Current Atherosclerosis Reports (2023) 25:405–415

https://doi.org/10.1007/s11883-023-01111-4

Childhood Obesity and Cardiovascular Disease Risk

Stephanie T. Chung1 · Andrea Krenek1 · Sheela N. Magge2

Accepted: 10 May 2023 / Published online: 31 May 2023

This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

Abstract
Purpose of Review The global epidemic of youth-onset obesity is tightly linked to the rising burden of cardiometabolic
disease across the lifespan. While the link between childhood obesity and cardiovascular disease is established, this contem-
porary review summarizes recent and novel advances in this field that elucidate the mechanisms and impact of this public
health issue.
Recent Findings The review highlights the emerging data supporting the relationship between childhood adverse events,
social determinants of health, and systemic and institutional systems as etiological factors. We also provide updates on new
screening and treatment approaches including updated nutrition and dietary guidelines and benchmarks for pediatric obesity
screening, novel pharmacological agents for pediatric obesity and type 2 diabetes such as glucagon-like 1 peptide receptor
agonists, and we discuss the long-term safety and efficacy data on surgical management of pediatric obesity.
Summary The global burden of pediatric obesity continues to rise and is associated with accelerated and early vascular
aging especially in youth with obesity and type 2 diabetes. Socio-ecological determinants of risk mediate and moderate
the relationship of childhood obesity with cardiometabolic disease. Recognizing the importance of neighborhood level
influences as etiological factors in the development of cardiovascular disease is critical for designing effective policies and
interventions. Novel surgical and pharmacological interventions are effective pediatric weight-loss interventions, but future
research is needed to assess whether these agents, within a socio-ecological framework, will be associated with abatement
of the pediatric obesity epidemic and related increased cardiovascular disease risk.

Keywords Pediatric · Overweight · Obesity · Cardiometabolic · Obesity · Cardiovascular disease

Introduction international recognition of this public health emergency,

no region in the world has successfully stemmed the rise
Childhood obesity and its comorbidities are risk factors for in pediatric obesity. In the USA, contemporary simulation
many chronic conditions, including three of the major non- models project continued increases in obesity prevalence
communicable diseases worldwide: type 2 diabetes, cardio- and three times higher risk for obesity in adults over the
vascular disease, and cancer [1]. Globally, the prevalence next 5–10 years [6]. While multiple publications address
of childhood obesity has increased dramatically in the last the scope of the problem and propose interventions to miti-
2–3 decades across all world regions, with the most devas- gate and prevent this chronic disease [1, 7], pediatric obesity
tating impact in low- to middle-income countries that have remains a top World Health Organization (WHO) initiative
the dual burden of undernutrition and obesity [2–5]. Despite with an expansive impact that worsened during the COVID-
19 pandemic [8].
Prior to the COVID-19 pandemic, studies indicated that
* Sheela N. Magge public health efforts implemented in high-income countries,
[email protected] such as the USA and UK, stabilized the rapid rises in child-
1
hood obesity prevalence [3, 9]. However, the COVID-19
Section on Pediatric Diabetes and Metabolism, National
Institute of Diabetes & Digestive & Kidney Disease, NIH
pandemic upended this short-term reprieve. During the
Bethesda, Bethesda, MD, USA COVID-19 pandemic era, epidemiologic studies report con-
2
Division of Pediatric Endocrinology and Diabetes, Johns
sistent and steep rises in the trajectory of weight gain among
Hopkins University School of Medicine, 200 N. Wolfe Street, many countries across all ages and BMI categories [10–17].
Rubenstein Bldg, Rm 3114, Baltimore, MD 21287, USA

13
Vol.:(0123456789)
406 Current Atherosclerosis Reports (2023) 25:405–415

Childhood overweight and obesity afflicts up to one-third excess adiposity to ASCVD, have been published [20,
of children in European and American regions [3, 5, 10]. 24–32]. Overall, it is well recognized that ASCVD begins in
Among low-income countries and small island developing childhood and that ASCVD risk and subsequent mortality is
states, the rates of rise childhood obesity are 30% higher significantly increased by childhood obesity and the cluster-
than in developed nations [4, 5, 18]. Two additional con- ing of metabolic risk factors, such as high triglycerides, low
siderations are noteworthy: (1) the co-occurrence of excess HDL-cholesterol, high blood pressure, and dysglycemia [33,
adiposity and nutritional stunting in youth from middle and 34•, 35, 36]. Childhood obesity is associated with at least
low-income countries [2] and (2) the continued steep trajec- twofold increased odds of dyslipidemia, hypertension, type
tory of weight gain among youth with severe obesity [10]. 2 diabetes, and metabolic diseases (such as non-alcoholic
Nutritional stunting with obesity portends a multitude of steatohepatitis and polycystic ovarian syndrome) [37–39]. In
complications among populations with limited resources and addition to metabolic risk factor clustering in childhood and
requires aggressive targeted interventions in those at highest adolescence, the cumulative ASCVD risk is compounded in
risk. In contrast, in high-income countries, the rate of weight young adulthood because youth with pediatric obesity have
gain during the COVID-19 pandemic was highest in youth a high prospective risk for obesity and type 2 diabetes as
with severe obesity [10], a group already at greatest risk for adults [34•, 40]. Among adolescents (median age 14 years),
obesity-related complications [19]. Therefore, the burden of severe class II/III obesity in adulthood occurred in ~ 50%
childhood obesity across the globe is differentially impacted of children with obesity and 80% of youth who had severe
by risks related to stunting and severity of obesity that— obesity [33].
individually and together—accelerate the development of Since our previous review publication [20], there has
atherosclerotic disease. been increasing recognition of the prognostic ability of
This contemporary review discusses recent advances in cardiovascular risk factors in childhood and the degree to
understanding the pathophysiology of cardiovascular disease which cardiometabolic risk is elevated across different phe-
in youth with overweight and obesity, and critically analyzes notypes and body compositions in youth. In one of the larg-
the role of social determinants of health and socio-ecological est pediatric cohort studies to evaluate cardiovascular risk,
factors that compound and hinder current obesity prevention the International Childhood Cardiovascular Cohort (i3C)
efforts. We also provide an update on the latest advances in Consortium evaluated the predictive potential of five tra-
nutrition science and behavioral interventions and highlight ditional risk factors (body mass index, systolic blood pres-
areas of future research that could support pragmatic and sure, total cholesterol, total triglyceride, and youth smok-
innovative solutions to address the double burden of child- ing) for fatal and non-fatal cardiovascular events in 38,589
hood malnutrition and obesity, and the high risk for cardio- participants after mean follow-up of 35 years [41]. This
metabolic disease. seminal and comprehensive analysis demonstrated strong
associations of childhood risk factors—independently and
in combination—with major cardiovascular events. Studies
Childhood Obesity and its Relationship have also demonstrated that all adiposity is not the same.
with Cardiometabolic Risk and Early Metabolically unhealthy excess weight is characterized by
Vascular Aging increased visceral fat, decreased subcutaneous fat, adipocyte
hypertrophy, increased secretion of inflammatory factors,
As childhood is a time of growth and pubertal development, and ectopic fat deposition [42]. Youth with excess visceral
pediatric overweight and obesity must be defined in relative adiposity have marked elevations in atherogenic lipoproteins
terms, standardized for sex and age. For a detailed review of and increased incidence of dysglycemia [43–46].
the definition, classification, and pathophysiology of child- Our understanding of the prevalence and progression
hood obesity, as well as its comorbidities, we refer the read- of cardiovascular risk markers and subclinical ASCVD in
ers to our prior publication [20]. Childhood obesity is an youth with obesity and type 2 diabetes has also improved
established risk marker for atherosclerotic cardiovascular [47]. Approximately 1 in 4 youth with type 2 diabetes have
disease (ASCVD), a progressive vascular disease that begins a microvascular complication or hypertension at diagno-
in childhood [21–23]. Comprehensive historical reviews sis and the cumulative prevalence rises to over 60% in
on the association of childhood obesity, including seminal 10–12 years [48]. In addition, although age remains one
autopsy (e.g., Bogalusa Heart Study, Pathobiological Deter- of the strongest drivers for the development of ASCVD
minants of Atherosclerosis in Youth (PDAY) study,) and [49], the extent to which childhood obesity and its meta-
epidemiological studies (Childhood Determinants of Adult bolic complications accelerate the progression through the
Health study, Cardiovascular Risk in Young Finns study, four stages of atherosclerosis (endothelial dysfunction,
Atherosclerosis Risk in Young Adults study, International lipid accumulation, plaque formation, plaque rupture) is
Childhood Cardiovascular Cohort Consortium) linking still emerging [50]. Both cross-sectional and longitudinal

13
Current Atherosclerosis Reports (2023) 25:405–415 407

youth cohort studies have suggested an accelerated tempo Social Determinants of Health, Childhood
in vascular aging—the deterioration of vascular structure Obesity, and Cardiovascular Disease
and function—among youth and emerging adults with obe-
sity with and without type 2 diabetes [51, 52••, 53–57]. The causative factors and pathways in the development of
Both obesity and type 2 diabetes were identified as major to ASCVD are multi-factorial across socio-ecological lev-
risk factors for accelerated vascular aging, measured as els. Within the socio-ecological framework—a paradigm
carotid-femoral pulse wave velocity (PWV) or augmenta- describing the inter-relationships between individual, family,
tion index [52••, 53]. Childhood obesity is independently and communities—social determinants of health (SDOH)
associated with increased carotid intima-media thickness may mediate and moderate the development of childhood
(cIMT) with the cumulative effects likely moderated by the obesity and cardiometabolic disease risk (Fig. 1). SDOH
association with dyslipidemia and insulin resistance [20, propagate non-communicable diseases and directly influence
56, 58, 59]. Furthermore, cumulative exposure to insulin the success of childhood obesity programs [65]. SDOH are
resistance and dysglycemia was shown to adversely impact structural and environmental, and include factors such as
left ventricular remodeling and function in middle aged neighborhood and built environment, education access, and
adults [60]. These findings support accelerated vascular social and community relationships. Specifically, low socio-
aging in youth-onset obesity and type 2 diabetes accelerate economic status, limited access to healthcare, early child-
and emphasize the need to identify the modifiable mecha- hood adversity, food insecurity, and social isolation may
nistic drivers of disease progression to effectively target directly increase chronic stress and allostasis or indirectly
early intervention efforts. promote risky and adverse lifestyle behaviors [66, 67]. Still,
In recent years, attention has also shifted to translat- many research studies on childhood obesity prevention do
ing these research findings into the clinical arena. Metrics not focus on socio-ecological determinants but instead target
used to evaluate early vascular aging include measures of individualistic determinants and solutions. Recognizing the
vascular structure (common, bulb, and internal cIMT) and importance of these systems-level influences on childhood
arterial stiffness (carotid-femoral PWV and augmentation obesity and risk for cardiometabolic disease is a major step
index). Efforts have focused on publishing normative data towards designing effective policies and interventions. Yet,
for PWV and cIMT percentiles in youth that may be used such new policies and interventions have been hindered by a
for risk stratification [56, 59]. However, cIMT can be dif- wide range of socio-ecological factors, including economic
ficult to obtain in the general pediatric population because slowdowns and downturns, political agendas, and ingrained
reproducibility and reliability are limited by intra-individ- structural racism and cultural norms [2].
ual variability in ultrasound techniques [61]. Alternatively, Two institutional level factors were recently highlighted
carotid-femoral PWV is less reliant on user skill but the as important mediators of cardiovascular disease risk: food
translation of this technique in clinical settings has been insecurity and adverse childhood experiences [68, 69].
slow in pediatric and youth populations [62]. International Food insecurity and malnutrition have reached a critical
efforts are underway to evaluate these methods, with addi- stage worldwide, according to the WHO 2021 report and
tional studies needed to standardize and validate vascular are associated with the development of childhood obesity
aging assessment techniques [63, 64]. and cardiometabolic disease in adults [70–73]. However,

Fig. 1  Conceptual model of

socio-ecological determinants
of cardiometabolic disease
in childhood obesity [68]
(Adapted from: Suglia, SF, et al.
Circulation, 2018;137:e15–e28;
with permission from Wolters
Kluwer Health, Inc.)

13
408 Current Atherosclerosis Reports (2023) 25:405–415

the relationship between food insecurity and cardiovascu- stress and resiliency factors and their relationships with
lar disease risk in youth with obesity is inconsistent. Some risky and unhealthy behaviors are needed in youth. For
studies indicate a moderate association of food insecurity example, while the impact of poor sleep quality and seden-
with dyslipidemia and fasting glucose in childhood [73, 74] tary time on ASCVD risk in adults is strong [81–83], addi-
{Lee, 2019 #10,064}. In contrast, other studies fail to show tional evidence is needed to determine the dose–response
an independent association of cardiovascular risk markers relationship between these unhealthy behaviors in childhood
with food insecurity among youth at risk [72, 75]. A con- and the future risk for ASCVD.
temporary analysis from the National Human and Nutrition Accumulating evidence also demonstrates that mental
Examination Survey 2007–2012 (NHANES) in adolescents health conditions such as depression and anxiety are impor-
at or below 300% of the poverty line did not find a relation- tant and potentially modifiable comorbidities of pediatric
ship between food insecurity and childhood cardiometabolic obesity. Depression is prevalent in youth with pediatric
risk factors [75]. In the NHANES analyses, outcomes were obesity and adolescent girls are at increased odds for symp-
adjusted for both institutional and neighborhood level vari- toms [84–86]. However, these data are mainly derived from
ables (income and parental education) as well as individual epidemiologic studies and a direct association of markers
level socio-ecological factors (physical activity, sedentary of vascular aging with depression in adolescence and adult-
time, and smoking status). These findings suggest that socio- hood is elusive [87]. Alternatively, a strong relationship
ecological factors may be interdependent mediators of car- exists between allostatic load and stress with increased risk
diovascular disease risk in youth. Large medical organiza- for ASCVD and major cardiovascular events [66]. What
tions, including the American Academy of Pediatrics and remains to be seen, however, is how this relationship is
the American Heart Association, emphasize the complex modified by pediatric obesity and whether it is the duration
inter-relationship of food insecurity and lifetime cardiometa- of obesity, the rapidity of weight gain, or the presence of
bolic risk [68, 76]. In the USA, ~ 10% of households were adult obesity that are major determinants of ASCVD.
food insecure, prompting governmental officials to acknowl-
edge the disproportionate impact on children, and fueling
new policies and strategies that promote nutrition and target Updates to Treatment of Childhood Obesity
obesity and cardiovascular diseases [77]. Compared to the and Mitigation of ASCVD Risk
general US population, youth and young adults with type
1 and type 2 diabetes report nearly twice the prevalence Lifestyle interventions alone or with concomitant pharma-
of food insecurity [78]. Among youth with diabetes in the cotherapy as indicated remain a cornerstone of treatment
USA, predictors of household food insecurity include youth across all risk levels and are underscored by multiple clini-
without insurance or receiving Medicaid or Medicare, level cal practice guidelines [88–90]. Although lifestyle modifi-
of parental education, and lower household income [78]. cations, including healthful dietary intake, daily physical
Adverse childhood experiences (ACEs) are also closely activity, avoidance of smoking and alcohol, stress manage-
associated with poor cardiovascular outcomes with or with- ment, social support, and sufficient high-quality sleep, are
out underlying food insecurity [68, 79••]. Notably, the cardi- recognized as first-line approaches for preventing and man-
ometabolic consequences of ACEs are increasingly observed aging childhood obesity and related disease risks, individual
in youth and emerging adults but may not manifest until lifestyle interventions may be unsuccessful in isolation [91,
later in adulthood [68]. The conceptual model describing 92]. Furthermore, lifestyle interventions without additional
the socio-ecological relationship of ACEs with ASCVD treatment approaches are less effective in youth from under-
includes a framework of three main mediating factors: (1) served and minority groups [93]. Lifestyle behavior inter-
unhealthy behaviors such as physical inactivity, poor-quality ventions that yield the greatest accessibility and efficacy in
diet, poor quality and duration of sleep, and smoking; (2) preventing harmful weight gain in adolescent populations
adverse physiologic mechanisms including inflammation remain a limited area of research [94]. Youth from under-
and hypercortisolemia; and (3) substance abuse and mental served communities have the lowest accrual, retention, and
health disorders (Fig. 1) [68]. Neighborhood and commu- completion rates for behavioral and activity interventions
nity level influences may mediate shifts in healthy lifestyle [93].
behaviors, promote mental health disorders, and/or induce
physiological stress and dysregulation (Fig. 1). These effects Diet
are compounded in individuals who have genetic predispo-
sition for ASCVD and its risk determinants [80]. Although Nutritional management targets reduction of cardiometa-
there is a strong link between ACEs and ASCVD, evidence bolic risk factors and comorbidities without adverse effects
to date is associative and observational. Future studies to on growth and development, while supporting a healthy rela-
elucidate the mechanisms and biomarkers of physiologic tionship with food and activities. Broad recommendations

13
Current Atherosclerosis Reports (2023) 25:405–415 409

include a balanced diet with age-specific nutritional and causative is unclear [120]. Plant-based diet patterns high in
energy intake values, limiting excess consumption of energy- dietary fiber further maintain a key role in beneficially shift-
dense, nutrient-poor foods (e.g., sugar-sweetened beverages, ing gut microbial composition—increasingly implicated in
highly processed items, red meats, and high-sodium foods) CVD risk and excess adiposity—potentially through mitigat-
while encouraging the consumption of whole fruit, vegeta- ing production and activity of compounds including reduc-
bles, whole grains, nuts, seeds, legumes, and other sources tion of trimethylamine-n-oxide (TMAO) and increasing
of lean proteins [95]. In collaboration with patient prefer- SCFAs [119, 121, 122]. TMAO is a metabolite derived from
ences and readiness, medical nutrition therapy provided by gut microbiota that is associated with poor cardiometabolic
a registered dietitian and reinforced by all members of an outcomes with evidence of direct activity in the pathogenesis
interdisciplinary care team emphasizes nutritionally ade- of atherosclerosis [123–125]. Synthesis of TMAO depends
quate heart-healthy dietary patterns. on production of trimethylamine (TMA) by gut microbiota
Guidance is provided on the age-appropriate total calories from nutrient precursors, including choline, phosphatidyl-
consumed while emphasizing diet quality, independent of choline, carnitine, and betaine, which are concentrated in
caloric intake, as important mediators of weight and meta- animal foods such as red meat, eggs, fish, and dairy [126,
bolic cardiovascular risk [96, 97]. Evidence for lower disease 127]. While accumulating evidence linking nutrition, obe-
risk in adolescents by implementing dietary interventions is sity, and microbial activity implicates TMAO in the patho-
derived from adult and multi-level pediatric interventional genesis of ASCVD in adults, scarce research exists in youth
studies [98–102]. Several studies support the conclusion that and young adults. Limited studies suggest mixed associa-
consuming a plant-centered, nutrient-rich diet in youth and tions of TMAO compared to TMAO precursors as appropri-
young adulthood has a positive effect on cardiovascular risk ate indicators of CVD risk at younger ages [128–130]. Fur-
reduction later in life [103–108]. In the Coronary Artery ther interventional and longitudinal studies are warranted to
Risk Development in Young Adults (CARDIA) cohort study, examine the impact and usefulness of TMAO and precursor
greater plant-centered diet quality at a younger age was asso- biomarkers in risk assessment and management of obesity
ciated with lower subsequent risks of ASCVD [104], type and CVD in childhood [131]. Another major class of gut
2 diabetes, and excess weight gain [103]. However, the evi- microbial metabolites, SCFAs—primarily acetate, butyrate,
dence supporting one dietary intervention over others, and and propionate—are produced by bacterial fermentation of
their safety in youth, has yet to be elucidated. non-digestible carbohydrates and exert widespread physi-
The Dietary Guidelines for Americans, Academy of ological effects relevant to development of obesity and CVD
Nutrition and Dietetics, American College of Cardiology, [131]. In contrast to TMAO, these signaling molecules are
and American Heart Association outline whole food, plant- broadly connected to positively influencing health status
rich patterns, including Dietary Approaches to Stop Hyper- through multiple processes, including appetite regulation,
tension, the Mediterranean diet, vegetarian and vegan diets, gut hormone production, anti-inflammatory and anti-neo-
and a Healthy US-style diet for risk reduction [89, 109]. plastic properties, glucose homeostasis, and lipid metabo-
A 2022 National Lipid Association clinical perspective on lism, in several target tissues [131]. For both TMAO and
nutrition interventions for youth with dyslipidemia rein- SCFAs as well as other bacterially produced compounds,
forced components of these dietary patterns, highlighting additional research is needed to elucidate mechanistic fea-
the effects of food sources of saturated and unsaturated fatty tures, ideal microbial composition for reducing chronic dis-
acids, dietary fiber, added sugars and refined carbohydrates, ease risk, and potential differences in biomarkers of risk in
and phytosterols on lipid metabolism. Incorporation of a both healthy and at-risk for disease youth and young adults
variety of lean protein foods, including plant-based sources compared to adults and elderly populations.
[110], and reduction of ultra-processed foods [111–113] are Other prominent dietary trends for treating or mitigat-
among other emphasized recommendations with opportuni- ing ASCVD in adults with obesity include intermittent
ties for future research. Additional interconnected mecha- fasting or time limited eating by which foods are con-
nisms may relate to (1) nutritional effects on hepatic LDL sumed within a defined window. Intermittent fasting is
receptor activity [114], (2) satiety-promoting low energy not currently recommended in children or adolescents due
dense foods within a greater food volume, (3) reduced intake to lack of evidence, conflicting data in adults [132], and
of inflammatory diet factors, (4) fiber-mediated effects on potential adverse effects on eating disorder risk. Small
glucose absorption, gut-microbial short-chain fatty acid pilot [133] and case series [134] implementing versions of
(SCFA) synthesis, and (5) and cholesterol synthesis through intermittent fasting in pediatric populations suggest flex-
binding and excretion of bile acids [115–119]. ible approaches may yield benefits on weight outcomes.
Emerging data supports associative links between meta- Additional data would be needed to determine the safety
bolically unhealthy obesity shifts in the gut microbiota com- of intermittent fasting time windows and the effects on
position, though whether the relationship is bi-directional or ASCVD risk reduction. In addition to personalized

13
410 Current Atherosclerosis Reports (2023) 25:405–415

nutrition counseling, multi-level innovative approaches global problem. However, gaps in knowledge still exist.
for supporting lifestyle changes that may be promising We are just beginning to understand how metabolic risk
include culinary medicine and teaching kitchen inter- factor clustering in childhood predicts hard cardiovas-
ventions [135–140] and produce prescription programs, cular outcomes in young to middle adulthood. Longi-
medically tailored meals or groceries, and mobile health tudinal studies with systematic and comprehensive data
applications [141]. collection are still needed, especially among youth with
obesity and diabetes, to inform the timing of mitigation
Pharmacological and Surgical Treatment strategies in the highest risk youth and young adults. For
example, current pediatric dyslipidemia guidelines were
The last 10 years have been monumental in therapeutic and largely based on adult ASCVD outcome trials, and there
surgical advancements for the treatment of pediatric obesity are no data supporting whether treatment of modest dys-
and type 2 diabetes [142]. In December 2020, liraglutide lipidemia in youth with obesity and diabetes will reduce
became the first pediatric anti-obesity drug to be approved ASCVD-related morbidity or mortality. Similarly, ideal
by the Federal Drug Administration (FDA) in over 2 dec- target values for LDL and total cholesterol concentra-
ades. Liraglutide’s weight-loss potential is modest (~ 3–5% tions are based on adult data. However, lipid guidelines
of body weight) for youth compared to adults, but it is asso- in adults now include a risk-based approach with statin
ciated with an improved glycemic and cardiometabolic pro- and cholesterol lowering medication recommendations
file. A second combination drug, phentermine/topiramate, derived from randomized controlled analyses of major
was approved in June 2022 for the management of chronic cardiovascular events. There are no parallel data in youth
obesity in youth based on clinical trials demonstrating 4–8% and the ideal cutoff or targets for statin therapy are based
reduction in BMI over 54 weeks. Alternative agents, such on expert advice rather than empirical data. There is also
as semaglutide and naltrexone, are approved for chronic a need to investigate the most reliable and reproducible
weight management in adults, but clinical trial data is just markers for early stage ASCVD and vascular aging, with
beginning to emerge in youth [143, 144]. Recent clinical a focus on which socio-ecological factors should be con-
trial results of semaglutide in adolescents were promising; sidered primary drivers of ASCVD risk in youth. Lastly,
semaglutide for 68 weeks resulted in a mean change in BMI the link between childhood obesity, cardiovascular dis-
of − 16.1% compared to 0.6% with placebo [144]. However, ease risk, and gut microbial dysbiosis with associated
it remains to be determined whether these medications will TMAO metabolites is intriguing but the evidence is pre-
have durable long-term weight loss effects and lead to over- liminary and many questions remain as to whether these
all ASCVD risk reduction. pathways are causal or associative.
Bariatric surgery, on other the hand, is the only available
therapy that results in sustained weight loss with demon-
strated long-term safety up to 10 years post-surgery [142,
145]. Furthermore, the Teen-Longitudinal Assessment of Conclusion
Bariatric Surgery (Teen-LABS) study showed improvement
of multiple cardiovascular risk factors after bariatric sur- Childhood obesity, its complications, and comorbidities
gery [146]. Vertical sleeve gastrectomy (VSG) is currently persist as significant ASCVD risk factors. The COVID-
the most common bariatric surgery recommended and per- 19 pandemic served to exacerbate pediatric obesity
formed in adolescents in the USA [147]. In 2018, the Ameri- rates, as well as many of its associated SDOH. Studies
can Society for Metabolic and Bariatric Surgery outlined show post-pandemic increases in psychosocial stress as
pediatric severe weight management guidelines [148] and well as depression and anxiety among youth [151, 152].
surgical options for chronic weight management of severe While progress has been made in our understanding of
obesity in youth were endorsed by the American Academy the increased cardiovascular disease risk associated
of Pediatrics in 2019 [149, 150]. with pediatric obesity, much is yet to be determined.
The pathophysiologic mechanisms behind the relation-
ships between SDOH and increased obesity-related car-
Research Gaps and Areas for Future diometabolic risk need to be clarified if we are to make
Research true progress in identifying youth at greatest risk for
ASCVD. Once identified, innovative treatment modali-
The last decade has seen significant advances in our ties will need to be implemented at the optimal time to
understanding of the severity and burden of pediatric stem the tide of youth-onset obesity and its cardiovas-
obesity as well as therapeutic advances to address this cular complications.

13
Current Atherosclerosis Reports (2023) 25:405–415 411

Funding STC is supported by the Intramural Program of the National 11. Woolford SJ, et al. Changes in body mass index among chil-
Institute of Diabetes, Digestive, and Kidney Diseases. dren and adolescents during the COVID-19 pandemic. JAMA.
2021;326(14):1434–6.
Declarations 12. Knapp EA, Dong Y, Dunlop AL, et al. Changes in BMI during
the COVID-19 pandemic. Pediatrics. 2022;150(3):e2022056552.
Conflict of Interest The authors have no conflicts of interest to dis- https://​doi.​org/​10.​1542/​peds.​2022-​056552.
close. 13. Shalitin S, Phillip M, Yackobovitch-Gavan M. Changes in body
mass index in children and adolescents in Israel during the
Human and Animal Rights and Informed Consent This article is a COVID-19 pandemic. Int J Obes (Lond). 2022;46(6):1160–7.
review article and does not contain any new studies with human or 14. Kang HM, et al. The impact of the coronavirus disease-2019
animal subjects performed by any of the authors. Studies cited in pandemic on childhood obesity and vitamin D status. J Korean
this review in which the authors were involved included statements Med Sci. 2021;36(3):e21.
that these studies were approved by their respective institutional 15. Vážná A, Vignerová J, Brabec M, et al. Influence of COVID-
review boards. Those studies were also performed in accordance 19-related restrictions on the prevalence of overweight and
with the ethical standards as laid down in the 1964 Declaration of obese Czech children. Int J Environ Res Public Health.
Helsinki and its later amendments or comparable ethical standards. 2022;19(19):11902. https://​doi.​org/​10.​3390/​ijerp​h1919​11902.
16. Lubrecht J, et al. Weight gain in children during the COVID-19
pandemic and the protective effect of lifestyle intervention in
children with obesity. Obes Facts. 2022;15(4):600–8.
17. Weaver RG, et al. COVID-19 leads to accelerated increases in
children’s BMI z-score gain: an interrupted time-series study.
References Am J Prev Med. 2021;61(4):e161–9.
18. Lobstein T, et al. Child and adolescent obesity: part of a bigger
Papers of particular interest, published recently, have picture. Lancet. 2015;385(9986):2510–20.
been highlighted as: 19. Zabarsky G, et al. Impact of severe obesity on cardiovascular
risk factors in youth. J Pediatr. 2018;192:105–14.
• Of importance 20. Chung ST, Onuzuruike AU, Magge SN. Cardiometabolic risk
•• Of major importance in obese children. Ann N Y Acad Sci. 2018;1411(1):166–83.
21. McGill HC Jr, et al. Origin of atherosclerosis in childhood and
1. World Health Organization. Report of the commission on adolescence. Am J Clin Nutr. 2000;72(5 Suppl):1307S-1315S.
ending childhood obesity. World Health Organization; 2016. 22 McGill HC Jr, et al. Associations of coronary heart disease
https://​apps.​who.​int/​iris/​handle/​10665/​204176. risk factors with the intermediate lesion of atherosclerosis in
2. Swinburn BA, et al. The Global Syndemic of Obesity, Under- youth. The Pathobiological Determinants of Atherosclerosis in
nutrition, and Climate Change: The Lancet Commission Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol.
report. Lancet. 2019;393(10173):791–846. 2000;20(8):1998–2004.
3. Collaboration NRF. Worldwide trends in body-mass index, 23. McGill HC Jr, et al. Association of coronary heart disease risk
underweight, overweight, and obesity from 1975 to 2016: a factors with microscopic qualities of coronary atherosclerosis
pooled analysis of 2416 population-based measurement stud- in youth. Circulation. 2000;102(4):374–9.
ies in 128·9 million children, adolescents, and adults. Lancet. 24 Berenson GS, et al. Association between multiple cardio-
2017;390(10113):2627–42. vascular risk factors and atherosclerosis in children and
4. Sobers N, Samuels TA. Diet and childhood obesity in small young adults. The Bogalusa Heart Study. N Engl J Med.
island developing states. Lancet Child Adolesc Health. 1998;338(23):1650–6.
2019;3(7):445–7. 25 McGill HC Jr, et al. Effects of coronary heart disease risk fac-
5. Moschonis G, Siopis G, Anastasiou C, et al. Prevalence of tors on atherosclerosis of selected regions of the aorta and right
childhood obesity by country, family socio-demographics, and coronary artery. PDAY Research Group. Pathobiological Deter-
parental obesity in Europe: The Feel4Diabetes study. Nutri- minants of Atherosclerosis in Youth. Arterioscler Thromb Vasc
ents. 2022;14(9):1830. https://​doi.​org/​10.​3390/​nu140​91830. Biol. 2000;20(3):836–45.
6. Ward ZJ, et al. Simulation of growth trajectories of 26. Magnussen CG, et al. The association of pediatric low- and high-
childhood obesity into adulthood. N Engl J Med. density lipoprotein cholesterol dyslipidemia classifications and
2017;377(22):2145–53. change in dyslipidemia status with carotid intima-media thick-
7. Styne DM, et al. Pediatric obesity-assessment, treatment, and ness in adulthood evidence from the cardiovascular risk in
prevention: an Endocrine Society clinical practice guideline. Young Finns study, the Bogalusa Heart study, and the CDAH
J Clin Endocrinol Metab. 2017;102(3):709–57. (Childhood Determinants of Adult Health) study. J Am Coll
8. World Health Organization. Consideration of the evidence on Cardiol. 2009;53(10):860–9.
childhood obesity for the commission on ending childhood 27. Juonala M, et al. Influence of age on associations between
obesity: report of the ad hoc working group on science and childhood risk factors and carotid intima-media thickness in
evidence for ending childhood obesity. Geneva, Switzerland: adulthood: the Cardiovascular Risk in Young Finns Study, the
World Health Organization. https://​apps.​who.​int/​iris/​handle/​ Childhood Determinants of Adult Health Study, the Bogalusa
10665/​206549. Accessed 9 Dec 2022. Heart Study, and the Muscatine Study for the International
9. Hu K, Staiano AE. Trends in obesity prevalence among chil- Childhood Cardiovascular Cohort (i3C) Consortium. Circula-
dren and adolescents aged 2 to 19 years in the US from 2011 tion. 2010;122(24):2514–20.
to 2020. JAMA Pediatr. 2022;176(10):1037–9. 28. Juhola J, et al. Tracking of serum lipid levels, blood pressure, and
10. Lange SJ, et al. Longitudinal trends in body mass index before body mass index from childhood to adulthood: the Cardiovascu-
and during the COVID-19 pandemic among persons aged 2–19 lar Risk in Young Finns Study. J Pediatr. 2011;159(4):584–90.
years - United States, 2018–2020. MMWR Morb Mortal Wkly 29. Oren A, et al. Change in body mass index from adolescence to
Rep. 2021;70(37):1278–83. young adulthood and increased carotid intima-media thickness at

13
412 Current Atherosclerosis Reports (2023) 25:405–415

28 years of age: the Atherosclerosis Risk in Young Adults study. 48. Group TS, et al. Long-term complications in youth-onset type 2
Int J Obes Relat Metab Disord. 2003;27(11):1383–90. diabetes. N Engl J Med. 2021;385(5): 416-426.
30. Oikonen M, et al. Ideal cardiovascular health in young adult 49. Yared GS, et al. Coronary artery calcium from early adulthood
populations from the United States, Finland, and Australia to middle age and left ventricular structure and function. Circ
and its association with cIMT: the International Childhood Cardiovasc Imaging. 2019;12(6):e009228.
Cardiovascular Cohort Consortium. J Am Heart Assoc. 50. Shah AS, et al. Influence of duration of diabetes, glycemic
2013;2(3):e000244. control, and traditional cardiovascular risk factors on early
31. Juonala M, et al. Childhood adiposity, adult adiposity, and car- atherosclerotic vascular changes in adolescents and young
diovascular risk factors. N Engl J Med. 2011;365(20):1876–85. adults with type 2 diabetes mellitus. J Clin Endocrinol Metab.
32. Caprio S, Santoro N, Weiss R. Childhood obesity and the 2009;94(10):3740–5.
associated rise in cardiometabolic complications. Nat Metab. 51. Shah AS, et al. Relationship between arterial stiffness and subse-
2020;2(3):223–32. quent cardiac structure and function in young adults with youth-
33. Woo JG, et al. Prediction of adult class II/III obesity from onset type 2 diabetes: results from the TODAY study. J Am Soc
childhood BMI: the i3C consortium. Int J Obes (Lond). Echocardiogr. 2022;35(6): 620–628 e4.
2020;44(5):1164–72. 52.•• Ryder JR, et al. Accelerated early vascular aging among ado-
34.• Hu T, et al. Childhood BMI and fasting glucose and insu- lescents with obesity and/or type 2 diabetes mellitus. J Am
lin predict adult type 2 diabetes: the International Childhood Heart Assoc. 2020;9(10):e014891. This longitudinal study
Cardiovascular Cohort (i3C) Consortium. Diabetes Care. characterized progression of vascular aging from adoles-
2020;43(11):2821–9. Findings from this large longitudinal cence to young adulthood and found that childhood obesity,
cohort study of youth confirm that adiposity is incrementally type 2 diabetes mellitus and elevated systolic blood pres-
associated with risk for type 2 diabetes in adults. sure were associated with accelerated vascular aging.
35. Saydah S, et al. Cardiometabolic risk factors among US adoles- 53. Higgins S, Zemel BS, Khoury PR, Urbina EM, Kindler JM.
cents and young adults and risk of early mortality. Pediatrics. Visceral fat and arterial stiffness in youth with healthy weight,
2013;131(3):e679–86. obesity, and type 2 diabetes. Pediatr Obes. 2022;17(4):e12865.
36. Magge SN, Goodman E, Armstrong SC, Committee on Nutri- https://​doi.​org/​10.​1111/​ijpo.​12865.
tion; Section on Endocrinology; Section on Obesity. The 54. Hudson LD, et al. Evidence for contemporary arterial stiffen-
metabolic syndrome in children and adolescents: shifting ing in obese children and adolescents using pulse wave veloc-
the focus to cardiometabolic risk factor clustering. Pediat- ity: a systematic review and meta-analysis. Atherosclerosis.
rics. 2017;140(2):e20171603. https://​doi.​org/​10.​1542/​peds.​ 2015;241(2):376–86.
2017-​1603. 55. Madsen NL, et al. Increased arterial stiffness is associated with
37. Li L, et al. Cardiometabolic risk factors among severely obese reduced diastolic function in youth with obesity and type 2
children and adolescents in the United States, 1999–2012. Child diabetes. Front Pediatr. 2021;9:781496.
Obes. 2016;12(1):12–9. 56. Buschges J, et al. Vascular aging in the young: new
38. Chung ST, et al. Nuclear magnetic resonance derived biomarkers carotid stiffness centiles and association with general and
for evaluating cardiometabolic risk in youth and young adults abdominal obesity - The KIGGS cohort. Atherosclerosis.
across the spectrum of glucose tolerance. Front Endocrinol 2022;355:60–7.
(Lausanne). 2021;12:665292. 57. Shah AS, et al. Longitudinal changes in vascular stiffness and
39. Chung ST, et al. The Relationship between lipoproteins and heart rate variability among young adults with youth-onset
insulin sensitivity in youth with obesity and abnormal glucose type 2 diabetes: results from the follow-up observational
tolerance. J Clin Endocrinol Metab. 2022;107(6):1541–51. treatment options for type 2 diabetes in adolescents and youth
40. Geserick M, et al. Acceleration of BMI in early child- (TODAY) study. Acta Diabetol. 2022;59(2):197–205.
hood and risk of sustained obesity. N Engl J Med. 58. Naylor LH, et al. Endothelial function and carotid intima-
2018;379(14):1303–12. medial thickness in adolescents with type 2 diabetes mellitus.
41. Jacobs DR Jr, et al. Childhood cardiovascular risk fac- J Pediatr. 2011;159(6):971–4.
tors and adult cardiovascular events. N Engl J Med. 59. Neuhauser HK, et al. Carotid intima-media thickness percen-
2022;386(20):1877–88. tiles in adolescence and young adulthood and their association
42. Goossens GH. The metabolic phenotype in obesity: fat mass, with obesity and hypertensive blood pressure in a population
body fat distribution, and adipose tissue function. Obes Facts. cohort. Hypertension. 2022;79(6):1167–76.
2017;10(3):207–15. 60. Kishi S, et al. Association of insulin resistance and glycemic
43. Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Car- metabolic abnormalities with LV structure and function in
diometabolic risk and body composition in youth with down middle age: The CARDIA Study. JACC Cardiovasc Imaging.
syndrome. Pediatrics. 2019;144(2):e20190137. https://​doi.​org/​ 2017;10(2):105–14.
10.​1542/​peds.​2019-​0137. 61. Laurent S, et al. Expert consensus document on arterial stiff-
44. Makri A, Cheung A, Sinaii N, et al. Lipoprotein particles in ness: methodological issues and clinical applications. Eur
patients with pediatric Cushing disease and possible cardiovas- Heart J. 2006;27(21):2588–605.
cular risks. Pediatr Res. 2019;86(3):375–81. https://​doi.​org/​10.​ 62. Reusz GS, et al. Reference values of pulse wave veloc-
1038/​s41390-​019-​0438-0. ity in healthy children and teenagers. Hypertension.
45. Wu AJ, et al. Associations of midchildhood to early adolescence 2010;56(2):217–24.
central adiposity gain with cardiometabolic health in early ado- 63. Climie RE, et al. Vascular ageing in youth: a call to action.
lescence. Obesity (Silver Spring). 2021;29(11):1882–91. Heart Lung Circ. 2021;30(11):1613–26.
46. Bland VL, et al. Visceral adipose tissue and cardiometabolic risk 64. Fong TS, et al. Youth Vascular Consortium (YVC) proto-
factors in young Hispanic and non-Hispanic girls. Front Pediatr. col: establishing reference intervals for vascular ageing in
2022;10:892206. children, adolescents and young adults. Heart Lung Circ.
47. Shah RD, et al. Cardiovascular risk factor progression in ado- 2021;30(11):1710–5.
lescents and young adults with youth-onset type 2 diabetes. J 65. Nobles J, et al. A secondary analysis of the childhood obesity
Diabetes Complications. 2022;36(3):108123. prevention Cochrane Review through a wider determinants

13
Current Atherosclerosis Reports (2023) 25:405–415 413

of health lens: implications for research funders, researchers, between sleep duration and sleep quality with arterial stiff-
policymakers and practitioners. Int J Behav Nutr Phys Act. ness: a systematic review and meta-analysis. Sleep Health.
2021;18(1):22. 2022;8(6):663–70. https://​doi.​org/​10.​1016/j.​sleh.​2022.​07.​001.
66. Powell-Wiley TM, et al. Social determinants of cardiovascular 84. Wang S, Sun Q, Zhai L, Bai Y, Wei W, Jia L. The prevalence
disease. Circ Res. 2022;130(5):782–99. of depression and anxiety symptoms among overweight/obese
67. Cené CW, et al. Effects of objective and perceived social isola- and non-overweight/non-obese children/adolescents in China: a
tion on cardiovascular and brain health: a scientific statement systematic review and meta-analysis. Int J Environ Res Public
from the American Heart Association. J Am Heart Assoc. Health. 2019;16(3):340. https://d​ oi.o​ rg/1​ 0.3​ 390/i​ jerph​ 16030​ 340.
2022;11:e026493. https://​doi.​org/​10.​1161/​JAHA.​122.​026493. 85. Quek YH, et al. Exploring the association between childhood
68. Suglia SF, et al. Childhood and adolescent adversity and car- and adolescent obesity and depression: a meta-analysis. Obes
diometabolic outcomes: a scientific statement from the Ameri- Rev. 2017;18(7):742–54.
can Heart Association. Circulation. 2018;137:e15–28. 86. Mannan M, et al. Prospective associations between depression
69. Te Vazquez J, et al. Food insecurity and cardiometabolic and obesity for adolescent males and females- a systematic
conditions: a review of recent research. Curr Nutr Rep. review and meta-analysis of longitudinal studies. PLoS ONE.
2021;10(4):243–54. 2016;11(6):e0157240.
70. McClain AC, Cory H, Mattei J. Childhood food insufficiency 87. Barinas-Mitchell E, et al. Childhood-onset depression and
and adulthood cardiometabolic health conditions among a pop- arterial stiffness in young adulthood. J Psychosom Res.
ulation-based sample of older adults in Puerto Rico. SSM Popul 2021;148:110551.
Health. 2022;17:101066. 88. Mach F, et al. 2019 ESC/EAS Guidelines for the management
71. FAO, IFAD, UNICEF, WFP and WHO. The state of food secu- of dyslipidaemias: lipid modification to reduce cardiovascular
rity and nutrition in the world 2022. Repurposing food and agri- risk. Eur Heart J. 2020;41(1):111–88.
cultural policies to make healthy diets more affordable. Rome: 89. Arnett DK, et al. 2019 ACC/AHA guideline on the primary
FAO; 2022. https://​doi.​org/​10.​4060/​cc063​9en. prevention of cardiovascular disease: executive summary: a
72. Clemens KK, et al. Childhood food insecurity and incident dia- report of the American College of Cardiology/American Heart
betes: a longitudinal cohort study of 34 042 children in Ontario, Association Task Force on Clinical Practice Guidelines. J Am
Canada. Diabet Med. 2021;38(5):e14396. Coll Cardiol. 2019;74(10):1376–414.
73. Lee AM, et al. Food insecurity is associated with prediabetes risk 90. Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clini-
among U.S. adolescents, NHANES 2003–2014. Metab Syndr cal practice guideline for screening and management of
Relat Disord. 2019;17(7):347–54. high blood pressure in children and adolescents. Pediat-
74. Maldonado LE, Sotres-Alvarez D, Mattei J, et al. Food insecurity rics. 2017;140(3):e20171904. https://​doi.​org/​10.​1542/​peds.​
and cardiometabolic markers: results from the study of Latino 2017-​1904.
youth. Pediatrics. 2022;149(4):e2021053781. https://​doi.​org/​10.​ 91. Jebeile H, Kelly AS, O'Malley G, Baur LA. Obesity in children
1542/​peds.​2021-​053781. and adolescents: epidemiology, causes, assessment, and man-
75. Fulay AP, et al. Household and child food insecurity and CVD agement. Lancet Diabetes Endocrinol. 2022;10(5):351–65.
risk factors in lower-income adolescents aged 12–17 years https://​doi.​org/​10.​1016/​S2213-​8587(22)​00047-X.
from the National Health and Nutrition Examination Survey 92. Savoye M, et al. Reversal of early abnormalities in glucose
(NHANES) 2007–2016. Public Health Nutr. 2022;25(4):922–9. metabolism in obese youth: results of an intensive lifestyle ran-
76. Thomas MMC, Miller DP, Morrissey TW. Food insecurity and domized controlled trial. Diabetes Care. 2014;37(2):317–24.
child health. Pediatrics. 2019;144(4):e20190397. https://d​ oi.o​ rg/​ 93. Ligthart KAM, et al. The association between ethnicity, socio-
10.​1542/​peds.​2019-​0397. economic status and compliance to pediatric weight-manage-
77. Stephenson J. White House releases strategy to address hun- ment interventions - a systematic review. Obes Res Clin Pract.
ger, nutrition, and health in the US. JAMA Health Forum. 2017;11(5 Suppl 1):1–51.
2022;3(10):e224293. 94. Hayba N, Rissel C, Allman FM. Effectiveness of lifestyle
78. Malik FS, Liese AD, Reboussin BA, et al. Prevalence and pre- interventions in preventing harmful weight gain among ado-
dictors of household food insecurity and supplemental nutri- lescents: a systematic review of systematic reviews. Obes Rev.
tion assistance program use in youth and young adults with 2021;22(2):e13109. https://​doi.​org/​10.​1111/​obr.​13109.
diabetes: the search for diabetes in youth study. Diabetes Care. 95. Liberali R, Kupek E, Assis MAA. Dietary patterns and
2023;46(2):278–85. https://​doi.​org/​10.​2337/​dc21-​0790. childhood obesity risk: a systematic review. Child Obes.
79.•• Suglia SF, et al. Social determinants of cardiovascular health: 2020;16(2):70–85.
early life adversity as a contributor to disparities in cardiovas- 96. Jennings A, Welch A, van Sluijs EM, Griffin SJ, Cassidy A. Diet
cular diseases. J Pediatr. 2020;219:267–73. This report sum- quality is independently associated with weight status in children
marizes the mounting evidence linking adverse childhood aged 9-10 years. J Nutr. 2011;141(3):453–9. https://​doi.​org/​10.​
events to cardiovascular events and related disparities. Key 3945/​jn.​110.​131441.
research gaps and recommendations are identified. 97. Hu T, Jacobs DR Jr, Larson NI, Cutler GJ, Laska MN, Neu-
80. Bagby SP, et al. From the outside in: biological mechanisms link- mark-Sztainer D. Higher diet quality in adolescence and dietary
ing social and environmental exposures to chronic disease and to improvements are related to less weight gain during the transi-
health disparities. Am J Public Health. 2019;109(S1):S56–63. tion from adolescence to adulthood. J Pediatr. 2016;178:188–
81. Barnett TA, et al. Sedentary behaviors in today’s youth: 193.e3. https://​doi.​org/​10.​1016/j.​jpeds.​2016.​08.​026.
approaches to the prevention and management of childhood obe- 98. Hoelscher DM, Brann LS, O'Brien S, Handu D, Rozga M. Pre-
sity: a scientific statement from the American Heart Association. vention of pediatric overweight and obesity: position of the acad-
Circulation. 2018;138(11):e142–59. emy of nutrition and dietetics based on an umbrella review of
82. Lisan Q, et al. Sleep apnea is associated with accelerated vas- systematic reviews. J Acad Nutr Diet. 2022;122(2):410–423.e6.
cular aging: results from 2 european community-based cohort https://​doi.​org/​10.​1016/j.​jand.​2021.​11.​003.
studies. J Am Heart Assoc. 2021;10(15):e021318. 99. Rozga M, Handu D. Current systems-level evidence on nutrition
83. Saz-Lara A, Lucerón-Lucas-Torres M, Mesas AE, Notario- interventions to prevent and treat cardiometabolic risk in the
Pacheco B, López-Gil JF, Cavero-Redondo I. Association

13
414 Current Atherosclerosis Reports (2023) 25:405–415

pediatric population: an evidence analysis center scoping review. 117. Satija A, Hu FB. Cardiovascular benefits of dietary fiber. Curr
J Acad Nutr Diet. 2021;121(12):2501–23. Atheroscler Rep. 2012;14(6):505–14.
100. Sikand G, Severson T. Top 10 dietary strategies for athero- 118. Dahl WJ, et al. Health benefits of fiber fermentation. J Am Coll
sclerotic cardiovascular risk reduction. Am J Prev Cardiol. Nutr. 2017;36(2):127–36.
2020;4:100106. 119. Satija A, Hu FB. Plant-based diets and cardiovascular health.
101. Belardo D, et al. Practical, evidence-based approaches to nutri- Trends Cardiovasc Med. 2018;28(7):437–41.
tional modifications to reduce atherosclerotic cardiovascular 120. Alcazar M, et al. Gut microbiota is associated with metabolic
disease: an American society for preventive cardiology clinical health in children with obesity. Clin Nutr. 2022;41(8):1680–8.
practice statement. Am J Prev Cardiol. 2022;10:100323. 121. Tomova A, Bukovsky I, Rembert E, et al. The effects of vegetarian
102. Children and adolescents: standards of medical care in diabetes and vegan diets on gut microbiota. Front Nutr. 2019;6:47. https://​
2020. Diabetes Care. 2020;43(Supplement_1): S163–82. https://​ doi.​org/​10.​3389/​fnut.​2019.​00047.
doi.​org/​10.​2337/​dc20-​S013. 122. Witkowski M, Weeks TL, Hazen SL. Gut microbiota and cardio-
103. Choi Y, Larson N, Gallaher DD, et al. A shift toward a plant- vascular disease. Circ Res. 2020;127(4):553–70.
centered diet from young to middle adulthood and subsequent 123. Schiattarella GG, et al. Gut microbe-generated metabolite trimethyl-
risk of type 2 diabetes and weight gain: the coronary artery risk amine-N-oxide as cardiovascular risk biomarker: a systematic review
development in young adults (CARDIA) study. Diabetes Care. and dose-response meta-analysis. Eur Heart J. 2017;38(39):2948–56.
2020;43(11):2796–803. https://​doi.​org/​10.​2337/​dc20-​1005. 124. Velasquez MT, Ramezani A, Manal A, Raj DS. Trimethylamine
104. Choi Y, et al. Plant-centered diet and risk of incident cardiovas- N-oxide: the good, the bad and the unknown. Toxins (Basel).
cular disease during young to middle adulthood. J Am Heart 2016;8(11):326. https://​doi.​org/​10.​3390/​toxin​s8110​326.
Assoc. 2021;10(16):e020718. 125. Li D, et al. Gut microbiota-derived metabolite trimethylamine-
105. Suhett LG, Hermsdorff HHM, Cota BC, et al. Dietary inflamma- N-oxide and multiple health outcomes: an umbrella review and
tory potential, cardiometabolic risk and inflammation in children updated meta-analysis. Am J Clin Nutr. 2022;116(1):230–43.
and adolescents: a systematic review. Crit Rev Food Sci Nutr. 126. Wang Z, et al. Gut flora metabolism of phosphatidylcholine pro-
2021;61(3):407–16. https://​doi.​org/​10.​1080/​10408​398.​2020.​ motes cardiovascular disease. Nature. 2011;472(7341):57–63.
17349​11. 127. Koeth RA, et al. Intestinal microbiota metabolism of l-carni-
106. Mokhtari E, Mirzaei S, Asadi A, Akhlaghi M, Saneei P. tine, a nutrient in red meat, promotes atherosclerosis. Nat Med.
Association between plant-based diets and metabolic health 2013;19(5):576–85.
status in adolescents with overweight and obesity. Sci Rep. 128. Dai Y, Zhang J, Wang Z, et al. Associations of diet with urinary
2022;12(1):13772. https://d​ oi.o​ rg/1​ 0.1​ 038/s​ 41598-0​ 22-1​ 7969-4. trimethylamine-N-oxide (TMAO) and its precursors among
107. Alexy U, et al. Nutrient intake and status of German children and free-living 10-year-old children: data from SMBCS. Nutrients.
adolescents consuming vegetarian, vegan or omnivore diets: results 2022;14(16):3419. https://​doi.​org/​10.​3390/​nu141​63419.
of the VeChi youth study. Nutrients. 2021;13(5):1707–1707. 129. Meyer KA, Benton TZ, Bennett BJ, et al. Microbiota-dependent
108. Buckland G, et al. Prospective association between a Mediter- metabolite trimethylamine N-oxide and coronary artery calcium in
ranean-style dietary score in childhood and cardiometabolic the coronary artery risk development in young adults study (CAR-
risk in young adults from the ALSPAC birth cohort. Eur J Nutr. DIA). J Am Heart Assoc. 2016;5(10):e003970. https://​doi.​org/​10.​
2022;61(2):737–52. 1161/​JAHA.​116.​003970.
109. U.S. Department of Agriculture and U.S. Department of Health 130. Brunt VE, et al. Trimethylamine-N-oxide promotes age-related
and Human Services. Dietary Guidelines for Americans, 2020- vascular oxidative stress and endothelial dysfunction in mice and
2025. 9th ed. 2020. Available at Dieta​ryGui​delin​es.​gov. healthy humans. Hypertension. 2020;76(1):101–12.
110. Song M, et al. Association of animal and plant protein intake 131. Koh A, et al. From dietary fiber to host physiology: short-chain
with all-cause and cause-specific mortality. JAMA Intern Med. fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332–45.
2016;176(10):1453–63. 132. Liu D, Huang Y, Huang C, et al. Calorie restriction with or
111. Chang K, Khandpur N, Neri D, et al. Association between childhood without time-restricted eating in weight loss. N Engl J Med.
consumption of ultraprocessed food and adiposity trajectories in the 2022;386(16):1495–504. https://​doi.​org/​10.​1056/​NEJMo​a2114​
avon longitudinal study of parents and children birth cohort. JAMA 833.
Pediatr. 2021;175(9):e211573. https://​doi.​org/​10.​1001/​jamap​ediat​rics.​ 133. Acharyya BC, Mukhopadhyay M, Acharyya S. Management of
2021.​1573. paediatric fatty liver disease by intermittent fasting – a pilot study.
112. Neri D, Steele EM, Khandpur N, et al. Ultraprocessed food con- J Clin Exp Hepatol. 2022;12. https://​doi.​org/​10.​1016/j.​jceh.​2021.​
sumption and dietary nutrient profiles associated with obesity: 10.​069.
a multicountry study of children and adolescents. Obes Rev. 134. Vidmar AP, Goran MI, Raymond JK. Time-limited eating in pedi-
2022;23(Suppl 1):e13387. https://​doi.​org/​10.​1111/​obr.​13387. atric patients with obesity: a case series. J Food Sci Nutr Res.
113. Sirkka O, Fleischmann M, Abrahamse-Berkeveld M, et al. Dietary 2019;2(3):236–44. https://​doi.​org/​10.​26502/​jfsnr.​2642-​11000​022.
patterns in early childhood and the risk of childhood overweight: 135 Irl B H, et al. Culinary medicine: advancing a framework for
the GECKO Drenthe birth cohort. Nutrients. 2021;13(6):2046. healthier eating to improve chronic disease management and pre-
https://​doi.​org/​10.​3390/​nu130​62046. vention. Clin Ther. 2019;41(10):2184–98.
114. Feingold KR. The effect of diet on cardiovascular disease and lipid 136. Kakareka R, et al. Fresh and savory: integrating teaching kitchens
and lipoprotein levels. In: Feingold KR, Anawalt B, Blackman with shared medical appointments. J Altern Complement Med.
MR, et al., editors. Endotext. South Dartmouth (MA): MDText. 2019;25(7):709–18.
com, Inc.; 2021. 137. La Puma J. What is culinary medicine and what does it do? Popul
115. Surampudi P, et al. Lipid Lowering with soluble dietary fiber. Curr Health Manag. 2016;19(1):1–3.
Atheroscler Rep. 2016;18(12):75. 138. Asher RC, et al. Culinary medicine and culinary nutrition education
116. Islam SU, Ahmed MB, Ahsan H, Lee YS. Recent Molecular Mecha- for individuals with the capacity to influence health related behaviour
nisms and Beneficial Effects of Phytochemicals and Plant-Based change: a scoping review. J Hum Nutr Diet. 2022;35(2):388–95.
Whole Foods in Reducing LDL-C and Preventing Cardiovascular 139. McManus CR, et al. 907-P: diabetes-inspired culinary education
Disease. Antioxidants (Basel). 2021;10(5):784. https://​doi.​org/​10.​ (dice): an innovative approach to type 1 diabetes management
3390/​antio​x1005​0784. through culinary medicine. Diabetes. 2021;70(Supplement_1).

13
Current Atherosclerosis Reports (2023) 25:405–415 415

140. Sharma SV, McWhorter JW, Chow J, Danho MP, Weston SR, 146. Michalsky MP, Inge TH, Jenkins TM, et al. Cardiovascu-
Chavez F, Moore LS, Almohamad M, Gonzalez J, Liew E, LaRue lar risk factors after adolescent bariatric surgery. Pediatrics.
DM, Galvan E, Hoelscher DM, Tseng KC. Impact of a virtual 2018;141(2):e20172485. https://​doi.​org/​10.​1542/​peds.​2017-​2485.
culinary medicine curriculum on biometric outcomes, dietary 147. Zitsman JL, et al. Pediatric and adolescent obesity: management,
habits, and related psychosocial factors among patients with options for surgery, and outcomes. J Pediatr Surg. 2014;49(3):491–4.
diabetes participating in a food prescription program. Nutrients. 148. Pratt JSA, et al. ASMBS pediatric metabolic and bariatric surgery
2021;13(12):4492. https://​doi.​org/​10.​3390/​nu131​24492. guidelines, 2018. Surg Obes Relat Dis. 2018;14(7):882–901.
141. Downer S, et al. Food is medicine: actions to integrate food and 149. Bolling CF, et al. Metabolic and bariatric surgery for pediatric
nutrition into healthcare. BMJ. 2020;369:m2482. patients with severe obesity. Pediatrics. 2019;144(6):e20193224.
142. Bensignor MO, Kelly AS, Arslanian S. Anti-obesity pharmaco- 150. Armstrong SC, Bolling CF, Michalsky MP, Reichard KW, Sec-
therapy for treatment of pediatric type 2 diabetes: review of the tion on Obesity, Section on Surgery. Pediatric metabolic and bari-
literature and lessons learned from adults. Front Endocrinol (Laus- atric surgery: evidence, barriers, and best practices. Pediatrics.
anne). 2022;13:1043650. 2019;144(6):e20193223. https://​doi.​org/​10.​1542/​peds.​2019-​3223.
143. Stancil SL, Abdel-Rahman S, Wagner J. Developmental considera- 151. Patrick SW, Henkhaus LE, Zickafoose JS, et al. Well-being of
tions for the use of naltrexone in children and adolescents. J Pediatr parents and children during the COVID-19 pandemic: a national
Pharmacol Ther. 2021;26(7):675–95. survey. Pediatrics. 2020;146(4):e2020016824. https://​doi.​org/​10.​
144. Weghuber D, Barrett T, Barrientos-Pérez M, et al. Once- 1542/​peds.​2020-​016824.
weekly semaglutide in adolescents with obesity. N Engl 152. Racine N, et al. Global prevalence of depressive and anxiety
J Med. 2022;387(24):2245–57. https://​d oi.​o rg/​1 0.​1 056/​ symptoms in children and adolescents during COVID-19: a meta-
NEJMo​a 2208​6 01. analysis. JAMA Pediatr. 2021;175(11):1142–50.
145. Goldenshluger M, Iluz R, Beck T, et al. Laparoscopic sleeve
gastrectomy in adolescents: ten-years follow-up. Obes Surg. Publisher's Note Springer Nature remains neutral with regard to
2023;33(1):32–7. https://​doi.​org/​10.​1007/​s11695-​022-​06348-7. jurisdictional claims in published maps and institutional affiliations.

13