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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Circulation. Author manuscript; available in PMC Aug 23, 2013.
Published in final edited form as:
PMCID: PMC3751579
NIHMSID: NIHMS324013
Reduction of Risk for Cardiovascular Disease in Children and Adolescents
Stephen R. Daniels, MD, PhD, FAHA,1 Charlotte A. Pratt, PhD, RD, FAHA,2 and Laura L. Hayman, RN, PhD, FAHA, FAAN3
1Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
2National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health Bethesda, MD
3College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA
Address for Correspondence: Stephen R. Daniels, MD, PhD, Professor and Chairman, Department of Pediatrics, University of Colorado School of Medicine, The Children’s Hospital, 13123 E. 16th Avenue, B065, Aurora, CO 80045, Phone: (720) 777-2766, Fax: (720) 777-7278, Daniels.stephen/at/tchden.org
Keywords: atherosclerosis, diet, hypertension, obesity
Atherosclerotic cardiovascular disease (CVD) is the number one cause of death in the United States and in 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, 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. This is critical, because this timing determines, at least in part, when interventions should occur. Prevention of risk factor development (primordial prevention) and modification of risk factors once they are established (primary prevention) are both important. An impediment to understanding the development of atherosclerosis has been the lack of simple, non-invasive methods to follow the atherosclerotic process longitudinally. This problem led to the pathology studies, the Bogalusa Heart Study and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY). (3,4,5,6). These 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 pressure, LDL-Cholesterol (C), low levels of HDL-Cholesterol (C), diabetes mellitus and the presence of cigarette smoking were all associated with greater atherosclerotic plaque coverage and more advanced atherosclerotic lesions (3,4,5,6).
Subsequent studies using non-invasive measures of atherosclerosis including carotid intima-medial thickness (CIMT) and arterial distensibility have resulted in similar findings (7,8,9,10). Therefore, the evidence is mounting that atherosclerosis does begin 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 age 50 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. (12).
In 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, review cutpoints for identifying risk factors, and approaches to ameliorate high risk status once it has developed. The National Heart, Lung and Blood Institute has formed an advisory group to review evidence and make recommendations regarding the prevention of cardiovascular disease 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.
Healthful 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. The evidence on the effectiveness of long-term dietary intervention for reduction of risk factors for CVD in children is limited, but ample data suggest that changes in specific dietary macro (e.g., dietary fat and carbohydrates) and micro (e.g., sodium and calcium) nutrients have an impact on the risk of CVD (13).
How much energy a child or adolescent should consume depends on age, sex, stage of growth, body weight and size, and level of physical activity (14,15). Table 1 presents an estimate of caloric needs by age, sex, and activity level. Children who are sedentary need less energy compared to those who are active. Thus, the types and amount of food groups needed to meet caloric needs also vary (15, http://www.mypyramid.gov).
Table 1
Table 1
Suggested caloric intake by gender, age, and activity levels
There is evidence linking diet to cardiovascular health (13,14). Supplemental Table 1 presents strong and moderately strong evidence relating macro- and micro- nutrients, and foods and food environment to health. There is strong and/or moderately strong evidence of a positive association between adiposity and macro-nutrients: dietary fat, total energy intake, energy density of foods; as well as sugar-sweetened beverages (16), and portion sizes (Supplemental Table 1). 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 (13,1719). Based on 21 years of follow-up data from youth 3–18 years, the Cardiovascular Risk in Young Finns Study (20) 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 (less than 30% of energy), saturated fat (8–10% of energy), and cholesterol (200–300 mg/d) significantly reduced total cholesterol, LDL-C, and C-reactive protein (21).
Because 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; provide youth with more fruits, vegetables, and fiber, and fat free or low-fat dairy; encourage the consumption of less dietary salt and sodium and limited or no intake of sugar-sweetened beverages; and control portion sizes in early childhood and throughout adolescence.
Evidence 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 to 18 years of age) and young adults (19 to 21 years of age) demonstrate associations between increased time spent in sedentary activities with 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 (24,25).
Tracking of levels of physical activity from childhood to young adulthood has also been documented with most consistent tracking observed for high levels of physical activity at 9–18 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 decrease sedentary time have demonstrated reductions in systolic and diastolic blood pressure (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 and older) include at least one hour of moderate to vigorous physical activity (MVPA) daily with vigorous intensity physical activity and muscle and bone-strengthening activities on at least three days of the week (22,33). Moderate level of intensity is defined as 3.0 to 6.0 metabolic equivalents (METs), whereas greater than 6.0 METs is considered vigorous, expending 3.5 to 7.0 kcal/min to greater than 7.0 kcal/min respectively. The reduction of sedentary time (leisure screen time) to less than two hours per day is also recommended (33).
While current guidelines recommend sixty minutes per day 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 from ages nine to fifteen indicate that levels of physical activity decrease significantly over that time period (35). By age 15 years, adolescents were engaging in MVPA for forty-nine minutes per weekday and thirty-five minutes per weekend day. Boys were more active than girls, spending eighteen and thirteen more minutes per day 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 U.S. children and youth (36).
Healthcare providers should assess physical activity and sedentary behaviors at every well-child visit (37,38,39). While 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 and 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 older than two 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 younger than five 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 less than two hours per day. Screen time should be zero from birth to age 2 years. 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 their children, is advised. During childhood and adolescence, recommendations suggested above for one hour per day of MVPA and vigorous intensity activity on at least three days per week and less than two hours per day of sedentary activity is recommended along with matching physical activity recommendations with 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 decrease sedentary behaviors. While 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 multi-component, tailored interventions that incorporate principles of behavior change and are delivered by multidisciplinary teams (36,40).
Childhood obesity has reached epidemic proportions in the United States, with an estimated 17% of obese children and adolescents (41). Obesity prevalence is estimated at 10.4% among pre-school children, 19.6% among 6–11 year olds, and 18.1% among adolescents, 12–19 years (41). Among infants and toddlers, about 10% were above the 95th percentile of the weight-for-recumbent-length growth charts (41). Mexican-American males and non-Hispanic black girls have a higher prevalence of obesity compared with non-Hispanic whites (29.2%, 26.8% vs. 14.5%, respectively). Higher obesity prevalence was reported in NHANES in children from low socioeconomic status (SES) (<130 of poverty level) (boys 21.1%, girls 19.3%) compared to those from high SES (>350% of poverty level) (boys 11.9%, girls 12%) (42).
Obesity in children and adolescents is determined using BMI (weight[kg]/height[m2]) and the corresponding BMI-for-age percentile on a CDC 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, metabolic syndrome, sleep apnea, left ventricular hypertrophy (44,45), and abnormal lipid profiles (e.g., 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 to 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 more than 4 times the likelihood of becoming obese adults compared with normal weight children (49). Eighty percent of children who were overweight at aged 10–15 years were obese adults at age 25 years (48). Twenty five percent of obese adults were overweight as children (48). Obesity in childhood has been associated with increased arterial stiffness and carotid intima thickness (CIMT) and increased risk of coronary heart disease in adult life (7,8,9,50,51).
Prevention of obesity in childhood and adolescence is the mainstay for CVD risk reduction. Improvement in weight status and decrease in adiposity are associated with decline in blood pressure, and improvement of blood lipids (i.e., total cholesterol, HDL-C and triglycerides), insulin resistance and inflammatory markers (see Supplemental Table 2) (36).
A 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 health care 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 (e.g., diabetes) are considered in the management of weight and in CVD risk reduction. For healthy weight children and adolescents (BMI 5th percentile to 84% percentile), the goal is to prevent excess weight gain through lifestyle modifications that include eliminating intake of sugar-sweetened beverages (13), increasing intake of fruits and vegetables to 5 or more servings daily, limiting TV and electronic media usage to no more than 2 hours daily, and participating in at least 60 minutes of MPVA daily (40) (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 percentile to 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 low-energy-dense and balanced diet, supervised physical activity of at least 60 minutes daily, one hour or less of screen time per day, and increased self-monitoring of dietary and physical activity behaviors (40).
Table 2
Table 2
Components of a staged approach to weight management for children and adolescents
Table 3
Table 3
Suggested Staged Approach to Weight Management and Healthy Weight Goals for Children and Adolescents
For 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 four-staged 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).
Supplemental Table 2 presents examples of obesity prevention and nutrition interventions that were reported in the literature from 2000 to 2010. Interventions that improved BMI were those that were multi-component (included dietary and physical activity improvements) (52) and multidisciplinary (included pediatricians or primary care physician and a registered dietitian 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 four years. The National Heart, Lung and Blood Institute Working Group on Childhood Obesity Prevention and Treatment recently provided research recommendations to prevent and treat obesity in children to reduce future CVD risk (54).
Elevated blood pressure is determined for children when measured blood pressure exceeds certain percentile values based on studies in normal populations. In order to determine the blood pressure percentile, it is important to take into account age, sex and height, which are all variables that are normally associated with the blood pressure level. The 4th Report on Blood Pressure in Children from the NHLBI has established levels of blood pressure that should trigger clinical action (55). Pre-hypertension is defined as blood pressure between the 90th and 95th percentile for age, sex and height percentile or 120/80 mmHg (the level for pre-hypertension in adults), whichever is lower. When pre-hypertension 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 the blood pressure is above the 95th percentile, but below the 99th percentile plus 5 mmHg (approximately 12 mmHg above the 95th percentile). Stage 2 hypertension is present when blood pressure is above the 99th percentile plus 5 mmHg (55).
The management approach to hypertension is presented in Figure 1. For Stage 1 hypertension, it is important to evaluate left ventricular mass to determine if 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 pre-hypertension. However, if the blood pressure elevation persists despite lifestyle change, or if target organ damage is present, then pharmacologic intervention may be indicated. When Stage 2 hypertension is present, this may signal the presence of a secondary form of hypertension. A work up for underlying causes of hypertension should be instituted based on the presence of suspicious history or abnormal physical examination. Stage 2 hypertension may also require earlier intervention with pharmacologic therapy (55).
Figure 1
Figure 1
Management Algorithm for Hypertension
The recommended approach to blood pressure elevation in children and adolescents comes from decades of epidemiologic and clinical research on children and adults. First, hypertension has been established as a very potent risk factor for cerebrovascular disease and coronary artery disease in adults (2,56). Treatment of high blood pressure has also been shown to directly lower the risk of CVD in adults (56,57). This has led to major initiatives to ensure that hypertension is recognized and treated and appropriate blood pressure is achieved in adults (58). While levels of awareness and effective treatment for adults are not optimum, they have steadily improved over time (58).
Elevated blood pressure levels are known to track over time. Thus, an adolescent with elevated blood pressure is much more likely to become an adult with high blood pressure (59,60). Factors that increase the likelihood of blood pressure remaining high are excess weight gain over time and initiation of cigarette smoking (60). Other factors that may increase persistence of high blood pressure but have been less well studied are low levels of physical activity and dietary patterns that result in elevated sodium. The use of oral contraceptives in adolescent girls and young women may also contribute (60).
Unfortunately, the prevalence of high blood pressure has been increasing in children and adolescents (61,62). This is due in part to the epidemic of obesity in this population, but it appears that there are likely to be other, yet to be discovered, factors responsible for this increase (63). Din-Dzietham et al used national survey data from 1963 to 2002 to evaluate trends in hypertension for 8–17 year old children and adolescents (61). They found that both pre-hypertension and hypertension are increasing in children and adolescents. They report that an increase in abdominal obesity over time may be more important than overall obesity in relation to blood pressure elevation. There were also differences by ethnic group. African Americans and Mexican Americans had a greater prevalence of pre-hypertension and hypertension than whites. Males had a higher prevalence of hypertension than females.
McNiece et al also evaluated the prevalence of hypertension in adolescents (62). After 3 screenings, they found 15.7% of adolescents had pre-hypertension while 3.2% had hypertension, including 2.6% with Stage 1 hypertension and 0.6% with Stage 2 hypertension. The only correlate of hypertension was obesity, while greater BMI, male sex and black race associated with pre-hypertension.
These results are quite important from a clinical perspective as they demonstrate that primary care providers can expect to see pre-hypertension and even hypertension relatively commonly in children and adolescents. Providers should be ready to identify and treat hypertension in this age group. Unfortunately, studies have shown that appropriate identification and treatment of hypertension is not occurring at an optimum level for pediatric patients. Hansen et al examined data on over 14,000 children via medical records with at least 3 blood pressure measurements (64). Of those, 3.6% met the criteria for hypertension. However, only 26% of those were actually diagnosed with hypertension. In all of the children with at least 1 blood pressure measurement documenting elevated blood pressure only 9% had a subsequent blood pressure recorded to determine if the elevation was persistent. This means that measurement of blood pressure, appropriate interpretation, and clinical intervention must be more systematically applied in pediatric primary care.
Blood pressure elevation in children and adolescents has been demonstrated to be associated with early atherosclerosis in autopsy studies (3,5) and has also been shown to be related to increased left ventricular mass. For example, Daniels et al showed that 8% of children and adolescents with hypertension already had left ventricular mass index elevated to a level that is associated with a 4 fold increased risk of CVD in adults with hypertension (65). Lande et al have also described problems with neurocognitive function in children with hypertension (66). These results underscore the clinical importance of blood pressure elevation in children and adolescents. It is clear that hypertension is already having an impact on the heart and vasculature even at an early age. Initial treatment should focus on weight loss if obesity is present and other non-pharmacologic approaches. Couch et al have shown that a DASH type diet can be successful in reducing blood pressure even without a reduction in BMI in adolescents (67). For those patients in whom lifestyle change is not effective, pharmacologic intervention may be needed. There is now substantial clinical trial evidence that pharmacologic agents from a variety of classes can be safe and effective in lowering elevated blood pressure in children and adolescents (55). Unfortunately, there are no studies that document comparative effectiveness of one agent or one class of agents over another. This means that several classes including diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers and beta adrenergic blockers could be chosen as first-line agents. There are preliminary data demonstrating that pharmacologic treatment can be effective in lowering left ventricular mass as well as blood pressure in children (68).
It is important to include blood pressure measurement as part of a cardiovascular risk assessment for children. Blood pressure should be a routine part of health maintenance visits starting at age 3 years. This should allow better lifetime control of blood pressure and lower risk for the development of CVD.
Over the past forty years, data have accumulated linking adverse levels and patterns of lipids and lipoproteins to initiation and progression of the atherosclerotic process in children and adolescents. However, no multi-decade, longitudinal population-based studies have been conducted linking absolute levels of lipids and lipoproteins in childhood to incident CVD in adult life, and no randomized controlled trials have demonstrated that reducing atherogenic lipids and lipoproteins in early life prevents CVD in adulthood. Several lines of evidence, however, clearly support the need for primary prevention, including reduction of adverse levels of lipids and lipoproteins beginning early in life. This evidence includes the natural history observed for individuals with genetic dyslipidemias, such as homozygous familial hypercholesterolemia in whom LDL-C levels are quite high, and there is substantial increased risk of evolving atherosclerotic cardiovascular disease.
Post-mortem studies conducted as part of the Bogalusa Heart Study and the PDAY Study have demonstrated that early atherosclerotic lesions (fatty streaks) and advanced lesions (fibrous plaques) are significantly related to elevations in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), and low levels of HDL-C, as well as to the presence and intensity of other potentially modifiable risk factors including obesity, hypertension and cigarette smoking (4,5,69). In subsequent analyses using a risk score derived from these results, non-HDL-C was found to be the major correlate of coronary atherosclerosis, with a 30 mg/dL increase in non-HDL-C equivalent to 2 years of vascular aging (70). Non-invasive imaging studies have also been used to examine the association of risk factors for CVD and vascular structure and function in childhood and adolescence and atherosclerosis in young adult life. In the Muscatine Study, a longitudinal, observational study of CVD risk factors in children and youth, carotid ultrasound in adults (33–42 years of age) indicated that CIMT was positively associated with levels of TC and BMI measured in childhood (7). Similar results were observed in the Bogalusa Heart Study where childhood LDL-C and BMI were found to predict increased CIMT in adulthood (71). In the Young Finns Study, a population-based prospective cohort study, associations between risk factor exposures in adolescence including LDL-C, BMI, cigarette smoking and systolic blood pressure predicted CIMT in adulthood independent of adult risk factor levels (8). Results of other imaging studies designed to assess sub-clinical atherosclerosis reaffirm these observations indicating that abnormal levels of atherogenic lipids and lipoproteins in childhood and adolescence are associated with endothelial dysfunction and coronary artery calcium as well as increased CIMT (72,73,74).
Taken together, the results of pathology and imaging studies indicate that adverse levels of lipids and lipoproteins (as well as other potentially modifiable established risk factors) are associated with accelerated atherosclerotic processes in childhood and adulthood and point to the importance of primordial and primary prevention beginning in early life.
Data from the National Health and Nutrition Examination Survey (NHANES) for 1999–2006 indicate that the prevalence of abnormal lipid levels among all youths aged 12–19 years was 20.3% (75). Abnormal serum lipid levels were classified based on cutoff points suggested in AAP and American Heart Association (AHA) guidelines (76,39): high LDL-C (>/= 130 mg/dL; low HDL-C (</= 35 mg/dL); and high triglyceride levels (>/= 150 mg/dL). Of note, the prevalence varied by BMI; 14.2% of normal weight, 22.3% of overweight and 42.9% of obese youths had at least one abnormal lipid level (75).
Tracking of lipids and lipoproteins, particularly TC and LDL-C, has also been documented in children from diverse racial/ethnic groups and is particularly evident in the upper and lower extremes of the distribution. In the Muscatine study, for example, 75% of children who were 5 to 18 years of age at baseline and had TC levels greater than the 90th percentile had elevated TC (>/= 200 mg/dL) at 20–25 years of age (77,78). The Bogalusa Heart Study reported that approximately 70% of children with elevated TC in childhood persisted with elevated levels in adulthood (79). Tracking is relevant to primary prevention because of the potential for identifying children at risk for CVD early in life.
Data from the Lipid Research Clinics (LRC) indicate that serum lipids and lipoproteins increase throughout the first 2 years of life and approximate young adult levels by 2 years of age (80). These observations of primarily non-Hispanic whites and blacks contributed to the first guidelines issued by NHLBI (National Cholesterol Education Panel {NCEP}) recommending selective screening for high-risk children after 2 years of age when lipids and lipoproteins begin to track (81). Data from LRC (82) and NHANES (83) indicate that puberty/maturation has an important impact on levels of lipids and lipoproteins. In addition, patterns of change during this developmental period vary by sex and race/ethnicity (83). For example, in the 1988–1994 NHANES, for ages 4 to 19, the mean cholesterol was 165 mg/dL; at 9 to 11 years of age, however, age-specific values for mean cholesterol peaked at 171 mg/dL (83). Females had higher TC and LDL-C than males and, after pubertal development, had higher HDL-C than males. Black children had higher HDL-C and lower triglyceride concentrations than their non-Hispanic white and Hispanic counterparts (83).
Current recommendations for management of dyslipidemia in children and youth issued the by AAP (76) and the AHA (84) reflect accumulating evidence. There is currently lack of consensus, within the pediatric healthcare and research communities, regarding targeted versus universal screening. The AAP recommends a targeted approach to screening. Specifically, this approach recommends screening children (after the age of 2 years) who have a family history of premature CVD or who have parents with dyslipidemia. Screening is also recommended for children for whom family history is unknown or children who present with other CVD risk factors including hypertension, obesity and diabetes mellitus. Since the NCEP recommended targeted screening, research has shown that the approach has limitations for capturing children at-risk (8590). Studies of the effectiveness of the targeted approach found that 35% to 46% of children and youth had cholesterol levels measured on the basis of positive family history or elevated cholesterol levels (85,89,91). Other research has shown that 30% to 60% of children and adolescents with elevated cholesterol levels will be missed by this approach (84,90,92). Clearly, with the increase in prevalence of childhood obesity and its co-morbidities, the number of children who qualify for screening has increased (76).
Cutpoints recommended by NCEP (82) and AAP (76) used to identify children and adolescents with abnormal lipid and lipoprotein levels are presented in Table 4. These cutpoints are recommended for children 2 to 18 years of age. The AHA has recommended that triglyceride levels of >/= 150 mg/dL and HDL-C levels of </= 35 mg/dL be considered abnormal for children and adolescents (39). A single cutpoint for all children and youth may be limited by differences in age, sexual maturation and race/ethnicity (93). Supplemental Table 3 presents lipid and lipoprotein distributions in children and youth aged 4 to 19 years (83). These data were collected in 1981 prior to the increase in prevalence of obesity, with standardized protocols and using plasma specimens. As suggested by AAP, these tables and percentiles, stratified by age, are applicable in clinical practice.
Table 4
Table 4
Cut Points for Total Cholesterol and LDL- Concentrations in Children and Adolescents
Optimizing cholesterol levels and managing dyslipidemia in children and youth, includes both a population approach and individual/high risk approach (76,84). The population approach focuses on promoting optimal lipid levels in all children and youth and emphasizes health behaviors, a cornerstone of cardiovascular health promotion and risk reduction in childhood (36,94). While dietary restrictions are generally not recommended for children during the first 2 years of life, research has demonstrated the safety and efficacy of a diet consisting of total fat <30% of caloric intake, saturated fat of < 10% of intake and cholesterol intake of < 200 mg/dL day, with 1.5% cow’s milk after 12 months of age (95). More recent data from this study (Special Turku Risk Intervention Program {STRIP}) indicate beneficial effects in boys (lowering of LDL-C) and decreased prevalence of obesity in girls as compared with age-matched controls (95). The updated AHA dietary recommendations for children and youth (>/= 2 years of age) emphasize a balanced caloric intake with sufficient physical activity (60 minutes day) to achieve a normal weight and increased consumption of fruits, vegetables, whole grains, fish and low-fat dairy products (96). In addition, reductions of daily intake of trans-fatty acids, which are known to increase LDL-C levels, to < 1% of total intake is recommended (96). Recently, the AHA published strategies designed to assist healthcare providers in implementing these guidelines with children and families (97).
The individual approach focuses on children and adolescents identified as at risk because of family history of CVD or because they present with elevated levels of LDL-C or other major risk factors. Management for these patients initially involves therapeutic lifestyle change with emphasis on an adequate trial of dietary therapy (and increased physical activity). Research has shown that with good adherence to a saturated fat and cholesterol restricted diet (<7 % and < 200 mg/day respectively), LDL-C levels may be decreased 10–15% from baseline (81). Children with genetic dyslipidemias may present with baseline levels that cannot be reduced to suggested goals. Inter-individual differences in LDL-C levels in response to reduced intakes of saturated fat and cholesterol are well documented and attributable to a number of factors. Thus, after an adequate trial of therapeutic-dietary lifestyle change, some children and adolescents will be candidates for pharmacologic intervention. Other non-pharmacologic approaches to reducing adverse LDL-C have also been recommended for children and adolescents including additional fiber (calculated as the child’s age plus 5 g/day- up to a dose of 20 g/day at 15 years of age (84). Results have not been consistent across studies, but some show modest (~7%) reductions of LDL-C (84). Plant stanols and sterols, currently added to several food products including margarines, orange juice and cereal bars, have been shown to reduce cholesterol concentrations by approximately 5% to 10% with minimal adverse effects (84).
The AAP currently recommends that pharmacologic interventions be considered in children 8 years of age or older if LDL-C levels persist >/= 190 mg/dL (with no other risk factors present); and, for children with levels that persist at >/= 160 mg/dL and have other risk factors such as obesity, hypertension, positive family history of CVD and/or cigarette smoking. For children with diabetes, the AAP recommends pharmacologic intervention for children whose LDL-C levels are >/= 130 mg/dL (approximately the 95th percentile) (76). Medications including HMG CoA reductase inhibitors (statins), bile-acid-binding resins (98), and cholesterol absorption inhibitors are currently available for treatment of dyslipidemia in children and adolescents (84). Therapeutic lifestyle change remains a cornerstone of CVD risk reduction in childhood and should continue along with pharmacologic intervention in children and adolescents.
Tobacco use continues to be the single leading preventable cause of death in the United States and is responsible for approximately 4 million annual deaths worldwide (99,100). Since more than 80% of established adult smokers begin smoking before 18 years of age (101) and in view of the unequivocal evidence linking tobacco use, particularly cigarette use, and adverse health and developmental outcomes (99,102), prevention of smoking initiation and cessation interventions are essential components of cardiovascular health promotion and risk reduction for children and adolescents (37,39,103).
Recent population-based data on tobacco use among middle and high school students in the United States prompt a call to action for pediatric healthcare providers and public health advocates (104). Specifically, data from the Centers for Disease Control and Prevention National Youth Tobacco Survey (NYTS) indicated that from 2000–2009, the prevalence of tobacco use among middle school students declined (15.1% to 8.2%), as did cigarette use (11.0% to 5.2%) and cigarette smoking experimentation (29.8% to 15.0%). Similar trends were observed for high school students (tobacco use: 34.5% to 23.9%; cigarette use: 28.0% to 17.2%; smoking experimentation (39.4% to 30.1%). No change was observed, however, in susceptibility to initiate cigarette smoking as measured by self-report of openness to trying cigarette smoking (104,105). In view of 2006–2009 prevalence and susceptibility data, both individual /clinical and public health strategies must continue unabated in order to reduce tobacco use. Restrictions on advertising, promotion and availability of tobacco products to children and adolescents should be combined with implementation of evidence-based, community-wide, comprehensive tobacco control policies (106,107).
The American Academy of Pediatrics Committee on Environmental Health called attention to the health hazards of Environmental Tobacco Smoke (ETS) in 1997 with evidence-based recommendations for pediatricians and child health care providers (108). ETS in childhood has been linked with acute and chronic respiratory conditions, middle ear effusions, risk factors and CVD processes (i.e., dyslipidemia, impaired endothelial function) and increased risk for selected cancers in adulthood (102). The adverse effects of intrauterine exposure to tobacco smoke on fetal and childhood development and overall health have also been well-documented including small birth-weight for gestational age and associations with selected behavioral and cognitive-information processing problems (102).
Smoking prevention and cessation interventions are effective in adults (103,109,110). Theory-based behavioral interventions are central to prevention of initiation and smoking cessation, and are generally applicable to children and youth although the evidence base is not as substantial. Office-based counseling directed at children and youth for prevention or cessation of tobacco use has been a cornerstone of cardiovascular health promotion and risk reduction and general pediatric preventive care (37,39).
Christakis and colleagues (110) conducted a systematic review of smoking prevention interventions delivered by healthcare providers; one study showed a significant positive effect on prevention of smoking initiation. A more recent systematic review of family-based smoking prevention interventions that included 14 randomized controlled trials (RCTs) (111) showed that 4 of the 9 RCTs that tested a multi-component family intervention and included a control group demonstrated significant positive effects while one of the 5 that tested a family intervention versus a school-based intervention had a significant positive outcome. Overall, a significantly lower rate of smoking initiation was achieved in approximately 40% of interventions. The quality of the implementation of the intervention and the amount of training of the implementer were related to positive outcomes; however, the number of intervention sessions was not. More recently, Pbert and colleagues completed an RCT designed to examine the effect of a pediatric practice- based smoking prevention and cessation intervention for adolescents (112). The provider- and peer-delivered intervention was based on the 5A Model (ask, advise, assess, assist, arrange) and consisted of brief counseling by the pediatric provider followed by 1 visit and 4 telephone calls by older peer counselors. Results indicated that compared with usual care, nonsmokers who received the provider- and peer delivered intervention were significantly more likely to self-report having remained abstinent at 6- and 12- month follow-up. Smokers who received the intervention, however, were more likely to self-report having quit at the 6-month but not the 12-month follow-up. Methodological limitations notwithstanding including self-report of abstinence, the results support the feasibility and short-term efficacy of theory-based multi-component interventions for prevention of smoking initiation and smoking cessation in primary care pediatric office settings. The results also underscore the need for prevention of initiation of smoking (112). Adding to the need for emphasis on prevention of smoking initiation in pediatric primary care settings are the conflicting results reported in recent systematic reviews of the benefits of office-based counseling on smoking cessation (113). This Cochrane review found that interventions that used pharmacologic aids were not effective; however, those that incorporated behavioral change strategies including motivational interviewing and stages of change achieved significant positive results at 6 month follow-up. Additional research on the efficacy and effectiveness of combining behavioral change strategies and pharmacotherapy for long term abstinence in adolescent smokers is warranted.
Evidence supports the need for both individual/clinical and population -based approaches to prevention of smoking initiation and interventions for smoking cessation for children and youth. Current recommendations for pediatric healthcare providers emphasize a developmental approach with assessment of smoking status at every well child visit (37,39). Parents and guardians are advised to maintain a smoke free home environment and avoid exposure to second-hand smoke in other environments. For infants and young children, intervention is directed at parents/guardians and others in the child’s household who smoke. Parents/guardians who smoke should be advised of the immediate health risks to their children and motivated to quit using behavioral prescriptions such as motivational interviewing, stages of change and/or the 5 A model, and referred to smoking cessation programs if appropriate. During the school-age years, assessment of smoking status with clear, firm and consistent messages about the importance of remaining smoke-free is advised. Five strategies for discussing smoking with children are suggested for pediatric healthcare providers. First, encourage young children to actively avoid environmental smoke whenever possible. Second, emphasize the importance of not experimenting with smoking - “not even a puff”. Third, point out the harmful health consequences of smoking and the addictive habit-forming qualities of nicotine. Fourth, present information to counter the myths of media influences (i.e., smoking is enjoyable). Fifth, pediatricians and pediatric health care providers, powerful role models for children and youth, are advised to deliver nonsmoking messages in clinical encounters, educational materials in the clinical/office-based setting, and advocate for efforts designed to reduce smoking initiation in community-based settings (37).
In counseling adolescents, a group most at risk for smoking initiation, pediatric health care providers are advised to assess personal smoking history at every non-urgent encounter and provide clear consistent messages regarding non-smoking. For adolescent smokers, ongoing support and counseling either personally or through community-based smoking cessation programs will most likely yield positive outcomes. Resources such as quitline numbers and community-based cessation programs as well as information on pharmacotherapy for cessation should be made readily available (37).
It is clear that risk factors for atherosclerotic CVD can develop during childhood and adolescence. This results from both genetic and environmental factors. When risk factors do develop at an early age, they are likely to track over time, maintaining a high risk status. This tracking is reinforced by ongoing and new adverse health behaviors.
This means that the development of cardiovascular disease has its origins in families, and that approaches to prevention must be directed at the developing child and adolescent and their family environment. Pediatricians and family physicians should view the prevention of risk factor development (primordial prevention) and the development of atherosclerotic lesions (primary prevention) as an important responsibility. This paper has outlined the main risk factors of concern. Healthcare providers should view this from an integrated perspective, meaning that each risk factor and the behaviors underlying it should be addressed using a developmental approach at every health maintenance visit.
Kavey et al (39) have presented a blue print for an integrated approach to pediatric primordial and primary prevention of atherosclerotic CVD. This approach is presented in Table 5. Using this approach should maximize opportunities for prevention. This improves the likelihood that children and adolescents will maintain low risk status into young adulthood.
Table 5
Table 5
Schedule for Integrated Cardiovascular Promotion in Children
Prevention of atherosclerotic CVD is best achieved by maintaining cardiovascular health. While this is challenging, it can be achieved by instituting and maintaining optimum health behaviors early in life and stressing improvement of the family environment as the most important strategy to achieve these goals.
Supplementary Material
Footnotes
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Disclosures
Stephen R. Daniels:
Consultant/Advisory Board: Merck, Shering-Plough, Amount: < $10,000
Charlotte A. Pratt: No disclosures
Laura L. Hayman:
Research Grant:
Amount: >= $10,000
NIH Improving Fitness in Children at Increased Cardiometabolic Risk Harvard Catalyst, IU56CA11 9635-01 Family Health Behaviors, Amount: >= $10,000
Science Moment UMASS Med Capacity building in Boston examines impact of behavioral lifestyle interventions on obesity-cardiometabolic risk in adolescents, Amount: >= $10,000
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