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Stress Health. Author manuscript; available in PMC 2021 August 27.
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Published in final edited form as:

Stress Health. 2021 August ; 37(3): 538–546. doi:10.1002/smi.3018.

Association between symptoms of psychological distress and

cognitive functioning among adults with coronary artery disease
Kasra Moazzami1,2, Mariana Garcia1,2, An Young1,2, Zakaria Almuwaqqat1,2, Bruno B.
Lima1,2, Afif Martini1, Mhmtjamil Alkhalaf1, Amit J. Shah1,2,3, Felicia C. Goldstein4,5,
Ihab Hajjar4,5,6, Allan I. Levey4,5, J. Douglas Bremner3,7,8, Arshed A. Quyyumi2, Viola
Vaccarino1,2
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1Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia,
USA
2Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research
Institute, Emory University School of Medicine, Atlanta, Georgia, USA
3Atlanta VA Medical Center, Decatur, Georgia, USA
4Department of Neurology, Emory University School of Medicine, Emory University, Atlanta,
Georgia, USA
5GoizuettaAlzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta,
Georgia, USA
6Division of General Internal Medicine and Geriatrics, Department of Medicine, Emory University,
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Atlanta, Georgia, USA

7Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine,
Atlanta, Georgia, USA
8Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta,
Georgia, USA

Abstract
Greater psychological distress is associated with cognitive impairment in healthy adults. Whether
such associations also exist in patients with coronary artery disease (CAD) is uncertain. We
assessed cognitive function in 496 individuals with CAD using the verbal and visual memory
subtests of the Wechsler Memory Scale and executive functioning measured by the Trail Making
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Test Parts A and B. We used a composite score of psychological distress derived through
summation of Z-transformed psychological distress symptom scales (depression, posttraumatic
stress, anxiety, anger, hostility and perceived stress) and scores for each individual psychological
scale. Multivariable linear regression models were used to determine the association between

Correspondence: Viola Vaccarino, Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton
Road NE, Atlanta, GA 30322, USA. viola.vaccarino@emory.edu.
CONFLICT OF INTERESTS
The authors have declared that they have no conflict of interests.
DATA ACCESSIBILITY STATEMENT
Data can be accessed up on reasonable request from the corresponding author.
 Moazzami et al. Page 2

memory scores (as outcomes) and the psychological distress scores (both composite score and
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individual scales). After adjusting for demographic and cardiovascular risk factors, a higher
psychological distress score was independently associated with worse memory and executive
functioning. Each standard deviation increase in psychological distress score was associated with
3% (95% confidence interval [CI], 1%–5%) to 5% (95% CI, 3–7%) worse cognitive performance
(higher Trail A and Trail B, and lower verbal and visual memory scores). Among individuals with
CAD, a higher level of psychological distress is independently associated with worse cognitive
performance. These findings suggest that psychological risk factors play a role in cognitive
trajectories of persons with CAD.

Keywords
cognitive impairment; coronary artery disease; psychological distress
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1| INTRODUCTION
Cognitive impairment is defined as deficits in memory with a detrimental impact on
individuals’ independent living and quality of life, which, if left undiagnosed and
untreated, could evolve into dementia over time (Mortamais et al., 2017). Cognitive
impairment and coronary artery disease (CAD) are two major and inter-related global health
challenges (Plassman et al., 2008; Virani et al., 2020), and individuals with CAD have
a disproportionate risk of cognitive impairment and dementia compared to those without
CAD (Schievink et al., 2017; Singh-Manoux et al., 2008; Stefanidis , Askew, Greaves, &
Summers, 2018; Xie, Zheng, Yan, & Zhong, 2019). Both conditions share common risk
factors that accelerate the atherosclerotic process (Meyer, Rauch, Rauch, & Haque, 2000;
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de la Torre, 2002; Viswanathan, Greenberg, & Scheltens, 2016). Given that more than 18
million individuals currently live with CAD in the United States (Virani et al., 2020), it
is important to understand the determinants and mechanisms of cognitive decline in this
population to develop appropriate interventions.

An understudied risk factor for both worse cognitive performance and CAD is psychological
distress. While the potential mechanistic links between psychological distress and cognitive
performance in the CAD population are not completely understood, putative factors
include dysregulation in the sympathetic nervous system and the hypothalamic pituitary
adrenal axis, resulting in higher cardiovascular reactivity with elevations in blood pressure
and autonomic function imbalance (Fontes et al., 2014; Herman et al., 2016; Marko &
Riecansky, 2018; Miller et al., 2019). Measuring psychological distress is notoriously
difficult, given its multiple domains and definitions (Kivimaki & Steptoe, 2018), so most
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previous studies have relied on the assessment of particular aspects of psychological

disturbance. Limited data have linked posttraumatic stress disorder (PTSD; Edmondson,
Kronish, Shaffer, Falzon, & Burg, 2013; Flatt, Gilsanz, Quesenberry, Albers, & Whitmer,
2018; Wang et al., 2016; Yaffe et al., 2010), anxiety (Batelaan, Seldenrijk, Bot, van Balkom,
& Penninx, 2016; Yang et al., 2020), anger (Sutin, Stephan, & Terracciano, 2018), and
hostility (Chida & Steptoe, 2009; Sutin et al., 2018) with dementia. Similarly, depression,
which is often a consequence of stressful experiences and has been conceptualized as part of

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stress spectrum disorders (Correll et al., 2017; Ritchie et al., 2020; Wager-Smith & Markou,
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2011; Yu, Jung, Go, Park, & Ha, 2020), has also shown to increase the risk of dementia by
twofold (Byers & Yaffe, 2011). Other studies showed deficits in verbal declarative memory
as measured with the Wechsler Memory Scale and other tests in PTSD and depression
(Bremner et al., 1993; Burt, Zembar, & Niederehe, 1995). No previous studies, however,
have examined whether these associations exist in the CAD population. Furthermore, no
previous research has considered these factors comprehensively. An integrative approach
may be useful as these psychological distress components may share common biological or
behavioral substrates, which could explain why they tend to cluster together (Suls & Bunde,
2005). A global measure of psychological distress defined as a combination of symptoms
related to depression, anxiety, anger, general distress, and perceived stress was previously
shown to be associated with the risk of cardiovascular disease (Blumenthal et al., 2016).
Given the importance of PTSD symptoms and hostility for cardiovascular risk, our group has
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added these two components to the global score for the prediction of future cardiovascular
events in the CAD population (Pimple, Hammadah, et al., 2019). Therefore, examining
them together as a global psychological distress phenotype may provide a more powerful
approach for our understanding of determinants of cognitive function in individuals with
CAD.

Accordingly, in the current study, we aimed to investigate the association of a composite

measure of psychological distress with cognitive function in a sample of individuals with
CAD with comprehensive measures of psychological distress. We also sought to understand
which individual components (depressive symptoms, PTSD, anxiety, anger, hostility, and
perceived stress) may have the strongest associations with cognitive parameters. We
hypothesized that a higher global psychological distress score would have a more robust
association with worse cognitive performance throughout all cognitive domains than any
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individual component.

2| METHODS
2.1 | Study sample
The Mental Stress Ischemia Mechanisms and Prognosis Study (MIPS) enrolled individuals
with stable CAD from Emory University-affiliated hospitals and clinics. From a total
number of 695 patients enrolled in MIPS, cognitive function measures were introduced after
the enrolment had already begun and thus were available on a subset of 496 individuals. A
detailed study protocol for MIPS has been previously published (Hammadah et al., 2017).
The presence of CAD was defined based on a positive nuclear stress test, the presence of
angiographic atherosclerosis, or a history of prior myocardial infarction or revascularization.
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Patients with a history of recent (<1 week) acute coronary syndrome or decompensated
heart failure, as well as those with end-stage renal disease, systolic blood pressure over
180 mm Hg or diastolic blood pressure over 110 mm Hg on the day of the clinic visit
or unstable psychiatric conditions such as schizophrenia, were excluded. Data regarding
sociodemographic characteristics, medical history, and medication use of all participants
were collected using standardized questionnaires, and clinical information was verified by

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medical record review. This study was approved by the institutional review board of Emory
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University, and all participants provided informed consent.

2.2 | Assessment of psychological distress

We used the Beck Depression Inventory for the assessment of depressive symptoms
consisting of a 21-item self-administered scale with excellent internal consistency
(Chronbach’s α = 0.91; Beck, Steer, & Brown, 1996); the PTSD Symptom Checklist for
the assessment of PTSD symptoms, a 17-item scale with Chronbach’s α of 0.94; Blanchard,
Jones-Alexander, Buckley, & Forneris et al., 1996); the State-Trait Anxiety Inventory for
the measurement of trait anxiety (Chronbach’s α = 0.95; Spielberger, Gorsuch, & Lushene
et al., 1970); the Spielberger’s State-Trait Anger Expression Inventory for the measurement
of trait anger (Chronbach’s α > 0.8; Spielberger, 1988); the Cook–Medley Hostility Scale
for the assessment of hostility (Cook & Medley, 1954); and the Perceived Stress Scale
for the assessment of general perceived stress (Chronbach’s α = 0.84; Cohen, Kamarck,
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& Mermelstein, 1983). We then constructed a composite distress index by integrating

these scales as previously described (Pimple, Hammadah, et al., 2019). Briefly, each
psychological scale was converted into a z score variable by subtracting each scale’s mean
from each score and then dividing the result by the standard deviation (SD) of each scale.
These individual z scores were then summed up to derive a composite psychological distress
index (Pimple, Hammadah, et al., 2019). In individuals with CAD, this composite score
was related to the extent of resting perfusion abnormalities and future cardiovascular events
(Pimple, Hammadah, et al., 2019; Pimple, Lima, et al., 2019). A similar composite score,
without PTSD and hostility, was shown to improve with a stress management intervention
(Blumenthal et al., 2016).

2.3 | Cognitive testing

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We administered the Visual Reproduction and Logical Memory subtests of the Wechsler
Memory Scale according to the Russell revision (Russell, 1975). The Visual Reproduction
subtest evaluates immediate and delayed visuospatial memory, and the Verbal Memory
subtest evaluates immediate and delayed verbal declarative memory. For the visual memory
test, each participant was asked to reproduce a series of line drawings, each presented for 10
s followed by immediate and then 30-min delayed recall. For the test of immediate verbal
memory, participants were asked to recall the details of a short story immediately after it
was read to them, and then, after a 30-min delay. Points were assigned, with higher scores
indicating better cognitive function.

We also administered the Trail Making Test Parts A and B to evaluate visuomotor
sequencing and set shifting, respectively (Filskov & Goldstein, 1974). During Trails A,
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an individual was instructed to draw lines sequentially connecting 25 encircled numbers

distributed on a sheet of paper. In contrast, during the more complex Trails B testing, the
individual was asked to switch between numbers and letters rapidly. The score on each part
represents the amount of time (in seconds required to complete the task. Lower scores on
Trails A and B indicate better cognitive function.

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2.4 | Statistical analysis

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As previously described (Pimple, Hammadah, et al., 2019), each psychological scale

was converted into a z-score and then z-scores were summed to derive a composite
psychological distress index. We then compared the study sample characteristics according
to quartiles of the composite psychological distress index, using either the analysis of
variance test for normally distributed variables or the χ2 test for categorical variables.
For the main analysis, multivariable linear regression models were used to determine the
association between memory scores (as outcomes) and the psychological distress index
(both as a continuous variable and categorical variable) as the main predictor variable.
Similar analyses were performed separately for each psychological scale. Models were
adjusted for demographic factors (age, sex, race/ethnicity, and education), cardiovascular
risk factors and comorbidities (history of smoking, hypertension, hyperlipidaemia, diabetes,
myocardial infarction, congestive heart failure, and revascularization), and medication use
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(aspirin, β-blockers, statins, and angiotensin-converting enzyme inhibitors). All analyses

were conducted using Stata 14 (StataCorp.).

3| RESULTS
The characteristics of the study sample are shown in Table 1. The mean age was 62
years, 71.6% were male, and 32.1% Black. History of dyslipidaemia was the most
common comorbidity, followed by obesity and hypertension. Study participants with higher
psychological distress were younger and more likely to be Black and less educated.
Individuals with higher psychological distress also had higher β-blocker use rates, but no
other important differences were observed in comorbidities or medication use according to
psychological distress levels. Table 1 also shows that individuals with higher psychological
scores had worse scores across all cognitive domains. Mean values for individual
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psychological measures are also shown in Table 1.

3.1 | Psychological distress and memory

As shown in Table 2 and Supplemental Table, after adjusting for demographic factors,
comorbidities, and medication use, higher psychological distress (either the total score as
a continuous variable or quartiles of increasing psychological distress) was associated with
worse performance in all cognitive domains. As shown in Table 2, every SD increase in
psychological distress score was associated with 3% (95% confidence interval [CI] [1%–
5%]) to 5% (95% CI [3%–7%]) worse cognitive performance (higher Trails A and Trails
B, and lower verbal and visual memory). Similarly, compared with the lowest quartile (low
psychological distress), individuals in the highest psychological distress quartile (Quartile
4) had an adjusted 23% (95% CI [3%–48%]) to 52% (95% CI, 27%–77%) worse cognitive
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performance (Table 2). There was no effect modification by race or sex on the association
between psychological distress scores and cognitive function.

Table 3 describes the associations between individual psychological measures and cognitive
function. All scales showed associations with several dimensions of cognitive performance.
Higher depressive symptoms were independently associated with higher Trail B scores
(worse executive function) and lower verbal memory scores (both immediate and delayed).

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Similar associations were found for anxiety scores. Scores for PTSD and hostility showed
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the most consistent associations with cognitive impairment, such that each SD increment
in either PTSD or hostility scores was associated with 10% (95% CI [1%–18%]) to 18%
(95% CI [9%–26%]) worse memory function in all cognitive domains. Higher scores for
State-Trait Anger were only associated with worse immediate and delayed verbal memory.
In contrast, a higher perceived stress score was associated with worse performance in both
Trails A and Trails B as well as the immediate and delayed verbal memory tests.

4| DISCUSSION
Among individuals with CAD, we observed that psychological distress, defined as a
composite measure of six scales (depression, PTSD, anxiety, anger, hostility, and perceived
stress) was associated with worse memory and executive function. When individual
psychological scales were examined separately, the magnitude of the effect size was
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fairly consistent across the various scale scores. However, the associations were most
consistent across cognitive domains for PTSD and hostility. These findings suggest that
multiple aspects of psychological distress are associated with worse cognitive performance
in the CAD population. Our results suggest that using a composite measure may show
a higher sensitivity for detecting impairments in cognitive function than individual scales
and highlights the potential advantage of measuring an individual’s overall psychological
distress in uncovering its impact on multiple cognitive domains (executive function and both
verbal and visual memory).

Previous reports have shown that a history of depression and current depressive symptoms
are associated with the risk of dementia (D. E. Barnes et al., 2012; Canton-Habas, Rich­
Ruiz, Romero-Saldana, & Carrera-Gonzalez, 2020; Ownby, Crocco, Acevedo, John, &
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Loewenstein, 2006; Ritchie et al., 2020; Yu et al., 2020). Consistent with these previous
data, in our study depressive symptoms were associated with both executive function and
memory performance. In addition to depression symptoms, symptoms of PTSD and hostility
showed consistent associations with cognitive impairment across all memory domains.
Symptoms of PTSD have previously shown to increase the risk of dementia among male
veterans as well as those from the general population (Flatt et al., 2018; Meziab et al., 2014;
Sutin et al., 2018; Wang et al., 2016; Yaffe et al., 2010). However, studies investigating the
association between hostility and cognition have shown mixed results (Albanese et al., 2016;
L. L. Barnes et al., 2009; Sutin et al., 2018). Our findings suggest that these psychological
stressors’ contribution to cognitive performance may be especially pronounced among those
with pre-existing CAD.

There are limited data on the relationship of anger with cognitive performance. Among
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9,913 participants in the Health and Retirement Study, anger was not associated with
cognitive impairment or dementia after 6–8 years of follow-up (Sutin et al., 2018). Our
results showed that a higher anger trait was associated with worse verbal memory in
individuals with CAD and suggest that anger might play a role in cognitive impairment
in this population. However, by examining a comprehensive panel of psychological scales,
our study shows that several psychological disturbances, not just a few in isolation, may
contribute to cognitive impairment.

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Behavioural and traditional cardiovascular risk factors such as diabetes, hypertension,

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obesity, physical inactivity, and smoking are important contributors to cognitive impairment
and dementia (Norton, Matthews, Barnes, Yaffe, & Brayne, 2014; Xing et al., 2020). These
risk factors are also commonly associated with psychological distress. However, our results
show that the associations between psychological distress and cognitive impairment were
independent of cardiovascular risk factors, suggesting that the latter do not account for much
of the relationship between psychological status and risk of cognitive impairment among
individuals with CAD.

Several biological mechanisms may be involved in the link between psychological distress
and cognitive impairment. Chronic or repeated psychological distress is accompanied by
dysregulation of the sympathetic nervous system and the hypothalamic pituitary adrenal
axis, cardiovascular reactivity with increase in blood pressure, reduced heart rate variability
and higher inflammatory activity (Fontes et al., 2014; Herman et al., 2016; Marko &
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Riecansky, 2018; Miller et al., 2019). These processes are also associated with worse
cognition through possible neuronal or glial injury, cerebrovascular dysfunction, and an
increase in β-amyloid deposition (Forte, Favieri, & Casagrande, 2019; Thayer & Lane,
2000; Walker et al., 2019). Future studies are needed to examine the exact mechanisms
for the association between psychological distress and cognitive function in high-risk
individuals like those with CAD.

While our findings suggest that psychological distress may increase the risk of cognitive
impairment, the opposite pathway is also possible, that is, worse memory and executive
function may cause psychological distress. For instance, individuals with cognitive
impairment have shown to be at a higher risk for anxiety and depressive disorders later
in life (Chen, Ganguli, Mulsant, & DeKosky, 1999; Mirza et al., 2017; Petkus, Reynolds,
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Wetherell, Kremen, & Gatz et al., 2017; Sussams et al., 2020). This phenomenon could
reflect ongoing brain disease, a psychological reaction of individuals to their awareness of
their cognitive decline or both. Previous studies have shown that individuals with dementia
and depression show a more pronounced degeneration of the locus coeruleus and substantia
nigra than those without depression (Daulatzai, 2016; Heneka et al., 2010). Also, those with
depression and early cognitive impairment have shown to have a higher self-awareness of
their memory loss (Chen et al., 1999; Wiels, Baeken, & Engelborghs, 2020). These findings
suggest that the association between psychological distress and cognitive impairment is
likely bidirectional and common pathological pathways may also be involved in linking
them together.

Our study had several strengths. This is the first study investigating the association between
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a comprehensive measure of psychological distress and cognitive function in a large sample

of individuals with CAD. Second, our study population was well characterized clinically
and thoroughly examined for psychological factors, as well as for cognitive function across
multiple domains. The main limitation of this study was the cross-sectional design, which
precluded any determination of causality between the psychological distress measures
and memory impairment. We also excluded individuals with a recent history of acute
coronary syndrome or decompensated heart failure, which may indicate more severe CAD
and potentially reduce the generalizability of our results to sicker patients. Although our

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 Moazzami et al. Page 8

psychological distress measures included symptom dimensions relevant for CAD patients,
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our findings should be replicated using other validated psychological scales. Less common
psychiatric manifestations are worth exploring, such as somatization, obsessive-compulsive
behaviours, and phobic anxiety. Larger studies are needed to explore the relationship
between these conditions and cognitive function.

In conclusion, we found that among individuals with CAD, a higher level of psychological
distress is associated with worse cognitive performance independent of demographic and
clinical risk factors. These findings suggest that psychological risk factors play a role
in cognitive trajectories of persons with CAD, although prospective studies are needed
to confirm this relationship. Future research is also needed to explore the possibility of
treatment modalities, such as stress reduction interventions to mitigate the risk of cognitive
impairment and dementia in this population.
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Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

ACKNOWLEDGEMENTS
This work was supported by the National Institutes of Health under grants P01HL101398, R01HL109413,
R01HL109413-02S1, R01HL125246, K24HL077506, K24 MH076955, UL1TR000454, KL2TR000455,
K23HL127251, and T32HL130025.

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TABLE 1

Characteristic of the study population according to quartiles of the psychological distress score

Quartile 1Low symptoms Quartile 2Mild Quartile 3Moderate Quartile 4High

All patients (496) (N = 124) symptoms (N = 124) symptoms (N = 124) symptoms (N = 124) p
Moazzami et al.

Demographics
Mean age, years (SD) 62 (9.2) 65 (8) 64 (8) 62 (9) 58 (9) <0.001
Male, N (%) 355 (71.6) 96 (77.4) 95 (76.6) 83 (66.9) 81 (65.3) 0.08
Blacks, N (%) 159 (32.1) 29 (23.4) 27 (21.8) 42 (33.9) 61 (49.2) <0.001
Education, years (SD) 15 (3) 15 (3) 15 (3) 14 (4) 14 (3) <0.001

Medical history, N (%)

Dyslipidaemia 418 (84.3) 103 (83.1) 110 (88.7) 101 (81.5) 104 (83.9) 0.43
Current smoking 73 (14.8) 18 (14.6) 15 (12.1) 22 (17.9) 18 (14.5) 0.40
Obesity 403 (81.7) 97 (78.2) 97 (78.2) 107 (87.0) 102 (82.9) 0.25
Hypertension 393 (79.2) 100 (80.6) 98 (79.0) 103 (83.1) 92 (74.2) 0.36
Diabetes mellitus 158 (31.9) 40 (32.3) 36 (29.0) 41 (33.1) 41 (33.1) 0.88
History of heart failure 66 (13.3) 10 (8.1) 18 (14.5) 18 (14.5) 20 (16.1) 0.24
History of myocardial infarction 183 (36.9) 42 (33.9) 41 (33.1) 52 (41.9) 48 (38.7) 0.42
Presence of positive stress test 160 (33.1) 45 (36.9) 42 (34.7) 39 (32.0) 34 (28.6) 0.55

Medications, N (%)
Aspirin 419 (84.6) 104 (83.9) 109 (87.9) 107 (86.3) 99 (80.5) 0.39
β-blocker 373 (75.4) 76 (61.3) 96 (77.4) 101 (81.5) 100 (81.3) <0.001
Statins 426 (86.2) 105 (84.7) 107 (86.3) 109 (88.6) 105 (85.4) 0.82

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Angiotensin-converting enzyme inhibitors 243 (49.2) 61 (49.2) 57 (46.0) 62 (50.4) 63 (51.2) 0.85

Memory function, mean (SD)

Immediate verbal memory (score points) 10.4 (3.3) 11.1 (3.1) 11.1 (3.4) 10.4 (3.2) 9.1 (3.1) <0.001
Delayed verbal memory (score points) 7.5 (3.7) 8.0 (3.3) 8.2 (3.8) 7.3 (3.4) 6.5 (4.0) 0.001
Immediate visual reproduction (score points) 8.7 (4.7) 8.7 (4.5) 9.2 (4.8) 9.2 (4.8) 7.7 (4.3) 0.03
Delayed visual reproduction (score points) 8.3 (4.7) 8.5 (4.7) 8.8 (4.8) 8.3 (4.9) 7.4 (4.4) 0.02
Trail A (s) 42 (19) 40.5 (17.2) 40.9 (14.5) 42.9 (22.2) 45.7 (20.6) 0.02
Trail B (s) 101 (49) 91.7 (43.4) 98.6 (39.3) 106.0 (51.4) 108.2 (59.1) 0.03
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Quartile 1Low symptoms Quartile 2Mild Quartile 3Moderate Quartile 4High

All patients (496) (N = 124) symptoms (N = 124) symptoms (N = 124) symptoms (N = 124) p

Psychological scales, mean (SD)

BDI score 8.0 (8.1) 2.2 (1.9) 4.7 (3.5) 8.2 (4.5) 16.8 (6.4)
PCL score 26.6 (11.2) 18.9 (2.3) 21.9 (5.1) 26.4 (6.8) 39.3 (13.5)
Moazzami et al.

STAI score 30.8 (10.8) 22.6 (3.4) 26.4 (6.4) 31.3 (8.2) 42.9 (10.6)
STAXI score 16.7 (4.6) 15.0 (0.2) 15.4 (1.0) 16.1 (2.2) 20.2 (8.0)
CMHS score 16.3 (7.9) 9.2 (4.0) 15.6 (5.5) 17.1 (7.1) 23.1 (7.5)
Perceived stress score 12.0 (7.4) 5.1 (3.1) 8.1 (3.7) 14.2 (4.5) 20.7 (5.8)

Note: Immediate verbal memory (minimum 2.1, maximum 20), delayed verbal memory (minimum 2.1, maximum 20), verbal memory consolidation (minimum 0, maximum 100), immediate visual
reproduction (minimum 0, maximum 20), delayed visual reproduction (minimum 0, maximum 19.5), visual reproduction consolidation (minimum 0, maximum 100), Trail A (minimum 15, maximum 150),
Trail B (minimum 20, maximum 300). A higher score in verbal and logical memory scales indicates a better cognitive function, while lower scores on the Trail A and B tests indicate better cognitive
function.

Abbreviations: BDI, Beck Depression Inventory; CMHS, Cook–Medley Hostility Score; PCL, PTSD Symptom Checklist; STAI, State-Trait Anxiety Inventory; STAXI, State-Trait Anger Expression
Inventory.

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TABLE 2

Association of the composite psychological distress score, as a continuous variable with cognitive scores

Verbal memory Visual memory

Trail A Trail B
Immediate Delayed Immediate Delayed
Moazzami et al.

Composite psychological distress score B (95% confidence interval)

Continuous score 0.03 (0.01, 0.05) 0.03 (0.01, 0.05) −0.05 (−0.07, −0.03) −0.04 (−0.06, −0.02) −0.03 (−0.05, −0.01) −0.03 (−0.05, −0.01)

Note: B represents the estimated point difference in cognitive scores (Trail A, Trail B, verbal memory, and visual memory) with 1SD increase in composite distress score and comparing Quartile
1 (reference) to Quartiles 2, 3, or 4 of the psychological distress score. Models were adjusted for demographic factors (age, sex, race/ethnicity, and education), cardiovascular risk factors, and
comorbidities (history of smoking, hypertension, hyperlipidaemia, diabetes, myocardial infarction, congestive heart failure, and revascularization), and medication use (aspirin, β-blockers, statins, and
angiotensin-converting enzyme inhibitors).

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TABLE 3

Association of individual psychological scales with cognitive scores

Trail A Trail B Verbal memory Immediate Delayed Visual memory Immediate Delayed
BDI score 0.08 (−0.001, 0.17) 0.11 (0.03, 0.20) −0.13 (−0.22, −0.04) −0.11 (−0.20, −0.02) −0.08 (−0.17, 0.008) −0.08 (−0.17, 0.007)
Moazzami et al.

PCL score 0.10 (0.01, 0.18) 0.12 (0.05, 0.21) −0.14 (−0.22, −0.05) −0.13 (−0.22, −0.05) −0.12 (−0.21, −0.04) −0.13 (−0.21, −0.05)
STAI score 0.10 (0.02, 0.19) 0.14 (0.05, 0.22) −0.13 (−0.21, −0.03) −0.08 (−0.17, −0.01) −0.07 (−0.16, 0.02) −0.07 (−0.16, 0.02)

STAXI score 0.02 (−0.06, 0.11) 0.01 (−0.07, 0.10) −0.15 (−0.24, −0.06) −0.14 (−0.22, −0.05) −0.07 (−0.16, 0.01)) −0.06 (−0.15, 0.02)

CMHS score 0.13 (0.04, 0.22) 0.10 (0.02, 0.18) −0.18 (−0.26, −0.09) −0.14 (−0.21, −0.04) −0.10 (−0.19, −0.02) −0.11 (−0.20, −0.03)
Perceived stress score 0.11 (0.02, 0.20) 0.13 (0.04, 0.21) −0.16 (−0.25, −0.07) −0.11 (−0.19, −0.02) −0.07 (−0.16, 0.01) −0.08 (−0.17, 0.01)

Notes: B represents the estimated point difference in cognitive scores (Trail A, Trail B, verbal memory, and visual memory) per 1SD increase in psychological disturbance scores. Models were adjusted for
demographic factors (age, sex, race/ethnicity, and education), cardiovascular risk factors, and comorbidities (history of smoking, hypertension, hyperlipidaemia, diabetes, myocardial infarction, congestive
heart failure, and revascularization), and medication use (aspirin, β-blockers, statins, and angiotensin-converting enzyme inhibitors). Bold: |P| value <0.05.

Abbreviations: BDI, Beck Depression Inventory; CMHS, Cook–Medley Hostility Score; PCL, PTSD Symptom Checklist; STAI, State-Trait Anxiety Inventory; STAXI, State-Trait Anger Expression
Inventory.

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