–5] notably because they are at odds with recommendations of highly respected and influential health professionals and scientific organizations, such as the US National Heart, Lung, and Blood Institute or the European Society of Hypertension, that children aged 3 years and older have their blood pressure level measured regularly [6,7]. There is indeed ample evidence that the pathogenic process of atherosclerosis causing CVD begins early in life, in particular, during childhood and adolescence [8]. Hence, elevated blood pressure in children has been shown to be associated with increased carotid intima–media thickness (a surrogate marker for atherosclerosis and a strong predictor of CVD in adults) and with atherosclerosis in childhood and in adulthood [7–9]. Further, elevated blood pressure tracks from childhood through adulthood [10] and is associated in children with end-organ damage such as cardiac left ventricular hypertrophy [11]. These observations support the view that screening and treatment of hypertension should begin from childhood. The fact that elevated blood pressure in children is a true risk factor for CVD is, however, not sufficient to justify a universal screen-and-treat strategy beginning in childhood [12]. Doubts about the benefits of hypertension screening during childhood are not new [13,14], but the debate has recently re-emerged [1,15], with strong positions seemingly impossible to reconcile [3–5]. In this viewpoint, we discuss the goals of hypertension screening in children, why there are doubts about its potential benefits and harms, and propose avenues to solve the controversy.
GOALS OF HYPERTENSION SCREENING IN CHILDREN Screening aims to identify early disease or risk factors for future disease in populations of asymptomatic individuals, to help manage the identified condition through early intervention [15,16]. Screening should not be confused with clinical case finding where diseases are sought in 1352
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individuals who consult health professionals with clinical signs or symptoms suggesting the presence of the condition. A commonly accepted goal of hypertension screening is to identify children at high risk of CVD due to the elevated blood pressure and to reduce this risk by early treatment. This is also the goal of hypertension screening in adults [17]. Another goal, which should be clearly distinguished from the goal mentioned above, is the early identification and treatment of diseases causing hypertension, that is, the screening for causes of secondary hypertension. A large part of the controversy about hypertension screening in children arises from the confusion between these two goals. USPSTF recommendations are for screening ‘for primary hypertension [...] to prevent subsequent CVDs’ [1], and not screening for secondary causes of hypertension. This is a problem because pediatricians afford more importance to the identification of diseases causing secondary hypertension than to the early diagnosis and treatment of hypertension for the prevention of CVD.
CONSIDERATIONS PRIOR TO RECOMMEND SCREENING Before making recommendations about hypertension screening in children, several issues should be addressed (Table 1). First, a method should exist to distinguish children with hypertension from children without hypertension. This method should be ideally easily applicable, valid, and reliable. The diagnosis of hypertension is, however, a serious challenge in children for several reasons [15,18,19]. Hence, it is difficult to define the level of blood pressure above which a child is considered as hypertensive and requires treatment [19]. In adults, elevated blood pressure is defined based on the substantial increase in the absolute
Journal of Hypertension 2015, 33:1352–1355 a Division of Chronic Diseases, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland and bDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
Correspondence to Arnaud Chiolero, MD, PhD, Senior Lecturer, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital (CHUV), Biopoˆle 2, 1010 Lausanne, Switzerland. Tel: +41 21 314 72 72; fax: +41 21 314 73 73; e-mail: [email protected] Received 28 November 2014 Revised 15 February 2015 Accepted 25 February 2015 J Hypertens 33:1352–1355 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000000579
Volume 33 Number 7 July 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Hypertension screening in children TABLE 1. Issues to address to decide whether screening should be recommended or not Issue
Commentary
Is it possible to identify with confidence children with hypertension?
There is no risk-based definition of hypertension in children; the high variability of blood pressure requires repeated blood pressure measurement at several visits to diagnose hypertension (defined as sustained elevated blood pressure). On the basis of the relatively few studies with blood pressure measured at several visits, the prevalence is likely 1–5% [22,23]. Elevated blood pressure in childhood is associated with elevated blood pressure and surrogate markers of CVD later in life. However, there is no information on the absolute risk of CVD or mortality associated with a given level of blood pressure in childhood [18]. The short-term efficacy and safety of lifestyle intervention and antihypertensive treatment has been documented in children; there are no data on the long-term efficacy and safety. There is no experimental evidence of the benefits and harms of hypertension screening beginning in childhood. One modeling study suggests that screen-and-treat strategies in adolescents would be less cost-effective than public health (population-based) interventions to decrease CVD risk [35].
What is the prevalence of hypertension in children? Is elevated blood pressure in children associated with an increased risk of CVD and mortality later in life? Is treatment for elevated blood pressure in children effective and safe? Does screening for hypertension in children reduce the risk of CVD and mortality later in life? Adapted from Chiolero et al. [15]. CVD, cardiovascular disease.
risk of CVD above a given level of blood pressure and the evidence that blood pressure reduction with antihypertensive treatment decreases this risk. Of note, the absolute risk of CVD also strongly depends on age and other factors, so that the sole information of a person’s blood pressures is moderately helpful in deciding whether to treat high blood pressure or not [12,20]. No such data exist in children since no cohort study of sufficient duration has shown an association between childhood blood pressure and CVD risk, and no clinical trial has linked blood pressure reduction in children with reduced risk of CVD. Therefore, elevated blood pressure in children is defined as blood pressure above a certain level, that is, the 95th percentile, on the basis of the distribution of blood pressure in a reference population [18,21]. Such distribution-based definition of elevated blood pressure is problematic because it depends on the reference population and raises never-ending discussion about the ideal blood pressure thresholds and how well these cut-off values may be validly used in different populations [19]. Further, the diagnosis of hypertension requires the measurement of blood pressure at several occasions. It is standard to require blood pressure to be elevated on at least three separate visits to diagnose hypertension [18,21]. This is important because most children with elevated blood pressure at an initial screening visit will have normal blood pressure at subsequent visits. For example, in a schoolbased study of 5207 children 10–12 years of age, the prevalence of elevated blood pressure was 11.4, 3.8, and 2.2% on first, second, and third visits, respectively [22]. Similar figures were found in other studies, with up to 20% of children having elevated blood pressure at the initial visit [23]. From a practical point of view, if 10–20% of initially screened children have elevated blood pressure, then one out of every 5–10 children would require subsequent visits for blood pressure measurement. There is also a growing consensus that blood pressure should be measured out of the office, for example, using ambulatory measurement or home blood pressure monitoring, to avoid white-coat effect and to identify masked hypertension [24,25]. This difficulty to obtain valid measurements of blood pressure is probably one of the reasons why pediatricians do not screen systematically for hypertension [26]. Second, the prevalence of hypertension in children in a particular population should be known prior to initiating Journal of Hypertension
screening. Surprisingly, relatively few studies have estimated the prevalence of hypertension in children on the basis of repeated measurements at multiple visits. It is estimated that 1–5% of children would be hypertensive on the basis of multiple blood pressure measurements [22,23]. An increasing prevalence of elevated blood pressure in children could be an argument in favor of screening. However, despite the increase in the prevalence of childhood obesity, blood pressure have not increased in several countries [27,28]. More recently, blood pressure may have increased in the USA [29] or China [30], but not in other countries [31,32]. Third, it is necessary to know the absolute risk of disease associated with a given level of blood pressure in childhood. In adults, estimating the absolute CVD risk is necessary to evaluate the indication for treatment [33,34]. Hence, for a given level of blood pressure, adults at high risk of CVD are eligible for a treatment, whereas adults at low risk of CVD are not. Below a certain level of absolute risk, there is indeed no individual benefit to expect from blood pressure treatment. It is reasonable to assume that children with elevated blood pressure have a higher long-term risk of CVD compared to children with low blood pressure. However, for a given period (e.g. 10 years), it is also reasonable to assume that the absolute risk of diseases related to elevated blood pressure is much lower than in adults. More fundamentally, the fact that CVD events will not occur before several decades strongly limits any substantial benefits of individual CVD risk factors screening and treatment in childhood. Fourth, all screening and early detection strategies can be justified only if a safe and efficient treatment exists. The short-term efficacy and safety of lifestyle intervention and antihypertensive treatments have been documented in children [18]. However, there are no data on the long-term efficacy and safety of treatments started in childhood and taken over several decades. Robust evidence is indeed needed to justify decades of preventive treatment. Finally, there is no experimental evidence of the benefits and harms of hypertension screening beginning in childhood. One modeling study suggests that screen-and-treat strategies in adolescents would be less cost-effective than populationwide interventions to decrease CVD risk [35]. All these issues and uncertainties are reasons why the USPSTF did not recommend hypertension screening in children. www.jhypertension.com
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BENEFITS VERSUS HARMS OF SCREENING Evaluating any screening procedure necessitates an assessment of the balance between benefits and harms [16]. Intuitively, the benefits of screening are evident and it is difficult to imagine any harm due to hypertension screening in children. While measurement of blood pressure in itself is not harmful, potential harms include the anxiety of being labeled hypertensive and the stress induced by investigations necessary to assess the causes or consequences of elevated blood pressure. Another issue is the fact that sorting out hypertensive from nonhypertensive children does not solve the dilemma that many cases of CVD will occur in individuals with normal blood pressure. Indeed, blood pressure, at an individual level, is a relatively weak prognostic factor for CVD, and the majority of CVD cases occur in persons with normal blood pressure [12,20]. Further, an earlier identification and treatment does not convey automatically more benefits than identification and treatment later in life. Lead time – a well known source of bias in the evaluation of cancer screening – has to be considered for blood pressure screening as well (Fig. 1). The lead time is the length of time between the detection of hypertension by screening and the occurrence of a CVD event. If screening begins in childhood, elevated blood pressure can be detected earlier and the lead time will be greater than with screening in adulthood. The increase in lead time is, however, not a good indicator of the benefit of childhood screening. To be useful, compared to screening and treatment in adulthood (known to help postpone or prevent CVD), screening of hypertension in children has to be associated with a further postponement of CVD events. Otherwise, screening in childhood leads to an earlier initiation and longer duration of treatment, implying greater costs and more opportunity for treatment side effects, without additional benefit compared to screening and treatment started in adulthood. In adults, screening for hypertension causes potentially the same harms and raises similar issues as in children. However, because hypertension is associated with a substantial increase in absolute risk of CVD and treatment of a)
Event
b)
Event
sc & ttt
c1)
sc & ttt
c2)
sc & ttt Childhood
Event ?? Adulthood
Event Time
FIGURE 1 Simplified and hypothetical clinical scenario of children with elevated blood pressure. (a) Natural history with the occurrence of an event (e.g. cardiovascular disease or death) relatively early in adulthood; (b) screening (sc) and treatment (ttt) in adulthood with postponement (if not prevention) of the event later in adulthood; (c1) useless screening and treatment in childhood: compared with (a), there is also a postponement of the event, but the event occurs at about the same age in adulthood as in scenario (b); hence, there is no additional benefit with early screening; (c2) Useful screening and treatment in childhood: compared with (a), (b), or (c1), there is an additional benefit since the event occurs later in life. Compared to screening in adulthood (b), screening in childhood is beneficial only in the scenario (c2).
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hypertension can substantially reduce this risk [17], the balance between benefits and harms is more favorable than in children and this is why screening is justified in adults.
WHAT ARE WE TO DO? Studies are needed to address the issues raised above (Table 1). Ideally, we would need cohort studies to estimate the absolute risk of disease associated with elevated blood pressure in children and clinical trials to quantify the effect on CVD risk and harms of hypertension screening and treatment beginning in childhood. While such studies are very difficult to conduct because of the very large sample sizes and several decades of follow-up to accumulate enough CVD events, tools like the International Childhood Cardiovascular Cohort (i3C) Consortium, collating data of several cohorts including over 40 000 children, will help assess the actual risk of elevated blood pressure (and other CVD risk factors) early in life [36]. Modeling studies evaluating various screening strategies [35] and clinical trials comparing the effects of these screening strategies on surrogate markers of CVD as outcomes are more easily feasible. Since the efficiency of universal screening is poor [37], strategies of targeted screening according to markers of elevated blood pressure risk, including body weight status, family history of hypertension, family history of CVD, or birth weight should also be evaluated [38]. In addition to further studies, it may be time to reframe radically the goals of hypertension screening, that is, distinguish screening for primary hypertension for the prevention of CVD from screening for diseases causing hypertension. Gillman [39] has recently argued against universal blood lipid screening in children and has proposed a ‘rare-disease’ conceptual framework for this screening. His idea is to restrain screening to the detection of children with very high risk of CVD due to familial hypercholesterolemia. By analogy, screening for hypertension could be reoriented toward the screening of diseases causing hypertension. These diseases are relatively rare, can be life-threatening if not treated, and there is no controversy about the potential benefits of early identification and treatment [18]. Such a strategy would be coherent with the concerns of clinicians who want to identify children with these diseases causing hypertension. Nevertheless, how to screen for such diseases (e.g. by targeted or cascade screening) remains to be defined and evaluated. Because secondary hypertension seems more frequent in younger than older children [18], it could be reasonable to consider and evaluate such screening strategies in the former. Finally, raising concerns about the benefits of screening hypertension in children does not mean that we deny that elevated blood pressure in childhood increases the risk of CVD or that prevention of CVD should start in childhood. We argue that prevention of CVD should, at this early age, focus on population-based primordial prevention strategies [40,41], to shift the blood pressure distribution of the entire population toward lower values, rather than to rely on universal screen-and-treat strategies. Volume 33 Number 7 July 2015
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Hypertension screening in children
ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.
22. 23.
REFERENCES 1. Moyer VA, U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2013; 159:613–619. 2. Thompson M, Dana T, Bougatsos C, Blazina I, Norris SL. Screening for hypertension in children and adolescents to prevent cardiovascular disease. Pediatrics 2013; 131:490–525. 3. Uy JD, Agawu A. Screening is not as simple as it may seem. Pediatrics 2013; 131:e1384–e1385. 4. Lo T, Malaga-Dieguez L, Trachtman H. U. S. Preventive Services Task Force recommendation and pediatric hypertension screening: dereliction of duty or call to arms? J Clin Hypertens 2014; 16:342–343. 5. Brady TM, Redwine KM, Flynn JT, American Society of Pediatric Nephrology. Screening blood pressure measurement in children: are we saving lives? Pediatr Nephrol 2014; 29:947–950. 6. National Heart, Lung, and Blood Institute (NHLBI). Integrated guidelines for cardiovascular health and risk reduction in children and adolescents, 2012. NHLBI website. http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm. [Accessed 16 September 2014] 7. Lurbe E, Cifkova R, Cruickshank JK, Dillon MJ, Ferreira I, Invitti C, et al., European Society of Hypertension. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 2009; 27:1719–1742. 8. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 1998; 338:1650–1656. 9. Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, Berenson GS. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA 2003; 290: 2271–2276. 10. Chen X, Wang Y. Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regression analysis. Circulation 2008; 117:3171–3180. 11. McNiece KL, Gupta-Malhotra M, Samuels J, et al., National High Blood Pressure Education Program Working Group. Left ventricular hypertrophy in hypertensive adolescents: analysis of risk by 2004 National High Blood Pressure Education Program Working Group staging criteria. Hypertension 2007; 50:392–395. 12. Wald NJ, Hackshaw AK, Frost CD. When can a risk factor be used as a worthwhile screening test? Br Med J 1999; 319:1562–1565. 13. de Swiet M, Dillon MJ. Hypertension in children. Br Med J 1989; 299:469–470. 14. Gillman MW, Cook NR, Rosner B, Evans DA, Keough ME, Taylor JO, Hennekens CH. Identifying children at high risk for the development of essential hypertension. J Pediatr 1993; 122:837–846. 15. Chiolero A, Bovet P, Paradis G. Screening for elevated blood pressure in children and adolescents: a critical appraisal. J Am Med Assoc Pediatr 2013; 167:266–273. 16. Raffle AE, Gray JAM. Screening: evidence and practice. Oxford [etc.]: Oxford University Press; 2007. 17. U.S. Preventive Services Task Force. Screening for high blood pressure: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med 2007; 147:783–786. 18. McCrindle BW. Assessment and management of hypertension in children and adolescents. Nat Rev Cardiol 2010; 7:155–163. 19. Chiolero A. The quest for blood pressure reference values in children. J Hypertens 2014; 32:477–479. 20. Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess 2003; 7:1–94. 21. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The
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fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114: 555 –576. Chiolero A, Cachat F, Burnier M, Paccaud F, Bovet P. Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight. J Hypertens 2007; 25:2209–2217. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004; 113:475–482. Lurbe E, Torro I, Alvarez V, Nawrot T, Paya R, Redon J, Staessen JA. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension 2005; 45:493–498. Stergiou GS, Rarra VC, Yiannes NG. Prevalence and predictors of masked hypertension detected by home blood pressure monitoring in children and adolescents: the Arsakeion School study. Am J Hypertens 2009; 22:520–524. Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA 2007; 298:874–879. McCarron P, Smith GD, Okasha M. Secular changes in blood pressure in childhood, adolescence and young adulthood: systematic review of trends from 1948 to 1998. J Hum Hypertens 2002; 16:677– 689. Chiolero A, Bovet P, Paradis G, Paccaud F. Has blood pressure increased in children in response to the obesity epidemic? Pediatrics 2007; 119:544–553. Din-Dzietham R, Liu Y, Bielo MV, Shamsa F. High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation 2007; 116:1488–1496. Liang YJ, Xi B, Hu YH, Wang C, Liu JT, Yan YK, et al. Trends in blood pressure and hypertension among Chinese children and adolescents: China Health and Nutrition Surveys 1991–2004. Blood Press 2011; 20:45–53. Chiolero A, Paradis G, Madeleine G, Hanley JA, Paccaud F, Bovet P. Discordant secular trends in elevated blood pressure and obesity in children and adolescents in a rapidly developing country. Circulation 2009; 119:558–565. Khang YH, Lynch JW. Exploring determinants of secular decreases in childhood blood pressure and hypertension. Circulation 2011; 124: 397–405. ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens 2013; 31:1925– 1938. Blood Pressure Lowering Treatment Trialists’ Collaboration, Sundstro¨m J, Arima H, Woodward M, Jackson R, Karmali K, et al. . Blood pressurelowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014; 384:591–598. Wang YC, Cheung AM, Bibbins-Domingo K, Prosser LA, Cook NR, Goldman L, Gillman MW. Effectiveness and cost-effectiveness of blood pressure screening in adolescents in the United States. J Pediatr 2011; 158:; 257-64.e1-7. International Childhood Cardiovascular Cohort (i3C). http://i3cconsortium.org/index.html. [Accessed 24 October 2014] Gillman MW, Cook NR, Rosner B, Evans DA, Keough ME, Taylor JO, Hennekens CH. Identifying children at high risk for the development of essential hypertension. J Pediatr 1993; 122:837–846. Bloetzer C, Paccaud F, Burnier M, Bovet P, Chiolero A. Performance of parental history for the targeted screening of hypertension in children. J Hypertens 2015; (in press). Gillman MW. Changing the conversation regarding pediatric cholesterol screening: the rare disease paradigm. Arch Pediatr Adolesc Med 2012; 166:1097–1098. Labarthe DR. Prevention of cardiovascular risk factors in the first place. Prev Med 1999; 29 (6 Pt 2):S72–78. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 2010; 121:586–613.
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Controversy about hypertension screening in children: a public health perspective Arnaud Chiolero a, Pascal Bovet a, and Gilles Paradis b
I
n 2013, the US Preventive Services Task Force (USPSTF) updated its recommendations about screening for elevated blood pressure in children and adolescents [1]. On the basis of a thorough review of the evidence [2], it concluded that ‘current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease (CVD)’ [1]. These recommendations have raised an important controversy [3–5] notably because they are at odds with recommendations of highly respected and influential health professionals and scientific organizations, such as the US National Heart, Lung, and Blood Institute or the European Society of Hypertension, that children aged 3 years and older have their blood pressure level measured regularly [6,7]. There is indeed ample evidence that the pathogenic process of atherosclerosis causing CVD begins early in life, in particular, during childhood and adolescence [8]. Hence, elevated blood pressure in children has been shown to be associated with increased carotid intima–media thickness (a surrogate marker for atherosclerosis and a strong predictor of CVD in adults) and with atherosclerosis in childhood and in adulthood [7–9]. Further, elevated blood pressure tracks from childhood through adulthood [10] and is associated in children with end-organ damage such as cardiac left ventricular hypertrophy [11]. These observations support the view that screening and treatment of hypertension should begin from childhood. The fact that elevated blood pressure in children is a true risk factor for CVD is, however, not sufficient to justify a universal screen-and-treat strategy beginning in childhood [12]. Doubts about the benefits of hypertension screening during childhood are not new [13,14], but the debate has recently re-emerged [1,15], with strong positions seemingly impossible to reconcile [3–5]. In this viewpoint, we discuss the goals of hypertension screening in children, why there are doubts about its potential benefits and harms, and propose avenues to solve the controversy.
GOALS OF HYPERTENSION SCREENING IN CHILDREN Screening aims to identify early disease or risk factors for future disease in populations of asymptomatic individuals, to help manage the identified condition through early intervention [15,16]. Screening should not be confused with clinical case finding where diseases are sought in 1352
www.jhypertension.com
individuals who consult health professionals with clinical signs or symptoms suggesting the presence of the condition. A commonly accepted goal of hypertension screening is to identify children at high risk of CVD due to the elevated blood pressure and to reduce this risk by early treatment. This is also the goal of hypertension screening in adults [17]. Another goal, which should be clearly distinguished from the goal mentioned above, is the early identification and treatment of diseases causing hypertension, that is, the screening for causes of secondary hypertension. A large part of the controversy about hypertension screening in children arises from the confusion between these two goals. USPSTF recommendations are for screening ‘for primary hypertension [...] to prevent subsequent CVDs’ [1], and not screening for secondary causes of hypertension. This is a problem because pediatricians afford more importance to the identification of diseases causing secondary hypertension than to the early diagnosis and treatment of hypertension for the prevention of CVD.
CONSIDERATIONS PRIOR TO RECOMMEND SCREENING Before making recommendations about hypertension screening in children, several issues should be addressed (Table 1). First, a method should exist to distinguish children with hypertension from children without hypertension. This method should be ideally easily applicable, valid, and reliable. The diagnosis of hypertension is, however, a serious challenge in children for several reasons [15,18,19]. Hence, it is difficult to define the level of blood pressure above which a child is considered as hypertensive and requires treatment [19]. In adults, elevated blood pressure is defined based on the substantial increase in the absolute
Journal of Hypertension 2015, 33:1352–1355 a Division of Chronic Diseases, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland and bDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
Correspondence to Arnaud Chiolero, MD, PhD, Senior Lecturer, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital (CHUV), Biopoˆle 2, 1010 Lausanne, Switzerland. Tel: +41 21 314 72 72; fax: +41 21 314 73 73; e-mail: [email protected] Received 28 November 2014 Revised 15 February 2015 Accepted 25 February 2015 J Hypertens 33:1352–1355 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000000579
Volume 33 Number 7 July 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Hypertension screening in children TABLE 1. Issues to address to decide whether screening should be recommended or not Issue
Commentary
Is it possible to identify with confidence children with hypertension?
There is no risk-based definition of hypertension in children; the high variability of blood pressure requires repeated blood pressure measurement at several visits to diagnose hypertension (defined as sustained elevated blood pressure). On the basis of the relatively few studies with blood pressure measured at several visits, the prevalence is likely 1–5% [22,23]. Elevated blood pressure in childhood is associated with elevated blood pressure and surrogate markers of CVD later in life. However, there is no information on the absolute risk of CVD or mortality associated with a given level of blood pressure in childhood [18]. The short-term efficacy and safety of lifestyle intervention and antihypertensive treatment has been documented in children; there are no data on the long-term efficacy and safety. There is no experimental evidence of the benefits and harms of hypertension screening beginning in childhood. One modeling study suggests that screen-and-treat strategies in adolescents would be less cost-effective than public health (population-based) interventions to decrease CVD risk [35].
What is the prevalence of hypertension in children? Is elevated blood pressure in children associated with an increased risk of CVD and mortality later in life? Is treatment for elevated blood pressure in children effective and safe? Does screening for hypertension in children reduce the risk of CVD and mortality later in life? Adapted from Chiolero et al. [15]. CVD, cardiovascular disease.
risk of CVD above a given level of blood pressure and the evidence that blood pressure reduction with antihypertensive treatment decreases this risk. Of note, the absolute risk of CVD also strongly depends on age and other factors, so that the sole information of a person’s blood pressures is moderately helpful in deciding whether to treat high blood pressure or not [12,20]. No such data exist in children since no cohort study of sufficient duration has shown an association between childhood blood pressure and CVD risk, and no clinical trial has linked blood pressure reduction in children with reduced risk of CVD. Therefore, elevated blood pressure in children is defined as blood pressure above a certain level, that is, the 95th percentile, on the basis of the distribution of blood pressure in a reference population [18,21]. Such distribution-based definition of elevated blood pressure is problematic because it depends on the reference population and raises never-ending discussion about the ideal blood pressure thresholds and how well these cut-off values may be validly used in different populations [19]. Further, the diagnosis of hypertension requires the measurement of blood pressure at several occasions. It is standard to require blood pressure to be elevated on at least three separate visits to diagnose hypertension [18,21]. This is important because most children with elevated blood pressure at an initial screening visit will have normal blood pressure at subsequent visits. For example, in a schoolbased study of 5207 children 10–12 years of age, the prevalence of elevated blood pressure was 11.4, 3.8, and 2.2% on first, second, and third visits, respectively [22]. Similar figures were found in other studies, with up to 20% of children having elevated blood pressure at the initial visit [23]. From a practical point of view, if 10–20% of initially screened children have elevated blood pressure, then one out of every 5–10 children would require subsequent visits for blood pressure measurement. There is also a growing consensus that blood pressure should be measured out of the office, for example, using ambulatory measurement or home blood pressure monitoring, to avoid white-coat effect and to identify masked hypertension [24,25]. This difficulty to obtain valid measurements of blood pressure is probably one of the reasons why pediatricians do not screen systematically for hypertension [26]. Second, the prevalence of hypertension in children in a particular population should be known prior to initiating Journal of Hypertension
screening. Surprisingly, relatively few studies have estimated the prevalence of hypertension in children on the basis of repeated measurements at multiple visits. It is estimated that 1–5% of children would be hypertensive on the basis of multiple blood pressure measurements [22,23]. An increasing prevalence of elevated blood pressure in children could be an argument in favor of screening. However, despite the increase in the prevalence of childhood obesity, blood pressure have not increased in several countries [27,28]. More recently, blood pressure may have increased in the USA [29] or China [30], but not in other countries [31,32]. Third, it is necessary to know the absolute risk of disease associated with a given level of blood pressure in childhood. In adults, estimating the absolute CVD risk is necessary to evaluate the indication for treatment [33,34]. Hence, for a given level of blood pressure, adults at high risk of CVD are eligible for a treatment, whereas adults at low risk of CVD are not. Below a certain level of absolute risk, there is indeed no individual benefit to expect from blood pressure treatment. It is reasonable to assume that children with elevated blood pressure have a higher long-term risk of CVD compared to children with low blood pressure. However, for a given period (e.g. 10 years), it is also reasonable to assume that the absolute risk of diseases related to elevated blood pressure is much lower than in adults. More fundamentally, the fact that CVD events will not occur before several decades strongly limits any substantial benefits of individual CVD risk factors screening and treatment in childhood. Fourth, all screening and early detection strategies can be justified only if a safe and efficient treatment exists. The short-term efficacy and safety of lifestyle intervention and antihypertensive treatments have been documented in children [18]. However, there are no data on the long-term efficacy and safety of treatments started in childhood and taken over several decades. Robust evidence is indeed needed to justify decades of preventive treatment. Finally, there is no experimental evidence of the benefits and harms of hypertension screening beginning in childhood. One modeling study suggests that screen-and-treat strategies in adolescents would be less cost-effective than populationwide interventions to decrease CVD risk [35]. All these issues and uncertainties are reasons why the USPSTF did not recommend hypertension screening in children. www.jhypertension.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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BENEFITS VERSUS HARMS OF SCREENING Evaluating any screening procedure necessitates an assessment of the balance between benefits and harms [16]. Intuitively, the benefits of screening are evident and it is difficult to imagine any harm due to hypertension screening in children. While measurement of blood pressure in itself is not harmful, potential harms include the anxiety of being labeled hypertensive and the stress induced by investigations necessary to assess the causes or consequences of elevated blood pressure. Another issue is the fact that sorting out hypertensive from nonhypertensive children does not solve the dilemma that many cases of CVD will occur in individuals with normal blood pressure. Indeed, blood pressure, at an individual level, is a relatively weak prognostic factor for CVD, and the majority of CVD cases occur in persons with normal blood pressure [12,20]. Further, an earlier identification and treatment does not convey automatically more benefits than identification and treatment later in life. Lead time – a well known source of bias in the evaluation of cancer screening – has to be considered for blood pressure screening as well (Fig. 1). The lead time is the length of time between the detection of hypertension by screening and the occurrence of a CVD event. If screening begins in childhood, elevated blood pressure can be detected earlier and the lead time will be greater than with screening in adulthood. The increase in lead time is, however, not a good indicator of the benefit of childhood screening. To be useful, compared to screening and treatment in adulthood (known to help postpone or prevent CVD), screening of hypertension in children has to be associated with a further postponement of CVD events. Otherwise, screening in childhood leads to an earlier initiation and longer duration of treatment, implying greater costs and more opportunity for treatment side effects, without additional benefit compared to screening and treatment started in adulthood. In adults, screening for hypertension causes potentially the same harms and raises similar issues as in children. However, because hypertension is associated with a substantial increase in absolute risk of CVD and treatment of a)
Event
b)
Event
sc & ttt
c1)
sc & ttt
c2)
sc & ttt Childhood
Event ?? Adulthood
Event Time
FIGURE 1 Simplified and hypothetical clinical scenario of children with elevated blood pressure. (a) Natural history with the occurrence of an event (e.g. cardiovascular disease or death) relatively early in adulthood; (b) screening (sc) and treatment (ttt) in adulthood with postponement (if not prevention) of the event later in adulthood; (c1) useless screening and treatment in childhood: compared with (a), there is also a postponement of the event, but the event occurs at about the same age in adulthood as in scenario (b); hence, there is no additional benefit with early screening; (c2) Useful screening and treatment in childhood: compared with (a), (b), or (c1), there is an additional benefit since the event occurs later in life. Compared to screening in adulthood (b), screening in childhood is beneficial only in the scenario (c2).
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hypertension can substantially reduce this risk [17], the balance between benefits and harms is more favorable than in children and this is why screening is justified in adults.
WHAT ARE WE TO DO? Studies are needed to address the issues raised above (Table 1). Ideally, we would need cohort studies to estimate the absolute risk of disease associated with elevated blood pressure in children and clinical trials to quantify the effect on CVD risk and harms of hypertension screening and treatment beginning in childhood. While such studies are very difficult to conduct because of the very large sample sizes and several decades of follow-up to accumulate enough CVD events, tools like the International Childhood Cardiovascular Cohort (i3C) Consortium, collating data of several cohorts including over 40 000 children, will help assess the actual risk of elevated blood pressure (and other CVD risk factors) early in life [36]. Modeling studies evaluating various screening strategies [35] and clinical trials comparing the effects of these screening strategies on surrogate markers of CVD as outcomes are more easily feasible. Since the efficiency of universal screening is poor [37], strategies of targeted screening according to markers of elevated blood pressure risk, including body weight status, family history of hypertension, family history of CVD, or birth weight should also be evaluated [38]. In addition to further studies, it may be time to reframe radically the goals of hypertension screening, that is, distinguish screening for primary hypertension for the prevention of CVD from screening for diseases causing hypertension. Gillman [39] has recently argued against universal blood lipid screening in children and has proposed a ‘rare-disease’ conceptual framework for this screening. His idea is to restrain screening to the detection of children with very high risk of CVD due to familial hypercholesterolemia. By analogy, screening for hypertension could be reoriented toward the screening of diseases causing hypertension. These diseases are relatively rare, can be life-threatening if not treated, and there is no controversy about the potential benefits of early identification and treatment [18]. Such a strategy would be coherent with the concerns of clinicians who want to identify children with these diseases causing hypertension. Nevertheless, how to screen for such diseases (e.g. by targeted or cascade screening) remains to be defined and evaluated. Because secondary hypertension seems more frequent in younger than older children [18], it could be reasonable to consider and evaluate such screening strategies in the former. Finally, raising concerns about the benefits of screening hypertension in children does not mean that we deny that elevated blood pressure in childhood increases the risk of CVD or that prevention of CVD should start in childhood. We argue that prevention of CVD should, at this early age, focus on population-based primordial prevention strategies [40,41], to shift the blood pressure distribution of the entire population toward lower values, rather than to rely on universal screen-and-treat strategies. Volume 33 Number 7 July 2015
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Hypertension screening in children
ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.
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