Abstract
Strong epidemiological evidence has shown that early life adversity (ELA) has a profound negative impact on health in adulthood, including an increased risk of cardiovascular disease, the leading cause of death worldwide. Here, we review cohort studies on the effects of ELA on cardiovascular outcomes and the possible underlying mechanisms. In addition, we summarize relevant studies in rodent models of ELA. This review reveals that the prevalence of ELA varies between regions, time periods, and sexes. ELA increases cardiovascular health risk behaviors, susceptibility to mental illnesses, and neuroendocrine and immune system dysfunction in humans. Rodent models of ELA have been developed and show similar cardiovascular outcomes to those in humans but cannot fully replicate all ELA subtypes. Therefore, combining cohort and rodent studies to further investigate the mechanisms underlying the association between ELA and cardiovascular diseases may be a feasible future research strategy.
1 Introduction
Since Felitti et al. conducted the Adverse Childhood Experiences Study in 1998, the relationship between Early Life Adversity (ELA) and negative long-term health outcomes has attracted much research attention (1). Also called adverse childhood experiences in human studies, ELA is defined as potentially traumatic events that occur before adulthood, including threats to the child’s bodily, familial, or social safety and security, and ranges from broad categories of abuse, neglect, and household dysfunction to more specific experiences of bullying, exposure to crime, victimization, and economic hardship (1–4). ELA is highly prevalent, with regional variations occur. According to data from the Behavioral Risk Factor Surveillance System, 61.55% of adults in the United States have experienced ELA (2); in European countries, this figure ranges from 20.4 to 69.4% (5). In Chinese middle-aged or older adults it can be up to 80.9%, according to data from the China Health and Retirement Longitudinal Study (6). Societal changes over time affect the prevalence of specific adverse experiences. For example, during the first 15–18 years of the 21st century, parental illness, sibling death, exposure to domestic violence, childhood poverty, parental divorce, serious childhood illness, physical abuse, sexual abuse, physical and emotional bullying, and exposure to community violence declined; however, parental alcohol and drug abuse increased (7).
ELA exposure has been strongly associated with the development of various health conditions in later life, including cardiovascular disease, which is the leading cause of death worldwide. Cohort studies indicate that ELA increases the odds of cardiovascular health risk behaviors, such as smoking and alcoholism, as well as having long-term effects on the stress response system, leading to autonomic, vascular, and inflammatory dysfunction, and contributing to the onset and development of cardiovascular disease (4). Rodent models such as maternal separation have been developed to study the underlying mechanisms of cardiovascular effects of ELA. Consistent with human cohort studies, negative cardiovascular outcomes were observed (8).
This review provides an overview of the epidemiological evidence linking ELA to the development of cardiovascular disease and the mechanisms underlying the effects of ELA on the cardiovascular system. In addition, we summarize the rodent models that have been developed to mimic ELA and mechanistic studies performed using these models. Finally, we discuss the direction of future research.
2 ELA and cardiovascular outcomes in humans
An increasing number of cohort studies have shown ELA to be strongly associated with negative cardiovascular outcomes (Table 1). Different types of adversities have been carefully classified, and their effects studied. Abuse, neglect, and household dysfunction are the three most common types of adversity; all of these have been shown to increase the risk of cardiovascular events in adulthood, including ischemic heart disease, myocardial infarction, coronary heart disease, stroke, and heart failure (9, 11, 13–15, 18, 19, 21). These correlations were dose-dependent, the more types of adversities experienced, the higher the risk (9, 13, 18). Exposure to a single adversity type has been associated with a 1.3- to 1.7-fold increase in the risk of ischemic heart disease compared with that of individuals not exposed to adversity (9). The risk of developing myocardial infarction was increased in individuals who experienced ELA compared with those who did not, while the risk of developing coronary heart disease and stroke was increased in individuals exposed to more than four types of ELA compared with those who experienced fewer types (13). The risk of developing heart failure doubled following exposure to three to five types of ELA (18).
Table 1
| Type of adversity | Participants | Cardiovascular outcomes | References |
|---|---|---|---|
| Abuse (emotional, physical, sexual), Neglect (emotional, physical), Household dysfunction (substance abuse, mental illness, domestic violence, criminal household member, parental marital discord) | Health plan members at Kaiser Permanente’s Health Appraisal Center in San Diego from 1995 to 1997 n = 17,337, 54% female, 75% Caucasian, aged 56 ± 15.2 years | Risk of ischemic heart disease increased following exposure to any individual adversity except parental marital discord | Dong et al. (9) |
| Parental divorce, Financial difficulties, Interpersonal conflicts, Fear of a family member, Longstanding illness, Alcohol-related problems | Finnish citizens n = 23,916, 59% female, aged 20–24, 30–34, 40–44, 50–54 years | Women: risk of cardiovascular disease increased following exposure to financial difficulties, interpersonal conflicts and longstanding illness of a relative Men: increased risk following longstanding illness of a relative | Korkeila et al. (10) |
| Physical abuse, Sexual abuse | Nurses’ Health Study 2 participants n = 66,798, 100% female, aged 25–42 years | Physical and sexual abuse in childhood predicts early onset of cardiovascular events | Rich-Edwards et al. (11) |
| Witnessed violence with a weapon, Victims of violence | National Longitudinal Study of Adolescent Health participants n = 7,971, 55.4% female, aged 24–31 years | Increased risk of hypertension in males who witnessed violence and females who were victims of violence | Ford and Browning (12) |
| Physical abuse, Sexual abuse, Emotional abuse, Household member mental illness, Alcoholism, Drug abuse, Imprisonment, Divorce, Intimate partner violence | 2010 Behavioral Risk Factor Surveillance System participants n = 53,998, 60.5% female, adults | Higher risk of myocardial infarction, coronary heart disease, and diabetes | Gilbert et al. (13) |
| Household dysfunction, Physical abuse, Verbal abuse, Sexual abuse | 2011–2012 Behavioral Risk Factor Surveillance System participants n = 78,435, 48.6% female, 82.3% Caucasian, adults | Positively associated with cardiovascular disease independent of depression | Salas et al. (14) |
| Physical abuse, Physical neglect, Emotional abuse, Emotional neglect, Sexual abuse | National Epidemiologic Study of Alcohol and Related Conditions participants n = 34,653, 52.1% female, aged ≥20 years | Associated with increased risk of myocardial infarction | Chou and Koenen (15) |
| Famine exposure | China Cardiometabolic Disease and Cancer Cohort Study participants n = 77,925, 69.5% female, aged ≥40 years | Increased risk of diabetes in fetal-exposed individuals | Lu et al. (16) |
| Famine exposure | REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study participants n = 234,219, 67.9% female, aged ≥40 years | Increased risk of total cardiovascular disease, myocardial infarction, stroke, and coronary heart disease | Du et al. (17) |
| Physical abuse, Physical neglect, Emotional abuse, Emotional neglect, Sexual abuse | 2006–2010 UK Biobank participants n = 153,287, 56.4% female, aged 55.9 ± 7.7 years | Increased risk of incident heart failure dose-dependent | Liang et al. (18) |
| Feel alone, Peer bullied, Relationship with parents, Relationship with neighbors, Relationship with friends, Self-reported health status, Health limitation, Death of parents, Death of siblings, Physical abuse, Parental mental health, Guardians’ bad habits, Hunger, Childhood neighborhood quality, Childhood neighborhood safety | 2011–2018 China Health and Retirement Longitudinal Study (CHARLS) participants n = 12,981, 51.2% female, aged ≥45 years | Associated with both onset and severity of symptoms and cardiovascular diseases | Liu et al. (19) |
| Household mental illness, Household substance abuse, Household incarceration, Parental separation/divorce, Witnessing household violence, Physical abuse, Emotional abuse, Sexual abuse | 2020 Behavioral Risk Factor Surveillance System participants n = 31,242, 54.6% female, 79.8% Caucasian, aged 68.7 ± 7.85 years | Men: household incarceration was most strongly associated with stroke Women: the strongest connection was between physical abuse and stroke, followed by sexual abuse and angina/coronary heart disease | Lee et al. (20) |
| Material deprivation (family poverty, parental long-term unemployment), Loss or threat of loss in the family (parental and sibling somatic illness and death), Family dynamics (foster care placements, parental and sibling psychiatric illness, parental alcohol and drug abuse, maternal separation) | Danish Life Course Cohort Study participants n = 1,263,013, 48.7% female, aged 16–38 years | Higher risk of developing cardiovascular disease in young adulthood | Bengtsson et al. (21) |
Large cohort studies on the correlation of ELA with cardiovascular outcomes.
Certain specific types of ELA have also been associated with cardiovascular events. The risk of hypertension was increased in males who have witnessed violence with a weapon and female victims of violence (12). Fetal exposure to famine increased the risk of diabetes (16), while famine experienced in early life increased the risk of total cardiovascular disease, myocardial infarction, stroke, and coronary heart disease (17). In addition, early exposure to air pollution increased the lifetime burden on the cardiovascular system, contributing to the development of cardiovascular disease (22).
Sex differences are observed in the incidence and effects of ELA. Within the same racial and ethnic population, females are more likely than males to experience ELA (23). The risk of cardiovascular disease increased in women who were exposed to financial difficulties, interpersonal conflicts, and chronic illness in a relative. For men, an increased risk was observed only following chronic illness in a relative (10). Stoke was most strongly associated with physical abuse in women and household incarceration in men (20).
3 Possible mechanisms linking ELA and cardiovascular disease in humans
3.1 Behavioral factors
Diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure are recognized as Life’s Essential 8, the eight most important contributors to cardiovascular health (24). ELA exposure significantly increases the incidence of smoking, alcoholism, physical inactivity, obesity, and poor sleep (Table 2) (1, 38, 40–44).
Table 2
| Type of adversity | Participants | Cardiovascular risk behaviors | References |
|---|---|---|---|
| Household mental illness, Household drinking problem, Household substance abuse, Household member incarceration, Parent separation or divorce, Household physical assault, Victim of physical assault, Victim of verbal abuse, Touched sexually, Forced to touch adult sexually, Forced to have sex | 2009 Behavioral Risk Factor Surveillance System participants n = 10,277, 51.3% female, aged ≥18 years | Cigarette smoking | Vander Weg (25) |
| Abuse (physical, verbal), Household dysfunction, Emotional neglect | Taiwan Youth Project participants n = 2,903, 50.5% female, aged 22 years | Heavy smoking | Lin and Chiao (26) |
| Lived with problem drinker/alcoholic, Lived with drug abuser, Parents divorced, Forced sex as a child, Childhood physical abuse by parents, Childhood verbal abuse by parents | 2010 Behavioral Risk Factor Surveillance System participants n = 19,356, 59.4% female, aged ≥18 years | Physical abuse was associated with smoking in males and females, sexual abuse and verbal abuse were associated with smoking in females but not males | Fuller-Thomson et al. (27) |
| Physical abuse, Sexual abuse, Verbal abuse, Mental illness in home, Substance abuse in home, Separation/divorce in home, Violence in adults at home, Incarceration at home | 2011 Behavioral Risk Factor Surveillance System survey participants n = 48,526, 50.43% female, aged ≥18 years | Binge drinking, heavy drinking, smoking | Campbell et al. (28) |
| Physical abuse, Household alcohol abuse, Household mental illness | US National Longitudinal Survey of Youth 1979 (NLSY79) and NLSY79 Children and Young Adults Survey participants n = 2,999 mothers; n = 6,596 children | Women are more likely to smoke during pregnancy; their children are more likely to start smoking before age 18 | Pear et al. (29) |
| Household mental health, Household alcohol abuse, Household drug abuse, Household incarceration, Parental separation or divorce, Household physical violence, Child physical abuse, Child verbal abuse, Sexual abuse | 2012 Behavioral Risk Factor Surveillance System participants n = 39,434, 60.5% female, aged ≥18 years | Heavy and binge drinking in men who lived with a drug abuser as a child; binge drinking in men and women exposed to verbal abuse | Fang et al. (30) |
| Abuse/child maltreatment, Household dysfunction | Australian Longitudinal Study on Women’s Health participants n = 8,915, 100% female, aged 19–26 years | E-cigarette use | Melka et al. (31) |
| Abuse, Neglect, Household dysfunction | National Epidemiological Survey on Alcohol and Related Conditions-III and National Institute on Alcohol Abuse and Alcoholism participants n = 26,855, 41.6% female, aged ≥18 years | High-intensity binge drinking | Jung et al. (32) |
| Bullying | Meta-analysis of 18 cross-sectional studies n = 386,740, 51.8% female, children and adolescents | Physical inactivity and sedentary behavior | García-Hermoso et al. (33) |
| Childhood maltreatment (emotional, physical, sexual, neglect), Household dysfunction (violence between parents, parental separation, household substance abuse, mental illness, incarceration) | Meta-analysis of 10 observational studies n = 118,691 | 46% increase in the risk of adult obesity following exposure to multiple adversities | Wiss and Brewerton (34) |
| Abuse (emotional, physical, and sexual), Household stressors | Community Health Needs Assessment in Florida participants n = 14,056, 74.1% female, aged ≥18 years | Cigarette and e-cigarette use | Martinasek et al. (35) |
| Child in care, Physical neglect, Offenders, Parental separation, Mental illness, Alcohol abuse | 1958 National Child Development Study participants n = 7,414, 51.5% female, aged 7–42 years | Smoking by age 16 and long-term smoking | Joannès et al. (36) |
| Childhood abuse (emotional, physical, sexual), Household dysfunction (mental illness, substance use, incarceration, separation/divorce, witnessing domestic violence) | 2019 Behavioral Risk Factor Surveillance System survey participants n = 41,322, 50.7% female, aged 18–64 years | Binge drinking risk was 1.36 times higher in females who experienced two types of adversities, and 1.58 times higher for females who experienced three | Baiden et al. (37) |
| Sexual abuse, Physical abuse, Emotional abuse, Neglect, Family dysfunction | Meta-analysis of 9 articles n = 108,330, participants from 5 high-income countries | Sleep deficiency and poor sleep quality | Yu et al. (38) |
| Physical abuse, Sexual abuse, Verbal abuse, Mental illness, Substance abuse, Separation/divorce, Violence in adults, Incarceration | 2020 Behavioral Risk Factor Database participants n = 42,786, 55.8% female, aged ≥65 years | Short and long sleep duration | Cheng et al. (39) |
Correlation of ELA with cardiovascular risk behaviors.
ELA increases the risk of both cigarette and e-cigarette smoking (25, 26, 31, 35), with exposed individuals more likely to start smoking by 16 years of age and smoke for a lifetime (36). Physical abuse was associated with smoking in both males and females; sexual and verbal abuse were associated with smoking in females but not males (27). This correlation has intergenerational effects, maternal exposure to childhood physical abuse was associated with an increased risk of both smoking during pregnancy and the child smoking (29).
ELA is also associated with high-intensity binge drinking (32). Heavy and binge drinking was more common in men who lived with a drug abuser as a child than in those who did not, and verbal abuse was correlated with binge drinking in both men and women (30). The greater the total number of adversities experienced, the higher the probability of binge drinking (28, 37). Although some studies suggest that moderate drinking may be beneficial for cardiovascular health, large cohort studies have shown that all levels of alcohol consumption are associated with an increased cardiovascular risk (45–47).
A meta-analysis showed that physical inactivity increased among children and adolescents exposed to bullying (33). A separate meta-analysis of 10 observational studies showed that the risk of obesity in adulthood increased 46% following ELA (34). Physical inactivity and obesity have been closely associated with high blood lipid, glucose, and blood pressure levels, which are major contributors to cardiovascular disease (48, 49).
A systematic review and meta-analysis indicated that ELA has a considerable impact on long-term sleep health: the greater the exposure, the higher the risk of sleep disorders (38). ELA exposure was associated with both short and long sleep duration: victims of childhood sexual abuse were 146% more likely to short sleep and 99% more likely to long sleep; reporting more than four types of adversities raised these risks to 3.10 and 2.13 times, respectively (39). Both short and long sleep duration and poor sleep quality are associated with an increased risk of all-cause mortality and cardiovascular events (50, 51).
3.2 Mental factors
ELA is associated with the development of mental illnesses in adulthood, including anxiety, depression, post-traumatic stress disorder (PTSD), and schizophrenia. Cohort studies have shown that ELA increases the incidence of anxiety, depression, and PTSD (52–54). ELA exposure has been associated with both the onset and severity of depression and cardiovascular disease (19). The number of adversity types experienced was a nonlinear predictor of depression (55). A meta-analysis including over 200,000 participants showed that individuals maltreated in childhood had an increased risk of depression and cardiometabolic disease, and were three times more likely to have comorbid depression and cardiometabolic disease (56). A systematic review and meta-analysis associated childhood trauma with the severity of hallucinations and delusions in individuals with psychotic disorders (57). In addition, patients with schizophrenia report more exposure to ELA than healthy controls (58).
Mental illness increases the burden on the cardiovascular system through biological pathways such as elevated cortisol, oxidative stress, inflammation, and autonomic nervous system dysfunction, as reviewed in detail by Treur et al. (59). Patients with severe mental illness have twice the cardiovascular mortality rate of the general population (60, 61). Both anxiety and depression are associated with an increased risk of mortality owing to cardiovascular events (62, 63). Schizophrenia reduces life expectancy by 15–20 years, with 40–50% of deaths due to cardiovascular disease (64). Thus, ELA may predispose individuals to cardiovascular diseases later in life through their susceptibility to mental illnesses.
3.3 Biological pathways
ELA disturbs the neuroendocrine and immune systems in adulthood; this dysregulation has been associated with cardiovascular diseases. Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has been observed in individuals exposed to ELA (65–68). A meta-analysis indicated that cortisol levels affected by ELA (67). Bullying, emotional abuse, and cumulative exposure to adversity have been associated with low daytime salivary cortisol levels in adolescents (66). Increased levels of hair cortisone were detected among middle-aged and older individuals exposed to ELA (65, 68). Meta analyses have indicated that ELA increases levels of inflammatory mediators such as C-reactive protein, interleukin-6, and tumor necrosis factor-α (69, 70). These effects persist into late adulthood (71). Dysregulated inflammation and cortisol levels may contribute to the development of mental illnesses such as depression (72–74), increasing the risk of cardiovascular disease.
ELA has been reported to directly increase circulating endothelin-1 levels in young adulthood, with greater numbers of adversity types faced further increasing endothelin-1 levels (75). Endothelin-1 is a peptide produced by the vascular endothelium in response to stress (76, 77) and is implicated in the pathogenesis of cardiovascular diseases (78). Physical exercise decreases endothelin-1 levels among women exposed to ELA and improves cardiovascular psychophysiological outcomes; endothelin-1 may therefore be a potential therapeutic target for the treatment of cardiovascular diseases following ELA (79).
4 Impact of ELA on the cardiovascular system in rodents
4.1 Rodent models of ELA
In humans, ELA primarily involves abuse, neglect, and household dysfunction. To mimic these adversities, several types of rodent models have been developed: (1) Maternal separation, in which pups are removed from their mother for several hours per day (at different times each day) during the postnatal period (2). Social deprivation, in which pups are separated from both their mother and littermates for several hours per day (at different times each day) during the postnatal period (3). Limited bedding and nesting, in which the mother and pups have limited access to nesting material during the postnatal period (4). Early weaning, in which pups are weaned before postnatal day 21, usually on postnatal day 17. Of these, maternal separation is the most widely used. To simulate multiple ELA exposures, these models are used in combination, such as maternal separation combined with limited bedding and nesting and maternal separation combined with early weaning (80, 81). These rodent models effectively simulate the negative outcomes of ELA, behavioral experiments have shown that rodents exposed to ELA elicit negative psychopathological outcomes in adulthood. Mice exposed to maternal separation and limited nesting were more susceptible to depression-like behaviors after social defeat (82). Social deprivation during postnatal days 1–14 increased the risk of social dysfunction later in life (83).
4.2 Mechanisms underlying the effect of ELA on the cardiovascular system in rodents
Consistent with results from human studies, ELA in rodents negatively affects the cardiovascular system (Table 3). Neuroendocrine, immune system and vascular dysfunction have been identified following ELA in rodents. Dysfunction in the HPA axis and renin-angiotensin-aldosterone system were detected in rats and mice following maternal separation, as evidenced by increased levels of corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, and angiotensin II (84, 86, 92). Circulating endothelin-1 levels were significantly increased in rats following maternal separation (85). In a mouse model of maternal separation, acute mixing stress induced lower blood pressure and heart rate responses (87). Maternal separation in rats resulted in misprogramming of resistance artery smooth muscle, increased vasoconstriction and blood pressure (88), and blood–brain barrier dysfunction (84, 95). ELA also increased oxidative stress and inflammation. Levels of the reactive oxygen species nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 (89, 90) and the inflammatory protein interleukin-1β and Toll-link receptor 4 (93, 95) were increased in rodents following ELA. ELA may be linked to oxytocin signaling, cardiac oxytocin receptors decreased following maternal separation on postnatal days 1–21, but increased following maternal separation on postnatal days 12–16 (91). Maternal separation and early weaning increased adiposity in female mice, which may be the mechanism underlying the development of obesity and diabetes following ELA (94).
Table 3
| Animal | Model | Molecular and/or structural alteration | References |
|---|---|---|---|
| Wistar rats | Prenatal stress (E10-20) and maternal separation (P2-20) | Plasma corticosterone, blood–brain barrier functional development | Gomez-Gonzalez and Escobar (84) |
| Rats | Maternal separation (P2-14) | Circulating endothelin-1, endothelin A and B receptors in aortic tissue | Loria et al. (85) |
| Wistar Kyoto rats | Maternal separation (P2-14) | Angiotensin II | Loria et al. (86) |
| BALB/c mice | Maternal separation (P2-14) | Blood pressure and heart rate, induced by acute mixing stress | Pote et al. (87) |
| Sprague–Dawley rats | Maternal separation (P2-14) | Small resistance mesenteric arteries | Reho and Fisher (88) |
| C57BL/6 J mice | Maternal separation (P2-16) with early weaning at P17 | Nicotinamide adenine dinucleotide phosphate oxidase 2 and 4 | Ho et al. (89) |
| Male Albino Wistar rats | Maternal separation (P2-14) | Reactive oxygen species, mitochondrial glutathione, ATP, cytochrome c | Sahafi et al. (90) |
| C57BL/6 mice | Long-Term Separation Stress: maternal separation (P1-21) Short-Term Separation Stress: maternal separation (P14-16) | Oxytocin receptor | Wigger et al. (91) |
| CD-1 mice | Maternal separation (P1-21) | Corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone | Campana et al. (92) |
| NMRI mice | Maternal separation (P2-14) | Malondialdehyde, nitrite, interleukin-1β, Toll-like receptor 4 | Arabi et al. (93) |
| C57BL/6 J female mice | Maternal separation (P2-16) with early weaning at P17 | Adipocyte, aldosterone, corticosterone | Leachman et al. (94) |
| Wistar rats | Maternal separation (P1-14) and lipopolysaccharide injection in juvenility or adulthood | Serum proinflammatory cytokines, blood–brain barrier permeability | Solarz et al. (95) |
Molecular and/or structural alteration following ELA on cardiovascular system in rodent.
5 Discussion and future directions
Despite the progress in community and family support, ELA remains highly prevalent and contributes to the morbidity and mortality of cardiovascular diseases worldwide. The prevalence of ELA varies between countries and regions, and between sexes. Over time, the prevalence of different subtypes of ELA changes. This means that the adoption of rigorous sampling strategies is required to dynamically surveil the prevalence of subtypes of ELA and minimize data bias (7). It also means that policymakers need to be flexible in the use of prevention strategies to reduce the incidence of ELA. Numerous cohort studies have revealed the association between ELA and cardiovascular disease, with the risk increasing with greater ELA exposure. However, the frequency, intensity, exposure duration, and exposure timing of each subtype of ELA, which may also have an impact on cardiovascular outcomes, have not been fully assessed (96). Each individual’s childhood experience is unique and may experience some specific subtypes of ELA. Therefore, how to accurately evaluate the effect of ELA on an individual’s cardiovascular system requires further investigation.
Mechanistic studies in humans have shown that ELA increases cardiovascular health risk behaviors, susceptibility to mental illnesses, and neuroendocrine and immune system dysfunction. But whether ELA directly affects the development of cardiovascular disease or whether the association between ELA and cardiovascular disease is fully mediated through risk behaviors remains to be determined. Rodent models have been developed to study the mechanisms underlying the effects of ELA on cardiovascular outcomes and result in cardiovascular dysfunction similar to that observed in humans. Rodents exposed to ELA showed similar behavioral tendencies to humans exposed to ELA, such as alcohol consumption (97), drug addiction (98), and depression-like behavior (82). However, whether these behavioral effects contribute to cardiovascular outcomes remains largely unknown. Rodent models provide an important research tool as they allow the association between ELA and cardiovascular disease to be analyzed in a homogenous population under controlled conditions. However, these models cannot fully replicate all of ELA subtypes. Therefore, combining cohort and rodent studies to analyze the association between ELA and cardiovascular diseases may be a feasible future research strategy.
Statements
Author contributions
HT: Conceptualization, Resources, Visualization, Writing – original draft, Writing – review & editing. HZ: Writing – review & editing. JC: Writing – review & editing. HR: Writing – review & editing. YG: Funding acquisition, Project administration, Supervision, Writing – review & editing. XJ: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Sustainable Development Science and Technology Project of the Shenzhen Science and Technology Innovation Commission (KCXFZ20201221173411032 and KCXFZ20201221173400001) and the “Five Threes” Clinical Research Program of Shenzhen People’s Hospital (SYWGSLCYJ202204).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
1.
FelittiVJAndaRFNordenbergDWilliamsonDFSpitzAMEdwardsVet al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study. Am J Prev Med. (1998) 14:245–58. doi: 10.1016/S0749-3797(98)00017-8
2.
SugliaSFKoenenKCBoynton-JarrettRChanPSClarkCJDaneseAet al. Childhood and adolescent adversity and Cardiometabolic outcomes: a scientific statement from the American Heart Association. Circulation. (2018) 137:e15–28. doi: 10.1161/CIR.0000000000000536
3.
CronholmPFForkeCMWadeRBair-MerrittMHDavisMHarkins-SchwarzMet al. Adverse childhood experiences: expanding the concept of adversity. Am J Prev Med. (2015) 49:354–61. doi: 10.1016/j.amepre.2015.02.001
4.
GodoyLCFrankfurterCCooperMLayCMaunderRFarkouhME. Association of Adverse Childhood Experiences with Cardiovascular Disease Later in life: a review. JAMA Cardiol. (2021) 6:228–35. doi: 10.1001/jamacardio.2020.6050
5.
HughesKFordKBellisMAGlendinningFHarrisonEPassmoreJ. Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis. Lancet Public Health. (2021) 6:e848–57. doi: 10.1016/S2468-2667(21)00232-2
6.
LinLWangHHLuCChenWGuoVY. Adverse childhood experiences and subsequent chronic diseases among middle-aged or older adults in China and associations with demographic and socioeconomic characteristics. JAMA Netw Open. (2021) 4:e2130143. doi: 10.1001/jamanetworkopen.2021.30143
7.
FinkelhorD. Trends in adverse childhood experiences (ACEs) in the United States. Child Abuse Negl. (2020) 108:104641. doi: 10.1016/j.chiabu.2020.104641
8.
MurphyMOCohnDMLoriaAS. Developmental origins of cardiovascular disease: impact of early life stress in humans and rodents. Neurosci Biobehav Rev. (2017) 74:453–65. doi: 10.1016/j.neubiorev.2016.07.018
9.
DongMGilesWHFelittiVJDubeSRWilliamsJEChapmanDPet al. Insights into causal pathways for ischemic heart disease: adverse childhood experiences study. Circulation. (2004) 110:1761–6. doi: 10.1161/01.CIR.0000143074.54995.7F
10.
KorkeilaJVahteraJKorkeilaKKivimakiMSumanenMKoskenvuoKet al. Childhood adversities as predictors of incident coronary heart disease and cerebrovascular disease. Heart. (2010) 96:298–303. doi: 10.1136/hrt.2009.188250
11.
Rich-EdwardsJWMasonSRexrodeKSpiegelmanDHibertEKawachiIet al. Physical and sexual abuse in childhood as predictors of early-onset cardiovascular events in women. Circulation. (2012) 126:920–7. doi: 10.1161/CIRCULATIONAHA.111.076877
12.
FordJLBrowningCR. Effects of exposure to violence with a weapon during adolescence on adult hypertension. Ann Epidemiol. (2014) 24:193–8. doi: 10.1016/j.annepidem.2013.12.004
13.
GilbertLKBreidingMJMerrickMTThompsonWWFordDCDhingraSSet al. Childhood adversity and adult chronic disease: an update from ten states and the District of Columbia, 2010. Am J Prev Med. (2015) 48:345–9. doi: 10.1016/j.amepre.2014.09.006
14.
SalasJvan den Berk-ClarkCSkiold-HanlinSSchneiderFDScherrerJF. Adverse childhood experiences, depression, and cardiometabolic disease in a nationally representative sample. J Psychosom Res. (2019) 127:109842. doi: 10.1016/j.jpsychores.2019.109842
15.
ChouPHKoenenKC. Associations between childhood maltreatment and risk of myocardial infarction in adulthood: results from the National Epidemiologic Survey on alcohol and related conditions. J Psychiatr Res. (2019) 116:172–7. doi: 10.1016/j.jpsychires.2018.12.001
16.
LuJLiMXuYBiYQinYLiQet al. Early life famine exposure, ideal cardiovascular health metrics, and risk of incident diabetes: findings from the 4C study. Diabetes Care. (2020) 43:1902–9. doi: 10.2337/dc19-2325
17.
DuRZhengRXuYZhuYYuXLiMet al. Early-life famine exposure and risk of cardiovascular diseases in later life: findings from the REACTION study. J Am Heart Assoc. (2020) 9:e014175. doi: 10.1161/JAHA.119.014175
18.
Liang YyMPAiSWengFFengHYangLHeZet al. Associations of childhood maltreatment and genetic risks with incident heart failure in later life. J Am Heart Assoc. (2022) 11:e026536. doi: 10.1161/JAHA.122.026536
19.
LiuYWangCLiuY. Association between adverse childhood experiences and later-life cardiovascular diseases among middle-aged and older Chinese adults: the mediation effect of depressive symptoms. J Affect Disord. (2022) 319:277–85. doi: 10.1016/j.jad.2022.09.080
20.
LeeCCaoJEagen-TorkkoMMohammedSA. Network analysis of adverse childhood experiences and cardiovascular diseases. SSM Popul Health. (2023) 22:101358. doi: 10.1016/j.ssmph.2023.101405
21.
BengtssonJElsenburgLKAndersenGSLarsenMLRieckmannARodNH. Childhood adversity and cardiovascular disease in early adulthood: a Danish cohort study. Eur Heart J. (2023) 44:586–93. doi: 10.1093/eurheartj/ehac607
22.
KimJBPrunickiMHaddadFDantCSampathVPatelRet al. Cumulative lifetime burden of cardiovascular disease from early exposure to air pollution. J Am Heart Assoc. (2020) 9:e014944. doi: 10.1161/JAHA.119.014944
23.
ColeABArmstrongCMGianoZDHubachRD. An update on ACEs domain frequencies across race/ethnicity and sex in a nationally representative sample. Child Abuse Negl. (2022) 129:105686. doi: 10.1016/j.chiabu.2022.105686
24.
Lloyd-JonesDMAllenNBAndersonCAMBlackTBrewerLCForakerREet 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:e18–43. doi: 10.1161/CIR.0000000000001078
25.
Vander WegMW. Adverse childhood experiences and cigarette smoking: the 2009 Arkansas and Louisiana behavioral risk factor surveillance systems. Nicotine Tob Res. (2011) 13:616–22. doi: 10.1093/ntr/ntr023
26.
LinWHChiaoC. The relationship between adverse childhood experience and heavy smoking in emerging adulthood: the role of not in education, employment, or training status. J Adolesc Health. (2022) 70:155–62. doi: 10.1016/j.jadohealth.2021.07.022
27.
Fuller-ThomsonEFilippelliJLue-CrisostomoCA. Gender-specific association between childhood adversities and smoking in adulthood: findings from a population-based study. Public Health. (2013) 127:449–60. doi: 10.1016/j.puhe.2013.01.006
28.
CampbellJAWalkerRJEgedeLE. Associations between adverse childhood experiences, high-risk behaviors, and morbidity in adulthood. Am J Prev Med. (2016) 50:344–52. doi: 10.1016/j.amepre.2015.07.022
29.
PearVAPetitoLCAbramsB. The role of maternal adverse childhood experiences and race in intergenerational high-risk smoking behaviors. Nicotine Tob Res. (2017) 19:623–30. doi: 10.1093/ntr/ntw295
30.
FangLMcNeilS. Is there a relationship between adverse childhood experiences and problem drinking behaviors? Findings from a population-based sample. Public Health. (2017) 150:34–42. doi: 10.1016/j.puhe.2017.05.005
31.
MelkaAChojentaCHollidayELoxtonD. Adverse childhood experiences and electronic cigarette use among young Australian women. Prev Med. (2019) 126:105759. doi: 10.1016/j.ypmed.2019.105759
32.
JungJRosoffDBMuenchCLuoALongleyMLeeJet al. Adverse childhood experiences are associated with high-intensity binge drinking behavior in adulthood and mediated by psychiatric disorders. Alcohol Alcohol. (2020) 55:204–14. doi: 10.1093/alcalc/agz098
33.
Garcia-HermosoAHormazabal-AguayoIOriol-GranadoXFernandez-VergaraODel PozoCB. Bullying victimization, physical inactivity and sedentary behavior among children and adolescents: a meta-analysis. Int J Behav Nutr Phys Act. (2020) 17:114. doi: 10.1186/s12966-020-01016-4
34.
WissDABrewertonTD. Adverse childhood experiences and adult obesity: a systematic review of plausible mechanisms and Meta-analysis of cross-sectional studies. Physiol Behav. (2020) 223:112964. doi: 10.1016/j.physbeh.2020.112964
35.
MartinasekMPWheldonCWParsonsCABellLALipskiBK. Understanding adverse childhood experiences as predictors of cigarette and E-cigarette use. Am J Prev Med. (2021) 60:737–46. doi: 10.1016/j.amepre.2021.01.004
36.
JoannesCCastagneRKelly-IrvingM. Associations of adverse childhood experiences with smoking initiation in adolescence and persistence in adulthood, and the role of the childhood environment: findings from the 1958 British birth cohort. Prev Med. (2022) 156:106995. doi: 10.1016/j.ypmed.2022.106995
37.
BaidenPOnyeakaHKKyeremehEPanischLSLaBrenzCAKimYet al. An Association of Adverse Childhood Experiences with binge drinking in adulthood: findings from a population-based study. Subst Use Misuse. (2022) 57:360–72. doi: 10.1080/10826084.2021.2012692
38.
YuHJLiuXYangHGChenRHeQQ. The association of adverse childhood experiences and its subtypes with adulthood sleep problems: a systematic review and meta-analysis of cohort studies. Sleep Med. (2022) 98:26–33. doi: 10.1016/j.sleep.2022.06.006
39.
ChengXDongXLiuJQuSXuHYaoYet al. Adverse childhood experiences and sleep duration among U.S. 65 years and older: results from the 2020 BRFSS. J Affect Disord. (2023) 336:35–41. doi: 10.1016/j.jad.2023.05.061
40.
AllenHWrightBJVartanianKDulackiKLiHF. Examining the prevalence of adverse childhood experiences and associated cardiovascular disease risk factors among low-income uninsured adults. Circ Cardiovasc Qual Outcomes. (2019) 12:e004391. doi: 10.1161/CIRCOUTCOMES.117.004391
41.
Flores-TorresMHComerfordESignorelloLGrodsteinFLopez-RidauraRde CastroFet al. Impact of adverse childhood experiences on cardiovascular disease risk factors in adulthood among Mexican women. Child Abuse Negl. (2020) 99:104175. doi: 10.1016/j.chiabu.2019.104175
42.
MillerNELaceyRE. Childhood adversity and cardiometabolic biomarkers in mid-adulthood in the 1958 British birth cohort. SSM Popul Health. (2022) 19:101260. doi: 10.1016/j.ssmph.2022.101260
43.
WooldridgeJSTynanMRossiFSGasperiMMcLeanCLBoschJet al. Patterns of adverse childhood experiences and cardiovascular risk factors in U.S. adults. Stress Health. (2023) 39:48–58. doi: 10.1002/smi.3167
44.
KajeepetaSGelayeBJacksonCLWilliamsMA. Adverse childhood experiences are associated with adult sleep disorders: a systematic review. Sleep Med. (2015) 16:320–30. doi: 10.1016/j.sleep.2014.12.013
45.
BiddingerKJEmdinCAHaasMEWangMHindyGEllinorPTet al. Association of Habitual Alcohol Intake with Risk of cardiovascular disease. JAMA Netw Open. (2022) 5:e223849. doi: 10.1001/jamanetworkopen.2022.3849
46.
ImPKWrightNYangLChanKHChenYGuoYet al. Alcohol consumption and risks of more than 200 diseases in Chinese men. Nat Med. (2023) 29:1476–86. doi: 10.1038/s41591-023-02383-8
47.
KrittanawongCIsathARosensonRSKhawajaMWangZFoggSEet al. Alcohol consumption and cardiovascular health. Am J Med. (2022) 135:1213–30 e3. doi: 10.1016/j.amjmed.2022.04.021
48.
ElagiziAKachurSCarboneSLavieCJBlairSN. A review of obesity, physical activity, and cardiovascular disease. Curr Obes Rep. (2020) 9:571–81. doi: 10.1007/s13679-020-00403-z
49.
ValenzuelaPLCarrera-BastosPCastillo-GarciaALiebermanDESantos-LozanoALuciaA. Obesity and the risk of cardiometabolic diseases. Nat Rev Cardiol. (2023) 20:475–94. doi: 10.1038/s41569-023-00847-5
50.
YinJJinXShanZLiSHuangHLiPet al. Relationship of sleep duration with all-cause mortality and cardiovascular events: a systematic review and dose-response Meta-analysis of prospective cohort studies. J Am Heart Assoc. (2017) 6:e005947. doi: 10.1161/JAHA.117.005947
51.
Saz-LaraALuceron-Lucas-TorresMMesasAENotario-PachecoBLopez-GilJFCavero-RedondoI. Association between sleep duration and sleep quality with arterial stiffness: a systematic review and meta-analysis. Sleep Health. (2022) 8:663–70. doi: 10.1016/j.sleh.2022.07.001
52.
KingAR. Childhood adversity links to self-reported mood, anxiety, and stress-related disorders. J Affect Disord. (2021) 292:623–32. doi: 10.1016/j.jad.2021.05.112
53.
WhitakerRCDearth-WesleyTHermanANBlockAEHoldernessMHWaringNAet al. The interaction of adverse childhood experiences and gender as risk factors for depression and anxiety disorders in US adults: a cross-sectional study. BMC Public Health. (2021) 21:2078. doi: 10.1186/s12889-021-12058-z
54.
KuzminskaiteEVinkersCHMilaneschiYGiltayEJPenninxB. Childhood trauma and its impact on depressive and anxiety symptomatology in adulthood: a 6-year longitudinal study. J Affect Disord. (2022) 312:322–30. doi: 10.1016/j.jad.2022.06.057
55.
TanMMaoP. Type and dose-response effect of adverse childhood experiences in predicting depression: a systematic review and meta-analysis. Child Abuse Negl. (2023) 139:106091. doi: 10.1016/j.chiabu.2023.106091
56.
SouamaCLamersFMilaneschiYVinkersCHDefinaSGarvertLet al. Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment: an individual participant data meta-analysis including over 200,000 participants. BMC Med. (2023) 21:93. doi: 10.1186/s12916-023-02769-y
57.
BaileyTAlvarez-JimenezMGarcia-SanchezAMHulbertCBarlowEBendallS. Childhood trauma is associated with severity of hallucinations and delusions in psychotic disorders: a systematic review and Meta-analysis. Schizophr Bull. (2018) 44:1111–22. doi: 10.1093/schbul/sbx161
58.
WellsRJacombISwaminathanVSundramSWeinbergDBruggemannJet al. The impact of childhood adversity on cognitive development in schizophrenia. Schizophr Bull. (2020) 46:140–53. doi: 10.1093/schbul/sbz033
59.
TreurJLVeenemanRRVermeulenJMVerweijKJH. Unravelling the relation between mental illness and cardiovascular disease by triangulating evidence from different methods. Eur Heart J. (2023) 44:1851–4. doi: 10.1093/eurheartj/ehad049
60.
GoldfarbMDe HertMDetrauxJDi PaloKMunirHMusicSet al. Severe mental illness and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol. (2022) 80:918–33. doi: 10.1016/j.jacc.2022.06.017
61.
LambertAMParrettiHMPearceEPriceMJRileyMRyanRet al. Temporal trends in associations between severe mental illness and risk of cardiovascular disease: a systematic review and meta-analysis. PLoS Med. (2022) 19:e1003960. doi: 10.1371/journal.pmed.1003960
62.
FlygareOBobergJRuckCHofmannRLeosdottirMMataix-ColsDet al. Association of anxiety or depression with risk of recurrent cardiovascular events and death after myocardial infarction: a nationwide registry study. Int J Cardiol. (2023) 381:120–7. doi: 10.1016/j.ijcard.2023.04.023
63.
NakadaSHoFKCelis-MoralesCJacksonCAPellJP. Individual and joint associations of anxiety disorder and depression with cardiovascular disease: a UK biobank prospective cohort study. Eur Psychiatry. (2023) 66:e54. doi: 10.1192/j.eurpsy.2023.2425
64.
RingenPAEnghJABirkenaesABDiesetIAndreassenOA. Increased mortality in schizophrenia due to cardiovascular disease - a non-systematic review of epidemiology, possible causes, and interventions. Front Psych. (2014) 5:137. doi: 10.3389/fpsyt.2014.00137
65.
GreenCStolicynAHarrisMAShenXRomaniukLBarbuMCet al. Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in generation Scotland. Transl Psychiatry. (2021) 11:523. doi: 10.1038/s41398-021-01644-9
66.
IobEBaldwinJRPlominRSteptoeA. Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study. Transl Psychiatry. (2021) 11:420. doi: 10.1038/s41398-021-01538-w
67.
KhouryJEBosquet EnlowMPlamondonALyons-RuthK. The association between adversity and hair cortisol levels in humans: a meta-analysis. Psychoneuroendocrinology. (2019) 103:104–17. doi: 10.1016/j.psyneuen.2019.01.009
68.
BevanKKumariM. Maternal separation in childhood and hair cortisol concentrations in late adulthood. Psychoneuroendocrinology. (2021) 130:105253. doi: 10.1016/j.psyneuen.2021.105253
69.
BaumeisterDAkhtarRCiufoliniSParianteCMMondelliV. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry. (2016) 21:642–9. doi: 10.1038/mp.2015.67
70.
BrownMWorrellCParianteCM. Inflammation and early life stress: an updated review of childhood trauma and inflammatory markers in adulthood. Pharmacol Biochem Behav. (2021) 211:173291. doi: 10.1016/j.pbb.2021.173291
71.
IobELaceyRSteptoeA. The long-term association of adverse childhood experiences with C-reactive protein and hair cortisol: cumulative risk versus dimensions of adversity. Brain Behav Immun. (2020) 87:318–28. doi: 10.1016/j.bbi.2019.12.019
72.
TaylorKSSteptoeAIobE. The relationship of adverse childhood experiences, hair cortisol, C-reactive protein, and polygenic susceptibility with older adults’ psychological distress during the COVID-19 pandemic. Mol Psychiatry. (2022) 27:5038–48. doi: 10.1038/s41380-022-01805-2
73.
YuanJPHoTCCourySMChahalRColichNLGotlibIH. Early life stress, systemic inflammation, and neural correlates of implicit emotion regulation in adolescents. Brain Behav Immun. (2022) 105:169–79. doi: 10.1016/j.bbi.2022.07.007
74.
LiCXiangS. Adverse childhood experiences, inflammation, and depressive symptoms in late life: a population-based study. J Gerontol B Psychol Sci Soc Sci. (2023) 78:220–9. doi: 10.1093/geronb/gbac179
75.
SuSWangXKapukuGKTreiberFAPollockDMHarshfieldGAet al. Adverse childhood experiences are associated with detrimental hemodynamics and elevated circulating endothelin-1 in adolescents and young adults. Hypertension. (2014) 64:201–7. doi: 10.1161/HYPERTENSIONAHA.113.02755
76.
YammineLKangDHBaunMMMeiningerJC. Endothelin-1 and psychosocial risk factors for cardiovascular disease: a systematic review. Psychosom Med. (2014) 76:109–21. doi: 10.1097/PSY.0000000000000026
77.
FoxBMBeckerBKLoriaASHyndmanKAJinCClarkHet al. Acute pressor response to psychosocial stress is dependent on endothelium-derived Endothelin-1. J Am Heart Assoc. (2018) 7:e007863. doi: 10.1161/JAHA.117.007863
78.
FordTJCorcoranDPadmanabhanSAmanARocchiccioliPGoodRet al. Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction. Eur Heart J. (2020) 41:3239–52. doi: 10.1093/eurheartj/ehz915
79.
RogersEMBanksNFTomkoPMSciarrilloCMEmersonSRThomasEBKet al. Progressive exercise training improves cardiovascular psychophysiological outcomes in young adult women with a history of adverse childhood experiences. J Appl Physiol. (2023) 134:742–52. doi: 10.1152/japplphysiol.00524.2022
80.
MurthySGouldE. Early life stress in rodents: animal models of illness or resilience?Front Behav Neurosci. (2018) 12:157. doi: 10.3389/fnbeh.2018.00157
81.
PenaCJNestlerEJBagotRC. Environmental programming of susceptibility and resilience to stress in adulthood in male mice. Front Behav Neurosci. (2019) 13:40. doi: 10.3389/fnbeh.2019.00040
82.
PenaCJKronmanHGWalkerDMCatesHMBagotRCPurushothamanIet al. Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science. (2017) 356:1185–8. doi: 10.1126/science.aan4491
83.
ShinSPribiagHLilascharoenVKnowlandDWangXYLimBK. Drd3 signaling in the lateral septum mediates early life stress-induced social dysfunction. Neuron. (2018) 97:195–208 e6. doi: 10.1016/j.neuron.2017.11.040
84.
Gomez-GonzalezBEscobarA. Altered functional development of the blood-brain barrier after early life stress in the rat. Brain Res Bull. (2009) 79:376–87. doi: 10.1016/j.brainresbull.2009.05.012
85.
LoriaASD’AngeloGPollockDMPollockJS. Early life stress downregulates endothelin receptor expression and enhances acute stress-mediated blood pressure responses in adult rats. Am J Physiol Regul Integr Comp Physiol. (2010) 299:R185–91. doi: 10.1152/ajpregu.00333.2009
86.
LoriaASKangKTPollockDMPollockJS. Early life stress enhances angiotensin II-mediated vasoconstriction by reduced endothelial nitric oxide buffering capacity. Hypertension. (2011) 58:619–26. doi: 10.1161/HYPERTENSIONAHA.110.168674
87.
PoteWTagwireyiDChinyangaHMMusaraCNyandoroGChifambaJet al. Cardiovascular effects of Boophone disticha aqueous ethanolic extract on early maternally separated BALB/C mice. J Ethnopharmacol. (2013) 148:379–85. doi: 10.1016/j.jep.2013.03.001
88.
RehoJJFisherSA. The stress of maternal separation causes misprogramming in the postnatal maturation of rat resistance arteries. Am J Physiol Heart Circ Physiol. (2015) 309:H1468–78. doi: 10.1152/ajpheart.00567.2015
89.
HoDHBurchMLMusallBMusallJBHyndmanKAPollockJS. Early life stress in male mice induces superoxide production and endothelial dysfunction in adulthood. Am J Physiol Heart Circ Physiol. (2016) 310:H1267–74. doi: 10.1152/ajpheart.00016.2016
90.
SahafiEPeeriMHosseiniMJAzarbayjaniMA. Cardiac oxidative stress following maternal separation stress was mitigated following adolescent voluntary exercise in adult male rat. Physiol Behav. (2018) 183:39–45. doi: 10.1016/j.physbeh.2017.10.022
91.
WiggerDCGrogerNLesseAKrauseSMerzTGundelHet al. Maternal separation induces long-term alterations in the cardiac oxytocin receptor and cystathionine gamma-Lyase expression in mice. Oxidative Med Cell Longev. (2020) 2020:4309605. doi: 10.1155/2020/4309605
92.
CampanaGLoizzoSFortunaARimondiniRMarocciaZScillitaniAet al. Early post-natal life stress induces permanent adrenocorticotropin-dependent hypercortisolism in male mice. Endocrine. (2021) 73:186–95. doi: 10.1007/s12020-021-02659-4
93.
ArabiMNasabSHLorigooiniZBoroujeniSNMortazaviSMAnjomshoaMet al. Auraptene exerts protective effects on maternal separation stress-induced changes in behavior, hippocampus, heart and serum of mice. Int Immunopharmacol. (2021) 93:107436. doi: 10.1016/j.intimp.2021.107436
94.
LeachmanJRCincinelliCAhmedNDalmassoCXuMGatineauEet al. Early life stress exacerbates obesity in adult female mice via mineralocorticoid receptor-dependent increases in adipocyte triglyceride and glycerol content. Life Sci. (2022) 304:120718. doi: 10.1016/j.lfs.2022.120718
95.
SolarzAMajcher-MaslankaIKrystJChocykA. Early-life stress affects peripheral, blood-brain barrier, and brain responses to immune challenge in juvenile and adult rats. Brain Behav Immun. (2023) 108:1–15. doi: 10.1016/j.bbi.2022.11.005
96.
AndaRFPorterLEBrownDW. Inside the adverse childhood experience score: strengths, limitations, and misapplications. Am J Prev Med. (2020) 59:293–5. doi: 10.1016/j.amepre.2020.01.009
97.
BendreMGranholmLDrennanRMeyerAYanLNilssonKWet al. Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats. Alcohol (Fayetteville, NY). (2019) 79:7–16. doi: 10.1016/j.alcohol.2018.11.001
98.
BaraczSJRobinsonKJWrightALTurnerAJMcGregorISCornishJLet al. Oxytocin as an adolescent treatment for methamphetamine addiction after early life stress in male and female rats. Neuropsychopharmacology. (2022) 47:1561–73. doi: 10.1038/s41386-022-01336-y
Summary
Keywords
early life adversity, adverse childhood experiences, cardiovascular disease, risk behavior, mental health
Citation
Tan H, Zhou H, Chen J, Ren H, Guo Y and Jiang X (2024) Association of early life adversity with cardiovascular disease and its potential mechanisms: a narrative review. Front. Public Health 12:1341266. doi: 10.3389/fpubh.2024.1341266
Received
20 November 2023
Accepted
15 January 2024
Published
24 January 2024
Volume
12 - 2024
Edited by
Michelle Plusquin, University of Hasselt, Belgium
Reviewed by
Yuna Koyama, Tokyo Medical and Dental University, Japan
Amanda Sonnega, University of Michigan, United States
Updates
Copyright
© 2024 Tan, Zhou, Chen, Ren, Guo and Jiang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yi Guo, xuanyi_guo@163.comXin Jiang, jiangxinsz@163.com
Disclaimer
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