KEY PERSPECTIVES

What is novel?

Primordial prevention of atherosclerotic cardiovascular disease (ASCVD) may be defined as the prevention of the onset of its modifiable risk factors, which have their origins in childhood. As ASCVD may begin in prenatal development with progression throughout childhood, each additional risk factor increases the likelihood of developing ASCVD in a linear fashion. The presence of ASCVD risk factors during childhood increases the risk of ASCVD prevalence and adverse cardiovascular events during adulthood.

What are the clinical and/or research implications?

A greater clinical focus on preventing childhood obesity, physical inactivity, hypercholesterolemia, hypertension, and hyperglycemia may reduce the risk of adverse cardiovascular events and mortality in adults. A multilevel approach involving individual, community, and population-wide components would likely be the most effective in preventing the early onset of ASCVD risk factors. Interventions targeting children and adolescents of low health literacy, low socioeconomic status, and/or minority status may have the strongest population-wide effect on ASCVD risk factor prevention, given that these groups are disproportionately affected.

The global prevalence of atherosclerotic cardiovascular disease (ASCVD) and its associated disabilities has nearly doubled over the past 30 yr.1 Some have called for a greater focus on primordial prevention to decrease the burden of ASCVD.2,3 In contrast to primary prevention, which treats risk factors to prevent progression to ASCVD, primordial prevention focuses on lifestyle modification to prevent the initial development of modifiable risk factors.2–4 These risk factors are smoking, physical inactivity, overweight and obesity, total cholesterol >130 mg/dL, blood pressure (BP) >120/80 mm Hg, and fasting blood glucose >100 mg/dL without medications.3,5–7

The American Heart Association (AHA) has targeted these risk factors, as well as guideline-based diet, physical activity (PA), and sleep as “Life's Essential 8” for ideal cardiovascular health.6 For the purposes of this article, childhood sleep will not be discussed as an independent risk factor for ASCVD, given that the majority of evidence supporting its link to ASCVD was derived from studies in adults.6 Five of the “Life's Essential 8” components were used to design a scale of optimal, intermediate, and poor cardiovascular health by O'Hearn et al,8 who found that the number of adults with optimal cardiovascular health has declined since 2000. They also found that minority ethnic groups are less likely to have optimal cardiovascular health.

Although studies consistently identify age as the strongest nonmodifiable risk factor for the development of ASCVD,9 lifestyle factors that define ideal cardiovascular health are protective if adopted early. For instance, the Tsimane tribe, a native group of the Bolivian Amazon, has the lowest documented rates of ASCVD in the modern world. Kaplan et al10 used coronary artery calcium scoring to measure the coronary disease burden among Tsimane adults aged 40-85 yr. They found that 85% of adults had no coronary artery calcium, 13% had calcium scores <100 (low risk), and 3% had calcium scores ≥100 (moderate to high risk). They also found that the development of elevated calcium scores in Tsimane adults occurred about 24 yr later in life than in US adults.10,11 Tsimane adults smoked tobacco less frequently than US adults.10,12 Tsimane participants had a mean body mass index (BMI) of 24.1 kg/m2 and mean body fat percentage of 22.1%.10 Because of a low-fat diet, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were lower in the Tsimane population than in the US population: the mean LDL-C level was 91 mg/dL and the mean HDL-C was 39.5 mg/dL.10 The mean BP of the Tsimane people was 116/73 mm Hg, with the prevalence of hypertension being 3.9% in women and 5.2% in men.10,13 Fasting blood glucose levels in the diabetic range were rare.10 Based on these findings, the Tsimane people may be considered a model for ideal cardiovascular health.6

Large-scale cohort studies indicate that cumulative modifiable cardiovascular risk factors developed during childhood and adolescence increase the risk of adverse cardiovascular events in adulthood.14 Therefore, primordial prevention efforts must begin in childhood to solidify healthy lifestyle behaviors throughout adulthood. This review describes (1) the association between smoking, adiposity, hypercholesterolemia, hypertension, and hyperglycemia in childhood and the development of ASCVD, and (2) interventions studied, including healthy dietary patterns and PA, to prevent the development of these risk factors.

LITERATURE REVIEW PRENATAL RISK FACTORS

Atherosclerosis may begin during prenatal development. A cross-sectional study by Napoli et al15 examined the prevalence of lipid accumulation and fatty streaks in the aortas of spontaneously aborted fetuses. Lipid accumulation progresses to fatty streaks, which represent the early stages of atherosclerotic lesion development that can later progress into plaques. The authors found that endothelial lipid accumulation was present in the aortas of 77.8% of fetuses from mothers with chronic hypercholesterolemia (present before pregnancy) and 75.6% of fetuses from mothers with gestational hypercholesterolemia (developed during pregnancy) independent of smoking status, which were both significantly higher than in fetuses from normocholesterolemic (total cholesterol <185-200 mg/dL depending on maternal age) mothers (63.3%).15 A similar study found an increased prevalence of fatty streaks in fetuses and infants of smoking mothers.16 Lifestyle modification, including a low glycemic-index diet, a low-sodium heart-healthy diet, and increased aerobic exercise during pregnancy, may have modest beneficial effects on maternal cholesterol levels.17–19 Maternal smoking cessation, even in late pregnancy, is associated with improvements in infant birth weight though an association with fetal fatty streaks has not been explored.20

Hypertension during pregnancy may also confer risk. A cohort study of UK children aged 9-12 yr reported that children born to mothers with either gestational hypertension or preeclampsia had a systolic BP of 1.82-2.04 mm Hg higher than children of mothers without these conditions.21 Hypertension in either parent increases the risk of the offspring of developing high BP, obesity, visceral adiposity, and metabolic syndrome in adolescence.22 Reducing maternal smoking during pregnancy may have a modest BP-lowering effect in offspring.23 Dietary and lifestyle modifications during pregnancy improve maternal cardiovascular risk factors but have mixed effects on offspring BP and adiposity.23,24

CHILDHOOD RISK FACTORS

The development of ASCVD may begin in childhood, but lifestyle modification can prevent its initiation and progression.4,25 This is best illustrated by familial hypercholesterolemia, an autosomal dominant disorder of lipoprotein metabolism that, if left untreated, causes manifestations of ASCVD before the age of 55 yr.26 Healthy lifestyle habits and lipid-lowering pharmacotherapy (where indicated) immediately upon diagnosis reduce the risk of atherosclerosis progression and cardiovascular events to rates similar to the general population.26,27

Five large-scale cohort and cross-sectional population studies, beginning in the 1970s and 1980s, have demonstrated strong correlations between cardiovascular risk factors in childhood and the development of ASCVD in adulthood (Table). These are the Muscatine Heart Study, the Bogalusa Heart Study, the Young Finns Study, the Childhood Determinants of Adult Health Study, and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study. These studies will be referenced throughout this review.

Table - A summary of the Five Large-Scale Population Studies That Support the Association Between Modifiable Childhood ASCVD Risk Factors and Early ASCVD Development Study Methods Subjects Primary Exposures Primary Outcomes Muscatine Heart Study (Iowa, United States; 1970-1991)78 Prospective cohort study Initial cohort of 4829 (later 11 377) subjects 6-18 yr followed through adulthood Adiposity: BMI and triceps skinfold thickness
Total serum cholesterol and serum triglycerides
BP, systolic and diastolic Subclinical atherosclerosis markers: coronary artery calcium scores, C-IMT, and brachial artery flow-mediated dilatation
Risk factor prevalence into adulthood Bogalusa Heart Study (Louisiana, United States; 1972—present)5 Prospective cohort study with cross-sectional (survey and autopsy) components Initial cohort: 4238 children 2-14 yr with follow-up through adulthood
Now 11 737 participants Adiposity: BMI and skinfold thickness
Hemoglobin
BP, systolic and diastolic
Serum lipids
Dietary patterns including salt intake
Smoking status Subclinical atherosclerosis markers: Visual grading of the extent of fatty streaks, raised fibrous plaques, complicated lesions, and calcified lesions covering intimal surface of the aorta and coronary arteries
Risk factor prevalence and cardiovascular mortality in adulthood
Cardiovascular Risk in Young Finns Study
(Finland; 1978—present)37 Prospective cohort study 7349 boys and girls aged 3, 6, 9, 12, 15, and 18 yr followed through adulthood Adiposity: BMI, skinfold thickness, and waist and hip circumference
Smoking status
BP, systolic and diastolic
Serum lipids: total cholesterol, LDL-C, HDL-C, triglycerides, apo-A1, apo-B
Dietary patterns
Physical activity Subclinical atherosclerosis markers: C-IMT, carotid artery compliance, brachial artery flow-mediated dilatation, coronary artery calcium scoring, and arterial pulse wave velocity
Risk factor prevalence in adulthood Childhood Determinants of Adult Health study (Australia; 1985 —present)79 Prospective cohort study 8498 subjects, 7-15 yr with follow-up between 2004-2006 and 2009-2011 Adiposity: BMI
Serum lipids: total cholesterol, triglycerides, HDL-C, and LDL-C
BP, systolic and diastolic
Dietary patterns Subclinical atherosclerosis markers: C-IMT via ultrasonography, carotid elasticity, and brachial artery flow-mediated dilatation
Risk factor prevalence in adulthood Pathobiological Determinants of Atherosclerosis in Youth (PDAY) (9 distinct multinational centers; 1986-1996)31 Cross-sectional examination of postmortem risk factors and autopsy specimens from young people who died of external causes 2 876 subjects 15-34 yr Adiposity: BMI
Serum lipids: very low-density lipoprotein cholesterol (VLDL-C), LDL-C, and HDL-C
Cigarette smoking
Diabetes/impaired glucose tolerance
BP measured by renal artery intimal thickness Subclinical atherosclerosis markers: percentage of intimal surface area involved by lipid deposition (fatty streaks or raised lesions) in the aorta and right coronary artery

Abbreviations: Apo, apolipoprotein; BMI, body mass index; BP, blood pressure; C-IMT, carotid artery intima-media thickness; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

In an analysis by Juonala et al,28 data from four of the aforementioned studies were pooled to determine the association between childhood risk factors, age group, and carotid artery intima-media thickness (C-IMT) measured via ultrasonography. Increased C-IMT can be considered a surrogate for future atherosclerosis and cardiovascular events.29,30 This study demonstrated an association between the number of modifiable ASCVD risk factors in childhood (cholesterol, BP, and BMI), between ages 9-18 yr, and increased C-IMT during adulthood.28 Additional ancillary studies using Bogalusa and PDAY data likewise showed a positive linear association between number of ASCVD risk factors and extent of coronary and aortic atherosclerosis measured via histologic examination.5,31,32

The International Childhood Cardiovascular Consortium (i3C) prospective cohort study pooled 39 598 subjects between 3-19 yr from the cohorts mentioned previously.14 This study demonstrated increased linear risk of cardiovascular events, beginning as early as 40 yr, with each additional modifiable childhood ASCVD risk factor. They found that a higher combined-risk z score (an averaged measurement of the distance of each value from the mean) correlated with a higher risk of both fatal and nonfatal cardiovascular events in adulthood when stratified by age and sex.14 The remainder of this review will focus on the prevention of each risk factor individually.

Tobacco Smoking

Among adolescents and young adults, atherosclerotic lesions are more prevalent in smokers than in nonsmokers.5,31 The i3C study found that youth smoking increases the risk for fatal cardiovascular events (HR = 1.61: 95% CI, 1.21-2.13) and nonfatal cardiovascular events (HR = 1.70: 95% CI, 1.49-1.93) in adulthood.14 Tobacco use often begins in adolescence: data from the 2018 National Survey on Drug Use and Health demonstrated that 31.3% of cigarette smokers began smoking between ages 12-17 yr while 42.8% of smokers started between ages 18-20 yr.7 These data also identified a growing prevalence of e-Cigarette utilization among youth, which is associated with new cigarette smoking.7

Interventions to prevent smoking in children and adolescents have demonstrated benefit. A recent systematic review from the United States Preventative Task Force suggested that primary care–based educational and behavioral interventions significantly reduced the rate of smoking initiation in children aged 7-17 yr from 9.2% to 7.4%, when compared with usual care or no intervention.33 The same systematic review reported that behavioral interventions targeted at preventing the initiation of tobacco smoking were more effective than behavioral interventions targeted at tobacco cessation.33

School curriculum–based interventions to prevent smoking have demonstrated positive results. A Cochrane systematic review of school-based initiatives suggested more success in preventing smoking initiation in youth aged 5-18 yr after implementing curricula focused on a combination of social competence (ie, problem-solving, decision making, and coping strategies) and social influence (ie, dealing with peer-pressure and high-risk situations) when compared with no intervention or focused and singular curricula.34 Family-based initiatives may also reduce the incidence of youth smoking. A systematic review and meta-analysis by Thomas et al35 reported that smoking prevention programs involving both parents and children, especially when an authoritative parenting style was emphasized, reduced the incidence of adolescent smoking by up to 32%.

Population-based approaches are also effective. A combination of focused media and educational campaigns, higher taxes on tobacco products, and community restrictions on public smoking have strong evidence supporting their efficacy in preventing smoking.36 There is also evidence supporting the efficacy of including health warnings on cigarette packages, reducing the density of retail centers selling tobacco products around schools, and restrictions on advertising tobacco.36 A combination of individual- and population-level interventions may be the most effective in preventing smoking initiation.

Overweight and Obesity

Overweight and obesity in childhood contribute to the early development of atherosclerotic lesions, predict adult obesity, and are directly correlated with adverse cardiovascular outcomes in adulthood. In the pooled analysis by Juonala et al,28 BMI had a positive association with C-IMT in subjects aged 3, 9, 15, and 18 yr. Autopsy examination of Bogalusa participants showed a positive correlation (r= 0.48) between BMI and atherosclerotic lesion development.5 An analysis of the Young Finns cohort demonstrated a positive correlation (r= 0.46) between a high childhood BMI and a high adult BMI over a 30-yr period.37 Obesity in PDAY males aged 15-34 yr was independently associated with more extensive atherosclerotic lesions in coronary arteries.31 Based on i3C data, being overweight (HR = 1.61: 95% CI, 1.14-2.27) and obese (HR = 3.34: 95% CI, 2.42-4.60) during childhood portend increased risks of fatal cardiovascular events in adulthood.14 The prevalence of overweight and obesity in US children ages 12-19 yr, however, is 35.4% with a disproportionately higher percentage of children from low socioeconomic backgrounds and minority groups affected.7

The prevention of childhood obesity has been an area of research for decades, but interventions demonstrate mixed results. In infancy, breastfeeding reduces the risk of developing childhood obesity compared with formula feeding, and duration of breastfeeding may have a dose-response effect on reducing the risk of childhood obesity.38 Mothers who breastfeed may also be more responsive to the hunger and satiety cues of their toddlers, allowing for a greater degree of self-regulation in the child and a subsequent lower risk of overeating and weight gain.39 Interventions with modest improvement in breastfeeding rates have focused on a combination of education and support immediately postpartum.40

Community-based programs may also be effective. A Cochrane review evaluated 153 obesity prevention interventions from multiple countries using subjects from birth to 18 yr.41 The interventions took place in multiple settings: home, preschool, school, and health care. Combined diet and exercise interventions were effective in preventing obesity in ages 0-5 yr (mean BMI difference: −0.07 kg/m2, 95% CI, −0.14 to −0.01) and 6-12 yr (mean BMI difference: −0.10 kg/m2, 95% CI, −0.14 to −0.05) compared with controls. In the 13-18 yr age group, PA alone showed improvements in BMI when compared with controls (mean BMI difference: −1.53 kg/m2, 95% CI, −2.67 to −0.39), but dietary interventions showed no significant benefits.

Technology-based interventions for the prevention of overweight and obesity in children aged 1-18 yr have also been studied. Of the 22 trials evaluated by a meta-analysis, there were no significant differences in adiposity or weight outcomes in children receiving a technology-based intervention (including smartphone apps, websites, text messages, and video games) compared with controls.42 However, the measurements of engagement and adherence differed between trials. These variables should be targeted in future studies of technology-based interventions.

There are growing data supporting population-wide approaches to preventing childhood overweight and obesity. Other countries have successfully combined both media/educational campaigns and policy change including subsidizing healthful foods, increasing taxes on less healthful foods, and standardizing nutrition facts labeling on packaged foods.36 Large-scale US programs to date have lacked a policy change component and have therefore been less effective than the multilevel initiatives in other high-income countries. Limited US data suggest that subsidizing and lowering the prices of healthful foods, such as fresh produce, may improve the sales of said food items but do not necessarily increase their consumption.43 Taxation of unhealthful food items, such as sugar-sweetened beverages, is also associated with lower demand and consumption, which may decrease overall caloric intake in the population. However, these studies did not account for differences in socioeconomic status, nor did they examine outcomes related to BMI or ASCVD risk.44

Serum Cholesterol

Dyslipidemia is directly associated with the development and progression of ASCVD. The cumulative exposure to elevated apolipoprotein-B-containing lipids determines one's risk of having a cardiovascular event.45 Elevated LDL-C and triglyceride levels have a positive correlation with atherosclerotic lesion prevalence that persists from childhood through early adulthood while HDL-C levels have a negative correlation.5,31 Follow-up data from the Young Finns cohort after 12 and 27 yr also demonstrated positive correlations between elevated childhood serum cholesterol and triglycerides to elevated levels in adulthood (r= 0.51-0.56 and r= 0.27, respectively).37 Children from the i3C cohort with high and borderline-high total cholesterol have 1.5 (95% CI, 1.23-1.83) to 2.13 (95% CI, 1.60-2.83) times the risk of both fatal and nonfatal cardiovascular events in adulthood than children without. In addition, i3C children with high and borderline-high triglycerides have 1.69 (95% CI, 1.28-2.24) to 2.47 (95% CI, 1.89-3.24) times the risk than children with normal triglycerides.14

Dietary interventions are effective in preventing dyslipidemia. A meta-analysis found that decreased consumption of saturated and trans-fats was associated with lower total cholesterol and LDL-C in children between ages 2-19 yr.46 A longitudinal intervention in Finland, involving children and their families receiving counseling by a nutritionist from ages 5 mo to 20 yr, demonstrated reductions in saturated fat intake with concomitant reductions in LDL-C.47 Another family-oriented intervention involving regular education from a dietitian focused on improving the family food environment also achieved reductions in saturated fat intake.48 These family-oriented interventions, however, did not account for socioeconomic status. Programs focused on combined dietary and PA may also improve both LDL-C and HDL-C, but results are mixed.49

Plant-based dietary patterns, which limit or exclude animal-based foods, may prevent dyslipidemia in children and adults.50 Both a plant-based, low-fat dietary pattern and an AHA “heart healthy” (Mediterranean style) dietary pattern adopted by children and their parents decreased serum total cholesterol and LDL-C: the plant-based group saw a total cholesterol reduction of 22.5 mg/dL and an LDL-C reduction of 13.1 mg/dL while the AHA diet group dropped total cholesterol by 16.5 and LDL-C by 11.0 mg/dL, respectively. The plant-based group consumed less saturated fat and more fiber.51 A plant-predominant Mediterranean diet is rich in polyunsaturated fatty acids from plant sources, fiber, and antioxidants from fresh produce, and low in saturated and trans-fats. A Mediterranean diet can also reduce serum cholesterol and LDL-C in children and adolescents when compared with the standard American diet.52

Blood Pressure

The worldwide prevalence of youth hypertension has increased over the past 20 yr.53 In the PDAY cohort, hypertension was positively associated with atherosclerotic lesion development as age increased.31 In the Bogalusa cohort, systolic BP had a positive association (r= 0.55) with atherosclerotic lesion prevalence while diastolic BP had a weaker association (r= 0.22). Based on data from the Young Finns cohort, hypertension during childhood was positively correlated with hypertension in adulthood (r= 0.27).37 Children with hypertension have an increased risk of both fatal (HR = 2.04; 95% CI, 1.24-3.35) and nonfatal (HR = 2.31; 95% CI, 1.74-3.07) cardiovascular events before age 60 yr based on i3C data.14

Increasing PA during childhood has shown beneficial BP effects. A 3-mo intervention was performed involving 60-min PA sessions during an after-school program three times/wk in obese children aged 6-11 yr. Children in the intervention group experienced reductions in 24-hr systolic (−4.9%) and diastolic (−3.2%) BP compared with the control group, independent of changes in adiposity. This study also found that at 3- and 6-mo follow-up, systolic BP continued to improve in the intervention group. Arterial stiffness, measured by radial artery pulse wave tonometry, and C-IMT also improved in the intervention group.54 Encouraging a reduction in daily screen time, which contributes to physical inactivity in children and adolescents, may also aid in preventing hypertension.55

Dietary interventions focused on decreasing sodium intake may also prevent hypertension in youth.55 In infants and toddlers, higher adherence to a Dietary Approaches to Stop Hypertension diet, which is low in sodium and high in fresh produce and nonprocessed foods, is associated with lower systolic BP and lower odds of developing hypertension by ages 5-7 yr.56 At the community level, educational interventions to improve adherence to a low sodium diet among children showed improvements in fruit and vegetable intake but no difference in systolic BP when compared with controls.57,58

On a larger scale, other countries have successfully decreased the sodium intake of their populations via policy change and national media-based educational programs. In North Karelia, Finland, cooperation with the food industry led to reductions in salt added to processed foods, which helped decrease the national salt intake by about 27%. Mean systolic BP, as a result, decreased from 149 to 134 mm Hg in men and 153 to 129 mm Hg in women.59 A similar cooperation between US food industries and the health care sector may reduce the incidence of childhood hypertension.

Blood Glucose

The prevalence of type 2 diabetes mellitus (T2DM) among youth has increased by >30% in 10 yr.60 Poor glycemic control is associated with greater arterial stiffness, which increases the risk of myocardial infarction and stroke.61–63 As age increased in the PDAY cohort, the association between poor glycemic control (glycated hemoglobin ≥8%) and extent of coronary atherosclerotic lesions increased eightfold.31 Based on combined Bogalusa and Young Finns data, metabolic syndrome (defined as ≥3 of the following: obesity, hyperglycemia, hypertension, hypercholesterolemia, and hypertriglyceridemia) in childhood was associated with a higher risk of T2DM and high C-IMT in adulthood. This study, however, did not examine fasting blood glucose as an independent variable.64

Preventing the development of T2DM during childhood is an important target for reducing the risk of ASCVD. Two separate meta-analyses found associations between increased PA and improvements in both fasting insulin levels and insulin resistance in children without T2DM, although there were no significant improvements in fasting blood glucose.65,66 In a study of obese adolescent boys, resistance exercise improved insulin sensitivity to a greater degree than aerobic PA.67 The Special Turku Coronary Risk Factor Intervention Project demonstrated that longitudinal dietary counseling from infancy to 20 yr, focused on low-saturated-fat diets, improved insulin sensitivity in Finnish adolescents compared with controls.68

Community-based lifestyle intervention programs focused on PA, nutrition, and behavioral education may be effective. Lifestyle modification-based trials in adolescents implementing regular nutrition education classes, group exercise sessions, and psychosocial support have shown improvement in short-term insulin sensitivity markers compared with controls, though at follow-up, the effects did not persist.69,70

Population-based interventions have limited data on the prevention of T2DM development in children. Some studies indicate positive correlations between density of convenience stores and fast food restaurants in a given area and increased prevalence of childhood T2DM, while other studies suggest an inverse relationship between availability of fresh produce and prevalence of T2DM.36 However, more study in this area is needed.

Healthy Dietary Pattern

A heart-healthy diet is described previously as a means to improve modifiable ASCVD risk factors. However, diet may also be examined as an independent risk factor for cardiovascular disease. Data from the Young Finns cohort show a correlation between persistently high fruit and vegetable consumption from childhood to adulthood and decreased risk of arterial stiffness independent of other risk factors.71 The AHA heart-healthy dietary pattern, which overlaps considerably with low-sodium and Mediterranean diets, is recommended to promote ideal cardiovascular health (Figure 1).72 Implementing these dietary patterns early in a child's life could play a strong role in diminishing the incidence of modifiable ASCVD risk factors and improving cardiovascular risk. Government collaboration with the food industry, as in the North Karelia project, may be an effective way to promote an AHA heart-healthy dietary pattern among the entire population.59,73

Figure 1.: Pictorial depiction of the American Heart Association heart-healthy dietary pattern. This figure is available in color online (www.jcrpjournal.com)Physical Activity

The World Health Organization recommends an average of 60 min/d of moderate to vigorous intensity PA for children and adolescents.74 However, only 26.1% of surveyed high school students met these recommendations in 2017.7 Increasing PA during childhood has been discussed previously as a means to reduce adiposity,41 optimize serum lipids,49 and improve glycemic control.65–67,69,70 Physical inactivity is also considered an independent risk factor for ASCVD, making up nearly 10-30% of health care spending and should therefore be emphasized as an important component of primordial prevention.25 Reducing screen time for children may be an important step toward reducing time spent sedentary7 along with the interventions previously discussed.

CONCLUSIONS

There are robust data linking modifiable childhood ASCVD risk factors including tobacco smoking, overweight/obesity, dyslipidemia, hypertension, hyperglycemia, poor diet, and physical inactivity to early development of atherosclerosis. Primordial prevention of modifiable ASCVD risk factors, both prenatally and in early childhood, would both promote ideal cardiovascular health and decrease cardiovascular mortality into adulthood. Successful interventions reviewed in this article are summarized in Figure 2. Behaviors acquired during childhood are more likely to be carried into adulthood, so intervening early is key. Positive role-modeling from parents and caretakers may also be beneficial in shaping healthy lifestyle habits in children that persist throughout the life span. In addition, minority and lower socioeconomic status groups are more likely to develop early ASCVD risk factors than higher socioeconomic groups.6,8 Educational and behavior-change interventions targeting these higher-risk groups have been effective and may have a greater population-wide impact.7,75 Policy interventions that promote social justice via equal access to healthy lifestyle behaviors and high-quality health care are needed to address these disparities.76

Figure 2.: Effective intervention strategies for each modifiable risk factor of ASCVD discussed in the body of the article. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; DASH, Dietary Approaches to Stop Hypertension; Low-SES, low socioeconomic status. This figure is available in color online (www.jcrpjournal.com)

Only 45% of US adolescents meet five or more ideal cardiovascular markers defined by “Life's Essential 8,” and <1% of youth meet all eight.6 As age increases, the number of ideal cardiovascular markers declines and atherosclerosis progresses.6,8 Childhood and adolescent life stages are a “window of opportunity” to establish lifelong healthy lifestyle habits and prevent disease progression into adulthood.77 An early, multifactorial approach to ASCVD risk factor prevention is likely the most efficacious, but more research is needed on the feasibility and long-term outcomes of individual, community, and population-based interventions.77 Research gaps also exist in the link between sleep quality and duration in childhood to risk of ASCVD and adverse cardiovascular outcomes. However, inadequate sleep during adulthood has been linked to multiple ASCVD risk factors and outcomes and could thus also play an important role in primordial prevention.6 Psychosocial health, including stress management, has also been identified as a powerful contributor to ASCVD risk in adults; however, more research is needed in younger age groups pertaining to metrics, cardiovascular outcomes, and interventions for psychosocial health improvement.6 Finally, future research regarding implementation of public health programs emphasizing health equity for higher-risk populations may be useful in guiding interventions that benefit these groups in particular.

The development of ASCVD is preventable with lifestyle modification.4,25 Keeping in mind the simple lifestyle of the Bolivian Tsimane tribe, a multilevel emphasis on optimizing cardiovascular health throughout the life span may make the primordial prevention of ASCVD attainable in the United States.

References 1. Roth GA, Mensah GA, Johnson CO, et al. global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982–3021. 2. Gillman MW. Primordial prevention of cardiovascular disease. Circulation. 2015;131(7):599–601. 3. D'Ascenzi F, Sciaccaluga C, Cameli M, et al. When should cardiovascular prevention begin? The importance of antenatal, perinatal, and primordial prevention. Eur J Prev Cardiol. 2021;28(4):361–369. 4. Franklin BA, Myers J, Kokkinos P. Importance of lifestyle modification on cardiovascular risk reduction: counseling strategies to maximize patient outcomes. J Cardiopulm Rehab Prev. 2020;40(3):138–143. 5. Berenson GS, Srinivasan SR, Bao W, Newman WP III, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338(23):1650–1656. 6. Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life's Essential 8: updating and enhancing the American Heart Association's construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146(5):e18–e43. 7. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics: 2021 update. Circulation. 2021;143(8):e254–e743. 8. O'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D. Trends and disparities in cardiometabolic health among U.S. adults, 1999-2018. J Am Coll Cardiol. 2022;80(2):138–151. 9. Head T, Daunert S, Goldschmidt-Clermont PJ. The aging risk and atherosclerosis: a fresh look at arterial homeostasis. Front Genet. 2017;8:216. 10. Kaplan H, Thompson RC, Trumble BC, et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet. 2017;389(10080):1730–1739. 11. Burke G, Lima J, Wong ND, Narula J. The multiethnic study of atherosclerosis. Glob Heart. 2016;11(3):267–268. 12. Bose J, Hedden S, Lipari RN, Park-Lee E. Key substance use and mental health indicators in the United States: results from the 2015 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality. https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR3-1-2015/NSDUH-FFR3-1-2015/NSDUH-FFR3-1-2015.pdf. Published 2020. Accessed 19 May 2022. 13. Gurven M, Blackwell AD, Rodríguez DE, Stieglitz J, Kaplan H. Does blood pressure inevitably rise with age?: longitudinal evidence among forager-horticulturalists. Hypertension. 2012;60(1):25–33. 14. Jacobs DR, Woo JG, Sinaiko AR, et al. Childhood cardiovascular risk factors and adult cardiovascular events. N Engl J Med. 2022;386(20):1877–1888. 15. Napoli C, D'Armiento FP, Mancini FP, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100(11):2680–2690. 16. Milei J, Ottaviani G, Lavezzi AM, Grana DR, Stella I, Matturri L. Perinatal and infant early atherosclerotic coronary lesions. Can J Cardiol. 2008;24(2):137–141. 17. Rhodes ET, Pawlak DB, Takoudes TC, et al. Effects of a low-glycemic load diet in overweight and obese pregnant women: a pilot randomized controlled trial. Am J Clin Nutr. 2010;92(6):1306–1315. 18. Strom CJ, McDonald SM, Remchak MM, et al. The Influence of maternal aerobic exercise, blood DHA and EPA concentrations on maternal lipid profiles. Int J Environ Res Public Health. 2022;19(6):3550. 19. Asemi Z, Tabassi Z, Samimi M, Fahiminejad T, Esmaillzadeh A. Favourable effects of the Dietary Approaches to Stop Hypertension diet on glucose tolerance and lipid profiles in gestational diabetes: a randomised clinical trial. Br J Nutr. 2013;109(11):2024–2030. 20. Patnode CD, Henderson JT, Melnikow J, Coppola EL, Durbin S, Thomas R. U.S. Preventive Services Task Force Evidence Syntheses, Formerly Systematic Evidence Reviews. Interventions for Tobacco Cessation in Adults, Including Pregnant Women: An Evidence Update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2021. 21. Lawlor DA, Macdonald-Wallis C, Fraser A, et al. Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and Children. Eur Heart J. 2012;33(3):335–345. 22. Yoo JE, Park HS. Relationship between parental hypertension and cardiometabolic risk factors in adolescents. J Clin Hypertens (Greenwich). 2017;19(7):678–683. 23. Brion MJ, Leary SD, Lawlor DA, Smith GD, Ness AR. Modifiable maternal exposures and offspring blood pressure: a review of epi- demiological studies of maternal age, diet, and smoking. Pediatr Res. 2008;63(6):593–598. 24. Brown J, Alwan NA, West J, et al. Lifestyle interventions for the treatment of women with gestational diabetes. Cochrane Database Syst Rev. 2017;5(5):CD011970. 25. Franklin BA, Brubaker PH, Harber MP, Lavie CJ, Myers J, Kaminsky LA. The Journal of Cardiopulmonary Rehabilitation and Prevention at 40 years and its role in promoting lifestyle medicine for prevention of cardiovascular diseases: PART 1. J Cardiopulm Rehab Prev. 2020;40(3):131–137. 26. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;337:a2423.