Observational Studies May Be More Important Than Randomized Clinical Trials: Weaknesses in US Preventive Services Task Force Recommendation on Blood Pressure Screening in Youth Elaine M. Urbina, Sarah de Ferranti and Julia Steinberger Hypertension. 2014;63:638-640; originally published online December 23, 2013; doi: 10.1161/HYPERTENSIONAHA.113.02662 Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2013 American Heart Association, Inc. All rights reserved. Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/63/4/638
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
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Brief Review Observational Studies May Be More Important Than Randomized Clinical Trials Weaknesses in US Preventive Services Task Force Recommendation on Blood Pressure Screening in Youth Elaine M. Urbina, Sarah de Ferranti, Julia Steinberger
O
n behalf of the Atherosclerosis, Hypertension, and Obesity in Youth committee of the American Heart Association (AHA), we appreciate the opportunity to comment on the recently published US Preventive Services Task Force (USPSTF) recommendation statement on Screening for Hypertension in Children and Adolescents (Table).1 Since the 1970s, the National Heart, Lung, and Blood Institute has recommended measurement of blood pressure (BP) in healthy children as part of routine health maintenance.2,3 The American Academy of Pediatrics4 and the AHA also advocate this approach.5,6 Recently, the USPSTF concluded that the “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) in childhood or adulthood.”7 The USPSTF approach, which limits the allowable evidence, primarily to randomized controlled trials, and additionally fails to address important questions on pediatric BP, may lead to an undervaluing of pediatric BP measurement and may contribute to practitioner confusion. The USPSTF performed an evidenced-based review to address the use of BP screening in childhood. The task force developed 8 key questions and performed a literature review that netted 6435 potentially relevant articles. After abstract review, 1059 articles were selected as applicable to the key questions, and they underwent full text review. Only 35 articles (describing 34 studies) were included in the statement. The others were excluded as wrong population, intervention, outcome, study design, language, duration, no original data, inadequate duration, or inadequate reference standard. The search strategy, key questions, and references can be found at http:// www.uspreventiveservicestaskforce.org/uspstf/uspshypechld. htm. The evidence considered (34 articles in all) was, in our opinion, unnecessarily restrictive. For example, the evidence used to address the question “Is screening for hypertension in children/adolescents effective in delaying the onset or reducing adverse health outcomes related to hypertension?” gave little weight to important observational data. Unfortunately, there are no randomized controlled trials comparing CVD outcomes in children screened versus not screened for hypertension
(HTN); such a study would require following up children to the point of clinical events 40 to 50 years later. However, multiple observational studies have shown that BP levels in childhood have some (although not perfect) use in predicting adult HTN. The Muscatine study reported significant correlations between childhood and adulthood BP levels after 17 years of follow-up as early as 1989.8 This finding was replicated in the Bogalusa Heart Study with additional Bogalusa data showing clinically diagnosed HTN as an adult was ≈4 times higher with BP level above the 80th percentile as a child. If elevated BP was identified on multiple occasions as a child, the prevalence of adult HTN was even higher.9 Recent analyses from the CV Risk in Young Finns study examined subjects up to 27 years since baseline childhood measures were obtained. Higher childhood BP level increased the odds for adult HTN significantly even after adjustment for childhood obesity, family history of HTN, and genetic risk score (odds ratio, 1.65; P20 years of pediatric usage of these drugs in clinical practice, and no new systematic adverse class-effects have been identified. However, these data were given less importance because many of the trials were of short duration, perhaps so as not to leave placebo patients untreated for too long. Recent studies included year-long open-label extension periods demonstrating sustained BP reductions in pediatric patients with drug treatment.21 The Task Force report did not include consideration of these data. Other important key questions were simply not addressed by the USPSTF. For example, “what is the evidence that identification and treatment of HTN in youth can prevent target organ damage?” such as left ventricular hypertrophy (LVH). Cross-sectional studies show an association between childhood BP and concurrent target organ damage, including LVH, increased cIMT, and arterial stiffness.22 Intervention studies in hypertensive youth demonstrate that antihypertensive therapy leads to regression of LVH,23,24 reduction in carotid thickness,25 and reversal of microalbuminuria.26 Reversal of target organ damage in adults is associated with reduction in hard CVD events,27 suggesting that treatment in youth may modify adult event rates, even if long-term follow-up data from randomized, controlled trials are not available in adolescent HTN. Another important issue not considered in the USPSTF guidelines was whether screening for and treatment of HTN in youth may indeed lead to additional positive outcomes beyond BP reduction, resulting in reduction in clustering of CV risk factors. The identification of prehypertension (before progression to sustained HTN) may lead to positive lifestyle changes that could contribute to improved short-term (target organ damage) and long-term (reduced CVD mortality) outcomes. Most importantly, BP screening identifies the small but significant number of children with severe secondary HTN who would otherwise have been missed.
In summary, we believe that the Task Force’s I (inconclusive) recommendation is flawed because the evidence was too narrowly selected, and available shorter term and observational studies were not considered. In the absence of perfect data, the practitioner must use common sense, not ignore research that is given a lower grade where superior evidence does not exist. “What is the evidence that adult HTN can be prevented or modified by earlier intervention” will never be answered if we do not continue screening for BP in youth. Ongoing collaboration among the worlds’ largest childhood CV studies (http://i3cconsortium.org/index.html) may soon provide answers. The International CV Childhood Cohorts Consortium is gathering and harmonizing data from the largest international children’s cohorts that contain measurements of major CV risk factors in childhood with follow-up through adulthood. The 7 cohorts (Bogalusa Heart Study, CV Determinants of Adult Health, Minneapolis Childhood Cohorts Studies, Muscatine Study, National Growth & Health, Princeton Lipid Research Study, and CV Risk in Young Finns) have data on >40 000 participants who are now reaching 50 years of age when CV events are beginning to occur. Continued follow-up of these cohorts will provide data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence. However, the restrictive exclusion criteria in the USPSTF approach would preclude consideration of even these robust data. Until the consortium can complete their work, our group continues to recommend routine screening for HTN at all well child visits, with the goal of achieving the AHA’s 2020 goals for CV Health.28
Disclosures E.M. Urbina is consultant, Midmark Medical, Inc. The other authors report no conflicts.
References 1. Moyer VA; U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: US Preventive services task force recommendation statement. Pediatrics. 2013;132:907–914. 2. Blumenthal S, Epps RP, Heavenrich R, Lauer RM, Lieberman E, Mirkin B, Mitchell SC, Boyar Naito V, O’Hare D, McFate Smith W, Tarazi RC, Upson D. Report of the task force on blood pressure control in children. Pediatrics. 1977;59(5 2 suppl):797–820. 3. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics. 2011;128(Suppl 5):S213–256.
Downloaded from http://hyper.ahajournals.org/ at University of Arizona on June 3, 2014
640 Hypertension April 2014 4. Hagan JF, Shaw, J.S., Duncan, P.M., eds. Bright futures: Guidelines for health supervision of infants, children and adolescents. Elk Grove Village, IL: American Academy of Pediatrics; 2008. 5. Kavey RE, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K; American Heart Association. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation. 2003;107:1562–1566. 6. Hayman LL, Meininger JC, Daniels SR, McCrindle BW, Helden L, Ross J, Dennison BA, Steinberger J, Williams CL. Primary prevention of cardiovascular disease in nursing practice: Focus on children and youth: A scientific statement from the American Heart Association committee on atherosclerosis, hypertension, and obesity in youth of the council on cardiovascular disease in the young, council on cardiovascular nursing, council on epidemiology and prevention, and council on nutrition, physical activity, and metabolism. Circulation. 2007;116:344–357. 7. Moyer VA; U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: US Preventive services task force recommendation statement. Pediatrics. 2013;132:907–914. 8. Lauer RM, Clarke WR. Childhood risk factors for high adult blood pressure: the Muscatine Study. Pediatrics. 1989;84:633–641. 9. Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens. 1995;8:657–665. 10. Juhola J, Oikonen M, Magnussen CG, et al. Childhood physical, environmental, and genetic predictors of adult hypertension: the cardiovascular risk in young Finns study. Circulation. 2012;126:402–409. 11. Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR. Cardiovascular outcomes in Framingham participants with diabetes: the importance of blood pressure. Hypertension. 2011;57:891–897. 12. Franklin SS, Lopez VA, Wong ND, Mitchell GF, Larson MG, Vasan RS, Levy D. Single versus combined blood pressure components and risk for cardiovascular disease: the Framingham Heart Study. Circulation. 2009;119:243–250. 13. Raitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, Järvisalo MJ, Uhari M, Jokinen E, Rönnemaa T, Akerblom HK, Viikari JS. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003;290:2277–2283. 14. Baldassarre D, Hamsten A, Veglia F, de Faire U, Humphries SE, Smit AJ, Giral P, Kurl S, Rauramaa R, Mannarino E, Grossi E, Paoletti R, Tremoli E. Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: Results of the improve (carotid intima media thickness [imt] and imt-progression as predictors of vascular events in a high risk European population) study. J Am Coll Cardiol. 2012;60:1489–1499. 15. 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. 16. Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, Chen W, Srinivasan SR, Daniels SR, Kähönen M, Laitinen T, Taittonen L, Berenson GS, Viikari JS, Raitakari OT. Influence of age on associations
between childhood risk factors and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010;122:2514–2520. 17. Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J, Daniels S. Ambulatory blood pressure monitoring in children and adolescents: Recommendations for standard assessment: A scientific statement from the American Heart Association atherosclerosis, hypertension, and obesity in youth committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008;52:433–451. 18. Lurbe E, Cifkova R, Cruickshank JK, 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. 19. Couch SC, Saelens BE, Levin L, Dart K, Falciglia G, Daniels SR. The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure. J Pediatr. 2008;152:494–501. 20. Torrance B, McGuire KA, Lewanczuk R, McGavock J. Overweight, physical activity and high blood pressure in children: a review of the literature. Vasc Health Risk Manag. 2007;3:139–149. 21. Flynn JT. Management of hypertension in the young: role of antihypertensive medications. J Cardiovasc Pharmacol. 2011;58:111–120. 22. Urbina EM, Khoury PR, McCoy C, Daniels SR, Kimball TR, Dolan LM. Cardiac and vascular consequences of pre-hypertension in youth. J Clin Hypertens (Greenwich). 2011;13:332–342. 23. Ramaswamy P, Lytrivi ID, Paul C, Golden M, Kupferman JC. Regression of left ventricular hypertrophy in children with antihypertensive therapy. Pediatr Nephrol. 2007;22:141–143. 24. Seeman T, Gilík J, Vondrák K, Simková E, Flögelová H, Hladíková M, Janda J. Regression of left-ventricular hypertrophy in children and adolescents with hypertension during ramipril monotherapy. Am J Hypertens. 2007;20:990–996. 25. Litwin M, Niemirska A, Sladowska-Kozlowska J, Wierzbicka A, Janas R, Wawer ZT, Wisniewski A, Feber J. Regression of target organ damage in children and adolescents with primary hypertension. Pediatr Nephrol. 2010;25:2489–2499. 26. Assadi F. Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatr Cardiol. 2007;28:27–33. 27. Kostis WJ, Thijs L, Richart T, Kostis JB, Staessen JA. Persistence of mortality reduction after the end of randomized therapy in clinical trials of blood pressure-lowering medications. Hypertension. 2010;56:1060–1068. 28. Lloyd-Jones DM, Hong Y, Labarthe D, et al; American Heart Association Strategic Planning Task Force and Statistics Committee. 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.
Downloaded from http://hyper.ahajournals.org/ at University of Arizona on June 3, 2014
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/63/4/638
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
Downloaded from http://hyper.ahajournals.org/ at University of Arizona on June 3, 2014
Brief Review Observational Studies May Be More Important Than Randomized Clinical Trials Weaknesses in US Preventive Services Task Force Recommendation on Blood Pressure Screening in Youth Elaine M. Urbina, Sarah de Ferranti, Julia Steinberger
O
n behalf of the Atherosclerosis, Hypertension, and Obesity in Youth committee of the American Heart Association (AHA), we appreciate the opportunity to comment on the recently published US Preventive Services Task Force (USPSTF) recommendation statement on Screening for Hypertension in Children and Adolescents (Table).1 Since the 1970s, the National Heart, Lung, and Blood Institute has recommended measurement of blood pressure (BP) in healthy children as part of routine health maintenance.2,3 The American Academy of Pediatrics4 and the AHA also advocate this approach.5,6 Recently, the USPSTF concluded that the “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) in childhood or adulthood.”7 The USPSTF approach, which limits the allowable evidence, primarily to randomized controlled trials, and additionally fails to address important questions on pediatric BP, may lead to an undervaluing of pediatric BP measurement and may contribute to practitioner confusion. The USPSTF performed an evidenced-based review to address the use of BP screening in childhood. The task force developed 8 key questions and performed a literature review that netted 6435 potentially relevant articles. After abstract review, 1059 articles were selected as applicable to the key questions, and they underwent full text review. Only 35 articles (describing 34 studies) were included in the statement. The others were excluded as wrong population, intervention, outcome, study design, language, duration, no original data, inadequate duration, or inadequate reference standard. The search strategy, key questions, and references can be found at http:// www.uspreventiveservicestaskforce.org/uspstf/uspshypechld. htm. The evidence considered (34 articles in all) was, in our opinion, unnecessarily restrictive. For example, the evidence used to address the question “Is screening for hypertension in children/adolescents effective in delaying the onset or reducing adverse health outcomes related to hypertension?” gave little weight to important observational data. Unfortunately, there are no randomized controlled trials comparing CVD outcomes in children screened versus not screened for hypertension
(HTN); such a study would require following up children to the point of clinical events 40 to 50 years later. However, multiple observational studies have shown that BP levels in childhood have some (although not perfect) use in predicting adult HTN. The Muscatine study reported significant correlations between childhood and adulthood BP levels after 17 years of follow-up as early as 1989.8 This finding was replicated in the Bogalusa Heart Study with additional Bogalusa data showing clinically diagnosed HTN as an adult was ≈4 times higher with BP level above the 80th percentile as a child. If elevated BP was identified on multiple occasions as a child, the prevalence of adult HTN was even higher.9 Recent analyses from the CV Risk in Young Finns study examined subjects up to 27 years since baseline childhood measures were obtained. Higher childhood BP level increased the odds for adult HTN significantly even after adjustment for childhood obesity, family history of HTN, and genetic risk score (odds ratio, 1.65; P20 years of pediatric usage of these drugs in clinical practice, and no new systematic adverse class-effects have been identified. However, these data were given less importance because many of the trials were of short duration, perhaps so as not to leave placebo patients untreated for too long. Recent studies included year-long open-label extension periods demonstrating sustained BP reductions in pediatric patients with drug treatment.21 The Task Force report did not include consideration of these data. Other important key questions were simply not addressed by the USPSTF. For example, “what is the evidence that identification and treatment of HTN in youth can prevent target organ damage?” such as left ventricular hypertrophy (LVH). Cross-sectional studies show an association between childhood BP and concurrent target organ damage, including LVH, increased cIMT, and arterial stiffness.22 Intervention studies in hypertensive youth demonstrate that antihypertensive therapy leads to regression of LVH,23,24 reduction in carotid thickness,25 and reversal of microalbuminuria.26 Reversal of target organ damage in adults is associated with reduction in hard CVD events,27 suggesting that treatment in youth may modify adult event rates, even if long-term follow-up data from randomized, controlled trials are not available in adolescent HTN. Another important issue not considered in the USPSTF guidelines was whether screening for and treatment of HTN in youth may indeed lead to additional positive outcomes beyond BP reduction, resulting in reduction in clustering of CV risk factors. The identification of prehypertension (before progression to sustained HTN) may lead to positive lifestyle changes that could contribute to improved short-term (target organ damage) and long-term (reduced CVD mortality) outcomes. Most importantly, BP screening identifies the small but significant number of children with severe secondary HTN who would otherwise have been missed.
In summary, we believe that the Task Force’s I (inconclusive) recommendation is flawed because the evidence was too narrowly selected, and available shorter term and observational studies were not considered. In the absence of perfect data, the practitioner must use common sense, not ignore research that is given a lower grade where superior evidence does not exist. “What is the evidence that adult HTN can be prevented or modified by earlier intervention” will never be answered if we do not continue screening for BP in youth. Ongoing collaboration among the worlds’ largest childhood CV studies (http://i3cconsortium.org/index.html) may soon provide answers. The International CV Childhood Cohorts Consortium is gathering and harmonizing data from the largest international children’s cohorts that contain measurements of major CV risk factors in childhood with follow-up through adulthood. The 7 cohorts (Bogalusa Heart Study, CV Determinants of Adult Health, Minneapolis Childhood Cohorts Studies, Muscatine Study, National Growth & Health, Princeton Lipid Research Study, and CV Risk in Young Finns) have data on >40 000 participants who are now reaching 50 years of age when CV events are beginning to occur. Continued follow-up of these cohorts will provide data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence. However, the restrictive exclusion criteria in the USPSTF approach would preclude consideration of even these robust data. Until the consortium can complete their work, our group continues to recommend routine screening for HTN at all well child visits, with the goal of achieving the AHA’s 2020 goals for CV Health.28
Disclosures E.M. Urbina is consultant, Midmark Medical, Inc. The other authors report no conflicts.
References 1. Moyer VA; U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: US Preventive services task force recommendation statement. Pediatrics. 2013;132:907–914. 2. Blumenthal S, Epps RP, Heavenrich R, Lauer RM, Lieberman E, Mirkin B, Mitchell SC, Boyar Naito V, O’Hare D, McFate Smith W, Tarazi RC, Upson D. Report of the task force on blood pressure control in children. Pediatrics. 1977;59(5 2 suppl):797–820. 3. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics. 2011;128(Suppl 5):S213–256.
Downloaded from http://hyper.ahajournals.org/ at University of Arizona on June 3, 2014
640 Hypertension April 2014 4. Hagan JF, Shaw, J.S., Duncan, P.M., eds. Bright futures: Guidelines for health supervision of infants, children and adolescents. Elk Grove Village, IL: American Academy of Pediatrics; 2008. 5. Kavey RE, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K; American Heart Association. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation. 2003;107:1562–1566. 6. Hayman LL, Meininger JC, Daniels SR, McCrindle BW, Helden L, Ross J, Dennison BA, Steinberger J, Williams CL. Primary prevention of cardiovascular disease in nursing practice: Focus on children and youth: A scientific statement from the American Heart Association committee on atherosclerosis, hypertension, and obesity in youth of the council on cardiovascular disease in the young, council on cardiovascular nursing, council on epidemiology and prevention, and council on nutrition, physical activity, and metabolism. Circulation. 2007;116:344–357. 7. Moyer VA; U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: US Preventive services task force recommendation statement. Pediatrics. 2013;132:907–914. 8. Lauer RM, Clarke WR. Childhood risk factors for high adult blood pressure: the Muscatine Study. Pediatrics. 1989;84:633–641. 9. Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens. 1995;8:657–665. 10. Juhola J, Oikonen M, Magnussen CG, et al. Childhood physical, environmental, and genetic predictors of adult hypertension: the cardiovascular risk in young Finns study. Circulation. 2012;126:402–409. 11. Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR. Cardiovascular outcomes in Framingham participants with diabetes: the importance of blood pressure. Hypertension. 2011;57:891–897. 12. Franklin SS, Lopez VA, Wong ND, Mitchell GF, Larson MG, Vasan RS, Levy D. Single versus combined blood pressure components and risk for cardiovascular disease: the Framingham Heart Study. Circulation. 2009;119:243–250. 13. Raitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, Järvisalo MJ, Uhari M, Jokinen E, Rönnemaa T, Akerblom HK, Viikari JS. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003;290:2277–2283. 14. Baldassarre D, Hamsten A, Veglia F, de Faire U, Humphries SE, Smit AJ, Giral P, Kurl S, Rauramaa R, Mannarino E, Grossi E, Paoletti R, Tremoli E. Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: Results of the improve (carotid intima media thickness [imt] and imt-progression as predictors of vascular events in a high risk European population) study. J Am Coll Cardiol. 2012;60:1489–1499. 15. 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. 16. Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, Chen W, Srinivasan SR, Daniels SR, Kähönen M, Laitinen T, Taittonen L, Berenson GS, Viikari JS, Raitakari OT. Influence of age on associations
between childhood risk factors and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010;122:2514–2520. 17. Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J, Daniels S. Ambulatory blood pressure monitoring in children and adolescents: Recommendations for standard assessment: A scientific statement from the American Heart Association atherosclerosis, hypertension, and obesity in youth committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008;52:433–451. 18. Lurbe E, Cifkova R, Cruickshank JK, 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. 19. Couch SC, Saelens BE, Levin L, Dart K, Falciglia G, Daniels SR. The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure. J Pediatr. 2008;152:494–501. 20. Torrance B, McGuire KA, Lewanczuk R, McGavock J. Overweight, physical activity and high blood pressure in children: a review of the literature. Vasc Health Risk Manag. 2007;3:139–149. 21. Flynn JT. Management of hypertension in the young: role of antihypertensive medications. J Cardiovasc Pharmacol. 2011;58:111–120. 22. Urbina EM, Khoury PR, McCoy C, Daniels SR, Kimball TR, Dolan LM. Cardiac and vascular consequences of pre-hypertension in youth. J Clin Hypertens (Greenwich). 2011;13:332–342. 23. Ramaswamy P, Lytrivi ID, Paul C, Golden M, Kupferman JC. Regression of left ventricular hypertrophy in children with antihypertensive therapy. Pediatr Nephrol. 2007;22:141–143. 24. Seeman T, Gilík J, Vondrák K, Simková E, Flögelová H, Hladíková M, Janda J. Regression of left-ventricular hypertrophy in children and adolescents with hypertension during ramipril monotherapy. Am J Hypertens. 2007;20:990–996. 25. Litwin M, Niemirska A, Sladowska-Kozlowska J, Wierzbicka A, Janas R, Wawer ZT, Wisniewski A, Feber J. Regression of target organ damage in children and adolescents with primary hypertension. Pediatr Nephrol. 2010;25:2489–2499. 26. Assadi F. Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatr Cardiol. 2007;28:27–33. 27. Kostis WJ, Thijs L, Richart T, Kostis JB, Staessen JA. Persistence of mortality reduction after the end of randomized therapy in clinical trials of blood pressure-lowering medications. Hypertension. 2010;56:1060–1068. 28. Lloyd-Jones DM, Hong Y, Labarthe D, et al; American Heart Association Strategic Planning Task Force and Statistics Committee. 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.
Downloaded from http://hyper.ahajournals.org/ at University of Arizona on June 3, 2014
