Journal ofNeurology, Neurosurgery, and Psychiatry 1990;53:1024-1028

Life events and difficulties preceding stroke

Allan House, Martin Dennis, Liz Mogridge, Keith Hawton, Charles Warlow

AbstractLife events and difficulties were record-ed for the year before stroke, using astandardised semi-structured interview,in 113 surviving patients seen after theirfirst ever in a lifetime stroke. An age andsex-matched control group (n = 109) wasalso interviewed about the precedingyear. The stroke patients reported fewernon-threatening events and events withonly a short-term threat, while diffi-culties were reported with equalfrequency by the two groups. However,events which were severely threateningin the long-term were significantly morecommon in the stroke patients (in the 52weeks before stroke 26% versus 13%,odds ratio 2-3, 95% confidence interval1-1-4-9). The increased rate was apparentthroughout the year and not just in theweeks immediately before stroke onset.The number of stroke patients experi-encing severe events in the follow upyear fell to the level found in the controlgroup. Recognised risk factors for strokewere found equally in those patients withand without severe events before onset,except that hypertension was rather lesscommon in the patients who hadexperienced a severe event. It thereforeappears that severe life events may beone of the determinants of stroke onset.

Writing in 1954, Ecker' commented:"Preceding a cerebral stroke the patient hasoften suffered long-standing progressivedifficulty in settling emotional problems.Immediately before the stroke he may havefaced an overwhelming personal threat".Many people before and since have sharedthis view, but is it correct? In a recent review,Storey' concluded that there was littleevidence to support the idea that emotionalfactors could be linked with long-term pre-disposition to stroke, and at least one study ofType A behaviour as a risk factor hasproduced a negative result.' There are,however, a number of interesting anecdotalreports which suggest that severe threats mayprecipitate stroke, particularly caused bysubarachnoid or primary intracerebralhaemorrhage.' 7 Although the belief thatstress causes stroke is common among thegeneral public, most medical accounts of therisk factors for stroke either do not mentionemotional stress or refer to it in passing as anintriguing but unsubstantiated possibility.

One reason for scepticism is the lack ofmethodologically sound studies to support theclinical accounts noted above.The aim of this study was to examine the

hypothesis that stroke is preceded by anincrease in emotionally threatening experi-ences. In particular two types of stress werestudied: the experience of highly threateningevents in the period immediately beforestroke, which the anecdotal accounts wouldpredict as important; and the occurrence ofevents or difficulties with a more long-termthreat, which research into the relationshipbetween life events and other physical ill-nesses has indicated is important. We used acase-control design and a standardisedmethod of identifying and rating stressfulexperiences which is based on a semi-struc-tured interview of proven reliability.8 We alsoexamined the relationship between life eventsand difficulties and other risk factors forstroke.

Subjects and methodsThe Oxfordshire Community Stroke ProjectThe Oxfordshire Community Stroke Project(OCSP) has been described in detail else-where.9 Its basis is a register of all cases offirst ever in a lifetime stroke and transientischaemic attack occurring in a definedpopulation of approximately 105 000, which isserved by 50 general practitioners working in10 group practices. All patients notified to theOCSP were assessed by a neurologist (MD,CW). In addition to a full history and physicalexamination all patients had an ECG andblood tests to detect vascular risk factors, andin over 90% a CT brain scan was obtained.The final diagnosis of stroke was made at aweekly clinical consensus meeting, using amodification of the World Health Organisa-tion definition.'0

Patients and controlsPatients and controls were seen as part of awider study of the psychiatric aspects ofstroke, the details of which have been reportedelsewhere."

Stroke patients interviewed for this studyhad been notified about the project between1 November 1985 and 30 November 1986,during which time 157 consecutive patientswere seen and diagnosed as having had a firstever in a lifetime stroke. One hundred andtwenty eight (82%) of these patients survivedto be interviewed for the life events studybetween 1 April and 31 December 1986.

Department of LiaisonPsychiatry, GeneralInfirmary at Leeds,Great George Street,LeedsA HouseRadcliffe Infirmary,OxfordDepartment ofGeriatric MedicineM DennisDepartment ofNeurologyL MogridgeDepartment ofPsychiatry,Warneford Hospital,Headington, OxfordK HawtonUniversityDepartment ofClinical Neuroscience,Western GeneralHospital, Edinburgh,United KingdomC WarlowCorrespondence to:Dr House, Department ofLiaison Psychiatry, GeneralInfirmary at Leeds, GreatGeorge Street, LeedsLS1 3EX, United KingdomReceived 17 January 1990.Accepted 10 May 1990

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Life events and difficulties preceding stroke

A control group was identified by taking astratified random sample of the age-sexregisters of four of the general practices fromwhich the stroke patients were referred. Theoriginal sample (n = 141) was taken in 1986,for use in a different study related to theOCSP, but for practical reasons interviewingfor the present study was undertaken fromApril to December 1987. At this time 128control subjects were available to be seen; onepatient had had a stroke and was excluded,eight had died and four had left the areaand were uncontactable. These 128 wereapproached through their general practition-ers and asked to participate in a study of theeffects of stress on physical health; 15 refusedand two were too demented and infirm toparticipate, so that 111/128 (87%) were even-tually included. All controls were interviewedat home.

Satisfactory life events information wasobtained for 113/128 (88%) stroke patients.Reasons for inadequate interviews were con-fusion (n = 8), dysphasia (n = 6), and refusal(n = 1). Of these patients 84/113 were seen atone month after their stroke and 29 were seenfor the first time six months after the stroke.Follow up interviews were possible with 109/113; two had died and two were now de-mented. These interviews were undertakenbetween November 1986 and December 1987,so that follow up interviewing of strokepatients overlapped with interviewing of thecontrols. For the controls, 109/111 were ableto give adequate details of the preceding year;two lived alone and were unable to give reli-able information. The demographic and socialcharacteristics of the two groups are outlinedin table 1.

The Life Events and Difficulties ScheduleThe subjects were interviewed using theBedford College Life Events and DifficultiesSchedule (LEDS).8 During the first stage ofthe interview key members of the subject'ssocial network are identified, and then a sys-tematic enquiry is made about experiences inan identified time period. By convention life"events" are episodic in nature: acute ill-nesses, accidents, court appearances, deaths offamily, etc, while "difficulties" have persistedfor more than four weeks, for example chronicill health, protracted marital friction. Bothevents and difficulties are classified accordingto their content, for example, as health events,marital difficulties.Once all events and difficulties have been

identified, they are rated according to theseverity of the threat they involve for thesubject. Threat means the degree to whichthey might be expected to provoke emotionaldisturbance, and it is assessed on criteria,thatare called contextual by the Bedford Collegeteam. That is, the threat is rated not simply onthe basis of the subject's report, nor on thebasis of some predetermined rating scale, butaccording to a judgement about how threaten-ing the average person would have found suchan experience given the same circumstances.Events are rated on a 1-4 scale and difficulties

Table 1 Social characteristics of the stroke patients andcontrols who were able to complete the LEDS interview

Strokepatients Controls(n = 113) (n = 109)

Age: mean (SD) 69-9 yrs (13 7) 69-6 yrs (11-4)(range) (18-96 yrs) (30-86 yrs)

Sex: (M:F) 48:65 (0-74:1) 43:66 (0-65:1)

Social class (Registrar-General)I 2 (2%) 4(4%)II 28 (25%) 33 (30%)III 44 (39%) 36 (33%)IV 31 (27%) 31 (28%)V 8 (7%) 5 (5%)

HouseholdAlone 21 (19%) 23 (21%)Family 86 (76%) 85 (76%)Non family/institution 6 (5%) 3 (3%)

on a 1-6 scale of threat, with 1 the most severein both cases. In addition, events are ratedaccording to whether they are threateningonly in the short term, for example, manytransient illnesses, or carry long term implica-tions, for example, the death of a spouse, andaccording to whether they are specificallyfocussed on the subject or on other peopleclose to the subject. Events which rate 1 or 2on the 4 point scale for long-term threat, andwhich are focussed on the subject, are byconvention known as "severe" events. For adetailed discussion of these issues, with illus-trative cases, see Brown and Harris.8The two interviewers (AH, LM) were

trained in the reliable use of the LED S, whichinvolved attendance at an initial course organ-ised by the Bedford College team, followed bysupervision of the trainee's taped interviews.Thereafter, a comprehensive dictionary ofrated events and difficulties, plus annotationson rating conventions, was used to ensureconsistency.

Stroke patients were interviewed (by AH)about life events and difficulties experiencedin the 52 weeks before stroke, and wereinterviewed again approximately 12 monthslater about the 52 weeks after the stroke. Thecontrols were interviewed once about the 52weeks preceding interview (by LM). Toreduce bias resulting from the strokes andcontrols being interviewed by differentpeople, all control interviews were audio-taped and re-rated by AH. Events and diffi-culties in both cases and controls were ratedjointly by the two interviewers. During thecourse of the study events which raised par-ticular rating problems were discussed withTirril Harris at Bedford College, (who wasunaware of the medical status of the subjectwhose events were being considered) for adecision about final ratings. As an indepen-dent measure of reliability, 50 events werepresented to an independent rater withexperience of the LEDS, who re-rated themwithout knowledge of whether they wereevents experienced by stroke patients orcontrols.Although they are a major cause of stress in

the lives of older people, events and difficult-ies involving the physical health of the subject

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2House, Dennis, Mogridge, Hawton, Warlow

Figure I Rate ofreporting of life events ofall types in the year beforeonset (strokes) orinterview (controls). Theyear is divided into threeweek periods with lowernumbers representing morerecent weeks.

30.

E 20

8

c 10

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*tStrokes (n = 1 13)a Controls (n=109)

teIe tr

Weeks before stroke (patients) or interview (controls)

are excluded from the results here. We wantedto be sure that the events reported beforestroke were unrelated to the presence ofknown medical risk factors for stroke, and notsimply harbingers of the stroke itself. Wetherefore took the conservative approach ofexcluding all illness-related stressors from theanalysis.Odds ratios and confidence intervals were

calculated according to the method suggestedby Morris and Gardner."2

Table 2 Proportion of subjects who experienced at least one of the type of event ordifficulty indicated, over 52 weeks before stroke or interview (for controls)

Controls Stroke patients(n = 109) (n = 113)

EventsAny non-health event 79 (72%) 66 (58%) odds ratio 0 53

(95% CI 0 29-097)Non-health events rated 3-4 58 (53%) 35 (31%) odds ratio 0 4on short and long-term threat (95% CI 0-2-071)

Non-health events rated 1-2 34(31%) 16(14%) odds ratio0-37on short-term threat, but not (95% CI 0 18-071)on long-tenn threat

Difficulties(not involving subject's health)Rated 1-3 on threat 23 (21%) 28 (25%) odds ratio 1-25

(95% CI 0-52-2 5)Rated 4-6 on threat 43 (39%) 40 (35%) odds ratio 0-83

(95% CI 0-42-1-67)

ResultsStroke patients and controls experiencedsimilar rates of difficulties in the precedingyear.Both groups reported more life events for the

weeks nearer the interview than they did for theweeks at the beginning of the study year (fig 1).

In the control group 79/109 (72%) exper-ienced at least one event in the 52 weeks,compared with 66/113 (58%) stroke patients(odds ratio 1-9 95% CI 1-03-3 4). The controlsreported more events with little or no threatand more events with short-term threat ratingsof 1-2 but little or no long-term threat (table 2).Events with high long-term threat ratings

showed a different pattern. When only"severe" events were considered,- there was a

significant difference between the two groups;stroke patients experienced such events atabout double the rate of controls. Table 3shows the rate at which subjects experienced atleast one severe event, for four different timeperiods before interview or stroke. For thosesubjects with more than one such event in theyear, only that which was nearest to the strokeor interview was counted. When the relation-ship between timing of severe events and strokeonset was examined, the increase in severeevents was not restricted to the immediate pre-stroke period (fig 2).

In the follow up period the proportion ofpatients experiencing life events fell consider-ably in the stroke group. In the 38 weeks post-stroke 9/109 (8%) experienced at least one"severe"l event, and over the 52 weeks afterstroke 16/109 (15%) experienced such anevent. A total of 72/109 (66%) had at least oneevent of any sort during the 52 weeks post-stroke. None of these rates differs significantlyfrom those ofthe control group (tables 2 and 3).An indication of the content of the severe

events which preceded stroke is given in table4. It is important to emphasise the highthresholds employed. Illnesses of othersinvolved not just hospital admission but someserious long-term consequences for thesubjects, for example, a spouse's stroke ordiagnosis of cancer. Marital conflicts involved,for example, a separation or the spouse seeing asolicitor and not simply arguments. Not alldeaths reported by the subject are rated here.Although loss of a pet is a recognised source ofdistress to most people, perhaps particularly inthe elderly, it has not been rated as a "severe"event in previous life-events research, and wasnot therefore rated as a severe event in thisstudy. Neither are most deaths of in-laws orfriends unless the subject had an especiallyintimate relationship with them. Even death ofa sibling is not rated this high unless the subjectwas in regular contact. A total of34 deaths werereported by controls and 29 deaths were repor-ted by stroke patients for the 52 weeks preced-ing interview, although in each case less thanhalf met the criteria for severe events.A corollary of the high threshold used in

rating events as "severe" is that the rating isreliable between trained interviewers. Whenthe consensus ratings used in the study werecompared with the life-events ratings under-taken in the reliability study (by a rater withoutknowledge ofthe patient's clinical status), therewas a high degree of agreement on whether anevent was "severe". or not (kappa = 0 80).

Table 3 Proportion of subjects who experienced at least one severe event in the time period covered by the LEDSinterview. Results shown forfour time periods preceding stroke or interview (for controls); only the last event wascountedfor those with more than one

Preceding Preceding Preceding Preceding52 weeks 38 weeks 30 weeks 24 weeks

Stroke patients (n = 113) 29(26%) 27 (24%) 25 (22%) 19 (17%)Controls (n = 109) 14(13%) 13 (12%) 10(9%) 9(8%)

odds ratio 2-3 odds ratio 2-3 odds ratio 2-8 odds ratio 2-2(95% CI 1-14-9) (95% CI 1 1-5) (95% CI 1-2-64) (95% CI 0-9-57)

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a Strokes(n=113)0 Controls (n=l19

43-4e 37-42 31-36 25-0 19-2413-18o 7-12

Weeks before a stroke (patients) or interview (controls)

Table 4 Content of all severe events experienced bysubjects in the 52 weeks before stroke or interview (forcontrols) NB some subjects experienced more than oneevent in the year

Strokepatients Controls

Deaths 15 11Illness of others 10 3Marital conflict/separation 5 1Residence change (undesired) 3 0Separations other than marital 2 2Miscellaneous crises 4 I

39 18

CT brain scans had been obtained in 112/113stroke patients. Severe events were reported by3/12 (25%) ofthose with definite haemorrhagicstrokes (as diagnosed by CT scan) and 24/101(24%) of the remainder, where the CT scanshowed an infarct or the scan was negative butthe clinical diagnosis-was of definite or prob-able cerebral infarction.The relationship between the presence -of a

severe event preceding stroke, and other riskfactors (as determined independently by theresearch neurologist at the time ofnotification),is shown in table 5. The only positive findingwas that those who reported a severe event wereless likely to give a history of having beentreated for hypertension at some time in theirlives, or to have ever had a diastolic bloodpressure above 100 mm Hg recorded in theirmedical/general practice notes. Despite thisfinding there was no significant differencebetween those with and without severe eventsfor the last blood pressure recorded in theirmedical notes before stroke onset (diastolic BPt = 0-85, df 113; systolic BP t = 1-57;df= 113bothNS).

Table 5 Proportion ofpatients with various riskfactors for stroke, according towhether they had a severe event in the 52 weeks before onset of stroke

Severe event No severe event(n = 29) (n = 84)

Age: mean (SD) 67-3 (14-9) 70-8 (13-4)Sex: males (%) r-1 (41%) 37 (43%)

History of hypertension:Systolic BP ever > 180 11 (38%) 41 (48%)Diastolic BP ever > 100 7 (24%) 43 (50%)*Ever treated medically for hypertension 7 (24%) 44 (51%)t

Last recorded BP before stroke (mm Hg; mean (SD))Systolic blood pressure 147 (25) 156 (31)Diastolic blood pressure 85 (10) 87 (14)

Previous myocardial infarct 2 (7%) 10 (12%)Atrial fibrillation before stroke 3 (10%) 12 (14%)Current smoker 10 (34%) 17 (20%)Diabetes mellitus 2 (7%) 5 (6%)

*Odds ratio 2 9 (95% CI 10-8-1); todds ratio 2-9 (95% CI 10-8 1). Other differences non-

significant. ..

Finally, we made an attempt to determinewhether refusal among the control group couldhave biased the sample in favour of those withfewer life events. This was difficult because bythe nature of their refusal these people wereunwilling to discuss recent experiences withmembers of the research team, and our onlyother source of information was what thegeneral practitioner might know about thefamily. We identified 2/15 refusers (13%) whohad definitely had family deaths within theyear. Counting those as severe events does notmaterially change the results of the study. Infact statistically significant differences betweenthe stroke patients and controls only disappearif we assume that 5/15 of the refusers in thecontrol group had severe events in the 52 weeksbefore they would have been interviewed; anassumption for which we have no evidence.

DiscussionOur results provide interesting support forpopular opinion about the cause of stroke, butcould they be attributable to bias in the study?

First, the possibility of selection bias cannotbe excluded absolutely, its main potentialsource being exclusions among the controls.The response rate among controls was high(87% of those approached) and there are no apriori grounds for believing that refusers wouldbe different from the total group."2 In a com-munity-based study of older people living athome, Murphy"3 found a rate of severe events(excluding those involving the subject's health)almost identical to that among the respondersin our control group. Bias in the stroke sampleis far less likely. We contacted all survivors in acommunity-based sample, and had only onerefusal; all other exclusions were for inability toparticipate due to cognitive impairment anddysphasia. Bias would only therefore havearisen if stress-related strokes were different intheir severity, so that those who survived morethan one month were more likely to report lifeevents; we have no grounds for believing that tobe the case.

Second, we considered the problem ofobserved bias, which could have arisen in thisstudy from interviewers keen to find an associa-tion between stroke and stress, or from sys-tematic bias resulting from stroke patients andcontrols being interviewed by different people.We attempted to minimise rating bias by audio-tape recording and joint-rating of interviews,by the use of clearly defined criteria for makingjudgements about severity, and by recourse inborderline cases to an independent rater whowas unaware of the medical status of thesubject. In our study, as in others,'8 thejudgement about presence or absence of severeevents has been shown to be highly reliableamong trained interviewers.8The main potential source of reporting bias

in life events research is selective recall amongpatients who believe their condition to bestress-induced. A number of observationsargue against such selective recall. The strokepatients actually reported fewer events overall,

Figure 2 Proportion ofsubjects experiencing atleast one severe event ineach six week period of theinterview year; lowernumbers represent morerecent weeks.

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and fewer events with short-term threat (evenfor the six weeks immediately before onset)than the controls. This was probably because ofpoorer memory in the stroke patients, par-ticularly since they were being asked (unlikethe controls) about events experienced in a timeperiod ending one to six months previously.Difficulties, which accord closely with lay ideasabout stress, were no more common in thestroke group than in the controls. These find-ings would argue strongly against a generalover-reporting of stress among the strokepatients. The threshold for severe events ishigh, that is they are extremely unpleasantexperiences, so that it is unlikely that by theirnature they would be under-reported bycontrols.

It might be argued that the severe eventsreported by the stroke patients are not ofaetiological significance-that they are simply acorollary of the patients being more physicallyill than the controls. The fall in the rate ofsevere events experienced by the. strokepatients in the follow up year does not supportsuch a view. The relationship between severeevents and stroke onset is not specific, however.Such events have been shown to precede theonset of depression,8 13 of presumably psy-chosomatic disorders such as "functional"abdominal pain,'4 15 and of a variety of physicaldisorders including myocardial infarction'617and relapse in multiple sclerosis.'8 In fact it wasbecause of the existing literature on therelationship between severe events and otherillnesses that we examined their occurrence inthis study.

Is there a plausible hypothesis for the way inwhich an effect of severe events on stroke onsetmight be mediated? The mechanism involvedwould probably be akin to one of thoseproposed for the effect of stress on risk ofmyocardial infarction. That is, there might beacceleration of the arteriosclerotic processresulting from the neuro-endocrine response tostress, or an interaction with hypertension.'9Alternatively, the atheroma itself might beunaltered, but stroke might be provoked by aneffect on blood viscosity or coagulability.20Either possibility is plausible, since althoughevents are episodic in nature the severe eventswe studied here are defined by their propensityto exert a long-term influence on the subject'slife. In our study, patients who had experi-enced a severe event before stroke were nomore likely to have a past history of hyperten-sion or other risk factors than were those whohad not experienced such an event before theirstroke, so we did not get any obvious clues as tothe nature of the effect. The mechanisminvolved is worth pursuing, since the observa-tion that stroke did not follow immediatelyupon the stressful experience raises the pos-sibility of preventive action if mediating factorscouldbe elucidated.

In summary, our findings provide supportfor the view that severely threatening lifeevents increase the risk of stroke. Such aconclusion is in keeping with what is knownabout the relationship between severe eventsand other physical illnesses, particularlymyocardial infarction, in which many of thepathological processes are similar to thoseunderlying stroke. Before further considera-tion is given to possible mechanisms or thefeasibility of a therapeutic intervention, it isimportant that this result is replicated in adifferent population.

This work was supported by grants from the Medical ResearchCouncil and the Chest, Heart and Stroke Association. Thefollowing departments have collaborated in the OCSP: Univer-sity Department of Clinical Neurology (Dr P Sandercock, Dr JBamford, Dr M Dennis, Dr C Warlow, Ms L Mogridge, Ms CClifford, Ms S Price, Ms H Storey), Department ofNeuroradiology (Dr A Molyneux, Dr P Anslow), Department ofNeuropathology (Dr J Hughes), University Department ofCommunity Medicine and General Practice (Professor MVessey, Dr K McPherson, Dr G Fowler, Ms L Jones), Dr NQuizilbach helped with identification of the control group forthis study. General Practitioners collaborating (name of liaisonpartner for each practice only): Dr A McPherson, Oxford; Dr AMarkus, Thame; Dr D Leggatt, Oxford; Dr M Agass, Berins-field; Dr D Otterbum, Abingdon; Dr S Street. Kidlington; Dr VDrury, Wantage; Dr R Pinches, Abingdon; Dr N Crossley,Abingdon; Dr H O'Connell, Deddington. We also thank TirrilHarris for training in the use of the LEDS and for help andadvice during the study, and to Dr H B Andrews for undertakingthe independent ratings in the reliability study.

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