We saw an association between psychological distress and risk of cerebrovascular disease among our participants, all of whom had been free from cardiovascular disease at baseline. This association was similar in size to the association between psychological distress and ischemic heart disease in the same group. Our results were largely unchanged by controlling for a range of covariables relevant to cardiovascular disease outcomes.
To date, most of the research in this area has focused on coronary artery disease. Previous studies have been limited by the rarity of cerebrovascular events, a limited range of covariables, the unknown influence of existing comorbidity on psychological distress (reverse causality) and few data from women. Our study adds substantially to the extant literature, because it overcomes some of these weaknesses by employing a large, well-characterized cohort with a sufficient number of cardiovascular disease events.
Our results are consistent with what literature does exist.13,18
In the European Prospective Investigation into Cancer — Norfolk study, which involved 20 627 participants who were stroke-free at baseline, psychological distress as measured using the Mental Health Inventory was associated with fatal and nonfatal stroke; depressive symptoms did not show this association.13
Although the GHQ-12 includes items covering symptoms of depression, it is generally viewed as a measure of overall mental health; the GHQ-12 also includes items covering symptoms of anxiety, social dysfunction, sleep disturbance and loss of confidence. Nevertheless, the effect estimates for psychological distress and cerebrovascular disease we saw are comparable with those seen in a recent meta-analysis for depression and stroke (pooled adjusted HR 1.45, 95% CI 1.29–1.63).12
However, other aspects of psychological dysfunction may have importance. For example, sleeping problems have previously been associated with increased risk of death due to cardiovascular disease,19
but the link with anxiety is less clear.20
Although the effect estimates of psychological distress were similar for cerebrovascular and ischemic heart disease, the mechanisms might not necessarily be the same because of the differences in pathogenesis of atherosclerotic lesions in coronary and cerebral arteries.21,22
Blood pressure is a plausible mechanism linking psychological stress and risk of stroke. For example, men with exaggerated systolic blood pressure reactivity to stress had 72% greater risk of incident stroke over 11 years follow-up.23
Nevertheless, using the same cohort as in the current study, we recently showed that psychological distress is associated with patients knowing that they have hypertension, but not with elevated blood pressure in participants without a diagnosis of hypertension.24
In addition, adjustment for antihypertensive medications as a proxy of increased blood pressure had minimal effect on the association between distress and cerebrovascular disease in the present analysis. Thus, a possible causal association between distress and hypertension remains doubtful. Other plausible mechanisms might involve inflammatory pathways and dysregulated function of the autonomic nervous system, although existing data relating to psychological distress and cardiovascular disease have been equivocal.25,26
There has been a lack of research into the mechanisms that might explain the association between psychological distress and stroke, and further work is needed to address this need.
We found that the size of the association between psychological distress and death from cardiovascular disease diminished as the duration of follow-up increased (Appendix 1), which may suggest reverse causality. That is, undiagnosed somatic illness will be associated with both an increased prevalence of psychological distress and an increased risk of death. The impact of hidden somatic illness will diminish as the length of follow-up increases, because people with such disorders die — potentially resulting in the trend we saw in the current study. In addition, with greater time between measuring psychological distress and death from cardiovascular disease, there is greater opportunity for other risk factors to play a role in the association. An additional explanation for the dilution of this effect is changes in psychological distress during follow-up resulting in the misclassification of exposure; that is, as time passes, there is an increasing opportunity for those who had psychological distress at baseline to no longer have distress, and vice versa.
We used a large cohort representative of the general population to examine the associations between psychological distress and cerebrovascular disease. However, because of the lack of follow-up data on psychological distress, we were unable to account for the effects of changes in distress over time. Furthermore, the GHQ-12 is not designed to assess specific aspects of mental health such as anxiety and depression, although it has been specifically validated as a measure of depression as assessed by the Composite International Diagnostic Interview.17
Measuring symptoms of anxiety, depression and dysfunction as a unidimensional construct of psychological distress is particularly relevant in community-based samples such as ours, because mental health problems in the community are frequently characterized by shifting patterns of symptoms that resist precise clinical classification.27
We have previously shown that psychological distress (GHQ-12 score > 3) was associated with incident cardiovascular events independent of the use of antidepressant medications (HR 1.48, 95% CI 1.29–1.70).28
Thus, to some extent, the GHQ-12 might be independent of depression itself.
The participants excluded from our analyses were older, and thus probably had a greater risk of stroke and poorer mental health, which may have introduced bias into our analysis. In addition, we cannot discount the possibility of reverse causation — underlying disease at baseline might have increased psychological distress. However, we excluded all respondants with a clinical history of cardiovascular disease and performed our analyses again after removing all deaths that occurred in the first two years of follow-up; this additional analysis did not affect our results.
Finally, different subcategories of cerebrovascular disease could not be reliably separated using the information from death certificates (57.9% of all deaths due to cerebrovascular disease were unspecified). Further work is required to determine whether psychological risk factors have a uniform affect on different subcategories of cerebrovascular disease.
Little is known about the psychological risk factors for cerebrovascular disease. In this large cohort representative of the general population, we saw an association between psychological distress and risk of death from cerebrovascular disease. Our data suggest that questionnaires such as the GHQ-12 could be of value in systematic screening aimed at improving the recognition of common mental disorders for reducing the risk of cardiovascular disease. Our results have several implications for further research. In particular, data from controlled trials that examine the effects of reducing distress on cardiovascular disease outcomes are needed to confirm the results we have seen.