1. PEDIATRICSOFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICSDECEMBER 2011 VOLUME 128 SUPPLEMENT 5A SUPPLEMENT TO PEDIATRICSExpert Panel on Integrated Guidelines for CardiovascularHealth and Risk Reduction in Children and Adolescents:Summary ReportRae-Ellen W. Kavey, MD, MPH, Denise G. Simons-Morton, MD, MH, PhD,and Janet M. de Jesus, MS, RD, Supplement EditorsSponsored by the National Heart, Lung, and Blood Institute,National Institutes of HealthThese guidelines have been endorsed by the American Academy ofPediatrics. Statements and opinions expressed in this supplementare those of the authors and not necessarily those of Pediatricsor the Editor or Editorial Board of Pediatrics.PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright 2011 by theAmerican Academy of Pediatrics

2. SUPPLEMENT TO PEDIATRICSCONTENTS S 1. Introduction S 2. State of the Science: Cardiovascular Risk Factors and the Development of Atherosclerosis in Childhood S 3. Integrated Cardiovascular Health Schedule S 4. Family History of Early Atherosclerotic CVD S 5. Nutrition and Diet S 6. Physical Activity S 7. Tobacco Exposure S 8. High BP S 9. Lipids and Lipoproteins S 10. Overweight and Obesity S 11. DM and Other Conditions Predisposing to the Development of Accelerated Atherosclerosis S 12. Risk-Factor Clustering and the Metabolic Syndrome S 13. Perinatal Factors doi:10.1542/peds.2009-2107Awww.pediatrics.org A3

3. Expert Panel Members Stephen R. Daniels, MD, PhD, Panel Chair University of Colorado School of Medicine Denver, CO Irwin Benuck, MD, PhD Northwestern University Feinberg School of Medicine Chicago, IL Dimitri A. Christakis, MD, MPH University of Washington Seattle, WA Barbara A. Dennison, MD New York State Department of Health Albany, NY Samuel S. Gidding, MD Alfred I du Pont Hospital for Children Wilmington, DE Matthew W. Gillman, MD, MS Harvard Pilgrim Health Care Boston, MA Mary Margaret Gottesman, PhD, RN, CPNP Ohio State University-College of Nursing Columbus, OH Peter O. Kwiterovich, MD Johns Hopkins University School of Medicine Baltimore, MD Patrick E. McBride, MD, MPH University of Wisconsin School of Medicine and Public Health Madison, WI Brian W. McCrindle, MD, MPH Hospital for Sick Children Toronto, Ontario, Canada Albert P. Rocchini, MD C. S. Mott Childrens Hospital Ann Arbor, MI Elaine M. Urbina, MD Cincinnati Childrens Hospital Medical Center Cincinnati, OH Linda V. Van Horn, PhD, RD Northwestern University-Feinberg School of Medicine Chicago, IL Reginald L. Washington, MD Rocky Mountain Hospital for Children Denver, CO NHLBI Staff Rae-Ellen W. Kavey, MD, MPH Panel Coordinator National Heart, Lung, and Blood Institute Bethesda, MDA4

4. Christopher J. ODonnell, MD, MPHNational Heart, Lung, and Blood InstituteFramingham, MAKaren A. Donato, SMNational Heart, Lung, and Blood InstituteBethesda, MDRobinson Fulwood, PhD, MSPHNational Heart, Lung, and Blood InstituteBethesda, MDJanet M. de Jesus, MS, RDNational Heart, Lung, and Blood InstituteBethesda, MDDenise G. Simons-Morton, MD, MPH, PhDNational Heart, Lung, and Blood InstituteBethesda, MDContract StaffThe Lewin Group, Falls Church, VAClifford Goodman, MS, PhDChristel M. Villarivera, MSCharlene Chen, MHSErin Karnes, MHSAyodola Anise, MHSdoi:10.1542/peds.2009-2107B A5

5. SUPPLEMENT ARTICLESExpert Panel on Integrated Guidelines forCardiovascular Health and Risk Reduction in Childrenand Adolescents: Summary ReportEXPERT PANEL ON INTEGRATED GUIDELINES FOR Atherosclerotic cardiovascular disease (CVD) remains the leadingCARDIOVASCULAR HEALTH AND RISK REDUCTION IN cause of death in North Americans, but manifest disease in childhoodCHILDREN AND ADOLESCENTS and adolescence is rare. By contrast, risk factors and risk behaviorsABBREVIATIONS that accelerate the development of atherosclerosis begin in childhood,CVDcardiovascular diseaseNHLBINational Heart, Lung, and Blood Institute and there is increasing evidence that risk reduction delays progres-RCTrandomized controlled trial sion toward clinical disease. In response, the former director of thePDAYPathobiological Determinants of Atherosclerosis in National Heart, Lung, and Blood Institute (NHLBI), Dr Elizabeth Nabel,YouthBPblood pressure initiated development of cardiovascular health guidelines for pediatricHDLhigh-density lipoprotein care providers based on a formal evidence review of the science withDMdiabetes mellitus an integrated format addressing all the major cardiovascular riskCIMTcarotid intima-media thicknessLDLlow-density lipoprotein factors simultaneously. An expert panel was appointed to develop theT1DMtype 1 diabetes mellitus guidelines in the fall of 2006.T2DMtype 2 diabetes mellitusTCtotal cholesterol The goal of the expert panel was to develop comprehensive evidence-AAPAmerican Academy of Pediatrics based guidelines that address the known risk factors for CVD (TableDGADietary Guidelines for Americans 1-1) to assist all primary pediatric care providers in both the promo-NCEPNational Cholesterol Education ProgramDASHDietary Approaches to Stop Hypertension tion of cardiovascular health and the identication and management ofCHILDCardiovascular Health Integrated Lifestyle Die specic risk factors from infancy into young adult life. An innovativeFLPfasting lipid prole approach was needed, because a focus on cardiovascular risk reduc-CDCCenters for Disease Control and Prevention tion in children and adolescents addresses a disease process (athero-AMAAmerican Medical AssociationMCHBMaternal and Child Health Bureau sclerosis) in which the clinical end point of manifest CVD is remote. TheFDAFood and Drug Administration recommendations, therefore, need to address 2 different goals:AHAAmerican Heart Association the prevention of risk-factor development (primordial prevention) andwww.pediatrics.org/cgi/doi/10.1542/peds.2009-2107C the prevention of future CVD by effective management of identied riskdoi:10.1542/peds.2009-2107C factors (primary prevention).Accepted for publication Aug 4, 2009 The evidence review also required an innovative approach. Most sys-Address correspondence to Janet M. de Jesus, MS, RD, 31Center Dr, Building 31, Room 4A17, MSC 2480, Bethesda, MD tematic evidence reviews include 1 or, at most, a small number of nite20892. E-mail: dejesusjm@nhlbi.nih.gov questions that address the impact of specic interventions on specicPEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). health outcomes, and a rigorous literature review often results in onlyCopyright 2011 by the American Academy of Pediatrics a handful of in-scope articles for inclusion. Typically, evidence is limitedFINANCIAL DISCLOSURE: Dr Daniels has served as a consultant to randomized controlled trials (RCTs), systematic reviews, and meta-for Abbott Laboratories, Merck, and Schering-Plough and has analyses published over a dened time period. There is a dened for-received funding/grant support for research from the National mat for abstracting studies, grading the evidence, and presenting ofInstitutes of Health (NIH); Dr Gidding has served as a consultantfor Merck and Schering-Plough and has received funding/grant results. The results of the review lead to the conclusions, independentsupport for research from GlaxoSmithKline; Dr Gillman has of interpretation.given invited talks for Nestle Nutrition Institute and Danone andhas received funding/grant support for research from Mead By contrast, given the scope of the charge to the expert panel, thisJohnson, Sano-Aventis, and the NIH; Dr Gottesman has servedon the Health Advisory Board, Child Development Council of evidence review needed to address a broad array of questions con-Franklin County, was a consultant to Early Head Start for Region cerning the development, progression, and management of multiple5B, has written for iVillage and taught classes through Garrison risk factors extending from birth through 21 years of age, including (Continued on last page) studies with follow-up into later adult life. The time frame extended back to 1985, 5 years before the review for the last NHLBI guideline addressing lipids in children published in 1992.1 This evidence is largely available in the form of epidemiologic observational studies PEDIATRICS Volume 128, Supplement 6, December 2011 S1

6. TABLE 1-1 Evaluated Risk Factors TABLE 1-2 Evidence Grading System: Quality GradesFamily history Grade EvidenceAge A Well-designed RCTs or diagnostic studies performed on a population similar to the guidelinesGender target populationNutrition/diet B RCTs or diagnostic studies with minor limitations; genetic natural history studies;Physical inactivity overwhelmingly consistent evidence from observational studiesTobacco exposure C Observational studies (case-control and cohort design)BP D Expert opinion, case reports, or reasoning from rst principles (bench research or animalLipid levels studies)Overweight/obesity Adapted from American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Pediatrics.Diabetes mellitus 2004;114(3):874 877.Predisposing conditionsMetabolic syndromeInammatory markersPerinatal factors titioners, physician assistants, and dations. The summary report will be registered dietitians. The full report released simultaneously with online contains complete background infor- availability of the full report with refer-(rather than RCTs) that, therefore, mation on the state of the science, ences for each section and the evidencemust be included in the review. In ad- methodology of the evidence review tables at www.nhlbi.nih.gov/guidelines/dition, the review required critical ap- and the guideline-development pro- cvd_ped/index.htm.praisal of the body of evidence that ad- cess, summaries of the evidence re- It is the hope of the NHLBI and the expertdresses the impact of managing risk views according to risk factor, discus- panel that these recommendations will befactors in childhood on the develop- sion of the expert panels rationale for useful for all those who provide cardiovas-ment and progression of atherosclero- recommendations, and 1000 cita- cular health care to children.sis. Because of known gaps in the evi- tions from the published literature anddence base relating risk factors and is available at www.nhlbi.nih.gov/ 2. STATE OF THE SCIENCE:risk reduction in childhood to clinical guidelines/cvd_ped/index.htm. The CARDIOVASCULAR RISK FACTORSevents in adult life, the review must in- complete evidence tables will be avail- AND THE DEVELOPMENT OFclude the available evidence that justi- able as a direct link from that site. This ATHEROSCLEROSIS IN CHILDHOODes evaluation and treatment of risk summary report presents the expertfactors in childhood. The process of Atherosclerosis begins in youth, and this panels recommendations for patientidentifying, assembling, and organiz- process, from its earliest phases, is re- care relative to cardiovascular healthing the evidence was extensive, the re- and risk-factor detection and manage- lated to the presence and intensity of theview process was complex, and the ment with only the references cited in known cardiovascular risk factorsconclusions could only be developed the text provided. It begins with a state- shown in Table 1-1. Clinical events suchby interpretation of the body of evi- of-the-science synopsis of the evi- as myocardial infarction, stroke, pe-dence. Even with inclusion of every rel- dence, which indicates that athero- ripheral arterial disease, and rup-evant study from the evidence review, sclerosis begins in childhood, and the tured aortic aneurysm are the culmi-there were important areas in which extent of atherosclerosis is linked di- nation of the lifelong vascular processthe evidence was inadequate. When rectly to the presence and intensity of of atherosclerosis. Pathologically, thethis occurred, recommendations were known risk factors. This is followed by process begins with the accumulationmade on the basis of a consensus of a cardiovascular health schedule (Sec- of abnormal lipids in the vascular in-the expert panel. The schema used in tion 3), which summarizes the expert tima, a reversible stage, progresses tograding the evidence appears in Ta- panels age-based recommendations an advanced stage in which a core ofbles 1-2 and 1-3; expert consensus according to risk factor in a 1-page pe- extracellular lipid is covered by a bro-opinions are identied as grade D. riodic table. Risk factor specic sec- muscular cap, and culminates inThe NHLBI expert panel integrated tions follow, with the graded conclu- thrombosis, vascular rupture, or acuteguidelines for cardiovascular health sions of the evidence review, normative ischemic syndromes.and risk reduction in children and ad- tables, and age-specic recommenda-olescents contain recommendations tions. These recommendations are often Evidence Linking Risk Factors inbased on the evidence review and are accompanied by supportive actions, Childhood to Atherosclerosis atdirected toward all primary pediatric which represent expert consensus sug- Autopsycare providers: pediatricians, family gestions from the panel provided to sup- Atherosclerosis at a young age waspractitioners, nurses and nurse prac- port implementation of the recommen- rst identied in Korean and VietnamS2 EXPERT PANEL

7. SUPPLEMENT ARTICLESTABLE 1-3 Evidence Grading System: Strength of Recommendations Statement Type Denition ImplicationStrong recommendation The expert panel believes that the benets of the recommended approach Clinicians should follow a strong recommendation clearly exceed the harms and that the quality of the supporting unless a clear and compelling rationale for an evidence is excellent (grade A or B). In some clearly dened alternative approach is present. circumstances, strong recommendations may be made on the basis of lesser evidence when high-quality evidence is impossible to obtain and the anticipated benets clearly outweigh the harms.Recommendation The expert panel feels that the benets exceed the harms but that the Clinicians should generally follow a quality of the evidence is not as strong (grade B or C). In some clearly recommendation but remain alert to new dened circumstances, recommendations may be made on the basis of information and sensitive to patient lesser evidence when high-quality evidence is impossible to obtain and preferences. when the anticipated benets clearly outweigh the harms.Optional Either the quality of the evidence that exists is suspect (grade D) or well- Clinicians should be exible in their decision- performed studies (grade A, B, or C) have found little clear advantage making regarding appropriate practice, to one approach versus another. although they may set boundaries on alternatives; patient and family preference should have a substantial inuencing role.No recommendation There is both a lack of pertinent evidence (grade D) and an unclear Clinicians should not be constrained in their balance between benets and harms. decision-making and be alert to new published evidence that claries the balance of benet versus harm; patient and family preference should have a substantial inuencing role.Adapted from American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Pediatrics. 2004;114(3):874 877.War casualties. Two major contempo- (determined by renal artery thick- young people with severe abnormali-rary studies, the Pathobiological De- ness), tobacco use (thiocyanate con- ties of individual risk factors:terminants of Atherosclerosis in Youth centration), diabetes mellitus (DM) In adolescents with a marked eleva-(PDAY) study2 and the Bogalusa Heart (glycohemoglobin), and (in men) obe- tion of low-density lipoprotein (LDL)Study,3 subsequently evaluated the ex- sity. There was a striking increase in cholesterol level caused by familialtent of atherosclerosis in children, ad- both severity and extent as age and the heterozygous hypercholesterol-olescents, and young adults who died number of risk factors increased. By emia, abnormal levels of coronaryaccidentally. The Bogalusa study3 mea- contrast, the absence of risk factors calcium, increased CIMT, and im-sured cardiovascular risk factors was shown to be associated with a vir- paired endothelial function have(lipid levels, blood pressure [BP], BMI, tual absence of advanced atheroscle- been found.and tobacco use) as part of a compre- rotic lesions, even in the oldest sub-hensive school-based epidemiologic jects in the study. Children with hypertension havestudy in a biracial community. These been shown to have increased CIMT,results were related to atherosclero- Evidence Linking Risk Factors in increased left ventricular mass, andsis measured at autopsy after acciden- Childhood to Atherosclerosis eccentric left ventricular geometry.tal death. Strong correlations were Assessed Noninvasively Children with type 1 DM (T1DM) haveshown between the presence and in- Over the last decade, measures of sub- signicantly abnormal endothelialtensity of risk factors and the extent clinical atherosclerosis have devel- function and, in some studies, in-and severity of atherosclerosis. In the oped, including the demonstration of creased CIMT.PDAY study,2 risk factors and surro- coronary calcium on electron beam Children and young adults with agate measures of risk factors were computed tomography imaging, in- family history of myocardial infarc-measured after death in 15- to 34-year creased carotid intima-media thick-olds who died accidentally of external ness (CIMT) assessed with ultrasound, tion have increased CIMT, highercauses. Strong relationships were endothelial dysfunction (reduced arte- prevalence of coronary calcium,found between atherosclerotic sever- rial dilation) with brachial ultrasound and endothelial dysfunction.ity and extent, and age, non imaging, and increased left ventricular Endothelial dysfunction has beenhigh-density lipoprotein (HDL) choles- mass with cardiac ultrasound. These shown by ultrasound and plethys-terol, HDL cholesterol, hypertension measures have been assessed in mography in association with ciga- PEDIATRICS Volume 128, Supplement 6, December 2011 S3

8. rette smoking (passive and active) in non-HDL cholesterol level was asso- gard to tobacco-use rates, obesity and obesity. In obese children, im- ciated with a visible incremental in- prevalence, hypertension, and dyslipi- provement in endothelial function crease in the extent and severity of demia. Low socioeconomic status in occurs with regular exercise. atherosclerosis. In natural-history and of itself confers substantial risk. Left ventricular hypertrophy at lev- studies of DM, early CVD mortality is so However, evidence is not adequate for els associated with excess mortality consistently observed that the pres- the recommendations provided in this in adults has been found in children ence of DM is considered evidence of report to be specic to racial or ethnic with severe obesity. vascular disease in adults. Consonant groups or socioeconomic status. with this evidence, in 15- to 19-yearFour longitudinal studies have found The Impact of Risk-Factor olds in the PDAY study, the presence ofrelationships of risk factors measured Clustering in Childhood on the hyperglycemia was associated within youth (specically LDL cholesterol, Development of Atherosclerosis the demonstration of advanced ath-non-HDL cholesterol and serum apoli- erosclerotic lesions of the coronary From a population standpoint, cluster-poproteins, obesity, hypertension, to- arteries. In the PDAY study, there was ing of multiple risk factors is the mostbacco use, and DM) with measures of also a strong relationship between ab- common association with prematuresubclinical atherosclerosis in adult- dominal aortic atherosclerosis and to- atherosclerosis. The pathologic stud-hood. In many of these studies, risk bacco use. Finally, in a 25-year follow- ies reviewed above clearly showedfactors measured in childhood and ad- up, the presence of the metabolic that the presence of multiple risk fac-olescence were better predictors of syndrome risk-factor cluster in child- tors is associated with striking evi-the severity of adult atherosclerosis hood predicted clinical CVD in adult dence of an accelerated atheroscle-than were risk factors measured at subjects at 30 to 48 years of age.4 rotic process. Among the mostthe time of the subclinical atheroscle- prevalent multiple-risk combinationsrosis study. The Impact of Racial/Ethnic are the use of tobacco with 1 other risk Background and Socioeconomic factor and the development of obesity,Evidence Linking Risk Factors in Status in Childhood on the which is often associated with insulinChildhood to Clinical CVD Development of Atherosclerosis resistance, elevated triglyceride lev-The most important evidence relating CVD has been observed in diverse geo- els, reduced HDL cholesterol levels,risk in youth to clinical CVD is the ob- graphic areas and all racial and ethnic and elevated BP, a combination knownserved association of risk factors for backgrounds. Cross-sectional re- in adults as the metabolic syndrome.atherosclerosis to clinically manifest search in children has found differ- There is ample evidence from bothcardiovascular conditions. Genetic dis- ences according to race and ethnicity cross-sectional and longitudinal stud-orders related to high cholesterol are and according to geography for preva- ies that the increasing prevalence ofthe biological model for risk-factor im- lence of cardiovascular risk factors; obesity in childhood is associated withpact on the atherosclerotic process. these differences are often partially the same obesity-related risk-factorWith homozygous hypercholesterol- explained by differences in socioeco- clustering seen in adults and that itemia, in which LDL cholesterol levels nomic status. No group within the continues into adult life. This high-riskexceed 800 mg/dL beginning in infancy, United States is without a signicant combination is among the reasonscoronary events begin in the rst de- prevalence of risk. Several longitudi- that the current obesity epidemic withcade of life and life span is severely nal cohort studies referenced exten- its relationship to future CVD and DM isshortened. With heterozygous hyper- sively in this report (Bogalusa Heart considered one of the most importantcholesterolemia, in which LDL choles- Study,3 the PDAY study,2 and the Coro- public health challenges in contempo-terol levels are minimally 160 mg/dL nary Artery Risk Development in Young rary society. One other prevalentand typically 200 mg/dL and total Adults [CARDIA] study5) have included multiple-risk combination is the asso-cholesterol (TC) levels exceed 250 racially diverse populations, and other ciation of low cardiorespiratory t-mg/dL beginning in infancy, 50% of studies have been conducted outside ness (identied in 33.6% of adoles-men and 25% of women experience the United States. However, longitudi- cents in the National Health andclinical coronary events by the age of nal data on Hispanic, Native American, Nutrition Examination Surveys [NHANES]50. By contrast, genetic traits associ- and Asian children are lacking. Clini- from 1999 to 20026) with overweightated with low cholesterol are associ- cally important differences in preva- and obesity, elevated TC level and sys-ated with longer life expectancy. In the lence of risk factors exist according to tolic BP, and a reduced HDL cholesterolPDAY study,2 every 30 mg/dL increase race and gender, particularly with re- level.S4 EXPERT PANEL

9. SUPPLEMENT ARTICLESRisk-Factor Tracking From bariatric surgery, but the long-term out- have less atherosclerosis and will col-Childhood Into Adult Life come of those with T2DM diagnosed in lectively have lower CVD rates. ThisTracking studies from childhood to childhood is not known. concept is supported by research thatadulthood have been performed for all As already discussed, risk-factor has found that (1) societies with lowthe major risk factors. clusters such as those seen with levels of cardiovascular risk factors obesity and the metabolic syndrome have low CVD rates and that changes Obesity tracks more strongly than have been shown to track from in risk in those societies are associ- any other risk factor; among many childhood into adulthood. ated with a change in CVD rates, (2) reports from studies that have dem- in adults, control of risk factors onstrated this fact, one of the most CVD Prevention Beginning in Youth leads to a decline in morbidity and recent is from the Bogalusa study,7 The rationale for these guidelines mortality from CVD, and (3) those in which 2000 children were fol- comes from the following evidence. without childhood risk have minimal lowed from initial evaluation at 5 to atherosclerosis at 30 to 34 years of 14 years of age to adult follow-up at Atherosclerosis, the pathologic ba- age, absence of subclinical athero- a mean age of 27 years. On the basis sis for clinical CVD, originates in childhood. sclerosis as young adults, extended of BMI percentiles derived from the life expectancy, and a better quality study population, 84% of those with Risk factors for the development of of life free from CVD. a BMI in the 95th to 99th percentile atherosclerosis can be identied in as children were obese as adults, childhood. The Pathway to Recommending and all of those with a BMI at the Development and progression of Clinical Practice-Based Prevention 99th percentile were obese in atherosclerosis clearly relates to adulthood. Increased correlation is The most direct means of establishing the number and intensity of cardio- seen with increasing age at which evidence for active CVD prevention be- vascular risk factors, which begin in the elevated BMI occurs. ginning at a young age would be to ran- childhood. domly assign young people with For cholesterol and BP, tracking Risk factors track from childhood dened risks to treatment of cardio- correlation coefcients in the range into adult life. vascular risk factors or to no treat- of 0.4 have been reported consis- Interventions exist for the manage- ment and follow both groups over tently from many studies, correlat- ment of identied risk factors. sufcient time to determine if cardio- ing these measures in children 5 to The evidence for the rst 4 bullet vascular events are prevented without 10 years of age with results 20 to 30 points is reviewed in this section, and undue increase in morbidity arising years later. These data suggest that the evidence surrounding interven- from treatment. This direct approach having cholesterol or BP levels in tions for identied risk factors is ad- is intellectually attractive, because the upper portion of the pediatric dressed in the risk-factorspecic atherosclerosis prevention would be- distribution makes having them as sections of the guideline to follow. gin at the earliest stage of the disease adult risk factors likely but not cer- process and thereby maximize the tain. Those who develop obesity It is important to distinguish between benet. However, this approach is as have been shown to be more likely the goals of prevention at a young age unachievable as it is attractive, pri- to develop hypertension or dyslipi- and those at older ages in which ath- marily because such studies would be demia as adults. erosclerosis is well established, mor- extremely expensive and would be sev- Tracking data on physical tness bidity may already exist, and the pro- cess is only minimally reversible. At a eral decades in duration, a time period are more limited. Physical activity in which changes in environment and levels do track but not as strongly young age, there have historically been 2 goals of prevention: (1) prevent the medical practice would diminish the as other risk factors. relevance of the results. development of risk factors (primor- By its addictive nature, tobacco use dial prevention); and (2) recognize and The recognition that evidence from persists into adulthood, although manage those children and adoles- this direct pathway is unlikely to be 50% of those who have ever cents who are at increased risk as a achieved requires an alternative step- smoked eventually quit. result of the presence of identied risk wise approach in which segments of T1DM is a lifelong condition. factors (primary prevention). It is well an evidence chain are linked in a man- The insulin resistance of T2DM can be established that a population that en- ner that serves as a sufciently rigor- alleviated by exercise, weight loss, and ters adulthood with lower risk will ous proxy for the causal inference of a PEDIATRICS Volume 128, Supplement 6, December 2011 S5

10. clinical trial. The evidence reviewed in This document provides recommenda- studies have found that a family his-this section provides the critical ratio- tions for preventing the development tory of premature coronary heart dis-nale for cardiovascular prevention be- of risk factors and optimizing cardio- ease in a rst-degree relative (heartginning in childhood: atherosclerosis vascular health, beginning in infancy, attack, treated angina, percutaneousbegins in youth; the atherosclerotic that are based on the results of the coronary catheter interventional pro-process relates to risk factors that can evidence review. Pediatric care provid- cedure, coronary artery bypass sur-be identied in childhood; and the ers (pediatricians, family practitio- gery, stroke, or sudden cardiac deathpresence of these risk factors in a ners, nurses, nurse practitioners, in a male parent or sibling before thegiven child predicts an adult with risk physician assistants, registered dieti- age of 55 years or a female parent orif no intervention occurs. The remain- tians) are ideally positioned to rein- sibling before the age of 65 years) is aning evidence links pertain to the dem- force cardiovascular health behaviors important independent risk factor foronstration that interventions to lower as part of routine care. The guideline future CVD. The process of atheroscle-risk will have a health benet and that also offers specic guidance on pri- rosis is complex and involves many ge-the risk and cost of interventions to mary prevention with age-specic, netic loci and multiple environmentalimprove risk are outweighed by the re- evidence-based recommendations for and personal risk factors. Nonethe-duction in CVD morbidity and mortal- individual risk-factor detection. Man- less, the presence of a positive paren-ity. These issues are captured in the agement algorithms provide staged tal history has been consistently foundevidence reviews of each risk factor. care recommendations for risk reduc- to signicantly increase baseline riskThe recommendations reect a com- tion within the pediatric care setting for CVD. The risk for CVD in offspring isplex decision process that integrates and identify risk-factor levels that re- strongly inversely related to the age ofthe strength of the evidence with quire specialist referral. The guide- the parent at the time of the indexknowledge of the natural history of lines also identify specic medical con- event. The association of a positiveatherosclerotic vascular disease, esti- ditions such as DM and chronic kidney family history with increased cardio-mates of intervention risk, and the phy- disease that are associated with in- vascular risk has been conrmed forsicians responsibility to provide both creased risk for accelerated athero- men, women, and siblings and in dif-health education and effective disease sclerosis. Recommendations for ferent racial and ethnic groups. The ev-treatment. These recommendations ongoing cardiovascular health man- idence review identied all RCTs, sys-for those caring for children will be agement for children and adolescents tematic reviews, meta-analyses, andmost effective when complemented by with these diagnoses are provided. observational studies that addresseda broader public health strategy. A cornerstone of pediatric care is the family history of premature athero- provision of health education. In the US sclerotic disease and the developmentThe Childhood Medical Ofce Visit health care system, physicians and and progression of atherosclerosisas the Setting for Cardiovascular nurses are perceived as credible mes- from childhood into young adult life.Health Management sengers for health information. The childhood health maintenance visit Conclusions and Grading of theOne cornerstone of pediatric care is provides an ideal context for effective Evidence Review for the Role ofplacing clinical recommendations in a delivery of the cardiovascular health Family History in Cardiovasculardevelopmental context. Those who message. Pediatric care providers Healthmake pediatric recommendationsmust consider not only the relation of provide an effective team educated to Evidence from observational stud-age to disease expression but the abil- initiate behavior change to diminish ies strongly supports inclusion of aity of the patient and family to under- risk of CVD and promote lifelong car- positive family history of early coro-stand and implement medical advice. diovascular health in their patients nary heart disease in identifyingFor each risk factor, recommenda- from infancy into young adult life. children at risk for accelerated ath-tions must be specic to age and devel- erosclerosis and for the presence ofopmental stage. The Bright Futures 4. FAMILY HISTORY OF EARLY an abnormal risk prole (grade B).concept of the American Academy of ATHEROSCLEROTIC CVD For adults, a positive family historyPediatrics8 (AAP) is used to provide a A family history of CVD represents the is dened as a parent and/or siblingframework for these guidelines with net effect of shared genetic, biochemi- with a history of treated angina,cardiovascular risk-reduction recom- cal, behavioral, and environmental myocardial infarction, percutane-mendations for each age group. components. In adults, epidemiologic ous coronary catheter interven-S6 EXPERT PANEL

11. SUPPLEMENT ARTICLES tional procedure, coronary artery risk. Evidence relative to diet and the specic nutrition area with grades are bypass grafting, stroke, or sudden development of atherosclerosis in summarized. Where the evidence is in- cardiac death before 55 years in childhood and adolescence was identi- adequate yet nutrition guidance is men or 65 years in women. Because ed by the evidence review for this needed, recommendations for pediat- the parents and siblings of children guideline and, collectively, provides ric care providers are based on a con- and adolescents are usually young the rationale for new dietary preven- sensus of the expert panel (grade D). themselves, it was the panel con- tion efforts initiated early in life. The age- and evidence-based recom- sensus that when evaluating family This new pediatric cardiovascular mendations of the expert panel follow. history of a child, history should guideline not only builds on the recom- also be ascertained for the occur- mendations for achieving nutrient ad- In accordance with the Surgeon Gen- rence of CVD in grandparents, equacy in growing children as stated erals Ofce, the World Health Organi- aunts, and uncles, although the evi- zation, the AAP, and the American in the 2010 DGA but also adds evidence dence supporting this recommen- Academy of Family Physicians, exclu- regarding the efcacy of specic di- dation is insufcient to date (grade sive breastfeeding is recommended etary changes in reducing cardiovas- D). for the rst 6 months of life. Contin- cular risk from the current evidence Identication of a positive family ued breastfeeding is recommended review for use by pediatric care pro- history for cardiovascular disease to at least 12 months of age with the viders in the care of their patients. Be- and/or cardiovascular risk fac- addition of complementary foods. If cause the focus of these guidelines is tors should lead to evaluation of breastfeeding per se is not possible, on cardiovascular risk reduction, the all family members, especially feeding human milk by bottle is sec- evidence review specically evaluated parents, for cardiovascular risk ond best, and formula-feeding is the dietary fatty acid and energy compo- factors (grade B). third choice. nents as major contributors to hyper- Family history evolves as a child ma- cholesterolemia and obesity, as well tures, so regular updates are a nec- as dietary composition and micronu- Long-term follow-up studies have essary part of routine pediatric trients as they affect hypertension. found that subjects who were care (grade D). New evidence from multiple dietary tri- breastfed have sustained cardio- als that addressed cardiovascular risk vascular health benets, including Education about the importance of reduction in children has provided lower cholesterol levels, lower accurate and complete family important information for these BMI, reduced prevalence of type 2 health information should be part of recommendations. DM, and lower CIMT in adulthood routine care for children and ado- (grade B). lescents. As genetic sophistication increases, linking family history to Conclusions and Grading of the Ongoing nutrition counseling has specic genetic abnormalities will Evidence Review for Diet and been effective in assisting children provide important new knowledge Nutrition in Cardiovascular Risk and families to adopt and sustain about the atherosclerotic process Reduction recommended diets for both nutri- (grade D). The expert panel concluded that there ent adequacy and reducing cardio-Recommendations for the use of fam- is strong and consistent evidence that vascular risk (grade A).ily history in cardiovascular health good nutrition beginning at birth has Within appropriate age- and gender-promotion are listed in Table 4-1. profound health benets and the po- based requirements for growth and tential to decrease future risk for CVD. nutrition, in normal children and in5. NUTRITION AND DIET The expert panel accepts the 2010 DGA8 children with hypercholesterolemiaThe 2010 Dietary Guidelines for Ameri- as containing appropriate recommen- intake of total fat can be safely lim-cans (DGA)8 include important recom- dations for diet and nutrition in chil- ited to 30% of total calories, satu-mendations for the population aged 2 dren aged 2 years and older. The rec- rated fat intake limited to 7% to 10%years and older. In 1992, the National ommendations in these guidelines are of calories, and dietary cholesterolCholesterol Education Program (NCEP) intended for pediatric care providers limited to 300 mg/day. Under thePediatric Panel report1 provided di- to use with their patients to address guidance of qualied nutritionists,etary recommendations for all chil- cardiovascular risk reduction. The this dietary composition has beendren as part of a population-based ap- conclusions of the expert panels re- shown to result in lower TC and LDLproach to reducing cardiovascular view of the entire body of evidence in a cholesterol levels, less obesity, and PEDIATRICS Volume 128, Supplement 6, December 2011 S7

12. less insulin resistance (grade A). tervention should be tailored to activity. Calorie intake needs to Under similar conditions and with each specic childs needs. match growth demands and physi- ongoing follow-up, these levels of fat Optimal intakes of total protein and cal activity needs (grade A). Esti- intake might have similar effects total carbohydrate in children were mated calorie requirements ac- starting in infancy (grade B). Fats not specically addressed, but with cording to gender and age group at are important to infant diets be- a recommended total fat intake of 3 levels of physical activity from the cause of their role in brain and cog- 30% of energy, the expert panel rec- dietary guidelines are shown in Ta- nitive development. Fat intake for in- ommends that the remaining 70% of ble 5-2. For children of normal fants younger than 12 months calories include 15% to 20% from weight whose activity is minimal, should not be restricted without protein and 50% to 55% from carbo- most calories are needed to meet medical indication. hydrate sources (no grade). These nutritional requirements, which The remaining 20% of fat intake leaves only 5% to 15% of calorie recommended ranges fall within should comprise a combination of intake from extra calories. These the acceptable macronutrient dis- monosaturated and polyunsatu- calories can be derived from fat or tribution range specied by the rated fats (grade D). Intake of trans sugar added to nutrient-dense 2010 DGA: 10% to 30% of calories fats should be limited as much as foods to allow their consumption as from protein and 45% to 65% of cal- possible (grade D). sweets, desserts, or snack foods ories from carbohydrate for chil- (grade D). For adults, the current NCEP guide- dren aged 4 to 18 years. Dietary ber intake is inversely as- lines9 recommend that adults con- Sodium intake was not addressed sociated with energy density and in- sume 25% to 35% of calories from by the evidence review for this sec- creased levels of body fat and is pos- fat. The 2010 DGA supports the Insti- tion on nutrition and diet. From the itively associated with nutrient tute of Medicine recommendations evidence review for the High BP density (grade B); a daily total di- for 30% to 40% of calories from fat section, lower sodium intake is as- etary ber intake from food sources for ages 1 to 3 years, 25% to 35% of sociated with lower systolic and di- of at least age plus 5 g for young calories from fat for ages 4 to 18 astolic BP in infants, children, and children up to 14 g/1000 kcal for years, and 20% to 35% of calories adolescents. older children and adolescents is from fat for adults. For growing chil- Plant-based foods are important recommended (grade D). dren, milk provides essential nutri- low-calorie sources of nutrients in- ents, including protein, calcium, The expert panel supports the 2008 cluding vitamins and ber in the di- AAP recommendation for vitamin D magnesium, and vitamin D, that are ets of children; increasing access to supplementation with 400 IU/day for not readily available elsewhere in fruits and vegetables has been all infants and children.10 No other the diet. Consumption of fat-free shown to increase their intake vitamin, mineral, or dietary supple- milk in childhood after 2 years of (grade A). However, increasing fruit ments are recommended (grade D). age and through adolescence opti- and vegetable intake is an ongoing The new recommended daily allow- mizes these benets without com- challenge. ance for vitamin D for those aged 1 promising nutrient quality while avoiding excess saturated fat and Reduced intake of sugar-sweetened to 70 years is 600 IU/day. calorie intake (grade A). Between beverages is associated with de- Use of dietary patterns modeled on the ages of 1 and 2 years, as chil- creased obesity measures (grade those shown to be benecial for dren transition from breast milk or B). Specic information about fruit adults (eg, Dietary Approaches to formula, reduced-fat milk (ranging juice intake is too limited for an Stop Hypertension [DASH] pattern) from 2% milk to fat-free milk) can be evidence-based recommendation. is a promising approach to improv- used on the basis of the childs Recommendations for intake of ing nutrition and decreasing cardio- growth, appetite, intake of other 100% fruit juice by infants was vascular risk (grade B). nutrient-dense foods, intake of made by a consensus of the expert All diet recommendations must be other sources of fat, and risk for panel (grade D) and are in agree- interpreted for each child and fam- obesity and CVD. Milk with reduced ment with those of the AAP. ily to address individual diet pat- fat should be used only in the con- Per the 2010 DGA, energy intake terns and patient sensitivities such text of an overall diet that supplies should not exceed energy needed as lactose intolerance and food al- 30% of calories from fat. Dietary in- for adequate growth and physical lergies (grade D).S8 EXPERT PANEL

13. 3. INTEGRATED CARDIOVASCULAR HEALTH SCHEDULE Risk Factor Age Birth to 12 mo 14 y 59 y 911 y 1217 y 1821 y Family At 3 y, evaluate family history for Update at each nonurgent health Reevaluate family history for early Update at each nonurgent health Repeat family-history evaluation with history of early CVD: parents, grand- encounter CVD in parents, grandparents, encounter patient early CVD parents, aunts/uncles, men aunts/uncles, men 55 y old, 55 y old, women 65 y old; women 65 y old review with parents and refer as needed; positive family history identies children for intensive CVD RF attention Tobacco Advise smoke-free home; Continue active antismoking Obtain smoke exposure history Assess smoking status of child; Continue active antismoking Reinforce strong antismoking message; exposure offer smoking-cessation advice with parents; offer from child Begin active active antismoking counseling counseling with patient; offer offer smoking-cessation assistance or assistance or referral smoking-cessation assistance antismoking advice with child or referral as needed smoking-cessation assistance or referral as needed to parents and referral as needed referral as needed Nutrition/diet Support breastfeeding as At age 1224 mo, may change to Reinforce CHILD-1 diet messages Reinforce CHILD-1 diet messages Obtain diet information from child Review healthy diet with patient optimal to 12 mo of age cows milk with 2% as needed and use to reinforce healthy diet if possible; add formula percentage of fat decided by and limitations and provide if breastfeeding family and pediatric care counseling as needed decreases or stops provider; after 2 y of age, before 12 mo of age fat-free milk for all; juice 4 oz/d; transition to CHILD-1 diet by the age of 2 y Growth, Review family history for Chart height/weight/BMI; Chart height/weight/BMI and Chart height/weight/BMI and Chart height/weight/BMI and review Review height/weight/BMI and norms for overweight/ obesity; discuss weight- classify weight-by BMI from review with parent; BMI review with parent and child; with child and parent; BMI 85th health with patient; BMI 85th obesity for-height tracking, age 2 y; review with parent 85th percentile, crossing BMI 85th percentile, percentile, crossing percentiles: percentile, crossing percentiles: growth chart, and percentiles: Intensify diet/ crossing percentiles: Intensify intensify diet/activity focus for 6 intensify diet/activity focus for 6 mo; healthy diet activity focus for 6 mo; if no diet/activity focus for 6 mo; if mo; if no change: RD referral, if no change: RD referral, manage per change: RD referral, manage no change: RD referral, manage per obesity algorithms; obesity algorithms; BMI 95th per obesity algorithms manage per obesity BMI 95th percentile, manage percentile, manage per obesity BMI 95th percentile, manage algorithms; BMI 95th per obesity algorithms algorithms per obesity algorithms percentile: manage per obesity algorithms Lipids No routine lipid screening Obtain FLP only if family history Obtain FLP only if family history Obtain universal lipid screen with Obtain FLP if family history newly Measure 1 nonfasting nonHDL or FLP in for CVD is positive, parent has for CVD is positive, parent nonfasting non-HDL TC positive, parent has all: review with patient; manage with dyslipidemia, child has any has dyslipidemia, child has HDL, or FLP: manage per lipid dyslipidemia, child has any other lipid algorithms per ATP as needed other RFs or high-risk any other RFs or high-risk algorithms as needed RFs or high-risk condition; condition condition manage per lipid algorithms as needed BP Measure BP in infants with Measure BP annually in all from Check BP annually and chart for Check BP annually and chart for Check BP annually and chart for Measure BP: review with patient; renal/urologic/cardiac the age of 3 y; chart for age/ age/gender/height: review age/gender/height: review with age/gender/height: review with evaluate and treat per JNC guidelines diagnosis or history of gender/height percentile and with parent; workup and/or parent, workup and/or adolescent and parent, workup neonatal ICU review with parent management per BP management per BP algorithm and/or management per BP algorithm as needed as needed algorithm as needed Physical Encourage parents to Encourage active play; limit Recommend MVPA of 1 h/d; Obtain activity history from child: Use activity history with adolescent Discuss lifelong activity, sedentary time activity model routine activity; sedentary/screen time to 2 limit screen/sedentary time recommend MVPA of 1 h/d to reinforce MVPA of 1 h/d and limits with patient no screen time before h/d; no TV in bedroom to 2 h/d and screen/sedentary time of leisure screen time of 2 h/d the age of 2 y 2 h/d Diabetes Measure fasting glucose level per Measure fasting glucose level per Obtain fasting glucose level if indicated; ADA guidelines; refer to ADA guidelines; refer to refer to endocrinologist as needed endocrinologist as needed endocrinologist as neededPEDIATRICS Volume 128, Supplement 6, December 2011 All algorithms and guidelines in this schedule are included in this summary report. RF indicates risk factor; RD, registered dietitian; ATP, Adult Treatment Panel III (Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults); JNC, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; MVPA, moderate-to-vigorous physical activity; ADA, American Diabetes Association. SUPPLEMENT ARTICLESS9 The full and summary reports of the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents can also be found on the NHLBI Web site (www.nhlbi.nih.gov).

14. TABLE 4-1 Evidence-Based Recommendations for Use of Family History in Cardiovascular review focused on the effects of activ- Health Promotion ity on cardiovascular health, becauseBirth to 18 y Take detailed family history of CVD at initial encounter and/or at 3, Grade B physical inactivity has been identied 911, and 18 ya Recommend as an independent risk factor for cor- If positive family history identied, evaluate patient for other onary heart disease in adults. Over the cardiovascular risk factors, including dyslipidemia, hypertension, last several decades, there has been a DM, obesity, history of smoking, and sedentary lifestyle steady decrease in the amount of time If positive family history and/or cardiovascular risk factors identied, Grade B that children spend being physically evaluate family, especially parents, for cardiovascular risk factors Recommend active and an accompanying increase Update family history at each nonurgent health encounter Grade D in time spent in sedentary activities. The Recommend evidence review identied many studies in youth ranging in age from 4 to 21 years Use family history to stratify risk for CVD risk as risk prole evolves Grade D that strongly linked increased time Recommend spent in sedentary activities with re- Supportive action: educate parents about the importance of family duced overall activity levels, disadvanta- history in estimating future health risks for all family members geous lipid proles, higher systolic BP,18 to 21 y Review family history of heart disease with young adult patient Grade B higher levels of obesity, and higher levels Strongly recommend of all the obesity-related cardiovascular Supportive action: educate patient about family/personal risk for risk factors including hypertension, in- early heart disease, including the need for evaluation for all cardiovascular risk factors sulin resistance, and type 2 DM.Grades reect the ndings of the evidence review; recommendation levels reect the consensus opinion of the expert panel;and supportive actions represent expert consensus suggestions from the expert panel provided to support implementation Conclusions and Grading of theof the recommendations (they are not graded). Evidence Review for Physicala Family includes parent, grandparent, aunt, uncle, or sibling with heart attack, treated angina, coronary artery bypassgraft/stent/angioplasty, stroke, or sudden cardiac death at 55 y in males and 65 y in females. Activity The expert panel felt that the evidence strongly supports the role of physicalGraded, age-specic recommenda- bles. This diet has been modied for activity in optimizing cardiovasculartions for pediatric care providers to use in children aged 4 years and older health in children and adolescents.use in optimizing cardiovascular on the basis of daily energy needs ac- There is reasonably good evidencehealth in their patients are summa- cording to food group and is shown in that physical activity patterns es-rized in Table 5-1. The Cardiovascular Table 5-3 as an example of a heart- tablished in childhood are carriedHealth Integrated Lifestyle Diet healthy eating plan using CHILD-1 forward into adulthood (grade(CHILD-1) is the rst stage in dietary recommendations. C).change for children with identied dys-lipidemia, overweight and obesity, 6. PHYSICAL ACTIVITY There is strong evidence that in-risk-factor clustering, and high-risk Physical activity is any bodily move- creases in moderate-to-vigorousmedical conditions that might ulti- ment produced by contraction of skel- physical activity are associated withmately require more intensive dietary etal muscle that increases energy ex- lower systolic and diastolic BP, de-change. CHILD-1 is also the recom- penditure above a basal level. Physical creased measures of body fat, de-mended diet for children with a posi- activity can be focused on strengthen- creased BMI, improved tness mea-tive family history of early cardiovas- ing muscles, bones, and joints, but be- sures, lower TC level, lower LDLcular disease, dyslipidemia, obesity, cause these guidelines address car- cholesterol level, lower triglycerideprimary hypertension, DM, or expo- diovascular health, the evidence level, higher HDL cholesterol level,sure to smoking in the home. Any di- review concentrated on aerobic activ- and decreased insulin resistance inetary modication must provide nutri- ity and on the opposite of activity: sed- childhood and adolescence (gradeents and calories needed for optimal entary behavior. There is strong evi- A).growth and development (Table 5-2). dence for benecial effects of physical There is limited but strong and con-Recommended intakes are adequately activity and disadvantageous effects of sistent evidence that physical exer-met by a DASH-style eating plan, which a sedentary lifestyle on the overall cise interventions improve subclini-emphasizes fat-free/low-fat dairy and health of children and adolescents cal measures of atherosclerosisincreased intake of fruits and vegeta- across a broad array of domains. Our (grade B).S10 EXPERT PANEL

15. SUPPLEMENT ARTICLESTABLE 5-1 Evidence-Based Recommendations for Diet and Nutrition: CHILD-1Birth to 6 mo Infants should be exclusively breastfed (no supplemental formula or other foods) until the age of 6 moa Grade B Strongly recommend6 to 12 mo Continue breastfeeding until at least 12 mo of age while gradually adding solids; transition to iron- Grade B fortied formula until 12 mo if reducing breastfeedinga Strongly recommend Fat intake in infants 12 mo of age should not be restricted without medical indication Grade D Recommend Limit other drinks to 100% fruit juice (4 oz/d); no sweetened beverages; encourage water Grade D recommend12 to 24 mo Transition to reduced-fatb (2% to fat-free) unavored cows milkc (see supportive actions) Grade B Recommend Limit/avoid sugar-sweetened beverage intake; encourage water Grade B Strongly recommend Transition to table food with: Total fat 30% of daily kcal/EERd Grade B Recommend Saturated fat 8%10% of daily kcal/EER Grade B Recommend Avoid trans fat as much as possible Grade D Strongly recommend Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER Grade D recommend Cholesterol 300 mg/d Grade B Strongly recommend Supportive actions The fat content of cows milk to introduce at 1224 mo of age should be decided together by parents and health care providers on the basis of the childs growth, appetite, intake of other nutrient-dense foods, intake of other sources of fat, and potential risk for obesity and CVD 100% fruit juice (from a cup), no more than 4 oz/d