Editorial
Psychological Distress as a Risk Factor for Stroke-Related Mortality
Robert M. Carney, PhD; Kenneth E. Freedland, PhD
I
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n this issue, May et al report that psychological distress is
a predictor of fatal ischemic stroke. What is “psychological distress”? It is a nonspecific term that encompasses
sadness, frustration, anxiety, and a number of other negative
mood states. It includes both mild and severe forms of these
mood states, as well as both transient and persistent ones. It
also refers both to symptoms of psychiatric disorders and to
normal emotional responses to adversity.
Although several varieties of psychological distress have
been investigated as potential risk factors for cardiovascular
or cerebrovascular disease in community cohorts, and as risk
factors for cardiac events, stroke, and mortality in patients
with established coronary or cerebrovascular disease, depression is the variety of psychological distress that has received
the most attention in all of these lines of research. Psychological distress, particularly in the form of depression, has a
number of adverse effects in stroke patients. It impairs social
functioning and quality of life1 and interferes with the
recovery of motor2,3 and language functions.3 It may also be
a risk factor for stroke and stroke-related mortality.4 – 6
In a 14-year follow-up of 2201 middle-aged male participants in the Caerphilly study, May et al report that psychological distress, as measured at baseline by the 30-item
version of the General Health Questionnaire (GHQ-30), was
an independent risk factor for fatal ischemic stroke, after
adjusting for potential confounds. In contrast, the hazard
ratios for nonfatal ischemic stroke and for transient ischemic
attack (TIA) were not statistically significant, even in univariate analyses. Because this is the first study to conduct
separate analyses of fatal and nonfatal stroke, the findings
represent a unique contribution to this line of research.
The results raise a number of questions about the relationship between psychological distress and stroke. First, in the
Caerphilly cohort, as in many prospective studies of psychological risk factors for adverse health outcomes, we know
something about the psychological state of the subjects at the
time of enrollment but nothing about the course of their
psychological distress over the follow-up interval. In this
study, cerebrovascular events were ascertained as long as 14
years after the subjects were classified as either currently
distressed or not distressed. Presumably, the risk of fatal
ischemic stroke is related either to the cumulative exposure to
psychological distress during the follow-up interval or to the
level of distress just prior to the fatal event, not simply to the
presence of distress at an essentially arbitrary point in time
years before the event.
Furthermore, all we know about the psychological state of
the subjects is that they were distressed at enrollment. We do
See article on page 7
not know, for example, how many of them had psychiatric
disorders such as major depression or generalized anxiety
disorder. Additional studies are needed in which standardized
psychiatric interviews, along with questionnaires that assess
depression and anxiety with higher specificity than the
GHQ-30, are administered repeatedly over time. Such studies
will be more complex and more difficult to implement than
the Caerphilly study, but they are essential if we are to gain
a thorough understanding of the parameters of exposure to
psychological distress and of how and why exposure increases the risk of fatal ischemic stroke.
Second, why does psychological distress predict fatal
ischemic stroke but not nonfatal stroke or TIA? The authors
raise 2 distinct possibilities: The distressed subjects might
have had more severe strokes than their nondistressed counterparts, or they might have had equally severe strokes yet, for
some reason, had a higher case fatality rate. These explanations, in turn, point to 2 distinct directions for mechanistic
research: Whereas the former would foster research on
mechanisms that could promote more severe strokes in
distressed individuals, the latter would require studies of
interactions between psychological distress and factors that
differentiate between fatal and nonfatal strokes. Unfortunately, data on stroke severity are not included in the report,
so it is difficult to discern the more promising direction for
future mechanistic research.
Nevertheless, mechanistic studies remain a high priority in
this line of research, just as they are in research on the
relationship between depression and cardiovascular morbidity and mortality. We have previously noted that despite the
well-documented relationship between depression and cardiac morbidity and mortality, depression may not contribute
to the onset or progression of coronary artery disease.7 An
equally plausible explanation is that atherosclerosis develops
and progresses for reasons unrelated to depression, and that
depression increases the risk of cardiac events only in the
presence of coronary artery disease, or perhaps only when the
disease becomes clinically significant. Similarly, psychological distress may not promote the development of cerebrovascular disease, but it may instead heighten the risk of fatal
stroke in patients with existing cerebrovascular disease.
Another explanation for the relationship between depression and stroke is that both may be caused by cerebrovascular
disease. There is considerable interest in a possible link
between late-onset depression and cerebrovascular disease.
The “vascular depression hypothesis” proposes that depression in older adults may be caused or exacerbated by
cerebrovascular disease.8 Brain imaging studies have documented both structural and functional brain abnormalities in
patients with late onset depression.9,10 The present study, like
(Stroke. 2002;33:5-6.)
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January 2002
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some of the earlier studies,6 followed a cohort with no
clinically apparent cerebrovascular disease at enrollment.
However, given the age of the subjects at enrollment in this
study (between 45 and 59 years), it is likely that some of them
had occult cerebrovascular disease at that time. Whether
“vascular depression” accounts for the findings is unclear, but
it would be premature to discount this possibility.
The Caerphilly study is an excellent beginning, but the
relationships between psychological distress and cerebrovascular disease, stroke, and stroke mortality deserve further
investigation. High priorities include studies designed to (1)
more precisely define exposure to psychological distress and
(2) identify stroke characteristics such as infarct size or
location that may differ between distressed and nondistressed
cohorts; and to test mechanistic hypotheses about the relationships between stroke and depression and other forms of
psychological distress. Clarification of the nature of the
underlying mechanisms that link depression to increased risk
for stroke mortality may enable clinicians to identify the
depressed patients who are at greatest risk, as well as to target
the most harmful components or concomitants of depression.
Should depression contribute to the development of vascular
disease, studies directed toward early prevention of disease
progression should also be undertaken.
Finally, whether treating depression can reduce the risk of
stroke mortality is not yet known. Effective treatment of
depression has been shown to enhance quality of life and to
improve physical, emotional, and social functioning.11 Thus,
we strongly recommend that clinicians screen for and treat
clinically significant depression as a problem in its own right,
even if there is uncertainty as to whether treating depression
can reduce the risk of stroke mortality.
This work was supported in part by NIH Grant No. 1 RO1
HL65356 to 01, and by the Lewis and Jean Sachs Charitable
Lead Trust.
References
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Psychological Distress as a Risk Factor for Stroke-Related Mortality
Robert M. Carney and Kenneth E. Freedland
Stroke. 2002;33:5-6
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