Childhood obesity and cardiovascular disease

Abstract

Childhood obesity has reached epidemic proportions. Many of these children have risk factors for later disease, including cardiovascular disease. For optimal cardiovascular health, health care professionals must be able to identify children and youth at risk and provide appropriate support as needed. The present article reviews the current medical literature on obesity and cardiovascular disease risk factors in the paediatric population, the long-term cardiovascular consequences of childhood obesity and the importance of early life. Recommendations promoting optimal cardiovascular health in all children and youth are discussed.

Childhood obesity has reached epidemic proportions worldwide (1). In Canada, 26% of children two to 17 years of age are considered to be overweight (body mass index [BMI] at the 85th percentile or greater) or obese (BMI at the 95th percentile or greater) (2). What is particularly worrisome is that many of these children have risk factors for later disease, including cardiovascular disease (CVD), and early signs of atherosclerosis (3). Not only are children presenting with risk factors for later disease, they are often now diagnosed with what were traditionally considered to be adult diseases, such as type 2 diabetes (4). The impact that childhood obesity has on an individual’s health, both in the short and long term, and the potential effect on the health care system in the future is so great that it has become one of the most critical public health issues today (5). Because of the potential consequences associated with obesity, it is vital for health care professionals to identify children at risk and provide appropriate help as needed.

ACCELERATED ATHEROSCLEROSIS

CVD is the leading cause of death in Canada. Evidence links known risk factors in adults to accelerated atherosclerosis. The atherosclerotic process has been shown to begin in childhood, and much of our understanding of the childhood precursors to adult CVD is based on pathology studies of children and youth. For most children, atherosclerosis is usually subclinical and progression is slow. In some children, however, the atherosclerotic process progresses more rapidly and is mediated by the same risk factors that are identified in adults. Pathological studies have shown that the extent of atherosclerosis is associated with the number and severity of the risk factors (6). Based on these studies, childhood obesity is associated with an earlier appearance of these lesions. Fatty streaks and fibrous plaques found in children who died from other causes were associated with previously measured BMIs (6–8).

The Pathological Determinants of Atherosclerosis in Youth Study (8) examined aortic and coronary artery pathology of approximately 3000 individuals, 15 to 34 years of age, who died from noncardiac-related causes. Risk scores were developed using coronary artery disease (CAD) risk factors (sex, age, serum lipoprotein concentrations, smoking, hypertension, obesity and hyperglycemia) to estimate the probability of advanced atherosclerosis lesions. Further studies (8,9) determined that these risk scores were also associated with earlier atherosclerotic lesions.

Recently, newer noninvasive techniques have made direct observation of CVD and its precursors in children and youth possible (10). One of the first abnormalities seen is endothelial dysfunction, which is a marker for arterial damage (11–13). Carotid intima-media thickening (IMT) is thought to be a marker for generalized atherosclerosis and has been studied using specialized ultrasonography. In adults, carotid IMT is associated with obesity and other CVD risk factors (14). In children, carotid IMT is also associated with obesity, hypercholesterolemia and hypertension in some studies (15). Recently, a study (16) examined the carotid IMT in over 70 children (57% were obese) with an average age of 13 years, and found that 75% of the cohort had advanced vascular age or arteries more typical of adults 45 years of age. The vascular age was advanced the furthest in children with obesity and high triglyceride levels. The Muscatine Heart Study (17) found BMI levels in children and adolescents eight to 18 years of age that were associated with carotid IMT in adults 33 to 42 years of age, but the findings were only significant in females.

The Cardiovascular Risk in Young Finns Study (18) measured CAD risk factors in a population-based cohort in almost 1300 individuals, 12 to 24 years of age, at the start of the study, and they followed these individuals for 15 years. At the end of the study, they measured carotid artery IMT. They found that the Pathological Determinants of Atherosclerosis in Youth risk score and the change in risk score over the 15 years were independent predictors of carotid IMT (18).

OBESITY AND CVD RISK FACTORS IN THE PAEDIATRIC POPULATION

Cardiovascular complications of excess weight in children include dyslipidemia, hypertension and insulin resistance. In adults, there is emerging evidence that obesity itself may be an independent risk factor, although the evidence directly linking obesity as an independent risk factor to CVD in children is not yet as strong (19).

Dyslipidemia

Children who are overweight or obese are at an increased risk of having an abnormal lipid profile, especially if they have an increased body fat percentage (20) or waist circumference (21–24). The lipid profile usually shows high triglyceride levels and low high-density lipoprotein cholesterol levels (22–24). Low-density lipoprotein cholesterol levels are usually normal, but there may be qualitative changes in the low-density lipoprotein particles so that they become smaller, more dense and more atherogenic (19).

Hypertension

Obese children are three times more likely to have hypertension than nonobese children (15,25,26). This is more likely to be seen during ambulatory blood pressure (BP) monitoring because regular office BP measurements may miss it (26,27). Accurate BP assessment is essential, and ambulatory BP monitoring is believed to be more accurate than clinical BP monitoring because it more precisely characterizes BP changes throughout the day (27).

Insulin resistance and the metabolic syndrome

In adults, the metabolic syndrome generally refers to a clustering of metabolic risk factors, including hypertension, dyslipidemia, abnormal glucose tolerance and abdominal obesity. This clustering of multiple risk factors also occurs in children, with obese children being at greatest risk (28). In adults, the metabolic syndrome is known to increase the risk of CVD. The long-term impact in children is not as clear, although being overweight during childhood is associated with high levels of insulin, lipids and BP in young adulthood (19).

The Bogalusa Heart Study (29), a long-term population-based study that tracked the natural history of CAD in Bogalusa, Louisiana (USA), showed a nonlinear relationship between BMI and abnormal lipid levels, hyperinsulinemia and hypertension in children. Among the five- to 17-year-old children studied, the prevalence of these risk factors increased dramatically at very high BMI levels. In the Bogalusa Heart Study, BMI was most strongly associated with insulin levels, with 40% of children with a BMI of greater than the 99th percentile having a high insulin level (29). Insulin resistance and hyperinsulinemia may be precursors of type 2 diabetes. It is well documented that the prevalence of type 2 diabetes has increased dramatically in youth; most of those diagnosed in childhood are obese (4).

Other nontraditional risk factors

Childhood obesity is also associated with other CVD risk factors, such as left ventricular hypertrophy (30), and increased levels of homocysteine, C-reactive protein and lipoprotein (31,32). Certain phenotypes may also predict CVD risk. A study by Zhu et al (33) showed that youth who were overweight had increased CVD risks and those who were obese had even greater risks compared with youth who had normal weights. The measures that predicted CVD risk included left ventricular mass index, cardiac output, overnight sodium excretion, and ambulatory and nocturnal BP measurements.

LONG-TERM CVD CONSEQUENCES OF CHILDHOOD OBESITY

Tracking into adulthood

Evidence shows that there is a moderate degree of tracking of BMI from childhood into adulthood, with an average of 40% (and up to 80%) of overweight children becoming obese as adults (34,35). It is well known that adult obesity is associated with an increased prevalence of risk factors for CVD. The relation of childhood obesity to CVD risk factors in adults has also been studied (36). Adults who have been obese as children may have an even greater prevalence of risk factors for CVD, including hypertension and dyslipidemia (37), compared with those who had normal weight as children. It has also been shown that childhood obesity and central adiposity increased the risk for the metabolic syndrome in adulthood (38).

Some argue that the increased prevalence of risk factors in adulthood may be partly due to their weight status as adults. Indeed, some of the associations between weight status in children and CVD risk factors in adults are weak; this may be partially due to the persistence of childhood obesity into adulthood (3). More studies are needed to determine the full effect of childhood obesity on CVD risk factors later in life.

Adult CAD

Several studies have examined the association of childhood obesity to CAD in adults, and have suggested that childhood obesity increases the risk of CAD in adulthood. A study by Baker et al (39) found a significant effect of childhood BMI on the cardiovascular events in adulthood, with the risk of fatal and nonfatal cardiovascular events in adulthood increasing linearly with BMI at each age. In the Harvard Growth Study (40), weight in childhood also had an independent effect on CAD risk. Some argue that it is the persistence of obesity into adulthood that matters and their studies (41) have found that the BMI in adulthood was more important.

CVD AND THE IMPORTANCE OF EARLY LIFE

Most studies of childhood precursors of adult CVD focus on children and youth. More recent studies (42) have investigated the origins of childhood and adulthood obesity and CVD risk factors during fetal life and infancy. This early environmental influence on later health is often referred to as imprinting or programming, and is defined by Lucas et al (43) as “the idea that stimuli or insults during critical or sensitive periods in early life can have lifetime consequences”. Three of these critical periods occur during fetal life, the first year of life and at the time of adiposity rebound in early childhood.

Fetal life

Evidence now shows that low birth weight is associated with an increased prevalence of CVD risk factors and CAD later in life. Studies (44–47) have demonstrated an association between low birth weight (and high birth weight in some studies) and hypertension, dyslipidemia, insulin resistance and the metabolic syndrome. It has been proposed that the association between birth weight and CVD risk is secondary to fetal malnutrition, leading to a programmed response in the fetus. This ‘fetal origins hypothesis’ suggests that an unfavourable environment in utero permanently changes the physiology of the fetus. However, it is not clear whether this is due to the fetus’s response to the malnutrition or to genetic factors that influence both birth weight and CVD risk factors. Twin studies (48) have shown that they both likely play a role.

The critical first year

Several observational studies (49–57) have reported that rapid weight gain in infancy may also be a risk factor for later obesity. In one study (52), postnatal weight gain was the most significant factor associated with CVD risk factors. However, not all studies have been consistent and more work needs to be done in this area. Of course, it is important for infants to have sufficient weight gain during infancy; undernutrition in infancy is associated with infant morbidity and mortality. What is not yet clear is whether weight gain above the expected is associated with later problems. Even for children born with intrauterine growth restriction, it is unclear whether rapid weight gain or catch-up growth is associated with later development of obesity.

The benefits of breastfeeding are great, and the observational studies have reported that breastfeeding may have a protective effect on later obesity. A recent meta-analysis (58) showed an association between longer duration of breastfeeding and decreased risk of being overweight. Two other systematic reviews (59,60) found similar results. Other observational studies (61–68) have been done since, and the results are mixed, with approximately 50% finding an association and the others finding no association.

An article by Stettler (69) reviewed the evidence for rapid infancy weight gain and breastfeeding as they related to later obesity. It is an excellent article for those who want more detailed information.

Early adiposity rebound

Body composition changes with normal growth. During the first year of life, there is a rapid increase in BMI. The BMI then declines and reaches a minimum at around five to six years of age (on average). There is then a gradual increase in BMI through adolescence. Adiposity rebound (AR) corresponds to the second rise in the BMI curve following the point at which the BMI was at its lowest. Several studies (70,71) have shown that the time of AR may be a critical period in childhood for the development of obesity and the earlier the AR, the greater the risk of obesity later.

RECOMMENDATIONS

For most children, the degree of atherosclerotic vascular change is minimal. Therefore, for these children, the focus should be on prevention of accelerated atherosclerosis and promotion of optimal cardiovascular health. Encouraging healthy active living (eating well, being physically active and feeling good about oneself) is the cornerstone. The following Web sites provide useful information and may help the health professional when promoting and counselling about healthy active living – The Canadian Paediatric Society <www.cps.ca> (click on ‘Healthy Active Living’ under ‘Children’s Health Topics’), Dietitians of Canada <www.dietitians.ca/healthystart> and American Academy of Pediatrics <www.aap.org/obesity>.

All children and their families, no matter what their weight, benefit from eating a healthy diet and being physically active. A diet that includes plenty of fruits, vegetables and whole grains, is low in saturated fat and is trans fat-free is the best for prevention of CVD. The latest Canada’s Food Guide published last year – Health Canada <www.hc-sc.gc.ca/fn-an/food-guide-aliment> – provides lots of helpful information and now includes more details for younger children as well. For optimal heart health, daily physical activity must be included. For children older than two years of age, it is recommended that they get at least 90 min of physical activity each day. The Physical Activity Guides for Children and Youth – Public Health Agency of Canada <www.paguide.com> – give more information on how to decrease sedentary activity, promote physical activity and how to gradually build this up in children who are not active.

For those children with risk factors associated with accelerated atherosclerosis, healthy active living also needs to be encouraged. They may need additional investigations and/or therapies, depending on the situation. A complete history and physical examination will help determine which children are at greater risk and may need further testing. The 2006 Canadian Clinical Practice Guidelines (CCPG) on the Management and Prevention of Obesity in Adults and Children provide useful information and can be found on the Canadian Obesity Network Web site <www.obesitynetwork.ca> as well as the Canadian Medical Association Journal Web site <www.cmaj.ca>.

Recommendations for optimal cardiovascular health

• Promote healthy active living for everyone, no matter what their body size.

• Understand the nature of obesity and the complex interactions among genetics, physiology and the environment in its etiology.

• Use a nonjudgmental, respectful, sensitive approach and be mindful that potential solutions cannot be recommended without consideration of well-being after treatment.

• Perform accurate height and weight measurements on all children during routine visits. Calculate and plot BMIs on everyone. Growth curves are available on the Centers for Disease Control and Prevention Web site <www.cdc.gov/growthcharts/>. Children with a BMI greater than the 95th percentile are considered obese and are at the greatest risk. The main intervention is lifestyle modification with healthy active living as the key message. Other interventions, including weight loss medication, are more controversial. The CCPG mentioned above provides a lot of useful information on the management and prevention of obesity in children. In 2007, the American Academy of Pediatrics published recommendations (72) for the treatment of child and adolescent overweight and obesity.

• Waist circumference measurements are recommended in the adult literature and are now also recommended in the paediatric literature. Normative values are available (73,74). However, waist circumference measurements can be technically difficult and inaccurate in many cases. Therefore, most paediatric practitioners may find it most helpful to use the BMI alone rather than waist circumference measurements, until more information is available.

• BP should be measured in all children after three years of age during all routine medical visits. It is critical to use the proper-sized cuff and technique, as well as the appropriate BP charts. An excellent reference from the American Heart Association provides these guidelines and charts (75).

• The American Heart Association and the American Academy of Pediatrics recommend performing targeted screening of fasting lipids in children older than two years of age with a family history of dyslipidemia or premature CVD. They also recommend screening children who are overweight or obese (76,77). Many argue that this degree of screening may be excessive and may use a lot of health care resources. Some experts have also questioned the American Academy of Pediatrics recommendations for the use of certain medical therapies at a very young age (78). The CCPG recommend determining a lipid profile in all overweight and obese children starting at 10 years of age.

• The recommendations from the CCPG and the Canadian Diabetes Association’s 2008 Clinical Practice Guidelines <www.diabetes.ca> state that starting at 10 years of age (earlier if puberty is established), children should have a fasting plasma glucose test every two years if they have two or more risk factors These risk factors include children who are overweight or obese, have a family history of type 2 diabetes, have a predisposition according to ethnicity (such as First Nations, South Asian and African Canadians) or have signs of insulin resistance, such as acanthosis nigricans.

• Promote built environments (the physical and social aspects of a community’s structure) that encourage and support healthy living.

The American Heart Association’s Committee on Atherosclerosis, Hypertension, and Obesity in the Young (76) has published a statement for health professionals to use as a guide to “provide strategies for promoting cardiovascular health that can be integrated into the comprehensive pediatric care of children”. This document gives background information, methods of assessment and possible interventions for major areas affecting cardiovascular health, including obesity, hypertension, insulin resistance, hyperlipidemia and physical activity. They also provide a schedule for ‘Integrated Cardiovascular Health Promotion in Children’, which gives recommendations for identifying risk factors, as well as education, intervention and follow-up at specific times throughout a child’s life (76).

CONCLUSION

The long-term implications of the childhood obesity epidemic and its consequences are extremely serious. Childhood obesity has a great influence on risk factors for CVD and the development of atherosclerosis. Given the obesity trends and the associated risks, some predict that by 2020, the prevalence of heart disease will increase by 16% and heart disease deaths by 19% in adults 35 to 50 years of age, unless something is done (77). Fortunately, some studies have shown that lifestyle interventions and/or medications may have an impact on some of these risk factors and markers of atherosclerosis. Therefore, it may be possible to reverse or at least minimize the risks with proper interventions in many of these children. Of course, even with our best efforts, there will still be many children who will grow up with obesity and its associated risk factors from an early age.

The potential short- and long-term consequences of childhood obesity are significant. Health professionals must teach children and their families the skills and habits that support a healthy active lifestyle, no matter what their body size. It is imperative that they identify children with CVD risk factors so that they can provide proper counselling and management. Of course, we need effective interventions aimed at both the treatment and prevention of obesity and much more research is needed in this area of major public health importance. Hopefully, with the commitment of health professionals and others, we will see a reversal of these trends in the years to come.