Life Events and Risk of Subarachnoid Hemorrhage
The Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS)
Background and Purpose— Because little evidence exists and the topic often raises concerns, we aimed to determine the relationship between life events and subarachnoid hemorrhage (SAH) in a population-based case–control setting.
Methods— In 388 SAH incident cases and 473 frequency-matched community SAH-free control subjects, information on the occurrence of 12 types of adverse life events in the preceding 1 and 2 to 12 months was obtained by interview using a questionnaire based on the Social Behavior Assessment Schedule. Analyses involved logistic regression models with adjustment for confounding variables.
Results— Among 12 life events, only 2 (“financial/legal problems” and “other”) in the past month were marginally associated with SAH (P=0.04 and 0.03, respectively), whereas “physical attack/assault” and “injury/disease of a relative/friend/pet” during the past 2 to 12 months also showed similarly marginally significant and imprecise associations (inversely) with SAH. There were no clear associations between multiple life events and SAH for both the prior month and 2 to 12 months (both P>0.4).
Conclusions— Life events are unlikely to have appreciable effects on the risk of SAH.
Subarachnoid hemorrhage (SAH) is 1 of the most lethal types of stroke.1 Life events and subsequent psychological stress are often regarded as being important causes of SAH (like in other illnesses) by patients, their families and sometimes, clinicians.2,3 However, little evidence is available for the association between life events and SAH.4,5 We aimed to determine the relationship between major adverse life events and the risk of SAH in a population-based case–control setting.
As described elsewhere,6 the Australasian Cooperative Research On Subarachnoid hemorrhage Study (ACROSS) was a population-based case–control study of SAH. In brief, 432 first-ever cases of primary SAH defined according to standard criteria7 that occurred over 12-month periods and 473 control subjects frequency-matched (by city, age, sex, and use of proxy sources in 30% of subjects) randomly selected from the electoral rolls were included from 4 Australasian cities from 1995 to 1998. All cases and control subjects underwent standardized structured interviews as soon as possible after their event/registration in the study. The interview included questions on the occurrence of 12 adverse life events separately in the past month and 2 to 12 months using questions from the Social Behavior Assessment Schedule.8 Effects of life events and their number on the risk of SAH were estimated using OR with 95% CIs in logistic regression models with P<0.05 considered statistically significant and interpreted in light of multiple comparisons.
Table 1 presents the characteristics of participants, 388 cases and 473 control subjects, after excluding subjects with missing information on life events. Table 2 presents the effects of each life event on the risk of SAH. Among 12 life events in the past month, only 2 (“financial/legal problems” and “other”) were marginally associated with the risk of SAH (P=0.04 and 0.03, respectively). Significant associations were also observed for “physical attack/assault” and “injury/disease of a relative/friend/pet” (inversely) during the past 2 to 12 months, but not in the prior month, with SAH. There were comparable effects of each life event between 2 subject groups defined by source of information (all homogeneity P>0.1) except for “job redundancy,” for which ORs were 2.00 (95% CI, 0.42 to 9.58) in the past month and 0.61 (95% CI, 0.21 to 1.78) in the past 2 to 12 months among subjects who directly provided information. The corresponding ORs were 1.07 (95% CI, 0.07 to 16.48) and not calculable because of no events recorded for control subjects in those with information obtained by proxy. There were no clear associations between multiple life events and SAH for both the prior month and 2 to 12 months (both P>0.4; data not shown).
This population-based case–control study has shown that 2 life events during the past month were marginally significantly associated with SAH. However, because these positive associations were identified among 12 comparisons, they are likely due to chance or possibly recall bias. Effects of 2 other types of life events that were related in the prior 2 to 12 months but not in the past month may suggest possible effects on aneurysm formation and/or growth, but again these data are more likely chance findings due to multiple testing. Thus, taken together with there being no clear associations between multiple life events and SAH, it appears unlikely that life events cause SAH.
ACROSS differs from other studies indicating an association of life events with SAH4,5; the sample of incident cases was larger and control subjects were drawn from the community. Yet, because the frequencies of several life events were relatively low and the 95% CIs around the OR were wide, the analysis may still have had insufficient power to define reliably relationships for some life events. Another limitation is selection bias due to missing data on life events in patients with rapid death and/or no reliable proxy information, but there were no clear differences in characteristics between cases with and without missing data. There is potential for recall bias to complicate results from interviews being conducted postevent and the questionnaire we used may not have been appropriate. However, the objective nature of the life events elicited by in-person interview is likely to validate the reliability of the findings. Finally, we lack information regarding the effect of “positive” life events.
In conclusion, major adverse life events are unlikely to have appreciable effects on the risk of SAH.
Sources of Funding
The ACROSS study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia, the Health Research Council of New Zealand, and the Sylvia and Charles Viertel Charitable Foundation of Queensland, Australia. I.S. holds a University of Sydney Doctoral Fellowship; H.A. holds a University of Sydney Post Doctoral Research Fellowship; and C.S.A. holds an NHMRC Senior Principal Research Fellowship.
For a full list of investigators of the ACROSS study, see The ACROSS Group.6
- Received December 6, 2009.
- Revision received February 7, 2010.
- Accepted February 27, 2010.
Ogden JA, Mee EW, Henning M. Life-events stress: a significant precursor to subarachnoid hemorrhage. Cogn Behav Neurol. 1993; 6: 219–228.
The ACROSS Group. Epidemiology of aneurysmal subarachnoid hemorrhage in Australia and New Zealand: incidence and case fatality. Stroke. 2000; 31: 1843–1850.
Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 1990; 53: 365–372.