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• W2056703411 abstract "HomeCirculationVol. 124, No. 15Reduction of Risk for Cardiovascular Disease in Children and Adolescents Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessResearch ArticlePDF/EPUBReduction of Risk for Cardiovascular Disease in Children and Adolescents Stephen R. Daniels, MD, PhD, Charlotte A. Pratt, PhD, RD and Laura L. Hayman, RN, PhD Stephen R. DanielsStephen R. Daniels From the Department of Pediatrics, University of Colorado School of Medicine, Aurora (S.R.D.); National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (C.A.P.); and College of Nursing and Health Sciences, University of Massachusetts Boston, Boston (L.L.H.). Search for more papers by this author , Charlotte A. PrattCharlotte A. Pratt From the Department of Pediatrics, University of Colorado School of Medicine, Aurora (S.R.D.); National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (C.A.P.); and College of Nursing and Health Sciences, University of Massachusetts Boston, Boston (L.L.H.). Search for more papers by this author and Laura L. HaymanLaura L. Hayman From the Department of Pediatrics, University of Colorado School of Medicine, Aurora (S.R.D.); National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (C.A.P.); and College of Nursing and Health Sciences, University of Massachusetts Boston, Boston (L.L.H.). Search for more papers by this author Originally published11 Oct 2011https://doi.org/10.1161/CIRCULATIONAHA.110.016170Circulation. 2011;124:1673–1686IntroductionAtherosclerotic cardiovascular disease (CVD) is the number 1 cause of death in the United States and other developed nations.1 After decades of study, risk factors for the development of atherosclerotic CVD have been identified. These risk factors include older age, male sex, a positive family history, hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, and obesity.2 As these risk factors have been studied, it has become clear that both genetics and lifestyle are important contributors to increased risk. The primary lifestyle components are diet, physical activity, and smoking.A fundamental issue has been the timing of the development of atherosclerosis. Timing is critical because it determines, at least in part, when interventions should occur. Both the prevention of risk factor development (primordial prevention) and modification of risk factors once they are established (primary prevention) are important. An impediment to understanding the development of atherosclerosis has been the lack of simple, noninvasive methods to follow the atherosclerotic process longitudinally. This problem led to the Bogalusa Heart Study and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY).3–6 These pathology studies investigated the aorta and coronary arteries in autopsies of young individuals who died of accidental causes. The investigators were able to evaluate the extent of atherosclerosis and the presence of risk factors. They found that even relatively advanced levels of atherosclerosis, including fibrous plaques, can be present in adolescents and young adults. They also found that increased body mass index (BMI), systolic and diastolic blood pressures, and low-density lipoprotein cholesterol (LDL-C); low levels of high-density lipoprotein cholesterol (HDL-C); diabetes mellitus; and the presence of cigarette smoking were all associated with greater atherosclerotic plaque coverage and more advanced atherosclerotic lesions.3–6Subsequent studies using noninvasive measures of atherosclerosis, including carotid intima-medial thickness (CIMT) and arterial distensibility, have resulted in similar findings.7–10 Therefore, evidence is mounting that atherosclerosis begins in childhood and is directly associated with the same CVD risk factors that are well established in adults.When these results are taken together, they emphasize the need for appropriate CVD prevention strategies in children and adolescents. Through these preventive efforts, it should be possible to maintain low-risk status into adulthood. Low-CVD-risk status maintained to 50 years of age is associated with a very low future risk of CVD.11 This is a fundamental principle behind the American Heart Association's 2020 goals, which are focused on achieving and monitoring cardiovascular health.12In this report, we summarize the evidence and the current published recommendations regarding the epidemiology of risk factors for atherosclerotic CVD in childhood. We outline the recommended clinical approaches to prevent risk factor development and review cut points for identifying risk factors and approaches for ameliorating high-risk status once it has developed. The National Heart, Lung and Blood Institute (NHLBI) has formed an advisory group to review evidence and to make recommendations regarding the prevention of CVD in children and adolescents. This work is in progress and has not been published. This report is an overview and a synthesis of previously published recommendations.DietHealthful dietary patterns develop in childhood and are important for primordial and primary prevention of risk factors related to CVD from childhood and adolescence through adulthood. Evidence of the effectiveness of long-term dietary intervention for the reduction of risk factors for CVD in children is limited, but ample data suggest that changes in specific dietary macronutrients (eg, dietary fat and carbohydrates) and micronutrients (eg, sodium and calcium) have an impact on the risk of CVD.13How much energy a child or adolescent should consume depends on age, sex, stage of growth, body weight and size, and level of physical activity.14,15Table 1 presents an estimate of caloric needs by age, sex, and activity level. Children who are sedentary need less energy compared with those who are active. Thus, the types and amount of food groups needed to meet caloric needs also vary15 (http://www.mypyramid.gov).Table 1. Suggested Caloric Intake by Sex, Age, and Activity LevelSexAge, yActivity LevelSedentary*Moderately Active†Active‡Female2–31000–12001000–12001000–14004–81200–14001400–16001400–18009–131400–16001600–20001800–220014–1818002000–22002400Male2–31000–12001000–12001000–14004–81200–14001400–16001600–20009–131600–20001800–22002000–260014–181800–24002400–28002800–3200Source: Britten P, Marcoe K, Yamini S, Davis C. Development of food intake patterns for the MyPyramid food guidance system. J Nutr Educ Behav. 2006;38:S78-S92.15http://www.cnpp.usda.gov/Publications/MyPyramid/DevelopmentMaterials/JNEBsupplement/JNEBDevelPatterns.pdf. Based on Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; 2002.14*Sedentary means a lifestyle that includes only the physical activity of independent living.†Moderately active means a lifestyle that includes physical activity equivalent to walking about 1.5 to 3 miles/d at 3 to 4 mph, in addition to the activities of independent living.‡Active means a lifestyle that includes physical activity equivalent to walking >3 miles/d at 3 to 4 mph, in addition to the activities of independent living.There is evidence linking diet to cardiovascular health.13,14 Table I in the online-only Data Supplement presents strong and moderately strong evidence relating macronutrients, micronutrients, foods, and food environment to health. There is strong and/or moderately strong evidence of a positive association between adiposity and macronutrients: dietary fat, total energy intake, and energy density of foods, as well as sugar-sweetened beverages16 and portion sizes (Table I in the online-only Data Supplement). Children and adolescents who consume large portion sizes, more calories than they expend, and high-energy-dense foods gain excess weight and body fat and increase their CVD risks. Those who eat breakfast have been reported to be at lower risk of being overweight or obese and more likely to consume adequate intakes of essential nutrients such as calcium and iron.13,17–19 Based on 21 years of follow-up data from youth 3 to 18 years of age, the Cardiovascular Risk in Young Finns Study20 demonstrated that healthful dietary patterns developed in childhood and the cardiovascular health benefits accrued from such patterns track into adulthood. Clinical trials have demonstrated that diets low in total fat (<30% of energy), saturated fat (8%–10% of energy), and cholesterol (200–300 mg/d) significantly reduced total cholesterol (TC), LDL-C, and C-reactive protein.21Because dietary habits and preferences are established in early childhood, it is important to intervene early to improve dietary patterns of children and adolescents. Clearly, improvements in dietary patterns and physical activity and maintenance of a healthy weight throughout childhood and adolescence are likely to prevent the development of CVD in children and adolescents and subsequently in adults. Primary care providers should counsel their pediatric patients and their families to adhere to prudent dietary patterns of low total and saturated fat and cholesterol; to provide youth with more fruits, vegetables, fiber, and fat-free or low-fat dairy; to encourage the consumption of less dietary salt and sodium and limited or no intake of sugar-sweetened beverages; and to control portion sizes in early childhood and throughout adolescence.Physical ActivityEvidence accumulated over the past several decades supports a multitude of benefits associated with a physically active lifestyle in children and youth.22 Health-related benefits of regular physical activity documented in clinical and epidemiological studies and summarized in recent comprehensive reviews include improved cardiovascular fitness, increased bone mass, improved psychological well-being, and lower risk of obesity and elevated blood pressure.22,23 In contrast, results of several observational studies of children and adolescents (4–18 years of age) and young adults (19–21 years of age) demonstrate associations between increased time spent in sedentary activities and decreased levels of physical activity, adverse lipid profiles, increased levels of obesity, and related cardiovascular risk factors, including hypertension and insulin resistance.24,25 Longitudinal data from the Cardiovascular Risk in Young Finns Study and the Muscatine Study, similar to observations of adults, indicate that optimal cardiovascular risk profiles are seen in individuals who are consistently physically active.24,25Tracking of levels of physical activity from childhood to young adulthood has also been documented, with the most consistent tracking observed for high levels of physical activity at 9 to 18 years of age predicting higher levels of physical activity in adulthood.26 Physically active children and youth are more likely to engage in other health-promoting behaviors and less likely to engage in health-compromising behaviors than their less active counterparts.27 Finally, results of studies that include interventions designed to increase physical activity and to decrease sedentary time have demonstrated reductions in systolic and diastolic blood pressures,28 decreased measures of body fat,29 decreased BMI,30 improved cardiorespiratory fitness,31 and improved cardiometabolic risk profiles.32 However, the results are not consistent across studies, and the dose (duration and intensity) of physical activity required to modify cardiovascular risk factors in children and youth remains to be clarified. Current recommendations for healthy children and youth (≥6 years of age) include at least 1 hour of moderate to vigorous physical activity (MVPA) daily with vigorous-intensity physical activity and muscle- and bone-strengthening activities on at least 3 days of the week.22,33 Moderate intensity is defined as 3.0 to 6.0 metabolic equivalents (METs), and >6.0 METs is considered vigorous, expending 3.5 to 7.0 and >7.0 kcal/min, respectively. The reduction of sedentary time (leisure screen time) to <2 h/d is also recommended.33Although current guidelines recommend 60 min/d of MVPA, nationally representative data indicate that the majority of youth (56.3%) are not achieving this goal.34 Data from the Study of Early Child Care and Youth Development, designed to examine the patterns and determinants of MVPA of children from ethnically and economically diverse backgrounds followed up from 9 to 15 years of age, indicate that levels of physical activity decrease significantly over that time period.35 By 15 years of age, adolescents were engaging in MVPA for 49 minutes per weekday and 35 minutes per weekend day. Boys were more active than girls, spending 18 and 13 more min/d in MVPA on weekdays and weekends, respectively. Clearly, both individual/clinical- and population-based strategies, including advocacy and support for daily physical education in schools, are needed to improve levels of physical activity in US children and youth.36Healthcare providers should assess physical activity and sedentary behaviors at every well-child visit.37–39 Although no valid and reliable instruments are currently available for assessment of physical activity in pediatric primary care settings, general topics for questions include the amount of time regularly spent walking, bicycling, and in outdoor play; use of playgrounds, parks, and gymnasiums; and interactive play/games with other children and adolescents. Time spent participating in age-appropriate organized sports should also be addressed, along with time spent in school or day-care physical education that includes a minimum of 30 minutes of coordinated large-muscle exercise (for children >2 years of age). Sedentary behaviors, including the number of hours per day spent in leisure screen time such as television viewing and computer gaming, should also be assessed.Primary healthcare providers should provide age-appropriate suggestions (that consider the child and family's resources and preferences) for increasing physical activity and limiting sedentary behaviors in children and youth. For example, for families with children <5 years of age, recommendations would include unlimited active play time in a safe supportive environment, family activity at least once a week, and limitation of screen time to <2 h/d. Screen time should be zero from birth to 2 years of age. In addition, television should not be permitted in the child's bedroom. Beginning early in life and extending through adolescence, parental role modeling of physical activity behaviors is important in promoting physical activity behaviors in offspring. Encouragement of parent engagement in physical activities, optimally with the children, is advised. During childhood and adolescence, 1 h/d of MVPA and vigorous-intensity activity on at least 3 d/wk and <2 h/d of sedentary activity are recommended, along with matching physical activity recommendations with the child's energy intake. Theory-based age-appropriate behavioral change strategies should be included as part of individual and family counseling designed to increase levels of physical activity and to decrease sedentary behaviors. Although additional research is needed to determine the most efficient and effective methods for implementation in pediatric primary care settings, available evidence points to the promise and potential of multicomponent, tailored interventions that incorporate principles of behavior change and are delivered by multidisciplinary teams.36,40ObesityChildhood obesity has reached epidemic proportions in the United States, with an estimated 17% of children and adolescents being obese.41 Obesity prevalence is estimated at 10.4% among preschool children, 19.6% among 6 to 11 year olds, and 18.1% among adolescents 12 to 19 years of age.41 Among infants and toddlers, ≈10% were above the 95th percentile of the weight-for-recumbent-length growth charts.41 Mexican American male boys and non-Hispanic black girls have a higher prevalence of obesity compared with non-Hispanic whites (29.2%, 26.8%, and 14.5%, respectively). Higher obesity prevalence was reported in the National Health and Nutrition Examination Survey (NHANES) in children of low socioeconomic status (<130% of poverty level; boys, 21.1%; girls, 19.3%) compared with those of high socioeconomic status (>350% of poverty level; boys, 11.9%; girls, 12%).42Obesity in children and adolescents is determined from BMI (weight in kilograms divided by height in meters squared) and the corresponding BMI-for-age percentile on a Centers for Disease Control BMI-for-age growth chart (http://apps.nccd.cdc.gov/dnpabmi/Calculator.aspx); obesity is defined as BMI ≥95th percentile and overweight as BMI ≥85th to <95th percentile.43 Obesity in childhood and adolescence is associated with numerous adverse health outcomes. Cardiovascular risk factors such as hypertension, type 2 diabetes mellitus, metabolic syndrome, sleep apnea, left ventricular hypertrophy,44,45 and abnormal lipid profiles (eg, high triglycerides, low HDL) are higher in obese than in normal-weight youth.36,46 For example, obese girls had a 6-fold higher prevalence and a 2- to 3-fold higher incidence of hypertension compared with their normal-weight counterparts.47 Obesity in childhood and adolescence substantially increases the risk of adult obesity.48,49 Obese 2- to 5-year-olds had >4 times the likelihood of becoming obese adults compared with normal-weight children.49 Eighty percent of children who were overweight at 10 to 15 years of age were obese adults at 25 years of age.48 Twenty five percent of obese adults were overweight as children.48 Obesity in childhood has been associated with increased arterial stiffness and CIMT and increased risk of coronary heart disease in adult life.7–9,50,51Prevention of obesity in childhood and adolescence is the mainstay for CVD risk reduction. An improvement in weight status and a decrease in adiposity are associated with a decline in blood pressure and an improvement of blood lipids (ie, TC, HDL-C, and triglycerides), insulin resistance, and inflammatory markers (see Table II in the online-only Data Supplement).36A suggested approach to overweight and obesity management in children and adolescents has been published.40 All children, regardless of their weight status, should have their weight and height measured and BMI calculated at every visit with the healthcare provider. The BMI percentile and, for infants and children, percentile for weight for recumbent height can then be determined. Parental obesity, family medical history, BMI trajectory, and CVD risk factors (eg, diabetes mellitus) are considered in the management of weight and in CVD risk reduction. For healthy-weight children and adolescents (BMI, 5th–84th percentile), the goal is to prevent excess weight gain through lifestyle modifications that include eliminating the intake of sugar-sweetened beverages,13 increasing the intake of fruits and vegetables to ≥5 servings daily, limiting television and electronic media use to ≤2 h/d, and participating in at least 60 minutes of MPVA daily40 (prevention stage).Table 2 describes the components of the staged approach to weight management, and Table 3 presents a suggested staged approach to weight management and healthy weight goals for children and adolescents by age and BMI percentiles. For children and adolescents who are overweight (85th–94th percentile) or obese (≥95th percentile), a staged lifestyle behavioral approach of increasing intensity plus a structured weight management protocol and/or a comprehensive and multidisciplinary weight management protocol consisting of supervised counseling by a trained physician, nurse practitioner, or a registered trained dietitian are recommended.40 The management plan includes a low-energy-dense and balanced diet, supervised physical activity of at least 60 min/d, ≤1 h/d of screen time, and increased self-monitoring of dietary and physical activity behaviors.40Table 2. Components of a Staged Approach to Weight Management for Children and AdolescentsStageComponents1. Prevention plus (“plus” means providers must spend more time and increase intensity of the recommendation and follow-up 3–6 mo beyond usual care)≥5 servings of fruits and vegetable daily; ≤2 h of screen time daily; no television in child's bedroom; no sugar-sweetened beverages; ≥60 min of physical activity daily; (graded) family-based approach to lifestyle changes; acknowledge cultural differences2. Structured weight management (SWM)Prevention plus; family-based and balanced macronutrient diet emphasizing small amounts of energy-dense foods; high-quality, nutrient-rich diet to prevent muscle loss; controlled portion sizes; reduced television and screen time; self-monitoring of diet and physical activity; medical screening3. Comprehensive multidisciplinary interventionPrevention plus and structured weight management but more frequent patient-provider contact, more active use of behavioral strategies, more formal monitoring, and feedback to improve adherence; multidisciplinary teams; strong parental involvement for children <12 y of age; assessment of diet, physical activity, and body fat at specified intervals; food monitoring; structured dietary and physical activity intervention to improve diet quality and result in weight loss4. Tertiary care centerContinue diet and activity counseling in stages 2 and 3 plus meal replacement, very low-energy diet, medication, and/or surgerySource: Barlow SE; Expert Committee. Expert committee recommendations regarding the prevention, assessment and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120:S164–S192.40Table 3. Suggested Staged Approach to Weight Management and Healthy Weight Goals for Children and AdolescentsAge Range, yBMI Range (Percentile or Absolute Value)Staged ApproachHealthy Weight Goals2–55th–84thPrevention stage; foster healthful lifestyle in all children; follow national recommendations for food consumption and physical activityNormal weight; continue to maintain weight85th–94thPP; SWM after 3–6 mo of no weight change or parental obesityWeight maintenance until BMI <85th percentile or slowing of weight gain as indicated by downward deflection in BMI curve≥95thPP; SWM after 3–6 mo of no improvement on PPWeight maintenance until BMI <85th percentile or slowing of rate of weight gain≥99th or >21 kg/m2PP; SWM after 3–6 mo of no improvement on PP; comprehensive, multidisciplinary intervention after 3–6 mo of no improvement on SWM, comorbidity, or family history of obesityGradual, carefully monitored weight loss of no more than 1 lb/mo until BMI is <85th percentile6–115th–84thPrevention stage; prevention; foster healthful lifestyle in all children; follow national recommendations for food consumption and physical activityNormal weight; continue to maintain normal weight85th–94thPP; SWM after 3–6 mo if increasing BMI percentile or medical condition persistsWeight maintenance until BMI is <85th percentile or slowing of weight gain as indicated by downward deflection in BMI curve95th–98thPP; SWM depending on responses, age, health risks, and motivation; comprehensive multidisciplinary intervention if no improvement on SWMWeight maintenance until BMI is <85th percentile or carefully monitored weight loss of no more than 1 lb/mo until <85th percentile≥99thPP; SWM depending on age, response to treatment, health risks, and motivation; advance to comprehensive multidisciplinary intervention after 3–6 mo on SWM if comorbidity persists; refer for tertiary care center for evaluationWeight loss not to exceed an average of 2 lb/wk (0.9 kg/wk) until <85th percentile12–185th–84thPrevention stage; foster healthful lifestyle in all children; follow national recommendations for food consumption and physical activityNormal weight; continue to maintain normal weight85th–94thPP; SWM after 3–6 mo of PP if BMI percentile or medical condition persistsWeight maintenance until BMI is <85th percentile or slowing of weight gain as indicated by downward deflection in BMI curve95th–98thPP or SWM depending on age, degree of obesity, health risks, and motivation; advance to intensive intervention depending on response to treatment, age, health risks, and motivationWeight loss until BMI is <85th percentile; no more than 2 lb/wk; if greater weight loss is noted, monitor patient for causes of weight loss >2 lb/wk≥99thPP; SWM depending on age, response for treatment, degree of obesity, health risks, and motivation; advance from SWM to comprehensive multidisciplinary intervention stage after 3–6 mo with comorbidity and no improvement; refer to tertiary care center for evaluationWeight loss not to exceed an average of 2 lb/wk until <85th percentileBMI indicates body mass index; PP, prevention plus; and SWM, structured weight management. Source: Barlow SE; Expert Committee. Expert committee recommendations regarding the prevention, assessment and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120:S164–S192.40For overweight and obese youth, the goal is to improve BMI to less than the 85th percentile (Table 3). Lower energy (caloric) intake is strongly associated with reduced adiposity in children,13 and caloric expenditure must exceed intake to achieve weight loss. Referral of severely obese children and those with obesity-related comorbidities to a pediatric weight management program is highly recommended. The 4-stage intervention and treatment modality for overweight and obese youth has been endorsed by many organizations, including the American Academy of Family Physicians and the American Academy of Pediatrics (AAP).Table II in the online-only Data Supplement presents examples of obesity prevention and nutrition interventions that were reported in the literature from 2000 to 2010. Interventions that improved BMI were multicomponent (included dietary and physical activity improvements)52 and multidisciplinary (included pediatricians or primary care physicians and registered dietitians or nurses).53 Interventions that resulted in weight loss or reduction in excess weight gain were often family based and included behavioral therapy. Intervention duration varied from 4 weeks to 4 years. The NHLBI Working Group on Childhood Obesity Prevention and Treatment recently provided research recommendations to prevent and treat obesity in children to reduce future CVD risk.54Blood PressureElevated blood pressure is determined for children when measured blood pressure exceeds certain percentile values based on studies in normal populations. To determine the blood pressure percentile, it is important to take into account age, sex, and height, variables that are normally associated with blood pressure level. The Fourth Report on Blood Pressure in Children from the NHLBI has established levels of blood pressure that should trigger clinical action.55 Prehypertension is defined as blood pressure between the 90th and 95th percentiles for age, sex, and height or 120/80 mm Hg (the level for prehypertension in adults), whichever is lower. When prehypertension is identified, the recommended clinical approach is lifestyle intervention to improve BMI when obesity is present, to lower dietary sodium, and to increase the level of physical activity. Blood pressure elevation or hypertension is defined by systolic or diastolic blood pressure above the 95th percentile on a persistent basis. Persistence is defined by elevation on 3 consecutive occasions. Stage 1 hypertension is present when blood pressure is above the 95th percentile but below the 99th percentile plus 5 mm Hg (≈12 mm Hg above the 95th percentile). Stage 2 hypertension is present when blood pressure is above the 99th percentile plus 5 mm Hg.55The management approach to hypertension is presented in the Figure. For stage 1 hypertension, it is important to evaluate left ventricular mass to determine whether left ventricular hypertrophy is present. Left ventricular hypertrophy is the most useful marker of hypertensive target organ abnormality and, when present, is an indication that more aggressive treatment is indicated. The initial treatment for stage 1 hypertension is management of lifestyle and improvement of BMI as for prehypertension. However, if blood pressure elevation persists despite lifestyle change or if target organ damage is present, then pharmacological intervention may be indicated. When stage 2 hypertension is present, this may signal the presence of a secondary form of hypertension. A workup for underlying causes of hypertension should be instituted on the basis of the presence of suspicious history or abnormal physical examination. Stage 2 hypertension may also require earlier intervention with pharmacological therapy.55Download figureDownload PowerPointFigure. Management algorithm for hypertension. BP indicates blood pressure; BMI, body mass index; Rx, prescription; and Q, every. *Diet modification and physical activity; †especially if younger, very high BP, little or no family history, diabetic, or other risk factors. Source: National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, American Academy of Pediatrics. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114:555–576.55The recommended approach to blood pressure elevation in children and adolescents comes from decades of epidemiological and clinical research on children and adults. First, hypertension has been established as a very potent risk factor" @default.
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• W2056703411 title "Reduction of Risk for Cardiovascular Disease in Children and Adolescents" @default.
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• W2056703411 doi "https://doi.org/10.1161/circulationaha.110.016170" @default.
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