Download Table S1. Studies examining childhood adversity in association with

Table S1. Studies examining childhood adversity in association with cardiovascular diseases and biological risks, organized by primary study outcome
Author, year
Sample
Age at
outcome
Timing of
adversity
Adversity definition,
measures
How adversity
treated in analysis
Outcomes examined
Primary findings
Mean 4.6
years,
prospective
Parental separation
(evacuation abroad
without parents during
WWII)
Single variable
Medication use for
coronary heart
disease and
hypertension;
hospitalization for
coronary events,
stroke; all cause
and cardiovascular
deaths
56 years
<18 years,
retrospective
Adverse childhood
experiences (ACEs),
assessed via the ACEs
questionnaire
Unweighted
summary score
Ischemic heart
disease
Adults who were
separated from
parents as children
used coronary heart
disease medications
more frequently; No
associations between
separation and
hospitalizations or
mortality observed.
Dose response
association between
ACEs and heart disease
risk.
56.1
years
<18 years,
retrospective
Adverse childhood
experiences, assessed
via the ACEs
questionnaire
Unweighted
summary score
25-74
years
<18 years,
retrospective
27 adversities in
childhood, including:
Sent away from home,
unemployed parent(s)
parental drinking/drug
problem, death of
parent, physical or
sexual assault, divorce,
Unweighted
summary scores for
quantity, timing
and type.
Chronic conditions
including ischemic
heart disease, and
stroke; Also
examined
cardiovascular risks
including obesity and
smoking.
Diabetes, heart
disease, obesity
Cardiovascular Disease Endpoints (n=10)
Over 60
Alastalo et al. n=12,915
years of
(2012)
follow up
Finland
Helsinki
Birth Cohort
Study
Dong et al.
(2004)
n=17,337
USA
Felitti et al.
(1998)
Adverse
Childhood
Experiences
Study
n=9,508
USA
Friedman et
al. (2015)
Adverse
Childhood
Experiences
Study
n=3,996
USA
Midlife in the
United States
study
(MIDUS)
Dose-response
association between
ACEs and adulthood
chronic conditions and
risk factors.
Dose-response
association between
ACEs and
cardiometabolic risk.
Heart disease risk higher
among women
experiencing abuse at
ages 6-10 years.
1
lost home to
fire/flood/disaster, jail.
Hakulinen et
al. (2016)
n=2265
27 years
3-18 years,
prospective
Composite of 20 factors
relating to four
domains: stressful life
events, parental health
behaviors,
socioeconomic factors,
socioemotional factors.
Parental
divorce/separation,
financial difficulties,
serious conflicts, fear of
a family member, major
family illness, alcohol
problem.
Unweighted
summary score
Carotid intima media
thickness (IMT) in
2007, and IMT
progression from
2001-2007
49.9 55.3
years
<18 years,
retrospective
Unweighted
summary score
High childhood
adversity and high adult
neighborhood
disadvantage jointly
associated with CVD
and CVD risks.
<18 years ,
retrospective
Risky family
environment,
assessed via Risky
Family Questionnaire
Unweighted
summary score
Coronary heart
disease,
cerebrovascular
disease, and CVD
risks including
hypertension,
dyslipidemia,
diabetes, and obesity.
Carotid intima media
thickness (IMT)
directly assessed via
ultrasound
37-52
years
25-74
years
<18 years,
retrospective
Socioeconomic,
household structure,
maltreatment, poor
health domains.
Unweighted
summary score
Myocardial
infarction (MI)
Accumulated childhood
adversity associate with
increased MI risk.
≥55
years
0-16 years ,
retrospective
Early disadvantage,
fatherless, poor
childhood health
Derived 3 latent
clusters of
adversity
Heart attack
Early disadvantage and
poor childhood health
associated with risk of
heart attack.
Finland
Young Finns
Study
Halonen et al.
(2015)
n=37,699
Finland
Finnish
Public Sector
Study
Loucks et al.
(2014)
n=2,659
USA
Morton et al.
(2014)
Coronary
Artery Risk
Development
in Young
Adults study
(CARDIA)
n=3,032
USA
O’Rand and
Hamil-Luker
(2005)
MIDUS
n=9,760
USA
Associations strongest
among more severe
types of adversity.
Cumulative adversity
was associated with
higher IMT in 2007 and
increased IMT
progression from 2001
to 2007.
Higher risky family
scores associated with
increased IMT in white
but not black
participants.
Health and
Retirement
Study
2
Wilson et al.
(2012)
n=192
88.5
years
<18 years,
retrospective
Adapted Childhood
Trauma Questionnaire,
includes subscores of
emotional neglect,
parental intimidation,
violence, family
turmoil/divorce,
financial need
Unweighted
summary scores
Cerebral infarctions,
directly assessed via
post mortem brain
autopsy
Higher adversity scores
associated with higher
cerebral infarction risk.
Cardiometabolic Biomarkers (n=8)
n=650
Mean
Bleil et al.
39.9
(2013)
USA
years
<18 years,
retrospective
Family environment,
assessed via Family
Environment Scale;
Stressful life events,
assessed with an
adapted Life Events
Checklist
Unweighted
summary scores
Total cholesterol,
HDL, LDL,
triglycerides, fasting
glucose, body
composition,
hypertension
32-47
years
<18 years,
retrospective
Risky family
environment, assessed
via Risky Family
Questionnaire (warmth
and abuse subscales)
Unweighted
summary score
32 years
<10 years,
prospective
Socioeconomic status,
maltreatment/abuse,
social isolation.
Unweighted
summary score,
also examined
independent effects
of adversities
Allostatic load:
Count of high risk
levels of blood
pressure, heart rate,
norepinephrine and
epinephrine, cortisol,
cholesterol,
triglycerides,
glucose, insulin,
waist circumference,
C-reactive protein
fibrinogen, IL-6
CRP and metabolic
risk factor clustering
(high body mass,
blood pressure,
cholesterol, HbA1c,
02 consumption).
In a structural
equation model, greater
childhood adversity was
related to younger
menarcheal age
and younger
menarcheal age was
related to greater CVD
risk. Direct and indirect
effects of childhood
adversity on CVD risk
were non-significant.
Risky family
environment and
childhood abuse
associated with greater
allostatic load. Higher
parental warmth scores
mitigated risk.
USA
Rush
Memory and
Aging Project
Ovarian
Aging Study
Carroll et al.
(2013)
n=756
USA
CARDIA
Danese et al.
(2009)
n=1,037
New Zealand
Dunedin
Multidisciplin
Independent and
cumulative adverse
childhood experiences
associated with elevated
inflammation and
metabolic risk.
3
Friedman et
al. (2015)
ary Health
and
Development
Study
n=1,180
25-74
years
<18 years,
retrospective
Composite of
socioeconomic
adversity, parental
death, divorce, abuse
Unweighted
summary score
42.5
years
0-7 years,
prospective
Parental reported family
stability (e.g., sibling
death, moved residence)
and socioeconomic
risks (poverty,
unemployed father,
crowded dwelling).
Unweighted
summary score
USA
MIDUS
Non et al.
(2014)
n=387
USA
New England
Family Study
(NEFS)
Schooling et
al. (2011)
n=28,771
China
Guangzhou
Biobank
Cohort Study
≥50
years
<18 years,
retrospective
Early life parental
death
Single variable,
also considered
timing of parental
death
Allostatic load:
count of high risk
levels of blood
pressure, resting
pulse, CRP,
fibrinogen, IL-6,
epinephrine,
norepinepherine,
heart rate variability,
cortisol
Cardiometabolic
Risk Score: Count of
biomarkers
indicating clinical
risk (blood pressure,
triglycerides,
cholesterols, HbA1c,
waist circumference,
CRP)
Chronic Disease
Score: Count of selfreported conditions
including: heart
disease, COPD,
cancer, diabetes,
hypertension,
hypercholesterolemi
a, arthritis.
Blood pressure,
fasting glucose,
LDL, HDL,
triglycerides, BMI,
waist-hip ratio,
white blood cell
count, seated height
Cumulative adversity
positively associated
with allostatic load.
Increased childhood
social disadvantage
associated with higher
adult cardiometabolic
and chronic disease
scores.
Mixed findings. Parental
death associated with
shorter height, lower
BMI, and triglicerides.
No associations found
for blood pressure,
cholesterols, or glucose.
4
Slopen et al.
(2014)
n=550
44.3
years
<12 years,
retrospective
Composite of frequency
of physical abuse,
verbal abuse, felt loved,
physically held,
participated in school
activities, read to, went
to bed hungry, and
socioeconomic
affluence
Composite of child in
care, neglect, household
dysfunction, parental
separation, family
member with mental
illness/alcohol
abuse/criminal offender.
Unweighted
summary score
44-45
years
7, 11, and 16
years,
prospective
57.3
years
<18 years,
retrospective
Childhood trauma
questionnaire, items
including
physical/emotional/sexu
al abuse, neglect,
divorce, parent abusing
alcohol or drugs, and
parental depression.
44 years
<16 years,
prospective
15-19
<18 years,
USA
Chicago
Community
Adult Health
Study
Solis et al.
(2015)
n=7,535
Great Britain
National
Child
Development
Study
(NCDS)
Inflammation (n=11)
Hostinar et al. n=1,180
(2015)
USA
MIDUS
Lacey et al.
(2013)
n=7,462
Great Britain
Miller and
National
Child
Development
Study
n=147
Count of biomarkers
exceeding clinical
risk levels including:
blood pressure,
resting heart rate,
CRP, waist
circumference,
hemoglobin A1c,
cholesterol
Allostatic load:
cortisol, IGF1, CRP,
fibrinogen, IgE,
cholesterol,
triglycerides,
glycosylated
hemoglobin, blood
pressure, peak
expiratory flow
Childhood adversity
associated with elevated
cardiometabolic risk in
adulthood.
Unweighted
summary score,
timing of exposure
assessed
CRP, IL-6,
fibrinogen, Eselectin, ICAM-1
Parental separation
(divorce, breakdown of
parents relationship)
Single variable
CRP
Child adversities
independently
associated with
inflammation; effects of
child adversities and
adult stressors were
additive. Relationship
partially mediated by
waist circumference and
CV risk behaviors.
Those with parental
separation have higher
CRP levels as adults.
Association mediated
by BMI, material and
psychosocial factors.
Index indicating birth to
Unweighted
CRP, IL6, depression
Unweighted
summary score
Child adversities
associated with higher
allostatic load.
Relationship largely
mediated by adulthood
factors (health
behaviors, education,
wealth, smoking, BMI).
Higher levels of
5
Cole (2012)
females
years
retrospective
teenage mother, familial
disruption, history of
affective illness in
parents, low household
education, limited
economic resources
Index indicating
separation from mother,
paternal involvement,
residential relocations,
duration of breastfeeding.
Questionnaire based
indicators of father's
occupation, parents
owned home, bully
victim, parents owned
car, overcrowding, leg
length, trunk length.
Maternal
psychopathology,
parental discord, harsh
discipline, family
income, parental
criminal behavior.
summary score
44-46
years
0-7 years,
prospective
35-64
years
At age 11,
retrospective
22-25
years
0-5 years,
prospective
42.9
years
<18 years
old,
retrospective
35-86
years
<18 years
old,
Canada
Nettle (2014)
n=8,959
women
Great Britain
Packard et al.
(2011)
NCDS
n=666
Scotland
Raposa et al.
(2014)
n=389
Australia
Runsten et al.
(2013)
MaterUniversity of
Queensland
Study of
Pregnancy
n=116
women
Finland
Slopen et al.
(2010)
Health and
Social
Support
Study
(HeSSup)
n=999
childhood adversity
associated with
inflammation and
depression.
Unweighted
summary score
CRP
Higher levels of
adversity associated
with increased
adulthood CRP.
No summary score;
each childhood
factor examined
individually
CRP, IL-6, ICAM
Father's occupation and
childhood home status
associated with
inflammation and
endothelial function.
Unweighted
summary score
CRP and sTNF-RII,
body mass index
Early adversity
associated with higher
levels of inflammation;
potential mediation by
smoking and BMI
Risky Families
Questionnaire, HeSSup
questionnaire listing 17
adverse childhood
events
Unweighted
summary score
CRP
Interaction effect
between adulthood
social support and
childhood adversity in
relation to CRP. Social
support may buffer
effects of childhood
adversity.
Failing school, parental
drug problem, moved
Unweighted
summary score
CRP, IL-6,
fibrinogen, E-
Early life adversity
associated with each
6
USA
retrospective
MIDUS
Slopen et al.
(2013)
n=4,6553,286
Slopen et al.
(2015)
n=210
Adverse events in
middle childhood and
cumulative adversity
from birth to age 8
associated with higher
CRP and IL-6 and CRP
at age 10. Cumulative
adversity and adverse
events in early or middle
childhood associated
with higher CRP at age
15.
Prenatal and childhood
adversity associated
with CRP in adulthood.
When modelled
together, prenatal and
not age7 adversity was
associated with elevated
adult CRP.
Prenatal and age 7
assessments of family
stability (e.g., moved
residence, sibling death)
and socioeconomic
risks (e.g., poverty,
unemployed father,
crowded dwelling).
Unweighted
summary scores
CRP
32-47
years
<18 years,
retrospective
Childhood SES, and
risky family
environment as assessed
with the Risky Family
questionnaire
Unweighted
summary score
CRP, BMI,
psychosocial
functioning
Childhood SES and
risky family scores
associated with adult
CRP via adult
psychosocial
functioning.
8.13
years
(range 021 years)
8.13 years
(range 0-21
years)
Unweighted
summary score
Overweight/obesity,
behavior/learning
problems as listed in
the medical record
45.8
years
<18 years,
retrospective
Adverse childhood
experiences assessed
with and adapted ACEs
checklist, collected via
medical chart review
Summarized
information from the
Derived four
measures of
BMI, obesity and
waist-hip ratio
Higher ACE scores
associated with risk of
overweight/obesity and
learning/behavior
problems.
Overall adversity
significantly with waist-
CARDIA
Davis et al.
(2014)
CRP, IL-6
Prenatal, age
7 years,
prospective
USA
Anthropometry (n=8)
Burke et al.
n=701
(2011)
USA
Derived an
unweighted
summary score,
and also a
perceived impact
score
42.2
years
New England
Family Study
(NEFS)
n=3,248
inflammatory marker for
black adults, but not for
white adults.
0-7 years,
prospective
USA
Taylor et al.
(2006)
selectin, sICAM-1
10, 15
years
United
Kingdom
Avon
Longitudinal
Study of
Parents and
Children
(ALSPAC)
n=355
neighborhood >2 times,
relationship with
parents, verbal and
physical abuse.
Repeated measures of 5
adverse events at 7 time
points including: child
taken into foster care,
physically hurt by
someone, sexually
abused, separated from
mother, separated from
father.
7
USA
Evans et al.
(2012)
n=244
Evaluation of Lifetime
Stressors Interview,
SCID, and an
attachment assessment
13 years
9 years,
prospective
36.6
years
<18 years
old,
retrospective
USA
Gunstad et al.
(2006)
n=696
Multiple
countries
(Australia,
USA, United
Kingdom, the
Netherlands)
Composite of 9 risk
factors including
poverty, single-parent
status, maternal high
school drop-out,
residential crowding,
noise, housing
problems, family
turmoil, child
separation from family,
exposure to violence.
Child Abuse and
Trauma scale, including
experiences of
physical/sexual abuse,
family conflict, war,
divorce/separation,
bullied, poverty/neglect,
natural disaster, death in
family, illness in
family, violence,
extended illness,
surgery/hospital,
adoption.
adversity:
(1) Cumulative
(number of events,
unweighted);
(2) Severity
(weighted sum
score);
(3) Chronicity
(chronic, single
episode, or mixed);
(4) Overall
adversity
(combined
cumulative,
severity and
chronicity).
Unweighted
summary score
Unweighted
summary score
hip ratio and BMI; more
sensitive predictor than
cumulative adversity.
Body mass index
Higher childhood
adversity associated
with greater adiposity
gains from age 9 to 13.
Obesity
Early adversity
positively associated
with obesity in men, but
not women.
8
Pretty et al.
(2013)
n=1,234
11-14
years
<14 years,
retrospective
15 events adapted from
the Childhood Trust
Events Survey., e.g.,
parental death, divorce,
major illness, attacked
by an animal, saw
someone get badly hurt.
Unweighted
summary score
Body mass index,
obesity, waist
circumference, blood
pressure and resting
heart rate.
Significant doseresponse associations
between adverse child
experiences and heart
rate, body mass index,
obesity, and waist
circumference.
7, 11
years
0-7 years,
prospective
Repeated measures of 8
social risk domains
including: maternal
psychopathology, one
adult in household,
legal problems, child
taken into care, physical
injury, sexual abuse,
financial strain,
neighborhood
disadvantage.
Maternal reports of
intimate partner
violence, food
insecurity, housing
insecurity, maternal
depressive symptoms,
maternal substance
abuse, father’s
incarceration.
Examined 16
retrospective selfreported types of abuse,
neglect, household
dysfunction. Also
examined prospective
maternal reports of 13
adversities related to
Derived
unweighted scores
for average
adversity over time
and chronic
exposure to high
adversity;
examined as
separate predictors.
BMI, blood pressure.
High adversity and
chronic adversity
associated with higher
BMI and behavior
problems, but not blood
pressure at age 7.
Adversity did not
predict change in BMI
or BP from age 7-11.
Derived
unweighted
summary score and
timing of exposure/
chronicity
BMI and obesity
Significant associations
between cumulative
adversities, timing of
adversities with obesity
risk at age 5 among
girls. No associations
among boys.
Examined each
childhood factor as
separate predictors.
BMI, waist
circumference,
Hba1c.
Some forms of adversity
associated with obesity,
central adiposity, and
Hba1c. Strongest
associations among
serious forms of
adversity like physical
abuse.
Canada
Slopen et al.
(2014)
Heart
Behavioural
and
Environmenta
l Assessment
Team
(HBEAT)
study
n=4,361 and
n=3,348
United
Kingdom
ALSPAC
Suglia et al.
(2012)
n=1,605
5 years
1 and 3 years,
prospective
45 years
0-16 years,
retrospective;
and
7, 11, 16
years
prospective
USA
Thomas et al.
(2008)
Fragile
Families and
Child
Wellbeing
Study
n=9,310
Great Britain
NCDS
Behavior problems
via Strengths and
difficulties
questionnaire.
9
neglect and household
dysfunction.
Blood Pressure and Hypertension (n=6)
Alastalo et al. n=1361 non- Mean 62
years
(2013)
obese
Mean 4.6
years,
prospective
Parental separation
(evacuation abroad
without parents during
WWII)
Single variable,
also considered
duration and age of
separation
Directly assessed
blood pressure, use
of blood pressure
medication
Early childhood parental
separation associated
with higher blood
pressure in adulthood,
Age at separation and
duration also associated
blood pressure.
35-55
years
<18 years,
retrospective
Summarized
information from the
Evaluation of Lifetime
Stressors Interview,
SCID, and an
attachment assessment
Mean arterial
pressure, systolic and
diastolic blood
pressures
Path analysis indicates
overall and cumulative
child adversity to affect
mean arterial and blood
pressures via hip-waist
ratio, leptin, and diet.
10-14
years
<14 years,
retrospective
15 events adapted from
the Childhood Trust
Events Survey., e.g.,
parental death, divorce,
major illness, attacked
by an animal, saw
someone get badly hurt.
Derived four
measures of
adversity:
(1) Cumulative
(number of events,
unweighted);
(2) Severity
(weighted sum
score);
(3) Chronicity
(chronic, single
episode, or mixed);
(4) Overall
adversity
(combined
cumulative,
severity and
chronicity).
Unweighted
summary score
ECG assessed pulse
wave velocity, a
measure of systemic
arterial stiffness
Significant sex by
adversity interaction
observed whereby four
or more ACEs was
associated with greater
arterial stiffness among
boys.
33-45
<18 years,
Childhood SES; risky
Unweighted
Blood pressure
Harsh family
Finland
Crowell et al.,
2015
Helsinki
Birth Cohort
Study
n=210
USA
Klassen et al.
(2016)
n=221
Canada
HBEAT
study
Lehman et al.
n=2,738
10
(2009)
years
retrospective
family environment
assessed via the Risky
Family Questionnaire
summary score
(initial blood
pressure and change
over time)
21-98
years
<18 years,
retrospective
Physical abuse, sexual
abuse, neglect, parental
death, divorce, parental
loss, parental mental
disorder, substance use,
criminal behavior,
family violence, family
economic adversity
Unweighted
summary score
Hypertension
5-38
years
<18 years,
retrospective
Adverse childhood
experiences, assessed
via the ACEs
questionnaire
Unweighted
summary score
Blood pressure,
directly measured up
to 16 times over 23
years
USA
CARDIA
Stein et al.
(2010)
n=18,630
Multiple
countries
Su et al.
(2015)
WHO World
Mental
Health
Surveys
n=394
USA
Georgia
Stress and
Heart Study
environment and low
parental SES associated
with adult blood
pressure and change in
blood pressure over
time, mediated by
emotionality and health
behaviors.
Presence of 3 or more
childhood adversities
associated with
hypertension.
Multiple ACEs
associated with higher
adulthood blood
pressure levels. Number
of ACEs associated with
different blood pressure
trajectories.
11