Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents:
Summary Report

Contents

Expert Panel Members

1. Introduction
2. State of the Science: CV Risk Factors and the Development of Atherosclerosis
3. Integrated Cardiovascular Health Schedule
4. Family History of Early Atherosclerotic Cardiovascular Disease
5. Nutrition and Diet
6. Physical Activity
7. Tobacco Exposure
8. High Blood Pressure
9. Lipids and Lipoproteins
10. Overweight and Obesity
11. Diabetes and Other Conditions Predisposing to the Development of Accelerated Atherosclerosis
12. Risk Factor Clustering and the Metabolic Syndrome
13. Perinatal Factors

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
The Hospital for Sick Children
Toronto, ON

Albert P. Rocchini, MD
C.S. Mott Children's Hospital
Ann Arbor, MI

Elaine M. Urbina, MD
Cincinnati Children's 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, MD

Christopher J. O'Donnell, MD, MPH
National Heart, Lung and Blood Institute 
Framingham, MA

Robinson Fulwood, PhD, MSPH
National Heart, Lung and Blood Institute
Bethesda, MD

Janet M. de Jesus, MS, RD
National Heart, Lung and Blood Institute
Bethesda, MD

Karen A. Donato, SM
National Heart, Lung and Blood Institute
Bethesda, MD

Denise G. Simons-Morton, MD, MPH, PhD   
National Heart, Lung and Blood Institute
Bethesda, MD  

Contract Staff

The Lewin Group, Falls Church, VA
Clifford Goodman, MS, PhD
Christel M. Villarivera, MS
Charlene Chen, MHS
Erin Karnes, MHS
Ayodola Anise, MHS

Relationship/Conflict of Interest/Financial/Other Disclosures

Dr. Benuck, Dr. Christakis, Dr. Dennison, Dr. O'Donnell, Dr. Rocchini, and Dr. Washington have declared no relevant relationships.

Dr. Daniels has served as a consultant for Abbott Laboratories and Merck, Schering-Plough. He has received funding/grant support for research from the NIH.

Dr. Gidding has served as a consultant for Merck, Schering-Plough. He has received funding/grant support for research from GlaxoSmithKline.

Dr. Gillman has given invited talks for Nestle Nutrition Institute and Danone. He has received funding /grant support for research from Mead Johnson, Sanofi-aventis and the NIH.

Dr. Gottesman has served on the Health Advisory Board, Child Development Council of Franklin County. She was a consultant to Early Head Start for Region 5B. She has written for iVillage and taught classes through Garrison Associates for the State of Ohio, Bureau of Early Intervention Services and Help Me Grow program. She has received funding /grant support for research from NIH.

Dr. Kwiterovich has served as a consultant or advisory board member for Merck, Schering-Plough, Pfizer, Sankyo, LipoScience and Astra Zeneca. He has served on speaker bureaus for Merck, Schering-Plough, Pfizer, Sankyo, Kos and Astra Zeneca. He has received funding/grant support for research from Pfizer, Merck, GlaxoSmithKline, Sankyo and Schering-Plough.

Dr. McBride has served as a consultant or advisory board member for Bristol-Myers Squibb, and Merck. He has served on speakers bureaus for Kos, Merck and Pfizer. He declared no relevant relationships since July 2007.

Dr. McCrindle has been a consultant for Abbott, Bristol-Myers Squibb, Daichii Sankyo and Roche. He owns stock in CellAegis. He reports funding/grant support for research from Astra Zeneca, Sankyo, Merck, Schering-Plough and the NIH.

Dr. Urbina reports funding/grant support for research from Merck, Schering-Plough, Sankyo and the NIH.

Dr. Van Horn has provided advice to Chartwells School Food Service. She has received funding/grant support for research from General Mills and the NIH.

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1. Introduction

Atherosclerotic cardiovascular disease (CVD) remains the leading cause of death in North Americans but manifest disease in childhood and adolescence is rare. By contrast, risk factors and risk behaviors that accelerate the development of atherosclerosis begin in childhood and there is increasing evidence that risk reduction delays progression towards clinical disease. In 2006, the Director of the National Heart, Lung and Blood Institute (NHLBI), Dr. Elizabeth Nabel, appointed an Expert Panel to develop cardiovascular (CV) health guidelines for pediatric care providers based on a formal evidence review of the science, with an integrated format addressing all the major CV risk factors simultaneously.

The goal of the Expert Panel was the development of comprehensive evidence-based guidelines addressing the known risk factors for CVD (Table 1–1) to assist all primary pediatric care providers in both the promotion of CV health and the identification and management of specific risk factors from infancy into young adult life. An innovative approach was needed because a focus on CV risk reduction in children and adolescents addresses a disease process – atherosclerosis – in which the clinical endpoint of manifest CVD is remote. The recommendations therefore need to address two different goals: the prevention of risk factor development – primordial prevention - and the prevention of future CVD by effective management of identified risk factors – primary prevention.

The evidence review also required an innovative approach. Most systematic evidence reviews include one or, at most, a small number of finite questions addressing the impact of specific interventions on specific health outcomes, and a rigorous literature review often results in only a handful of in-scope articles for inclusion. Typically, evidence is limited to randomized controlled trials (RCTs), systematic reviews and meta-analyses published over a defined time period. There is a defined format for abstracting studies, grading the evidence and presentation of results. The results of the review lead to the conclusions, independent of interpretation.

By contrast, given the scope of the charge to the Panel, this evidence review needed to address a broad array of questions concerning the development, progression and management of multiple risk factors extending from birth through 21 years of age, including studies with follow-up into later adult life. The time frame extended back to 1985, roughly 5 years before the review for the last NHLBI guideline addressing lipids in children published in 1992. Rather than RCTs, this evidence is largely available in the form of epidemiologic observational studies which must therefore be included in the review. In addition, the review required critical appraisal of the body of evidence that addresses the impact of managing risk factors in childhood on the development and progression of atherosclerosis. Finally, because of known gaps in the evidence base relating risk factors and risk reduction in childhood to clinical events in adult life, the review must include the available evidence justifying evaluation and treatment of risk factors in childhood. The process of identifying, assembling and organizing the evidence was extensive, the review process was complex and conclusions could only be developed by interpretation of the body of evidence. Even with inclusion of every relevant study from the evidence review, there were important areas where evidence was inadequate. Where this occurred, recommendations are a consensus of the Expert Panel. The schema used in grading the evidence appears in Table 1–2; expert consensus opinions are identified as Grade D.

The Expert Panel Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents contain recommendations based on the evidence review and are directed towards all primary pediatric care providers – pediatricians, family practitioners, nurses and nurse practitioners, physician assistants and registered dietitians. The Full Report contains complete background information on the state of the science, methodology of the evidence review and the guideline development process, summaries of the evidence reviews by risk factor, discussion of the Expert Panel's rationale for recommendations, and more than 1,000 citations from the published literature and is available at: http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm.  The complete evidence tables will be available as a direct link from that site. This Summary Report presents the Expert Panel recommendations for patient care relative to CV health and risk factor detection and management, without references. It begins with a state-of-the-science synopsis of the evidence that atherosclerosis begins in childhood and that the extent of atherosclerosis is linked directly to the presence and intensity of known risk factors. This is followed by the "Cardiovascular Health Schedule" which summarizes the Expert Panel's age-based recommendations by risk factor in a one page periodic table. Risk factor specific sections follow, with the graded conclusions of the evidence review, normative tables and age-specific recommendations. These are often accompanied by Supportive Actions which represent expert consensus suggestions from the panel provided to support implementation of the recommendations. The Summary Report will be released simultaneously with on-line availability of the Full Report with references for each section and the evidence tables at: http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm.

It is the hope of the Expert Panel that these recommendations will be useful for all those who provide cardiovascular health care to children.

Table 1–1. Evaluated Risk Factors

Table 1–2. Evidence Grading System: Quality Grades:

American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Pediatrics 2004;114:874-877.

Strength of Recommendations:

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2. State of the Science: Cardiovascular risk Factors and the Development of Atherosclerosis in Childhood

Atherosclerosis begins in youth and this process, from its earliest phases, is related to the presence and intensity of the known CV risk factors shown in Table 1–1. Clinical events such as myocardial infarction, stroke, peripheral arterial disease, and ruptured aortic aneurysm are the culmination of the lifelong vascular process of atherosclerosis. Pathologically, the process begins with the accumulation of abnormal lipid in the vascular intima, a reversible stage, progresses to an advanced stage in which a core of extracellular lipid is covered by a fibromuscular cap, and culminates in thrombosis, vascular rupture, or acute ischemic syndromes.

Evidence Linking Risk Factors in Childhood to Atherosclerosis at Autopsy

Atherosclerosis at a young age was first identified in Korean and Vietnam War casualties. Two major contemporary studies, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study and the Bogalusa Heart Study, have subsequently evaluated the extent of atherosclerosis in children, adolescents and young adults who died accidentally. The Bogalusa study measured CV risk factors (lipids, blood pressure, body mass index and tobacco use) as part of a comprehensive school-based epidemiologic study in a biracial community. These results were related to atherosclerosis measured at autopsy after accidental death. Strong correlations were shown between the presence and intensity of risk factors and the extent and severity of atherosclerosis. In the PDAY study, risk factors and surrogate measures of risk factors were measured post mortem in 15- to 34-year olds dying accidentally of external causes. Strong relationships were demonstrated between atherosclerotic severity and extent, and age, non HDL cholesterol, HDL cholesterol, hypertension (determined by renal artery thickness), tobacco use (thiocyanate concentration), diabetes mellitus(DM) (glycohemoglobin), and (in men), obesity. There was a striking increase in both severity and extent as age and the number of risk factors increased. By contrast, absence of risk factors was shown to be associated with a virtual absence of advanced atherosclerotic lesions, even in the oldest subjects in the study.

Evidence Linking Risk Factors in Childhood to Atherosclerosis Assessed Non-Invasively

Over the last decade, measures of sub-clinical atherosclerosis have developed, including the demonstration of coronary calcium on electron beam computed tomography (EBCT) imaging, increased medial thickness in the carotid artery assessed with ultrasound (CIMT), endothelial dysfunction (reduced arterial dilation) with brachial ultrasound imaging, and increased left ventricular mass with cardiac ultrasound. These measures have been assessed in young individuals with severe abnormalities of individual risk factors.

• In adolescents with marked elevation of LDL-cholesterol due to familial heterozygous hypercholesterolemia, abnormal levels of coronary calcium, increased CIMT and impaired endothelial function have been demonstrated.
• Children with hypertension have been shown to have increased CIMT, increased left ventricular mass and eccentric left ventricular geometry.
• Children with type 1 DM have significantly abnormal endothelial function and, in some studies, increased CIMT.
• Children and young adults with a family history of myocardial infarction have increased CIMT, higher prevalence of coronary calcium, and endothelial dysfunction.
• Endothelial dysfunction has been demonstrated by ultrasound and plethysmography in association with cigarette smoking (passive and active) and obesity. In obese children, improvement in endothelial function occurs with regular exercise.
• Left ventricular hypertrophy at levels associated with excess mortality in adults has been demonstrated in children with severe obesity.

Four longitudinal studies have shown relationships of risk factors measured in youth – specifically LDL cholesterol, non-HDL cholesterol and serum apolipoproteins, obesity, hypertension, tobacco use, and diabetes - to measures of subclinical atherosclerosis in adulthood. In many of these studies, risk factors measured in childhood and adolescence were better predictors of the severity of adult atherosclerosis than were risk factors measured at the time of the subclinical atherosclerosis study.

Evidence Linking Risk Factors in Childhood to Clinical CVD

The most important evidence relating risk in youth to clinical CVD is the observed association of risk factors for atherosclerosis to clinically manifest CV conditions. Genetic disorders related to high cholesterol are the biologic model for risk factor impact on the atherosclerotic process. In homozygous hypercholesterolemia, where LDL cholesterol levels exceed 800 mg/dL beginning in infancy, coronary events begin in the first decade of life and lifespan is severely shortened. In heterozygous hypercholesterolemia in which LDL cholesterol levels are minimally 160 mg/dL and typically over 200 mg/dL and total cholesterol levels exceed 250 mg/dL beginning in infancy, 50 per cent of men and 25 per cent of women experience clinical coronary events by age 50. By contrast, genetic traits associated with low cholesterol are associated with longer life expectancy. In PDAY, every 30 mg/dL increase in non-HDL cholesterol was associated with a visible incremental increase in the extent and severity of atherosclerosis. In natural history studies of DM, early CVD mortality is so consistently observed that the presence of DM is considered evidence of vascular disease in adults. Consonant with this, in 15- to 19-year olds in PDAY, the presence of hyperglycemia was associated with the demonstration of advanced atherosclerotic lesions of the coronary arteries. In PDAY, there is also a very strong relationship between abdominal aortic atherosclerosis and tobacco use. Finally, in a 25 year follow-up, the presence of the metabolic syndrome risk factor cluster in childhood predicted clinical CVD in adult subjects at 30- to 48-years of age.

The Impact of Racial/ Ethnic Background and Socioeconomic Status in Childhood on the Development of Atherosclerosis

CVD has been observed in diverse geographic areas and all racial and ethnic backgrounds. Cross sectional research in children has shown differences by race and ethnicity, and by geography for prevalence of CV risk factors; these differences are often partially explained by differences in socioeconomic status. No group within the United States is without a significant prevalence of risk. Several longitudinal cohort studies referenced extensively in this report (Bogalusa Heart Study, PDAY and CARDIA) are biracial and other studies have been conducted outside the United States. However longitudinal data in Hispanic, Native American, and Asian children are lacking. Clinically important differences in prevalence of risk factors exist by race and gender, particularly with regard to tobacco use rates, obesity prevalence, hypertension, and dyslipidemia. Low socioeconomic status in and of itself confers substantial risk. However, evidence is not adequate for the recommendations provided in this report to be specific to racial or ethnic groups or socioeconomic status.

Evidence for Risk Factor Clustering in Childhood on the Development of Atherosclerosis

From a population standpoint, clustering of multiple risk factors is the most common association with premature atherosclerosis. The pathologic studies reviewed above show clearly that the presence of multiple risk factors is associated with striking evidence of an accelerated atherosclerotic process. Among the most prevalent multiple risk combinations are the use of tobacco with one other risk factor, and the development of obesity which is often associated with insulin resistance, elevated triglycerides, reduced HDL cholesterol and elevated blood pressure, a combination known as the metabolic syndrome in adults. There is ample evidence from both cross sectional and longitudinal studies that the increasing prevalence of obesity in childhood is associated with the same obesity-related risk factor clustering seen in adults and that this continues into adult life. This high risk combination is among the reasons that the current obesity epidemic with its relationship to future CVD and DM is considered one of the most important public health challenges in contemporary society. One other prevalent multiple risk combination is the association of low cardiorespiratory fitness, identified in 33.6% of adolescents in the NHANES surveys from 1999-2002, with overweight and obesity, elevated total cholesterol and systolic blood pressure, and reduced HDL-C.

Risk Factor Tracking from Childhood into Adult Life

Tracking studies from childhood to adulthood exist for all the major risk factors:

• Obesity tracks more strongly than any other risk factor: among many reports demonstrating this, one of the most recent is a report from the Bogalusa study where more than 2,000 children were followed from initial evaluation at 5 to 14 yrs of age to adult follow-up at a mean age of 27 years. Based on BMI percentiles derived from the study population, 84% of those with a BMI in the 95^th to 99^th percentile as children were obese as adults and all of those with a BMI > 99^th percentile were obese in adulthood. Increased correlation is seen with increasing age at which the elevated BMI occurs.
• For cholesterol and blood pressure, tracking correlation coefficients in the range of 0.4 have been reported consistently across many studies, correlating these measures in children 5 to 10 years of age with results 20 to 30 years later.  These data suggest that having cholesterol or blood pressure levels in the upper portion of the pediatric distribution makes having these as adult risk factors likely but not certain. Those who develop obesity have been shown to be more likely to develop hypertension or dyslipidemia as adults.
• Tracking data on physical fitness are more limited. Physical activity levels do track but not as strongly as other risk factors.
• By its addictive nature, tobacco use persists into adulthood though approximately 50 per cent of those who have ever smoked eventually quit.
• Type I diabetes mellitus is a lifelong condition.
• The insulin resistance of type II DM can be alleviated by exercise, weight loss, and bariatric surgery, but the long term outcome of type II DM diagnosed in childhood is not known.
• As above, risk factor clusters such as those seen with obesity and the metabolic syndrome have been shown to track from childhood into adulthood.

Cardiovascular Disease Prevention Beginning In Youth

The rationale for these guidelines comes from the evidence:

• Atherosclerosis, the pathologic basis for clinical CVD, originates in childhood.
• Risk factors for the development of atherosclerosis can be identified in childhood
• Development and progression of atherosclerosis clearly relates to the number and intensity of CV risk factors, beginning in childhood
• Risk factors track from childhood into adult life
• Interventions exist for management of identified risk factors

The evidence for the first 4 bullets is reviewed in this section, while the evidence surrounding interventions for identified risk factors is addressed in the RF-specific sections of the guideline to follow.

It is important to distinguish between the goals of prevention at a young age and those at older ages where atherosclerosis is well established, morbidity may already exist, and the process is only minimally reversible. At a young age, there have historically been two goals of prevention: (1) prevent the development of risk factors (primordial prevention); and (2) recognize and manage those children and adolescents at increased risk due to the presence of identified risk factors (primary prevention). It is well established that a population that enters adulthood with lower risk will have less atherosclerosis and will collectively have lower CVD rates. This concept is supported by research that shows that: 1) societies with low levels of CV risk factors have low CVD rates and that changes in risk in those societies are associated with change in cardiovascular disease rates; 2) in adults, control of risk factors leads to decline in CVD morbidity and mortality; and 3) those without childhood risk have minimal atherosclerosis at age 30- to 34-years, absence of subclinical atherosclerosis as young adults, extended life expectancy and a better quality of life, free from CVD.

The Pathway to Recommending Clinical Practice-Based Prevention

The most direct means of establishing evidence for active CVD prevention beginning at a young age would be to randomize young individuals with defined risks to treatment of CV risk factors or to no treatment and follow both groups over sufficient time to determine if CV events are prevented without undue increase in morbidity arising from treatment. This direct approach is intellectually attractive because atherosclerosis prevention would begin at the earliest stage of the disease process, thereby maximizing benefit. Unfortunately, this approach is as unachievable as it is attractive primarily because such studies would be extremely expensive and would be several decades in duration, a time period in which changes in environment and medical practice would diminish the relevance of the results.

The recognition that evidence from this direct pathway is unlikely to be achieved requires an alternate stepwise approach, where segments of an evidence chain are linked in a manner that serves as a sufficiently rigorous proxy for the causal inference of a clinical trial. The evidence reviewed in this section provides the critical rationale for CV prevention beginning in childhood: evidence that atherosclerosis begins in youth, evidence that the atherosclerotic process relates to risk factors which can be identified in childhood, and evidence that the presence of these risk factors in a given child predicts an adult with risk if no intervention occurs. The remaining evidence links pertain to the demonstration that interventions to lower risk will have a health benefit, and that the risk and cost of interventions to improve risk are outweighed by the reduction in CVD morbidity and mortality. These issues are captured in the evidence reviews of each risk factor. The recommendations reflect a complex decision process that integrates the strength of the evidence with knowledge of the natural history of atherosclerotic vascular disease, estimates of intervention risk, and the physician's responsibility to provide both health education and effective disease treatment. These recommendations for those caring for children will be most effective when complemented by a broader public health strategy.

The Childhood Medical Office Visit as the Setting for CV Health Management

One cornerstone of pediatric care is placing clinical recommendations in a developmental context. Pediatric recommendations must consider not only the relation of age to disease expression but the ability of the patient and family to understand and implement medical advice. For each risk factor, recommendations must be specific to age and developmental stage. The "Bright Futures" concept of the American Academy of Pediatrics (AAP) is used to provide a framework for these guidelines with CV risk reduction recommendations for each age group.

This document provides recommendations for preventing the development of risk factors and optimizing CV health beginning in infancy, based on the results of the evidence review. Pediatric care providers – pediatricians, family practitioners, nurses, nurse practitioners, physician assistants, registered dietitians - are ideally positioned to reinforce CV health behaviors as part of routine care. The guideline also offers specific guidance on primary prevention, with age-specific, evidence-based recommendations for individual risk factor detection. Management algorithms provide staged care recommendations for risk reduction within the pediatric care setting and identify risk factor levels requiring specialist referral. The guidelines also identify specific medical conditions such as diabetes and chronic kidney disease that are associated with increased risk for accelerated atherosclerosis. Recommendations for ongoing CV health management for children and adolescents with these diagnoses are provided.

A cornerstone of pediatric care is the provision of health education. In the U.S. health care system, physicians and nurses are perceived as credible messengers for health information. The childhood health maintenance visit provides an ideal context for effective delivery of the CV health message. Pediatric care providers provide an effective team, educated to initiate behavior change to diminish risk of CVD and promote lifelong CV health in their patients, from infancy into young adult life.

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3. Integrated Cardiovascular Health Schedule

 Table 3–1. Integrated Cardiovascular Health Schedule

ABBREVIATIONS: m = months; y = years; FHx = family history; M = male; F = female; RF = risk factor; % = percent; BMI = body mass index; %ile = percentile; ADA = American Diabetes Association; MVPA = moderate-to-vigorous physical activity; ATP = Adult Treatment Panel III (Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults); CHILD 1= Cardiovascular Health Integrated Lifestyle Diet; JNC = The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; BP = blood pressure; h/d = hours per day 

 The Full and Summary Report of the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents may also be found on the NHLBI website at: http://www.nhlbi.nih.gov/

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4. Family History of Early Atherosclerotic Cardiovascular Disease

A family history of CVD represents the net effect of shared genetic, biochemical, behavioral and environmental components. In adults, epidemiologic studies have demonstrated that a family history of premature coronary heart disease in a first degree relative – heart attack, treated angina, percutaneous coronary catheter interventional procedure, coronary artery bypass surgery, stroke or sudden cardiac death in a male parent or sibling before the age of 55 years or a female parent or sibling before the age of 65 years – is an important independent risk factor for future CVD. The process of atherosclerosis is complex and involves many genetic loci and multiple environmental and personal risk factors. Nonetheless, the presence of a positive parental history has been consistently shown to significantly increase baseline risk for CVD. The risk for CVD in offspring is strongly inversely related to the age of the parent at the time of the index event. The association of a positive family history with increased CV risk has been confirmed for men, women and siblings and in different racial and ethnic groups. The evidence review identified all randomized controlled trials (RCTs), systematic reviews, meta-analyses and observational studies that addressed family history of premature atherosclerotic disease and the development and progression of atherosclerosis from childhood into young adult life.

Conclusions and Grading of the Evidence Review for the Role of Family History in Cardiovascular Health

• Evidence from observational studies strongly supports inclusion of a positive family history of early coronary heart disease in identifying children at risk for accelerated atherosclerosis and for the presence of an abnormal risk profile. (Grade B)
• For adults, a positive family history is defined as a parent and/or sibling with a history of treated angina, myocardial infarction, percutaneous coronary catheter interventional procedure coronary artery bypass grafting, stroke or sudden cardiac death before 55 years in men or 65 years in women. Because the parents and siblings of children and adolescents are usually young themselves, it was the panel consensus that when evaluating family history in a child, history should also be ascertained for the occurrence of cardiovascular disease in grandparents, aunts and uncles although the evidence supporting this is insufficient to date. (Grade D)
• Identification of a positive family history for CV disease and/or CV risk factors should lead to evaluation of all family members, especially parents, for CV risk factors. (Grade B)
• Family history evolves as a child matures so regular updates are necessary as part of routine pediatric care. (Grade D)
• Education about the importance of accurate and complete family health information should be part of routine care for children and adolescents. As genetic sophistication increases, linking family history to specific genetic abnormalities will provide important new knowledge about the atherosclerotic process. (Grade D)

Table 4–1. Evidence-Based Recommendations for Use of Family History in Cardiovascular Health Promotion

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

^a Parent, grandparent, aunt, uncle, or sibling with heart attack, treated angina, CABG/stent/angioplasty, stroke, or sudden cardiac death at < 55 y in males, < 65 y in females

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5. Nutrition and Diet

The 2010 Dietary Guidelines for Americans (2010 DGA) include important recommendations for the population over the age of two.  The National Cholesterol Education Program Pediatric Panel Report in 1992 provided dietary recommendations for all children as part of a population-based approach to reducing cardiovascular risk. Evidence relative to diet and the development of atherosclerosis in childhood and adolescence was identified by the evidence review for this guideline, and collectively, this provides the rationale for new dietary prevention efforts initiated early in life.

These new pediatric CV guidelines not only build upon the recommendations for achieving nutrient adequacy in growing children as stated in the 2010 DGA but also add evidence regarding the efficacy of specific dietary changes to reduce CV risk from the current evidence review for the use of pediatric care providers in the care of their patients. Because the focus of these guidelines is on CV risk reduction, the evidence review specifically evaluated dietary fatty acid and energy components as major contributors to hypercholesterolemia and obesity, as well as dietary composition and micronutrients as they affect hypertension. New evidence from multiple dietary trials addressing CV risk reduction in children provides important information for these recommendations.

Conclusions and Grading of the Evidence Review for Diet and Nutrition in Cardiovascular Risk Reduction

The Expert Panel concluded that there is strong and consistent evidence that good nutrition beginning at birth has profound health benefits, with the potential to decrease future risk for CVD. The Expert Panel accepts the 2010 DGA as containing appropriate recommendations for diet and nutrition in children 2 years and older. The recommendations in these guidelines are intended for pediatric care providers to use with their patients to address CV risk reduction. The conclusions of the Expert Panel's review of the entire body of evidence in a specific nutrition area with grades are summarized below. Where evidence is inadequate yet nutrition guidance is needed, recommendations for pediatric care providers are based on a consensus of the Expert Panel (Grade D). The age- and evidence-based recommendations of the Expert Panel follow.

Conclusions and grades from the evidence review are summarized below:

In accordance with the Surgeon General's Office, WHO, the AAP and the AAFP, exclusive breast-feeding is recommended for the first 6 months of life. Continued breastfeeding is recommended to at least age 12 months, with the addition of complementary foods. If breastfeeding per se is not possible, feeding human milk by bottle is second best, with formula-feeding as the third choice.

• Long term follow-up studies demonstrate that subjects who were breastfed have sustained CV health benefits, including lower cholesterol levels, lower BMI, reduced prevalence of type 2 diabetes, and lower cIMT in adulthood. (Grade B)
• Ongoing nutrition counseling has been effective in assisting children and families to adopt and sustain recommended diets for both nutrient adequacy and reducing CV risk. (Grade A)
• Within appropriate age- and gender-based requirements for growth and nutrition, in normal children and in children with hypercholesterolemia, intake of total fat can be safely limited to 30% of total calories, saturated fat intake limited to 7-10% of calories, and dietary cholesterol limited to 300 mg/d. Under the guidance of qualified nutritionists, this dietary composition has been shown to result in lower TC and LDL-C levels, less obesity, and less insulin resistance. (Grade A) Under similar conditions and with ongoing followup, these levels of fat intake may have similar effects starting in infancy. (Grade B) Fats are important to infant diets due to their role in brain and cognitive development. Fat intake in infants less than 12 months of age should not be restricted without medical indication.
• The remaining 20% of fat intake should be comprised of a combination of monosaturated and polyunsaturated fats. (Grade D) Intake of trans fats should be limited as much as possible. (Grade D).
• For adults, the current NCEP guidelines recommend that adults consume 25-35% of calories from fat. The 2010 DGA supports the IOM recommendations for 30-40% of calories from fat for ages 1-3 years, 25-35% of calories from fat for ages 4-18 years, and 20-35% of calories from fat for adults. For growing children, milk provides essential nutrients, including protein, calcium, magnesium, and vitamin D, that are not readily available elsewhere in the diet. Consumption of fat-free milk in childhood after age 2 years and through adolescence optimizes these benefits, without compromising nutrient quality while avoiding excess saturated fat and calorie intake (Grade A). Between ages 1 and 2 years as children transition from breast milk or formula, milk reduced in fat (ranging from 2% milk to fat-free milk) can be used based on the child's growth, appetite, intake of other nutrient-dense foods, intake of other sources of fat, and risk for obesity and CVD. Milk with reduced fat should be used only in the context of an overall diet that supplies 30% of calories from fat. Dietary intervention should be tailored to each specific child's needs.
• Optimal intakes of total protein and total carbohydrate in children were not specifically addressed, but with a recommended total fat intake of 30% of energy, the Expert Panel recommends that the remaining 70% of calories include 15-20% from protein and 50-55% from carbohydrate sources (no grade). These recommended ranges fall within the acceptable macronutrient distribution range specified by the 2010 DGA: 10-30% of calories from protein and 45-65% of calories from carbohydrate for children ages 4-18 years.
• Sodium intake was not addressed by the evidence review for this section on nutrition and diet. From the evidence review for Section VIII. High Blood Pressure, lower sodium intake is associated with lower systolic and diastolic BPs in infants, children, and adolescents.
• Plant-based foods are important low calorie sources of nutrients including vitamins and fiber in the diets of children; increasing access to fruits and vegetables has been shown to increase their intake. (Grade A) However, increasing fruit and vegetable intake is an ongoing challenge.
• Reduced intake of sugar-sweetened beverages is associated with decreased obesity measures. (Grade B) Specific information about fruit juice intake is too limited for an evidence-based recommendation. Recommendations for intake of naturally sweetened fruit juice (without added sugar) in infants are a consensus of the Expert Panel (Grade D) and are in agreement with those of the AAP.
• Per the 2010 DGA, energy intake should not exceed energy needed for adequate growth and physical activity. Calorie intake needs to match growth demands and physical activity needs. (Grade A) Estimated calorie requirements by gender and age group at three levels of physical activity from the Dietary Guidelines are shown in Table 5–2. For children of normal weight whose activity is minimal, most calories are needed to meet nutritional requirements, leaving only about 5-15% of calorie intake from extra calories. These calories can be derived from fat or sugar added to nutrient-dense foods to allow their consumption as sweets, desserts, or snack foods. (Grade D)
• Dietary fiber intake is inversely associated with energy density and with increased levels of body fat and is positively associated with nutrient density (Grade B); a daily total dietary fiber intake from food sources of at least age plus 5 g for young children up to 14 g/1,000 kcal for older children and adolescents is recommended. (Grade D).
• The Expert Panel supports the 2008 recommendation of the AAP for vitamin D supplementation with 400 IU/day for all infants and children. No other vitamin, mineral or dietary supplements are recommended. (Grade D) The new RDA for Vitamin D for those 1-70 years old is 600 IU/day.
• Use of dietary patterns modeled on those shown to be beneficial in adults (e.g., DASH pattern) is a promising approach to improving nutrition and decreasing CV risk. (Grade B)
• All diet recommendations must be interpreted for each child and family to address individual diet patterns and patient sensitivities such as lactose intolerance and food allergies. (Grade D)

Graded, age-specific recommendations for pediatric care providers to use in optimizing CV health in their patients are summarized below in Table 5–1: Cardiovascular Health Integrated Lifestyle Diet (CHILD 1). CHILD 1 is the first stage in dietary change for children with identified dyslipidemia, overweight and obesity, risk factor clustering, and high-risk medical conditions that may ultimately require more intensive dietary change. CHILD 1 is also the recommended diet for children with a positive family history of early CV disease, dyslipidemia, obesity, primary hypertension, diabetes, or children exposure to smoking in the home. Any dietary modification must provide nutrients and calories needed for optimal growth and development. Likewise, recommended intakes are adequately met by a DASH-style eating plan, which emphasizes fat free/ low fat dairy and increased intake of fruits and vegetables. This has been modified for use in children age 4 years and older based on daily energy needs by food group and is shown in Table 5–3 as one example of a heart healthy eating plan using the CHILD 1 recommendations.

Table 5–1. Evidence-Based Recommendations for Diet and Nutrition: Cardiovascular Health Integrated Lifestyle Diet (CHILD 1)

CHILD 1 is the recommended first step diet for all children and adolescents at elevated cardiovascular risk.

Grades reflect the findings of the evidence review.
Recommendation levels the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

^a Infants that cannot be fed directly at the breast should be fed expressed milk. Infants for whom expressed milk is not available should be fed iron-fortified infant formula.
^b Toddlers 12-24 m of age with a family history of obesity, heart disease, or high cholesterol, should discuss transition to reduced-fat milk with pediatric care provider after 12 months of age.
^c Continued breast-feeding is still appropriate and nutritionally superior to cow's milk. Milk reduced in fat should be used only in the context of an overall diet that supplies 30% of calories from fat.
^d EER = Estimated Energy Requirements/d for age/gender (Table 5-2)
^e Naturally fiber-rich foods are recommended (fruits, vegetables, whole grains); fiber supplements are not advised. Limit refined carbohydrates (sugars, white rice, and white bread)

Table 5–2. Estimated Calorie Needs per Day by Age, Gender, and Physical Activity Level^a

Estimated amounts of calories needed to maintain caloric balance for various gender and age groups at three different levels of physical activity. The estimates are rounded to the nearest 200 calories. An individual's calorie needs may be higher or lower than these average estimates

^a Based on Estimated Energy Requirements (EER) equations, using reference heights (average) and reference weights (health) for each age/gender group. For children and adolescents, reference height and weight vary. For adults, the reference man is 5 feet 10 inches tall and weighs 154 pounds. The reference woman is 5 feet 4 inches tall and weighs 126 pounds. EER equations are from the Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington (DC): The National Academies Press; 2002.

^b Sedentary means a lifestyle that includes only the light physical activity associated with typical day-to-day life. Moderately active means a lifestyle that includes physical activity equivalent to walking about 1.5 to 3 miles per day at 3 to 4 miles per hour, in addition to the light physical activity associated with typical day-to-day life. Active means a lifestyle that includes physical activity equivalent to walking more than 3 miles per day at 3 to 4miles per hour, in addition to the light physical activity associated with typical day-to-day life.

^c The calorie ranges shown are to accommodate needs of different ages within the group. For children and adolescents, more calories are needed at older ages. For adults, fewer calories are needed at older ages.

^d Estimates for females do not include women who are pregnant or breastfeeding.

Table 5-3. DASH Eating Plan: Servings per Day by Food Group and Total Energy Intake

(Table 5–2 provides estimated energy requirements (EER) by age, gender and activity level.)

The Food and Drug Administration (FDA) and the Environmental Protection Agency are advising women of childbearing age who may become pregnant, pregnant women, nursing mothers, and young children to avoid some types of fish and shellfish and eat fish and shellfish that are low in mercury. For more information, call the FDA's food information line toll free at 1-888-SAFEFOOD or visit http://www.cfsan.fda.gov/~dms/admehg3.html.

^* Whole grains are recommended for most grain servings as a good source of fiber and nutrients.

^** Serving sizes vary between 1/2 cup and 1-1/4 cups, depending on cereal type. Check product's Nutrition Facts label.

^†Since eggs are high in cholesterol, limit egg yolk intake to no more than four per week; two egg whites have the same protein content as 1 oz meat.

^‡Fat content changes serving amount for fats and oils. For example, 1 Tbsp regular salad dressing = 1 serving; 1 Tbsp low-fat dressing = 1/2 serving; 1 Tbsp fat-free dressing = zero servings. Abbreviations: oz = ounce; Tbsp = tablespoon; tsp = teaspoon.

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6. Physical Activity

Physical activity is any bodily movement produced by contraction of skeletal muscle that increases energy expenditure above a basal level. Physical activity can be focused on strengthening muscles, bones and joints but because these guidelines address CV health, the evidence review concentrated on aerobic activity and on the opposite of activity, sedentary behavior. There is strong evidence for beneficial effects of physical activity and disadvantageous effects of a sedentary lifestyle on the overall health of children and adolescents across a broad array of domains. Our review focused on the effects of activity on CV health because physical inactivity has been identified as an independent risk factor for coronary heart disease in adults. Over the last several decades, there has been a steady decrease in the amount of time that children spend being physically active and an accompanying increase in time spent in sedentary activities. The evidence review identified many studies in youth ranging in age from 4 to 21 years that strongly link increased time spent in sedentary activities with reduced overall activity levels and with disadvantageous lipid profiles, higher systolic blood pressure, higher levels of obesity and higher levels of all the obesity-related cardiovascular risk factors including hypertension, insulin resistance and type 2 diabetes.

Conclusions and Grading of the Evidence Review for Physical Activity

The Expert Panel felt that the evidence strongly supports the role of physical activity in optimizing cardiovascular health in children and adolescents.

• There is reasonably good evidence that physical activity patterns established in childhood are carried forward into adulthood. (Grade C)
• There is strong evidence that increases in moderate to vigorous physical activity are associated with lower systolic and diastolic blood pressure; decreased measures of body fat; decreased BMI; improved fitness measures; lower total cholesterol; lower LDL cholesterol; lower triglycerides; higher HDL cholesterol; and decreased insulin resistance in childhood and adolescence. (Grade A)
• There is limited but strong and consistent evidence that physical exercise interventions improve subclinical measures of atherosclerosis. (Grade B)
• Physical activity patterns, dietary choices, and smoking behaviors cluster together. (Grade C)
• There is no evidence of harm associated with increased physical activity or limitation of sedentary activity in normal children. (Grade A)
• There is strong evidence that physical activity should be promoted in schools. (Grade A)

There is less specific information on the type and amount of physical exercise required for optimum CV health. Reported activity interventions ranged from 20-60 minutes 2 to 5 times/week in children ages 3-17 years and included a wide variety of dynamic and isometric exercises. Extrapolating from these interventions that occurred in supervised settings to the real world of childhood and adolescence, the Expert Panel recommends at least 1 hour of moderate to vigorous activity every day of the week for children over 5 years of age. In agreement with the "Physical Activity Guidelines Advisory Committee Report, 2008" from the Department of Health and Human Services, the Expert Panel recommends that activity be vigorous on 3 days/week (www.health.gov/paguidelines).  In working with children and families, the Expert Panel suggested that moderate to vigorous activity could be compared to jogging or playing baseball and that vigorous physical activity could be compared with running, playing singles tennis or soccer. Similarly, reducing sedentary time is convincingly associated with a favorable CV profile, and the Expert Panel agreed with the recommendation from the AAP for limiting leisure screen time to less than 2 hrs/ day.

Table 6–1. Evidence-Based Activity Recommendations for Cardiovascular Health

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

^*Examples of moderate to vigorous physical activities are jogging or playing baseball.
^**Examples of vigorous physical activities are running, playing singles tennis or soccer.

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7. Tobacco Exposure

Tobacco dependence is responsible for approximately 4 million annual deaths worldwide, and in utero exposure to tobacco products, involuntary tobacco smoke exposure (second hand smoke), and tobacco use directly impair health in fetuses, infants, children, and adolescents. Based on an analysis of published causes of death, tobacco use is the leading actual cause of death in the U. S. The evidence that cigarette use is harmful and addictive is unequivocal. In childhood, nicotine is highly addicting with symptoms of tobacco dependence demonstrated after brief intermittent use. Cigarette use among high school students declined from 1997 to 2003. Rates were stable from 2003 to 2007 with more than 20% of high school students reporting daily smoking. From a public health standpoint, the need to reduce tobacco exposure is compelling, and a role for pediatric health care providers is essential.

A clinical practice guideline update from the U.S. Public Health Service published in May, 2008 systematically reviewed almost 9,000 publications and concluded that smoking prevention and cessation interventions are effective in adults. These same methods should be safely applicable in childhood and adolescence since behavioral interventions to alter smoking behaviors have little if any morbidity, and since morbidity with pharmacologic treatment is limited. Physicians who care for children are well positioned to provide prevention and treatment interventions for their patients. Youth interventions must target parents as well as children since parental smoking is both a risk factor for child smoking and provides second hand smoke exposure to fetuses and children. The evidence review assessed prevention and treatment interventions in each of these areas.

Conclusions and Grading of the Evidence on Preventing Tobacco Exposure

Among all the known risk factors for CVD, the dichotomy between known benefits of risk elimination and the paucity of evidence for effective interventions to achieve risk reduction in pediatric care provider settings is greatest for tobacco exposure. The quality of the evidence regarding the harm of smoking and the benefits of avoiding passive smoke exposure, smoking prevention and smoking cessation is uniformly Grade A. The reason that evidence grades in the recommendations are less than Grade A reflects the lack of existing evidence on interventions impacting smoking behaviors in specific pediatric age groups as opposed to the collective evidence.

• Good quality interventions in pediatric care settings to decrease children's environmental smoke exposure have shown mixed results. (Grade B)
• Intervention studies to prevent smoking initiation have had moderate success, although long-term results are limited. (Grade B)
• Practice-based interventions to achieve smoking cessation in adolescents have had moderate success with limited long term follow-up. (Grade B)
• School-based smoking prevention programs have been moderately successful, with limited long term follow-up. (Grade B)

Although the evidence base for effective office-based approaches to tobacco interventions is moderate and mixed, the evidence that cigarette use is harmful and addictive is unequivocal. The need to reduce tobacco exposure is so compelling that a role for pediatric health care providers is essential. The lack of harm associated with such interventions and the importance of communicating the message of risk associated with tobacco provides the rationale for "Strongly Recommend," despite the lack of conclusive evidence that office-based interventions reliably reduce tobacco initiation or smoking cessation. Physicians and nurses who care for children are well positioned to provide intervention to patients who smoke. The Expert Panel feels that such providers should routinely identify patients who smoke using the medical history. Patients should be explicitly informed about the addictive and adverse health effects of tobacco use. By using the 5 A's (ask, advise, assess, assist, arrange), providers can assess readiness to quit and assist in providing resources to support smoking cessation efforts. Information about telephone quit lines (e.g., 1-800-QUIT-NOW), community cessation programs, and pharmacotherapy should also be made available.

As described, practice-based interventions to decrease environmental smoke exposure have shown mixed results. Nonetheless, the Expert Panel believes that pediatric care providers should identify parents and other caregivers who smoke and explicitly recommend that children not be exposed to tobacco smoke in the home, in automobiles, and in any other space where exposure can occur. For the parent who smokes, information provided should include statements about health benefits to the individual, child and/or fetus as well as referral to smoking cessation care providers.

Table 7–1. Evidence-Based Recommendations to Prevent Tobacco Exposure

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

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8. High Blood Pressure

In 2004, an NHLBI Task Force published The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents. This report included a complete review of the current evidence on this subject and detailed recommendations for managing blood pressure throughout childhood. These recommendations were used as the basic recommendations for these guidelines, considered complete until 2003 when the review for the report ended. This evidence review for blood pressure for these guidelines was therefore limited to studies published between January 1, 2003, and June 30, 2007, with the addition of selected studies through June 30, 2008, identified by the Expert Panel that meet all the criteria for inclusion. Repeating the review performed by the Fourth Report Task Force was not felt to be necessary, given the short time since publication of that report, nor a judicious use of the resources available for development of these guidelines. Recommendations regarding blood pressure are all graded as expert opinion (Grade D) as they are based on the expert consensus conclusions of the Fourth Report.

Conclusions of the Evidence Review Update for High Blood Pressure (2003-2008)

• The evidence review for the defined time period resulted in no major changes in the approach to BP evaluation and management.
• In epidemiologic surveys of children and adolescents over the past 20 years, blood pressure levels are increasing, and the prevalence of hypertension and prehypertension are increasing, explained partially by the rise in obesity.
• Prehypertension progresses to hypertension at a rate of approximately 7 percent per year; hypertension persists in almost one-third of boys and one-fourth of girls on 2-year longitudinal follow-up.
• Breast-feeding and supplementation of formula with polyunsaturated fatty acids in infancy are both associated with lower blood pressure at follow-up.
• A DASH-style diet, which is rich in fruits, vegetables, low-fat or fat-free dairy products, whole grains, fish, poultry, beans, seeds and nuts, and lower in sweets and added sugars, fats, and red meats than the typical American diet is associated with lower blood pressure. The CHILD 1 diet combined with the DASH eating plan described in the Diet and Nutrition section is an appropriate diet for children, which meets the DASH study and Dietary Guidelines for Americans 2010 nutrient goals.
• Lower dietary sodium intake is associated with lower blood pressure levels in infants, children, and adolescents.
• Losartan, amlodipine, felodipine, fosinopril, lisinopril, metoprolol and valsartan can be added to the list of medications that are tolerated over short periods, and can reduce blood pressure in children from ages 6-17 years but predominantly are effective in adolescents. For African American children, greater doses of fosinopril may be needed for effective blood pressure control. Medications are shown in table 8–5.
• In one study in small-for-gestational-age babies, a nutrient-enriched diet that promoted rapid weight gain was associated with higher blood pressure on follow-up in late childhood. This potential risk should be considered when such diets are selected in the clinical setting.
• In one study, transcendental meditation effectively lowered blood pressure in non-hypertensive adolescents.

Recommendations

The Fourth Report of the National High Blood Pressure Education Program provided an algorithm and flow diagram to assist clinicians in identifying hypertension in children. For these guidelines, the Fourth Report recommendations are stratified here to provide an age-appropriate approach congruent with other risk factor recommendations in other sections and this is also reflected in a series of revised algorithms (Table 8–1, and Figures 8–1 and 8–2). Conditions under which children < 3 years old should have blood pressure measured are shown in Table 8–2. The blood pressure norms for age, sex, and height are shown in Tables 8–3 and 8–4 below and are taken directly from the Fourth Report. Age-specific percentiles of blood pressure measurements from birth to 12 months are provided in the Report of the 2^nd Task Force for Blood Pressure Control in Children, 1987. For all age groups the assessment of left ventricular mass by echocardiography is recommended as the best method to assess hypertensive target organ disease; this should be done for patients with Stage 2 hypertension and those with persistent Stage 1 hypertension. Elevated LV mass may be useful in establishing the need for pharmacologic treatment of hypertension. In Table 8–5, the medications used to achieve blood pressure control in children and adolescents are shown. At present, there are no data to support the use of specific antihypertensive agents for specific age groups.

Table 8–1 Age-Specific Recommendations for Blood Pressure (BP) Measurement and Diagnosis of Hypertension 

BP recommendations are based on The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Fourth Report), with the evidence review updated from 2003.

Recommendations are all graded as expert opinion (Grade D) as they are based on the expert consensus conclusions of the Fourth Report.

Table 8–2. Conditions Under Which Children < 3 Years Old Should Have BP Measured

• History of prematurity, very low birth weight, or other neonatal complication requiring intensive care
• Congenital heart disease (repaired or unrepaired)
• Recurrent urinary tract infections, hematuria, or proteinuria
• Known renal disease or urologic malformations
• Family history of congenital renal disease
• Solid-organ transplant
• Malignancy or bone marrow transplant
• Treatment with drugs know to raise BP
• Other systemic illnesses associated with hypertension (neurofibromatosis, tuberous sclerosis, etc.)
• Evidence of increased intracranial pressure

Figure 8-1. BP Measurement and Categorization

Figure 8-1 Description

The figure is a flow chart with 21 labeled boxes linked by arrows. The chart is in one direction with all arrows pointing downward to one or more boxes.

Below the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Select appropriate BP cuff size. Meaure BP at each well child visit over 3 years of age^* (auscultatory method preferred)
   1. Forward to Measure HT, WT & calculate BMI
2. Measure HT, WT & calculate BMI
   1. Foward to Determine BP category for age, HT, gender (Tables 8-3 & 8-4)
3. Determine BP category for age, HT, gender (Tables 8-3 & 8-4)
   Determine BMI category for age and gender (CDC growth charts)
   1. Forward to <90%ile (normal)
   2. Forward to ≥ 90th%ile or 120/80 mmHg to < 95th% (preHTN)
   3. Forward to ≥ 95th%ile < 99th% + 5 mmHg (stage 1)
   4. Forward to ≥ 99th%ile + 5 mmHg (stage 2)
4. <90th%ile (normal)
   1. Forward to Normotensive
   2. Forward to Repeat BP at next visit, plus
   3. Forward to Educate on CHILD-1^† activity levels^**
5. ≥ 90th%ile or 120/80 mmHg to < 95th% (preHTN)
   1. Foward to Repeat by auscultation if performed with oscillometric device
6. ≥ 95th%ile < 99th% + 5 mmHg (stage 1)
   1. Foward to Repeat by auscultation if performed with oscillometric device
7. ≥ 99th%ile + 5 mmHg (stage 2)
   1. Foward to Repeat by auscultation if performed with oscillometric device
8. Repeat by auscultation if performed with oscillometric device
   1. Forward to Average replicate BP measurements at initial visit
9. Average replicate BP measurements at initial visit
   Re-evaluate BP category
   1. Forward to Pre-Hypertensive
   2. Forward to Stage 1 Hypertension
   3. Forward to Stage 2 Hypertension
10. Pre-Hypertensive
    1. Forward to Repeat BP in 6 months
11. Stage 1 Hypertension
    1. Forward to Repeat BP in 1-2 weeks
12. Stage 2 Hypertension
    1. Forward to Evaluate or refer for treatment within 1 week
13. Repeat BP in 6 months, plus
    1. Forward to CHILD-1^†/activity education^** &/or Weight management^***
14. Repeat BP in 1-2 weeks
    Average BP over all 3 visits, plus
    1. Forward to CHILD-1^†/activity education^** &/or Weight management^***
15. Evaluate or refer for treatment within 1 week, plus
    1. Forward to CHILD-1^†/activity education^** &/or Weight management^***
16. CHILD-1^†/activity education^** &/or Weight management^***
17. CHILD-1^†/activity education^** &/or Weight management^***
18. CHILD-1^†/activity education^** &/or Weight management^***

Figure 8-1 Legend:
^* See Table 1;
^† Cardiovascular Health Integrated Lifestyle Diet - Section V. Nutrition and Diet;
^** Section VI. Physical Activity;
^*** Section X. Overweight and Obesity

Figure 8-2. BP Management by Category

Figure 8-2 Description

The figure is a flow chart with 29 labeled boxes linked by arrows. The chart is in one direction with all arrows pointing downward to one or more boxes.

Below the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Determine BP category from average of replicate readings at multiple visits (see measurement algorithm)
   1. Forward to Normotensive
   2. Forward to Pre-Hypertension
   3. Forward to Stage 1 Hypertension
   4. Forward to Stage 2 Hypertension
2. Normotensive
   1. Forward to Assess other CV risk factors
3. Pre-Hypertension
   1. Forward to Assess other CV risk factors^*
4. Stage 1 Hypertension
   1. Forward to Basic Work-up: Medical/Family/Sleep Hx, PEx, CBC, renal panel, U/A, Renal/Cardiac U/S, lipids, glucose
5. Stage 2 Hypertension
   1. Forward to Basic Work-up: &/or refer to Ped HTN expert for extended work-up
6. Assess other CV risk factors, plus
   1. Forward to CHILD-1^†/Activity Education^**
7. Assess other CV risk factors*, plus
   1. Forward to CHILD-1^†/activity education^** &/or Weight management^***
8. Basic Work-up: Medical/Family/Sleep Hx, PEx, CBC, renal panel, U/A, Renal/Cardiac U/S, lipids, glucose, plus
   1. Forward to CHILD-1^†/activity education^** &/or Weight management^***
9. Basic Work-up: &/or refer to Ped HTN expert for extended work-up
   1. Primary or Secondary HTN, forward to Anti-HTN Drug +/- Rx for 2⁰ cause + Weight management*** &/or CHILD-1^†/activity education**
10. CHILD-1^†/Activity Education^**
    1. Forward to Re-evaluate at next visit
11. CHILD-1^†/activity education^** &/or Weight management^***
    1. Forward to Monitor Q 6 Mo
12. CHILD-1^†/activity education^** &/or Weight management^***
    1. Primary HTN No LVH, Forward to Monitor Q3 to 6 Months
    2. Secondary HTN or LVH, Forward to Rx for 2⁰ cause + Anti-HTN Drug
13. Anti-HTN Drug +/- Rx for 2⁰ cause + Weight management^*** &/or CHILD-1^†/activity education**
    1. Forward to Follow until BP controlled, Q 1-2 wks
14. Monitor Q 6 Mo
    1. Forward to Re-evaluate BP cagegory**
15. Monitor Q 3 to 6 Months
    1. Forward to Re-evaluate BP cagegory
16. Rx for 2⁰ cause + Anti-HTN Drug
    1. Forward to Monitor Q 3-6 Months
17. Follow until BP controlled, Q 1-2 wks
    1. Monitor Q 1-3 Months
18. Re-evaluate BP Category**
    1. <90th %ile, 90<95th%ile (≥95th%ile → Stage 1 W/U) ≥95th%ile, forward to Consider basic W/U + cardiac U/S for TOD*
19. Re-evaluate BP category
    1. Forward to Anti-HTN Drug if no improvement
20. Monitor Q3-6 Months
    1. Forward to Consider re-evaluation of BP Category if BP well controlled, ↓BMI or s/p Rx for 2⁰ cause
21. Monitor Q 1-3 Months
    1. Forward to Consider re-evaluation of BP Category if BP well controlled, ↓BMI or s/p Rx for 2⁰ cause
22. Consider basic W/U + cardiac U/S for TOD*
    1. Forward to Monitor Q 6 Mo
23. Anti-HTN Drug if no improvement
    1. Forward to Continue moderate follow-up
24. Consider re-evaluation of BP Category if BP well controlled, ↓BMI or s/p Rx for 2⁰ cause
    1. Forward to Continue moderate follow-up
    2. Forward to Continue close follow-up
25. Re-evaluate at next visit
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
26. Monitor Q 6 Mo
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
27. Continue moderate follow-up
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
28. Continue close follow-up
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
29. GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage

Figure 8-2 Legend:
^*   Work up for target organ damage (TOD)/ LVH if obese or (+) for other CV risk factors;
^†  Cardiovascular Health Integrated Lifestyle Diet; See Section V. Nutrition and Diet;
^** Activity Education. See Section VI. Physical Activity;
^*** Weight management. See Section X. Overweight and Obesity.

Table 8-3. BP Norms For Boys By Age And Height Percentile

SD = standard deviation
The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Table 8–4. BP Norms For Girls By Age And Height Percentile

SD = standard deviation
The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Table 8-5. Anti-hypertensive Medications with Pediatric

Angiotensin-converting enzyme (ACE) inhibitor

Angiotensin-receptor blocker (ARB)

Alpha- and beta-antagonist

Beta-antagonist

Calcium channel blocker

Central alpha-agonist

Diuretic

Peripheral alpha-antagonist

Vasodilator

^* The maximal recommended adult dose should not be exceeded in routine clinical practice.
_† Level of evidence on which recommendations are based.
^‡ U.S. Food and Drug Administration (FDA) -approved pediatric labeling information is available for treatment of hypertension. Recommended doses for agents with FDA-approved pediatric labels contained in this table are the doses contained in the approved labels. Even when pediatric labeling information is not available, the FDA-approved label should be consulted for additional safety information.
^§ Comments apply to all members of each drug class except where otherwise stated.
^** Indicates drug added since The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (2004).
^*** Study did not reach primary end point (dose response for reduction in systolic blood pressure). Some prespecified secondary end points demonstrated effectiveness.

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9. Lipids and Lipoproteins

Since the last NHLBI guidelines for lipid management in children and adolescents were published in 1992, both the knowledge base surrounding dyslipidemia in childhood and clinical picture have changed. A series of critical observational studies have demonstrated a clear correlation between lipoprotein disorders and the onset and severity of atherosclerosis in children, adolescents and young adults. A major increase in the prevalence of obesity has led to a much larger population of children with dyslipidemia. At the time of the original guidelines, the focus was almost exclusively on identification of children with elevated low density lipoprotein cholesterol (LDL-C). Since then, the predominant dyslipidemic pattern in childhood is a combined pattern associated with obesity, with moderate to severe elevation in triglycerides (TG), normal to mild elevation in LDL-C and reduced high density lipoprotein cholesterol (HDL-C). Both dyslipidemic patterns have been shown to be associated with initiation and progression of atherosclerotic lesions in children and adolescents as demonstrated by pathology and imaging studies. Identification of children with dyslipidemias, which place them at increased risk for accelerated early atherosclerosis, must include a comprehensive assessment of serum lipids and lipoproteins.

The evidence review for lipids and lipoproteins addressed the association between dyslipidemia and atherosclerosis in childhood, lipid assessment in childhood and adolescence with tables of normative results provided, the dyslipidemias, dietary treatment of dyslipidemia and medication therapy.

Table 9–1. Acceptable, Borderline-High, and High Plasma Lipid, Lipoprotein and Apolipoprotein Concentrations (mg/dL) For Children and Adolescents^*

NOTE: Values given are in mg/dL; to convert to SI units, divide the results for TC, LDL-C, HDL-C and non-HDL-C by 38.6; for TG, divide by 88.6.

^* Values for plasma lipid and lipoprotein levels are from the National Cholesterol Education Program (NCEP) Expert Panel on Cholesterol Levels in Children. Non-HDL-C values from the Bogalusa Heart Study are equivalent to the NCEP Pediatric Panel cut points for LDL-C. Values for plasma apoB and apoA-1 are from the National Health and Nutrition Examination Survey III.
⁺ The cut points for high and borderline-high represent approximately the 95th and 75th percentiles, respectively. Low cut points for HDL-C and apoA-1 represent approximately the 10th percentile.

Table 9-2. Recommended Cut Points for Lipid and Lipoprotein Levels (mg/dL) in Young Adults^*

^* Values provided are from the Lipid Research Clinics Prevalence Study. The cut points for TC, LDL-C and non-HDL-C represent the 95th percentile for 20-24 year old subjects and are not identical with the cut points used in the most recent NHLBI adult guidelines, ATP III, which are derived from combined data on adults of all ages. The age-specific cut points given here are provided for pediatric care providers to use in managing this young adult age group. For TC, LDL-C and non-HDL-C, borderline high values are between the 75th and 94th percentile, while acceptable are < 75th percentile. The high TG cut point represents approximately the 90th percentile with borderline high between the 75th and 89th percentile and acceptable < 75th percentile. The low HDL-C cut point represents roughly the 25th percentile, with borderline low between the 26th and 50th percentile and acceptable > the 50th percentile.

Table 9–3. Causes of Secondary Dyslipidemia

EXOGENOUS

• Alcohol
• Drug therapy:
  • Corticosteroids
  • Isoretinoin
  • Beta-blockers
  • Some oral contraceptives
  • Select chemotherapeutic agents
  • Select antiretroviral agents

ENDOCRINE/METABOLIC

• Hypothyroidism/hypopituitarism
• Diabetes mellitus types 1 and 2
• Pregnancy
• Polycystic ovary syndrome
• Lipodystrophy
• Acute intermittent porphyria

RENAL

• Chronic renal disease
• Hemolytic uremic syndrome
• Nephrotic syndrome

INFECTIOUS

• Acute viral/bacterial infection^*
• Human immunodeficiency virus infection (HIV)
• Hepatitis

HEPATIC

• Obstructive liver disease/cholestatic conditions
• Biliary cirrhosis
• Alagille syndrome

INFLAMMATORY DISEASE

• Systemic lupus erythematosis
• Juvenile rheumatoid arthritis

STORAGE DISEASE

• Glycogen storage disease
• Gaucher's disease
• Cystine storage disease
• Juvenile Tay-Sachs disease
• Niemann-Pick disease

OTHER

• Kawasaki disease
• Anorexia nervosa
• Post solid organ transplantation
• Childhood cancer survivor
• Progeria
• Idiopathic hypercalcemia
• Klinefelter syndrome
• Werner's syndrome

^*Delay measurement until ≥ 3 weeks postinfection.

Table 9–4. Summary of Major Lipid Disorders in Children and Adolescents 

^*These are the two lipid and lipoprotein disorders seen most frequently in childhood and adolescence; the latter most often manifests with obesity.
HDL-C = high-density lipoprotein cholesterol; IDL-C = intermediate-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglyceride; VLDL-C = very-low-density lipoprotein cholesterol.

Conclusions and Grading of the Evidence Review for Lipid Assessment in Childhood and Adolescence

• Combined evidence from autopsy studies, vascular studies and cohort studies strongly indicates that abnormal lipid levels in childhood are associated with increased evidence of atherosclerosis. (Grade B)
• The evidence review supports the concept that early identification and control of dyslipidemia throughout youth and into adulthood will substantially reduce clinical CVD risk beginning in young adult life. Preliminary evidence in children with heterozygous FH with markedly elevated LDL-C indicates that earlier treatment is associated with reduced subclinical evidence of atherosclerosis. (Grade B)
• Multiple prospective screening cohort studies have demonstrated the normal lipid and lipoprotein distributions in childhood, adolescence, and young adult life (Tables 9–1 and 9–2) (Grade B). Cohort studies have also demonstrated significant tracking of elevated lipid levels from childhood into adulthood, with lipid and lipoprotein results in childhood predictive of future adult lipoprotein profiles; the strongest statistical correlation occurs between results in late childhood and in the third and fourth decades of life. (Grade B)
• TC and LDL-C levels fall as much as10-20% or more during puberty.(Grade B) Based on this normal pattern of change in lipid and lipoprotein levels with growth and maturation, age 10 years (range age 9-11 years) is a stable time for lipid assessment in children. (Grade D) For most children, this age range will precede onset of puberty.
• Significant evidence exists that using family history of premature CVD or of cholesterol disorders as the primary factor in determining lipid screening for children misses approximately 30-60% of children with dyslipidemias, and accurate and reliable measures of family history are not available. (Grade B) In the absence of a clinical or historic marker, identification of children with lipid disorders that predispose them to accelerated atherosclerosis requires universal lipid assessment. (Grade B)
• Non-HDL-C has now been identified as a significant predictor of the presence of atherosclerosis, as powerful as any other lipoprotein cholesterol measure in children and adolescents. For both children and adults, non-HDL-C appears to be more predictive of persistent dyslipidemia and therefore atherosclerosis and future events than TC, LDL-C or HDL-C alone. A major advantage of non-HDL-C is that it can be accurately calculated in a non-fasting state and is therefore very practical to obtain in clinical practice. The Expert Panel felt that non-HDL-C should be added as a screening tool for identification of a dyslipidemic state in childhood. (Grade B)
• In terms of other lipid measurements: (1) most but not all studies indicate that measurement of apoB and apoA-1 for universal screening provides no additional advantage over measuring non-HDL-C, LDL-C, and HDL-C; (2) measurement of Lp(a) is useful in the assessment of children with both hemorrhagic and ischemic stroke; (3) in offspring of a parent with premature CVD and no other identifiable risk factors, elevations of apoB, apoA-1, and Lp(a) have been noted; and (4) measurement of lipoprotein subclasses and their sizes by advanced lipoprotein testing has not been shown to have sufficient clinical utility in children at this time. (Grade B)  
• Obesity is commonly associated with a combined dyslipidemia pattern with mild elevation in TC and LDL-C, moderate to severe elevation in TG and low HDL-C. This is the most common dyslipidemic pattern seen in childhood, and lipid assessment of overweight and obese children identifies an important proportion with significant lipid abnormalities. (Grade B)
• Dyslipidemias can be acquired genetically but also secondary to specific conditions such as diabetes, nephrotic syndrome, chronic renal disease, postorthotopic heart transplant, history of Kawasaki disease with persistent coronary involvement, chronic inflammatory disease, hypothyroidism, and other causes as outlined in Table 9–3. There is impressive evidence for accelerated atherosclerosis both clinically and as assessed with noninvasive methods in some of these conditions, which accordingly have been designated as special risk diagnoses for accelerated atherosclerosis (Table 9–7); management of these is described in Section XI. Diabetes Mellitus and Other Conditions Predisposing to the Development of Accelerated Athersosclerosis. Lipid evaluation of these patients contributes to risk assessment and identifies an important proportion with Dyslipidemia. (Grade B)
• The complete phenotypic expression of some inherited disorders like FCHL may be delayed until adulthood. Evaluation in children and adolescents from high risk families with FCHL should therefore begin in childhood and continue through adulthood (per NCEP adult treatment guidelines) will lead to early detection of those with abnormalities. (Grade B)

Age-specific recommendations for lipid assessment are outlined in Table 9–5. Specific management for children with identified dyslipidemia is outlined in the algorithms in Figures 9–1 and 9–2. Definitions of the risk factors and special risk conditions for use with the recommendations and in the algorithms appear in Tables 9–6 and 9–7. The first step proposed for management of children with identified lipid abnormalities is a focused intervention on diet and physical activity.

Table 9–5. Evidence-Based Recommendations for Lipid Assessment

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.

NOTE: Values given are in mg/dL. To convert to SI units, divide the results for total cholesterol (TC), low-density lipoprotein cholesterol (LDL–C), high-density lipoprotein cholesterol (HDL–C), and non-HDL–C by 38.6; for triglycerides (TG), divide by 88.6.

^a Interval between FLP measurements: after 2 weeks but within 3 months.
^b Use Table 9-1 for interpretation of results; use lipid algorithms in Figures 9-1 and 9-2 for management of results.
^c Disregard TG and LDL-C in nonfasting sample.
^d Use Table 9-1 for interpretation of results; use lipid algorithms in Figures 9-1 and 9-2 for management of results.
^e Lipid screening is not recommended for those ages 12–16 years because of significantly decreased sensitivity and specificity for predicting adult LDL–C levels and significantly increased false-negative results in this age group. Selective screening is recommended for those with the clinical indications outlined.
^f Interval between FLP measurements: after 2 weeks but within 3 months.
^g Use Table 9-1 for interpretation of results of 7- to 19-year-olds and lipid algorithms in Figures 9-1 and 9-2 for management. Use Table 9-2 for interpretation of results of 20- to 21-year-olds and ATP III algorithms for management
^h Disregard TG and LDL-C in nonfasting sample.
ⁱ Interval between FLP measurements: after 2 weeks but within 3 months

Figure 9-1. Dyslipidemia Algorithm: TARGET LDL-C (Low-Density Lipoprotein Cholesterol)

NOTE: Values given are in mg/dL. To convert to SI units, divide results for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C by 38.6; for triglycerides (TG), divide by 88.6.

Figure 9-1 Description

The figure is a flow chart with 13 labeled boxes linked by arrows. The chart flows in one direction with arrows pointing downward and lateral arrows to one or more boxes.

Below the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Fasting lipid profile (FLP) x 2^*, average
   1. Forward to LDL-C > 130, < 250 mg/dL ^** → Target LDL-C TG > 100, < 500 mg/dL, < 10 y → Target TG > 130, < 500 mg/dL, 10-19 y
2. TG ≥ 500 mg/dL,
   → Consult lipid specialist
   1. Lateral to LDL-C ≥ 250 mg/dL → Consult lipid specialist
3. LDL-C ≥ 250 mg/dL
   → Consult lipid specialist
   1. Lateral to TG ≥ 500 mg/dL, → Consult lipid specialist
4. LDL-C ≥ 130, < 250 mg/dL ^** → Target LDL-C
   TG≥ 100, < 500 mg/dL, < 10 y → Target TG
   ≥ 130, < 500 mg/dL, 10-19 y (see TG algorithm, Figure 9-2)
   1. Forward to FLP
   2. Boxed text with no arrow between the two boxes: Exclude secondary causes. Evaluate for other risk factors (RFs). Start Cardiovascular Health Integrated Lifestyle Diet (CHILD 1) → CHILD 2-LDL (Table 9-8) + lifestyle change x 6 months^***
5. FLP
   1. Forward to LDL-C < 130 mg/dL
   2. Forward to LDL-C ≥130 to -189 mg/dL Family history (FHx) (-) No other RFs
   3. Forward to LDL-C ≥ 190 mg/dL
   4. Forward to LDL-C ≥ 160 to -189 mg/dL FHx (+) or 1 high-level RF or ≥ 2 moderate-level RFs
   5. Forward to LDL-C ≥ 130 to -159 mg/dL + 2 high-level RFs or 1 high-level + ≥ 2 moderate-level RFs OR clinical CVD
6. LDL-C < 130 mg/dL
   → Continue CHILD 2-LDL
   → Repeat FLP q. 12 months
7. LDL-C ≥130 to -189 mg/dL Family history (FHx) (-) No other RFs
   → Continue CHILD 2 LDL, Follow q. 6 m with FLP, FHx/ RF update
8. LDL-C ≥ 190 mg/dL
   → Initiate statin therapy (Tables 9-11, 9-12)
   1. Forward to Follow with FLPs, related chemistries per Table 9-12
9. LDL-C ≥ 160 to -189 mg/dL FHx (+) or 1 high-level RF or ≥ 2 moderate-level RFs
   →Initiate statin therapy (Tables 9-11, 9-12)
   1. Forward to Follow with FLPs, related chemistries per Table 9-12
10. LDL-C ≥ 130 to -159 mg/dL + 2 high-level RFs or 1 high-level + ≥ 2 moderate-level RFs OR clinical CVD
    → Initiate statin therapy (Tables 9-11, 9-12)
    1. Forward to Follow with FLPs, related chemistries per Table 9-12
11. Follow with FLPs, related chemistries per Table 9-12
    1. Forward to → LDL-C still≥130 mg/dL, TG <200 mg/dL, refer to lipid specialist for addition of second lipid-lowering agent; monitor per Table 9-12 → In high LDL-C patients, if non-HDL-C ≥145 mg/dL after effective LDL-C treatment, → Target TG (Figure 9-2)
12. → LDL-C still ≥130 mg/dL, TG <200 mg/dL, refer to lipid specialist for addition of second lipid-lowering agent; monitor per Table 9-12
    → In high LDL-C patients, if non-HDL-C ≥145 mg/dL after effective LDL-C treatment,
     → Target TG (Figure 9-2)