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doi:10.1136/bmj.a118
2008;337;118- BMJ
Archana Singh-Manoux
Hermann Nabi, Mika Kivimaki, Roberto De Vogli, Michael G Marmot and
cohort study
prospectivecoronary heart disease: Whitehall II
Positive and negative affect and risk of
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RESEARCH
Positive and negative affect and risk of coronary heart
disease: Whitehall II pros pective cohort study
Hermann Nabi, research fellow,
1,2
Mika Kivimaki, professor o f social epi demiology,
1
Roberto De V ogli,
lecturer,
1
Michael G Marmot, head of department and director,
1
Archana Singh-Manoux, senior research
fellow
1,2,3
ABSTRACT
Objective To examine the associations between positive
and negative affect and subsequent coronary heart
disease events independently of established risk factors.
Design Prospective cohort study with follow-up over
12 years.
Setting 20 civil service departments originally located in
London.
Participants 10 308 civil servants aged 35-55 years at
entry into Whitehall II study in 1985.
Main outcome measures Fatal coronary heart disease,
clinically verified incident non-fatal myocardial infarction,
and definite angina (n
=
619, mean follow-up 12.5 years).
Results In Cox regression analysis adjusted for age, sex,
ethnicity, and socioeconomic position, positive affect
(hazard ratio
=
1.01, 95% confidence interval 0.82 to 1.24)
and the balance between positive and negative affect,
referred to as the affect balance score (hazard ratio
=
0.89,
0.73 to 1.09), were not associated with coronary heart
disease. Further adjustment for behaviour related risk
factors (smoking, alcohol consumption, daily fruit and
vegetable intake, exercise, body mass index), biological
risk factors (hypertension, blood cholesterol, diabetes),
and psychological stress at work did not change these
results. However, participants in the highest third of
negative affect had an increased incidence of coronary
events (hazard ratio
=
1.32, 1.09 to 1.60), and this
association remained unchanged after adjustment for
multiple confounders.
Conclusions Positive affect and affect balance did not
seem to be predictive of future coronary heart disease in
men and women who were free of diagnosed coronary
heart disease at recruitment to the study. A weak positive
association between negative affect and coronary heart
disease was found and needs to be confirmed in further
studies.
INTRODUCTION
Smoking, hypertension, hypercholesterolaemia, and
diabetes are established risk factors for coronary heart
disease, a leading cause of morbidity and mortality in
Western industrialised countries.
12
However, psycho-
logical factors,suchasemotions, may also have a role in
the development of coronary heart disease.
34
Several
prosp ective stud ies have found anxiety, hostility/
anger, and depression to be associated with an
increased risk of coronary heart disease in healthy
participants.
35
As the relative importance of these three
negative emotions on risk of coronary heart disease
remains largely undefined,
67
they have been hypothe-
sised to be the components of a single underlying
factor, labelled negative affect. Negative affect refers to
“stable and pervasive individual differences in mood
and self-concept characterised by a general disposition
to experience a variety of aversive emotional states.”
58
High negative affect has been described as a general
tendency to report “distress, discomfort, dissatisfac-
tion, an d feelings of hopelessness over time and
regardless of the situation,” and low negative affect is
characterised by “calmness and serenity.”
89
Support-
ing this conceptualisation, a considerable neurobiolo-
gical and psychological overlap betwe en anxiety,
hostility/anger, and depression has previously been
shown.
10 11
As attempts to link psychological factors to heart
disease have focused on negative emotions, mostly
depression,
7
whether positive emotions might also
have a role in the development of coronary heart
disease remains unclear. Research suggests that
positive affect and negative affect are two independent
systems and that positive affect is not simply the
opposite of negative affect or an absence of negative
affect.
912
High positive affect refers to a general
tendency to experience a “state of high energy, full
concentration, and pleasurable engagement,” whereas
low positive affect is characterised by “sadness and
lethargy.”
89
Distinct neural networks may exist to
regulate positive and negative emotions; dopamine
metabolism may be associated with positive affect and
serotonin with negative affect,
13 14
supporting the
assertion of the independence of the two types of affect.
We are aware of no previous large scale prospective
studies on the independent effects of negative and
positive affect on coronary heart disease. A six year
follow-up of 2478 older participants in North Carolina
found that positive affect was associated with decreased
risk of stroke, but it did not examine coronary heart
disease as an outcome, and the assessment of negative
1
Department of Epidemiology and
Public Health, University College
London, London WC1E 6BT
2
INSERM U687-IFR69, Villejuif,
F-94807, France
3
H
ô
pital Sainte P
é
rine, Centre de
G
é
rontologie, Paris, F-75781,
France
Correspondence to: H Nabi
H.Nabi@public-health.ucl.ac.uk
Cite this as:
BMJ
2008;337:a118
doi:10.1136/bmj.a118
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affect was limited to depressive symptoms.
13
In this
report from the Whitehall II study, we examine the
independent associations of both negative affect and
positive affect with subsequent coronary heart disease
after taking account of established risk factors among
participants followed up over 12 years. In addition, we
examine whether the balance between positive and
negative affect is associated with subsequent coronary
heart disease.
METHODS
The Whitehall II study, established in 1985, is a
longitudinal study to examine the socioeconomic
gradient in health and disease among 10 308 civil
servants (6895 men and 3413 women).
15
All civil
servants aged 35-55 years in 20 London based
departments were invited to participate by letter, and
73% agreed. Each participant gave written informed
consent. Baseline examination (phase 1) took place
during 1985-8 and involved a clinical examination and
a self administered questionnaire.
Measures
We assessed positive affect and negative affectat phases
1 (1985-8) and 2 (1989-90) by using the Bradburn affect
balance scale,
16
a widely used measure of psychological
wellbeing. The affect balance scale consists of 10 items,
five of which are used to asse ss positive affect
(Cronbach’s α=0.80) and the other five to assess
negative affect (Cronbach’s α=0.67). All items are
formulated in general terms, as questions about the
participant’s feelings during the previous few weeks.
The items ar e phrased to elicit responses of t he
pleasurable or unpleasurable character of an experi-
ence instead of the context of the experience.
Responses in this study are on a four point Likert-
type scale from 0 (not at all) to 3 (a great deal). Scores for
each subscale range from 0 to 15; higher scores indicate
higher positive affect or higher negative affect. The
affect balance score is calculated by subtracting the
negative affect score from the positive affect score and
adding a constant of 15 to avoid negative values. The
affect balance score ranges fro m 0 (lowest affect
balance) to 30 (highest affect balance). Neither natural
thresholds nor clinically based thresholds are defined,
so we divided each scale into low, middle, and high
exposure on the basis of the distribution in the total
study population
—
positive affect score thirds: lowest
(0-4), middle (5-7), highest (8-15); negative affect score
thirds: lowest (0-1), middle (2-3), highest (4-15); affect
balance score thirds: lowest (0-16), middle (17-20),
highest (21-30). Only 75% of participants were asked to
complete the affect balance scale at phase 1, as this
measure was introduced after the start of the baseline
survey. Where phase 1 data were missing, we used
positive and negative affect scores at phase 2. The
percentages of replacement were 15.0% for positive
affect and 14.3% for negative affect. Correlation
coefficients of scores at phase 1 (1985-8) and phase 2
(1989-90) suggest a moderate degree of consistency of
positive affect (r= 0.52, P<0.001), negative affect
(r=0.55 P<0.001) and affect balance (r=0.54, P<0.001)
across time.
We assessed the incidence of coronary heart disease
from phase 2 (1989-90) to phase 7 (2003-4), a mean
follow-up of 12.5 (SD 3.8) years. Coronary heart
disease included fatal coronary heart disease (defined
by the international classification of diseases, 9th
revision (ICD-9) codes 410-414 or ICD-10 codes I20-
25), first non-fatal myocardial infarction, or first
“definite” angina. We assessed fatal coronary heart
disease by flagging participants at the NHS central
registry, which provided information on the date and
cause of death. We ascertained potential non-fatal
myocardial infarction through questionnaire items on
chest pain (the World Health Organization’s Rose
questionnaire
17
) and the physician’s diagnosis of heart
attack. We based confirmation of myocardial infarc-
tion according to MONICA (multinational monitoring
of trends and determinants in cardiovascular disease
18
)
criteria on electrocardiograms, markers of myocardial
necrosis, and history of chest pain from the medical
records. We assessed angina on the basis of partici-
pants’ reports of symptoms with corroboration in
medical records or abnormalities on a resting electro-
cardiogram, an exercise electrocardiogram, or a
coronary angiogram.
Covariates
Sociodemographic measures included age, sex, and
socioeconomicposition assessed by British civil service
grade of employment t aken from the phase 1
questionnaire. Conventional risk factors assessed at
phase 1 included smoking status (never, ex-smoker,
and current), hypertension (systolic and diastolic blood
pressure >140/90 mm Hg or treatment for hyperten-
sion), blood cholesterol (<6.2 or ≥6.2 mmol/l), exercise
(≥1.5 or <1.5 hours of moderate or vigorous exercise/
week), daily fruit and vegetable intake (yes/no), alcohol
consumption in units of alcohol consumed a week (low:
<22 for men and <15 for women; moderate: 22-51 for
men and 15-35 for women; or high: >51 for men and
>35 for women), body mass index (<20, 20-24.9, 25-
29.9, or ≥30 kg/m
2
),andselfreporteddiabetes.
Psychosocial stress at work (job strain) was measured
at phase 1 with the self administrated job strain model
questionnaire,
19
including scales of psychological job
demands, decision latitude, and social support at
work.
20 21
We replaced missing values at phase 1 with
information at phase 2.
Statistical analyses
We assessed differences in positive affect, negative
affect, and affect balance scores as a function of
sociodemographic characteristics and traditional cor-
onary heart disease risk factors by using one way
analysis of variance, with a linear trend fitted across the
hierarchical variables. We used Cox regression to
assess the age and sex adjusted association between
various covariates and coronary heart disease.
We used six serially adjusted Cox regression models
to model the associations of positive affect, negative
RESEARCH
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affect, and affect balance scores with incident coronary
heart disease. We adjusted model 1 for the association
between positive affect and incident coronary heart
disease for sex, age, ethnicity, and employment grade
(that is, potential confounding factors), and the
subsequent models included potential mediators for
the association. Thus, in addition to potential con-
founders, we adjusted model 2 for behaviour related
risk factors, model 3 for biological risk factors, and
model 4 for psychosocial stress at work. We adjusted
model 5 for all of the covariates outlined above and
model 6 for negative affect. We repeated this whole
exercise starting out with negative affect (using positive
affect in model 6) and the affect balance score. We also
checked for interactions between affect measures and
sex in relation to coronary heart disease on a
Table 1
|
Sample characteristics as a function of positive and negative affect subscales and affect balance scale scores (n
=
8918)
Variables No
Positive affect Negative affect Affect balance
Mean (SD) P value or for trend Mean (SD) P value or for trend Mean (SD) P value or for trend
Sex: <0.001 <0.001 <0.001
Male 6093 6.20 (2.91) 2.72 (2.27) 18.48 (4.01)
Female 2825 5.81 (3.19) 2.94 (2.60) 17.87 (4.59)
Age (years): 0.002 <0.001 <0.001
39-45 2469 6.15 (2.96) 3.15 (2.42) 18.06 (4.23)
45-50 2340 6.19 (2.98) 2.92 (2.41) 18.26 (4.24)
50-55 1827 6.03 (3.07) 2.63 (2.32) 18.40 (4.19)
55-64 2282 5.91 (3.02) 2.40 (2.29) 18.51 (4.16)
Employment grade: <0.001 0.005 <0.001
High 2704 6.55 (2.80) 2.67 (2.19) 18.88 (3.87)
Middle 4370 6.06 (2.99) 2.84 (2.36) 18.21 (4.18)
Low 1844 5.44 (3.20) 2.85 (2.69) 17.58 (4.61)
Ethnicity: <0.001 0.553 <0.001
White 8134 6.17 (2.95) 2.79 (2.36) 18.39 (4.16)
Other 784 5.01 (3.39) 2.84 (2.64) 17.17 (4.58)
Hypertension: 0.147 <0.001 0.113
No 7273 6.10 (3.00) 2.85 (2.39) 18.25 (4.22)
Yes 1645 5.98 (3.04) 2.55 (2.34) 18.44 (4.15)
Smoking status: 0.992 <0.001 0.018
Never smoker 4461 6.02 (2.99) 2.71 (2.31) 18.31 (4.12)
Ex-smoker 2893 6.25 (3.02) 2.80 (2.33) 18.45 (4.20)
Current smoker 1564 5.92 (3.01) 3.01 (2.67) 17.90 (4.43)
Alcohol consumption: 0.028 <0.001 0.527
Low 7515 6.04 (3.00) 2.76 (2.37) 18.29 (4.20)
Moderate 1198 6.30 (3.00) 2.92 (2.38) 18.38 (4.21)
High 205 6.10 (3.09) 3.36 (2.64) 17.75 (4.51)
Exercise (hours/week): <0.001 <0.001 <0.001
≥
1.5 1659 6.83 (2.98) 2.59 (2.20) 19.24 (4.00)
<1.5 7259 5.90 (2.98) 2.84 (2.42) 18.07 (4.22)
Daily fruit and vegetables: <0.001 <0.001 <0.001
Yes 5260 6.26 (3.03) 2.72 (2.36) 18.54 (4.22)
No 3658 5.82 (2.95) 2.90 (2.41) 17.92 (4.16)
Body mass index: 0.234 0.001 0.005
<20 539 5.63 (3.06) 3.19 (2.49) 17.43 (4.42)
20-24.9 4960 6.11 (2.96) 2.81 (2.37) 18.30 (4.13)
25-29.9 2850 6.14 (3.02) 2.68 (2.34) 18.45 (4.23)
≥
30 569 5.92 (3.23) 2.78 (2.54) 18.14 (4.56)
Diabetes: 0.048 0.055 0.13
No 8837 6.08 (3.00) 2.79 (2.39) 18.30 (4.20)
Yes 81 5.42 (3.26) 3.30 (2.33) 17.12 (4.59)
Job strain: <0.001 <0.001 <0.001
No 7859 6.22 (2.99) 2.67 (2.31) 18.55 (4.12)
Yes 1059 5.03 (2.87) 3.66 (2.68) 16.37 (4.33)
Blood cholesterol (mmol/l): 0.179 <0.001 0.107
<6.2 5424 6.11 (3.01) 2.88 (2.41) 18.23 (4.26)
≥
6.2 3494 6.02 (2.99) 2.65 (2.33) 18.38 (4.13)
RESEARCH
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multiplicative scale. The assumption of proportional
hazards assessed by examining the time dependent
interaction term between each predictor and logarithm
of the follow-up period (time variable) held (all
P>0.05).
RESULTS
Of the 9745 participants with no history of clinically
validated coronary heart disease at phase 2, 9568
(98.1%) completed the positive affect subscales and
9605 (98.6%) completed the negative affect subscales,
either at phase 1 or phase 2. Among the 8918
participants with complete data on positive and
negative affect and all covariates, 619 coronary events
were documented between phases 2 and 7. The 827
participants who were not included in the analyses
owing to missing data on affect scales (n=614) or on
covariates (n=213) were more likely than the included
participants to be women (11.5% v 7.0%), non-white
(15.7% v 7.0%), and from the lowest employment grade
(13.1% v 7.2%). No difference in age was seen.
Table 1 shows the difference in mean positive affect,
negative affect, and affect balance scores as a function
of the characteristics of the sample. Table 2 shows the
age and sex adjusted associations between all of the
covariates and coronary heart disease events. Exam-
ination of the interactions between sex and the affect
variables in relation to coronary heart disease showed
no evidence of sex differences. Therefore, we com-
bined men and women in the subsequent multivariate
analyses.
Associations of positive affect, negative affect, and affect
balance score with c oronary heart dis ease
Table 3 shows the six serially adjusted Cox regression
models designed to estimate the associations of affect
measures with coronary heart disease. We found no
association between higher positive affect scores and
the incidence of coronary heart disease (hazard ratio
1.01, 95% confidence interval 0.82 to 1.24) in the
analysis adjusted for age, sex, socioeconomic position,
and ethnicity (model 1) or after further adjustment for
behaviour related risk factors (model 2), biological risk
factors (model 3), psychological stress at work (model
4), all covariates (model 5), and negative affect (model
6). However, participants with negative affect scores in
the highest third had a slightly higher risk (hazard ratio
1.32, 1.09 to 1.60) of coronary heart disease (model 1).
Further serial adjustment (models 2 to 6) showed no
substantial change in this association. Finally, partici-
pants with affect balance scores in the highest third had
a lower, but statistically non-significant, risk (hazard
ratio 0.89, 0.73 to 1.09) of coronary heart disease,
which was little affected by adjustments (models 2 to 6).
Sensitivity analysis
To explore the effect of unmeasured comorbidity at
baseline, we examined the association between nega-
tive affect and incidence of coronary heart disease
events after removing from the analysis any events that
occurred within the first five years of the follow-up. The
number of events was reduced by 31.5% (n=424) in this
analysis, but we found no change in the magnitude of
the association between higher negative affect and
coronary heart disease (hazard ratio adjusted for age,
sex, ethnicity, and socioeconomic position 1.32, 1.05 to
1.67; P=0.016), sugge sting that this association is
unlikely to be attributable to unmeasured comorbidity
at baseline. In the main analysis reported in this paper,
we have replaced missing negative affect scores at
phase 1 with scores at phase 2 if available. We did
sensitivity analysis using negative affect scores at each
phase to test their association with coronary heart
disease incidence without any replacement. In both
Table 2
|
Age and sex adjusted associations between
covariates and coronary heart disease among 8918
participants (619 events)
Variables
Risk of coronary heart disease
No events/No participants
Hazard ratio
(95% CI)
Employment grade:
High 208/2704 1
Middle 283/4370 1.05 (0.88 to 1.26)
Low 128/1844 1.29 (1.00 to 1.66)
Ethnicity:
White 531/8134 1
Other 88/784 1.88 (1.50 to 2.36)
Hypertension:
No 425/7273 1
Yes 194/1645 1.85 (1.55 to 2.19)
Smoking status:
Never smoker 286/4461 1
Ex-smoker 206/2893 1.02 (0.85 to 1.22)
Current smoker 127/1564 1.42 (1.15 to 1.75)
Alcohol consumption:
Low 519/7515 1
Moderate 87/1198 1.09 (0.87 to 1.37)
High 13/205 1.07 (0.62 to 1.86)
Exercise:
≥
1.5 h/week 105/1659 1
<1.5 h/week 514/7259 1.14 (0.92 to 1.41)
Daily fruits and vegetables:
Yes 354/5260 1
No 265/3658 1.13 (0.96 to 1.32)
Body mass index:
<20 14/539 1
20-24.9 291/4960 1.87 (1.09 to 3.20)
25-29.9 250/2850 2.60 (1.51 to 4.45)
≥
30 64/569 3.81 (2.13 to 6.80)
Diabetes:
No 610/8837 1
Yes 9/81 1.54 (0.79 to 2.98)
Job strain:
No 537/7859 1
Yes 82/1059 1.23 (0.98 to 1.56)
Blood cholesterol (mmol/l):
<6.2 288/5424 1
≥
6.2 331/3494 1.55 (1.32 to 1.82)
RESEARCH
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cases, the pattern of associations was similar to that
obtained for measures with replaced missing values.
DISCUSSION
We examined the associations of positive and negative
affect with incident coronary heart disease,followed up
over a 12 year period, in the Whitehall II cohort. We
found no real association between positive affect or
affect balance and incidence of coronary heart disease.
Participants in the highest third of negative affect had a
slightly increased risk of incident coronary heart
disease, and this association remained unchanged
after taking into account the eff ects of age, sex,
employment grade, ethnicity, health related beha-
viours, biological markers, job strain, and positive
affect.
Findings in context of the literature and possible
mechanisms
To our knowledge, this is the first prospective cohort
study to examine the effects of both negative and
positive affect on incident coronary heart disease,
independently of known risk factors and of each other.
The findings are based on a large well characterised
cohort with coronary heart disease ascertained by
medical records and biological risk factors assessed by
clinical examination.
The finding showing negative affect as an indepen-
dent predictor of coronary heart disease incidence is
consistent with some epidemiological investigations on
negative emotions and coronary heart disease. A recent
review of negative emotions, measured as anxiety,
hostility/anger, and depression, supports their status as
risk factors for coronary heart disease.
3
Anger in men
has been found to be associated with a greater risk of
coronary events and coronary mortality.
22 23
Among
men from the Northwick Park study and women from
the Framingham heart study, greater anxiety predicted
fatal coronary heart disease.
24 25
According to a recent
meta-analysis of 21 aetiological studies and 34 prog-
nostic studies, depressive symptoms are associated
with an 80% excess risk of developing coronary heart
disease or dying from coronary heart disease.
26
The magnitude of the association between negative
affect and coronary heart disease in our study is small
and needs to be replicated in studies using measures of
both positive and negative affect. To test the robustness
of our findings, we repeated the analysis using
continuous affect scores with assessments of the
increase in risk of coronary events across the extremes
of the distribution of the affect score. These results also
supported the status of negative affect as a risk factor
andprovidednosuchsupportforotheraffect
measures.
Further research is needed to examine the precise
mechanisms through which negative affect might
increase the risk of coronary heart disease. As negative
affect is thought to subsume high negative emotions
such as anxiety and depression,
827
it may be linked to
coronary heart disease through physiological (cardio-
vascular and neuroendocrine) responses related to
these emotions. Depression has been found to be
associated with pathophysiological changes that may
increase the risk of cardiac morbidity and mortality,
including autonomic nervous system dysfunction
(such as elevated heart rate, low heart rate variability,
and exaggerated heart rate responses to physic al
stressors),
28
hypothalamic-pituitary-adrenal axis dys-
regulation (increased cortisol secretion),
29
enhanced
inflammatory processes (higher concentrations of
interleukin 6, C reactive protein, and fibrinogen),
30
and accelerated progression of atherosclerosis as
indicated by change in carotid intima-media
thickness.
731
Negative affect could also be linked to
coronary heart disease through health related
behaviours.
22
In our study, negative affect was not
associated with hypertension, higher body mass index,
or self reported diabetes and was inversely associated
with blood cholesterol concentration, suggesting that
thesefactors are notmajor mediators for the association
seen. The association between negative affect and
coronary heart disease was not attenuated after
adjustment for behavioural factors; thus stable
Table 3
|
Associations between positive affect, negative affect, and affect balance scores in
thirds and coronary heart disease (number of events/number of participants
=
619/8918*)
Scores in thirds
Hazard ratio (95% CI)
Positive affect Negative affect Affect balance
Model 1
††
Lowest 1 1 1
Middle 1.19 (0.98 to 1.44) 1.12 (0.92 to 1.36) 0.97 (0.80 to 1.17)
Highest 1.01 (0.82 to 1.24) 1.32 (1.09 to 1.60) 0.89 (0.73 to 1.09)
Model 2
‡‡
Lowest 1 1 1
Middle 1.18 (0.97 to 1.43) 1.13 (0.93 to 1.37) 0.97 (0.80 to 1.18)
Highest 1.01 (0.82 to 1.25) 1.33 (1.10 to 1.61) 0.89 (0.72 to 1.09)
Model 3
§§
Lowest 1 1 1
Middle 1.22 (1.01 to 1.48) 1.15 (0.94 to 1.39) 0.98 (0.81 to 1.19)
Highest 1.02 (0.83 to 1.26) 1.37 (1.13 to 1.66) 0.89 (0.73 to 1.09)
Model 4
¶¶
Lowest 1 1 1
Middle 1.20 (0.99 to 1.46) 1.11 (0.92 to 1.35) 0.98 (0.81 to 1.19)
Highest 1.03 (0.83 to 1.27) 1.30 (1.07 to 1.50) 0.91 (0.74 to 1.11)
Model 5**
Lowest 1 1 1
Middle 1.22 (1.01 to 1.48) 1.15 (0.94 to 1.40) 1.00 (0.82 to 1.21)
Highest 1.04 (0.85 to 1.29) 1.36 (1.12 to 1.65) 0.91 (0.74 to 1.12)
Model 6
††††
Lowest 1 1
–
Middle 1.26 (1.04 to 1.53) 1.16 (0.95 to 1.41)
–
Highest 1.10 (0.89 to 1.36) 1.39 (1.14 to 1.69)
–
* No of events/No (percentage) participants for lowest, middle, and highest scores thirds were 183/2746 (30.8),
257/3403 (38.2), and 179/2769 (31) for po sitive affect; 208/3135 ( 35.2), 197/2856 (32), and 214/2927
(32.8) for negative affect; and 200/2817 (31.6), 236/3357 (37.6), and 183/2744 (30.8) for a ffect balance.
†
Hazard ratio adjusted for age, sex, socioeconomic position, and ethnicity.
‡
Model 1 additionally adjusted for health related behaviours (body mass index, smoking status, exercise, da ily
fruit and vegetable intake, alcohol consumption).
§
Model 1 additionally adjusted for biological risk factors (b lood cholesterol, diabetes, hypertension).
¶
Model 1 additionally a djusted for psychosocial stress at wor k.
**Model 1 + model 2 + model 3 + model 4.
††
Model 5 additionally adjusted for positive or negative affect.
RESEARCH
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differences in these factors do not seem to be likely
mediators. Further research should examine whether
negative affect is related to risk factor trajectories over
time or whether it increases episodic elevations in risk
factors, such as blood pressure, that could act as a
trigger for coronary events among employees with
subclinical coronary heart disease.
Lack of a robust association between positive affect
and reduced risk of coronary heart disease in our study
is in contrast to some previous reports. An upsurge in
interest in positive affect or happiness and its associa-
tion with health has occurred recently.
32 33
In one study,
low level of positive affect was associated with
increased 10 year total mortality in older adults.
34
A
major limitation of that study was the assessment of
positive affect, done using the Center for Epidemiolo-
gic Studies of Depression scale. This scale, a measure of
depression, may not reliably distinguish between low
positive affect and high negative affect. Another study,
also in older adults, found that positive affect had a
protective association with stroke.
13
In that study, the
analysis was controlled for depressive symptoms but
not for the other components of negative affect, and
thus whether the observed association was indepen-
dent of the effect of negative affect remains unclear.
Moreover, the measure of stroke was self reported,
without corroboration from medical reports. As
positive and negative affect may be related to response
styles, a subjective component in the outcome measure
may introduce subjectivity bias that could artificially
inflate associations.
Limitations
Interpretation of our findings should be considered
within the context of the study limitations. Firstly, as
coronary heart disease develops during a long time
span, higher levels of negative affect in the long term
rather than the short term are assumed to influence the
incidence of coronary heart disease. However, the
relative temporal stability of negative affect scores
between the two phases was only moderate in this study
(test-retest reliability over three years=0.5). This
suggests the presence of a certain amount of variability
in negative affect levels over time and implies that we
might have underestimated the cumulative impact of
high negative affect on incidence of coronary heart
disease. On the other hand, the lack of stability and the
relatively low internal consistency coefficient, which
was slightly below the conventional threshold of 0.7 for
the negative affect scale, call into question what
precisely the scale measures. These factors are likely
to have influenced our results, and we cannot eliminate
the possibility that negative affect might in part
represent a marker of changing risk exposures rather
than being solely a stable disposition to experience
aversive emotional states. However, the proportional
hazards assumption held in the Cox regression,
suggesting relatively stable effects of negative affect
over the follow-up period.
A second limitation involves modelling potential
biological and behavioural confounders as time
independent covariates. Thus, we did not assess the
possible impact of changes in these factors on the riskof
coronary heart disease events. Thirdly, our cohort of
civil servants did not include blue collar workers and
unemployed people and is thus not representative of
the general population, which may limit the generali-
sability of our findings.
Conclusions
Data from a large occupational cohort provide no
evidence for associations between positive affect or
affect balance and coronary heart disease in men and
women who were free of diagnosed coronary heart
disease at recruitment to the study. However, we found
negative affect to be weakly predictive of incident
coronary heart disease events, independently of socio-
demographic characteristics, conventional risk factors,
and job strain. Further research is needed to examine
whether our findings are generalisable to other
populations as well as to disentangle the potential
pathways that may link negative affect to coronary
heart disease.
Contributors: HN analysed and interpreted the data and wrote the first
draft of the manuscript. MK and A S-M contributed to the analysis and
interpretation of data. MK, RDV, MGM, and AS-M made significant
contributions to all subsequent revisions . HN is the gua rantor.
Funding: HN and MK are suppor ted by the Academy of Finl and (gra nt
117604). AS-M is supported by a
“
EURYI
”
award from t he Euro pean
Science Foundati on and a
“
Chaire d
’
excellence
”
award from the French
Ministry of Research. MGM is supported by an MRC research
professorship. The Whitehall II stu dy is supported by grants from the
Medical Research Coun cil; British Heart Foundation ; Health and Safety
Executive; Department of Health; National Heart Lung and Blood Institute
(HL36310),US,NIH;NationalInstituteonAging,US,NIH;Agencyfor
Health Care Policy Research (HS06516); and the John D and Catherine T
MacArthur Foundation Research Networks on Successful Midlife
Development and Socio- economic Status a nd Health. Th e funding so urces
had no role in study d esign, data co llection, data analysis, data
interpretation, or writing of the report.
Competi ng interes ts: None declared.
Ethical approval: University College London Medical School committ ee on
the ethics of human research gave ethical approval for the Whitehall II
study.
Provenance and peer review: Not commissioned; externally peer
reviewed.
WHAT IS ALREADY KNOWN ON THIS TOPIC
Psychological factors are seen as important predictors of coronary heart disease; negative
affectivity may underlie these associations
No largescale studyhasexaminedthe association between negative affectand coronaryheart
disease
Whether positive emotions might have a protective role in the development of coronary heart
disease remains unclear
WHAT THIS STUDY ADDS
Negativeaffectwasaweakpredictorofincidentcoronaryheartdiseasein menand womenwho
were free of diagnosed coronary heart disease at recruitment to the study
This association was not accounted for by established coronary risk factors
No support was found for associations of positive affect and affectbalance with coronaryheart
disease
RESEARCH
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