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Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results from a Feasibility Study

DOI:10.1159/000481862
Authors:
Sebastian Karl at Central Institute of Mental Health
Sebastian Karl
Monica Fallon at Universität Mannheim
Monica Fallon
Roman Palitsky at Emory University
Roman Palitsky
Jessica A Martinez
Jessica A Martinez
Jessica A Martinez
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this visit. In this task, participants were asked to recall a situation
where they felt alone and abandoned.
The overall sample had a mean age of 58.59 (SD = 13.94), was
54.55% female, and 90.91% were White (vs. non-White). Bereaved
versus nonbereaved and aspirin versus placebo groups did not dif-
fer at p < 0.05 on any of these characteristics. Change scores were
used to reduce the number of variables in the analyses. Cohen’s d
is reported as a measure of effect size.
Bereaved participants reported more depressive symptoms
than nonbereaved participants at baseline: CES-D score 23.80
(SD = 10.29) versus 8.42 (SD = 9.18) (F = 10.09, p < 0.001, d = 1.46).
All 5 bereaved participants receiving aspirin reported fewer de-
pressive symptoms at the second visit, compared to only 1 (of 5)
bereaved participants receiving placebo. A dichotomous variable
(decrease vs. no decrease in depressive symptoms) showed a sig-
nificant difference (χ
2 = 6.67, p < 0.01, d = 3.54).
When including all participants, the separation recall task
elicited an increase in systolic blood pressure: 129.21 mm Hg
(SD = 13.64) to 137.60 mm Hg (SD = 13.16) ( t = 3.59, p < 0.01,
d = 0.63) and diastolic blood pressure: 78.36 mm Hg (SD = 11.46)
to 83.07 mm Hg (SD = 10.88) ( t = 4.58, p < 0.001, d = 0.42). There
was also an increase in anxiety measured with the State-Trait
Anxiety Inventory: 33.05 (SD = 7.75) to 39.85 (SD = 9.78) ( t =
4.47, p < 0.001, d = 0.78). Heart rate increased from 74.12 beats
per minute (bpm) (SD = 10.12) to 75.79 bpm (SD = 8.14) ( t = 2.17,
p < 0.05, d = 0.18) and decreased after the separation recall task:
from 74.12 bpm (SD = 10.12) to 69.62 bpm (SD = 7.97) ( t = 6.64,
p < 0.001, d = 0.50).
Participants receiving aspirin recovered faster from the separa-
tion recall than participants receiving placebo ( Fig.1 ). Heart rate
decreased significantly more in the aspirin group: 5.97 bpm (SD =
2.95) versus 2.32 bpm (SD = 1.50) ( F = 10.38, p < 0.005, d = 1.64).
Using post hoc analysis, we had 71% power to detect this effect.
HRV increased significantly in the aspirin group: log RSA 4.15
(SD = 1.96) to 4.57 (SD = 1.80) ( t = 2.31, p < 0.05, d = 0.22). The
change score of HRV was significantly higher in the aspirin group:
log RSA placebo group –0.17 (SD = 0.38) versus aspirin group
+0.42 (SD = 0.62) ( F = 5.69, p < 0.03, d = 1.18).
To summarize, our results show an attenuated physiological
reactivity to a grief-related stress task and a beneficial effect on
depressive symptoms in the aspirin group. Higher cardiovascular
reactivity to emotional stressors in bereavement could amplify in-
creased cardiovascular risk. Aspirin may have a potential preven-
tive benefit targeting increased cardiovascular risk in bereave-
ment. The effect of aspirin on depressive symptoms is consistent
with previous studies linking depressive symptoms with inflam-
mation
[8] . Further research is needed to investigate this potential
link.
The use of aspirin in secondary prevention of cardiovascular
disease is well established. In primary prevention, aspirin is de-
In the 24 h following the death of a significant person, the in-
cidence of acute myocardial infarction increases 21.1-fold
[1] . Be-
reavement acutely increases mortality and cardiovascular risk in
the surviving spouse for a limited time
[2] . Aside from expectable
psychological distress, acute bereavement is associated with an el-
evation of heart rate and blood pressure, a decrease in heart rate
variability (HRV), and inflammatory and prothrombotic changes
[2, 3] . Acute bereavement as a cardiovascular risk factor is ame-
nable to preventive approaches, because it is predictable and tem-
porary. Despite clear evidence for this risk, no studies to date have
attempted primary prevention.
Low-dose aspirin could be a suitable prevention strategy in
acute bereavement. It targets the main cardiovascular risk factors
during bereavement, is inexpensive, is widely available, does not
require a prescription, and is feasible in other short-term interven-
tions. Low-dose aspirin is widely used for its antiplatelet effect, has
anti-inflammatory properties, and positively influences depressed
mood
[4] , HRV [5] , and blood pressure [6] .
To investigate aspirin as a feasible preventive intervention,
acutely bereaved participants ( n = 10) were recruited on average
within 30 days (SD = 14.67) of the death of their spouse; nonbe-
reaved controls ( n = 12) were also recruited. We assessed hemody-
namic markers (blood pressure, heart rate, HRV) and depressive
symptoms (Center for Epidemiologic Studies Depression Scale;
CES-D) during 2 laboratory visits. The first laboratory visit was
used to assess baseline values. Using simple randomization, all par-
ticipants were then randomized to receive tablets containing either
81 mg of aspirin ( n = 12, 41.67% bereaved), the standard dosage
used for prevention in the USA, or placebo ( n = 10, 50% bereaved)
on the 5 days prior to the second laboratory visit. This visit was
scheduled on average 10.55 days (SD = 7.51) after the first visit. We
also included a separation recall task
[7] to assess reactivity during
Received: May 17, 2017
Accepted after revision: September 24, 2017
Published online: February 21, 2018
© 2017 S. Karger AG, Basel
www.karger.com/pps
Psychother Psychosom
DOI: 10.1159/000481862
L o w - D o s e A s p i r i n f o r P r e v e n t i o n o f C a r d i o v a s c u l a r
Risk in Bereavement: Results from a Feasibility
Study
Sebastian Karl a, e , Monica Fallon d , Roman Palitsky a ,
Jessica A. Martinez
b, c , Harald Gündel e , Mary-Frances O'Connor a
Departments of a Psychology and b Nutritional Sciences,
University of Arizona, and
c University of Arizona Cancer Center,
Tucson, AZ , USA; d University of Mannheim Business School,
Mannheim, and
e Department of Psychosomatic Medicine and
Psychotherapy, University Hospital of Ulm, Ulm , Germany
Mary-Frances O’Connor
Department of Psychology, University of Arizona
1503 E. University Boulevard, Room 430
Tucson, AZ 85721 (USA)
E-Mail mfoconnor
@ email.arizona.edu
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Karl/Fallon/Palitsky/Martinez/Gündel/
O’Connor
Psychother Psychosom
DOI: 10.1159/000481862
2
bated because the reduction in cardiovascular risk must outweigh
the risk of bleeding. In people with no history of ischemic heart
disease, risks and benefits cancel each other out approximately
[9] .
Increased cardiovascular risk during acute bereavement might
shift this equilibrium toward benefits, especially if aspirin is only
used for a limited time. The American Heart Association recom-
mends low-dose aspirin for patients with diabetes because they
have increased cardiovascular risk
[10] . This could also apply to
other conditions with increased cardiovascular risk, such as acute
bereavement.
Although intended as a feasibility study, the major limitation
of this study was its small sample size. Although this means that
the estimates of the effects may differ in another sample, we report
Cohen’s d for information on the size of the effects. Confounding
variables were controlled for through the within-subject, random-
ized, double-blind study design.
If aspirin has a protective effect for increased cardiovascular
risk in acute bereavement, it is preferable to commence aspirin
treatment as soon as possible after bereavement and continue it
while the risk is elevated. Although bereavement is a rare event, it
affects nearly everyone, creating significant public health concerns
due to increased morbidity and mortality risk. These results war-
rant a larger investigation to confirm the effects and determine the
safety of aspirin use in this population.
Disclosure Statement
The authors declare no conflict of interest.
Funding Sources
Funding was provided in the form of a scholarship to the first
author by the International Graduate School in Molecular Medi-
cine of Ulm University.
85
80
75
70
65
60
Beats per minute
Pre Mid-task Post
Heart rate
p < 0.01
p < 0.01
p < 0.01
5.1
4.9
4.7
4.5
4.3
4.1
log ms
Pre Post
log RSA
ab
Aspirin
Placebo
p < 0.01
p < 0.02
p < 0.01
p < 0.05
Fig. 1. Changes of heart rate ( a ) and heart
rate variability (log RSA; b ) from before
(pre) to after (post) the separation recall
task (mid-task). Statistically significant dif-
ferences are marked with a bracket and p
value. RSA, respiratory sinus arrhythmia.
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... Cardiovascular biomarkers have shown consistent changes in bereavement when comparing acute (e.g., <6 weeks) and chronic grief within bereaved individuals, and also between bereaved and nonbereaved groups. The shift is seen in tonic activity, although there are some indications that reactivity measures (i.e., phasic activity) may also differ (29,30). These biomarkers include increased heart rate (resting and 24-hour), heart rate variability, systolic and diastolic blood pressure, von Willebrand factor, and platelet/granulocyte aggregates (31)(32)(33)(34). ...
... Finally, as researchers with interest in translational applications, clinical trials should examine how intervention during acute and chronic grief could improve health. In acute grief, we have published a very small feasibility trial of low-dose aspirin as a potential primary prevention strategy (29). As a risk factor, bereavement is often predictable and the increased risk is temporary. ...
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Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A Scientific Statement From the American Heart Association and the American Diabetes Association
Article
The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.
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