Trigger Factors and Their Attributable Risk for Rupture of Intracranial Aneurysms

16 Pages·2011·1.44 MB·English

Trigger Factors and Their Attributable Risk for Rupture of
Intracranial Aneurysms
A Case-Crossover Study
Monique H.M. Vlak, MD; Gabriel J.E. Rinkel, MD, PhD; Paut Greebe, RN, PhD;
Johanna G. van der Bom, MD, PhD; Ale Algra, MD, PhD
Background and Purpose—Little is known about activities that trigger rupture of an intracranial aneurysm. Knowledge
on what triggers aneurysmal rupture increases insight into the pathophysiology and facilitates development of
prevention strategies. We therefore aimed to identify and quantify trigger factors for aneurysmal rupture and to gain
insight into the pathophysiology.
Methods—During a 3-year period, 250 patients with aneurysmal subarachnoid hemorrhage completed a structured
questionnaire regarding exposure to 30 potential trigger factors in the period soon before subarachnoid hemorrhage
(hazard period) and for usual frequency and intensity of exposure. We assessed relative risks (RR) of rupture after
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oooooooooooooo exposure to triggers with the case-crossover design comparing exposure in the hazard period with the usual frequency
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nnnnnnnnnnnnnn of exposure. Additionally, we calculated population-attributable risks.
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adadadadadadadadadadadadadad Results—Eighttriggersincreasedtheriskforsubarachnoidhemorrhage:coffeeconsumption(RR,1.7;95%CI,1.2–2.4),
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fro fro fro fro fro fro fro fro fro fro fro fro fro fro colaconsumption(RR,3.4;95%CI,1.5–7.9),anger(RR,6.3;95%CI,4.6–25),startling(RR,23.3;95%CI,4.2–128),
mmmmmmmmmmmmmm strainingfordefecation(RR,7.3;95%CI,2.9–19),sexualintercourse(RR,11.2;95%CI,5.3–24),noseblowing(RR,
h h h h h h h h h h h h h h
ttpttpttpttpttpttpttpttpttpttpttpttpttpttp 2.4;95%CI,1.3–4.5),andvigorousphysicalexercise(RR,2.4;95%CI,1.2–4.2).Thehighestpopulation-attributable
://s://s://s://s://s://s://s://s://s://s://s://s://s://s risks were found for coffee consumption (10.6%) and vigorous physical exercise (7.9%).
trotrotrotrotrotrotrotrotrotrotrotrotrotro Conclusions—Weidentifiedandquantified8triggerfactorsforaneurysmalrupture.Alltriggersinduceasuddenandshort
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.a.a.a.a.a.a.a.a.a.a.a.a.a.a increaseinbloodpressure,whichseemsapossiblecommoncauseforaneurysmalrupture.Sometriggersaremodifiable,
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jojojojojojojojojojojojojojo andfurtherstudiesshouldassesswhetherreductionofexposuretothesefactorsormeasurespreventingsuddenincrease
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rnrnrnrnrnrnrnrnrnrnrnrnrnrn in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm. (Stroke. 2011;42:
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b/ b/ b/ b/ b/ b/ b/ b/ b/ b/ b/ b/ b/ b/ Key Words: intracranial aneurysm (cid:1) subarachnoid hemorrhage (cid:1) risk factors (cid:1) rupture (cid:1) stroke prevention
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n An An An An An An An An An An An An An A Approximately 2% of the population has an intracranial comparing exposure in a period soon before the event with
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, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2 aneurysms are being detected.3 rupture helps to develop strategies to reduce the risk of
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77777777777777 TheriskofruptureofanIAiscomposedof“chronic”risk rupture. We therefore aimed to identify and quantify trigger
factors, such as being female, age, and hypertension,4 and factors for rupture of IA and to determine their attributable
“trigger” factors, which cause the actual rupture. Activities risks.
suchasphysicalexercise,sexualactivity,alcoholuse,smok-
ing,emotionalstress,andaValsalvamaneuveroftenprecede Subjects and Methods
rupture,5–8butthetriggeringpotentialofmostfactorshasnot
Design and Study Population
been quantified. Only physical exercise has been associated
We performed a case-crossover study among patients with aneu-
with an elevated risk for aneurysmal rupture.5,9
rysmalSAHadmittedintheUtrechtStrokeCenterandwhowere18
The case-crossover design enables studying the effect of
yearsofageorolder.Informedconsentwasgivenbyeitherpatient
transientexposuretopotentialtriggerfactorsontheriskofan orproxy.AneurysmalSAHwasdefinedasanabruptonsetofsevere
acute event, such as subarachnoid hemorrhage (SAH), by headacheorlossofconsciousnesswithorwithoutfocalneurological
ReceivedOctober22,2010;acceptedJanuary26,2011.
FromtheUtrechtStrokeCenter(M.H.M.V.,G.J.E.R.,P.G.,A.A.),DepartmentofNeurology,RudolfMagnusInstituteofNeuroscience,University
MedicalCenter,Utrecht,theNetherlands;JuliusCenterforHealthSciencesandPrimaryCare(M.H.M.V.,A.A.),UniversityMedicalCenter,Utrecht,
theNetherlands;DepartmentofClinicalEpidemiology(J.G.v.d.B.,A.A.),LeidenUniversityMedicalCenter,Leiden,theNetherlands.
Theonline-onlyDataSupplementisavailableathttp://stroke.ahajournals.org/cgi/content/full/STROKEAHA.110.606558/DC1.
CorrespondencetoAleAlgra,MD,PhD,DepartmentofNeurologyandJuliusCenter,UniversityMedicalCenterUtrecht,RoomSTR7.140,Mailbox
STR6.131,POBox85500,3508GAUtrecht,[email protected]
©2011AmericanHeartAssociation,Inc.
Strokeisavailableathttp://stroke.ahajournals.org DOI:10.1161/STROKEAHA.110.606558
1
2 Stroke July 2011
signswithsubarachnoidbloodprovenbyCTorlumbarpunctureand
radiologically proven IA. The study protocol was approved by our
Medico-EthicalReviewCommittee.
Few proxies of seriously ill or deceased patients consented to
participate and completed the questionnaire. Based on these initial
experiences,wedecidedtoonlyincludepatientswhocouldcomplete
the questionnaire themselves or with the help of a proxy. We
comparedmedicalrecordnotesforactivitiesatthetimeofonsetof
SAH (eg, sexual activity, toilet use, sleep, exercise) of patients
includedinourstudyandthosewithaneurysmalSAHwhowerenot
included.
Procedures
A structured questionnaire that was used previously in the Stroke
Onset Pilot Study was translated into Dutch and adapted for
Figure.Flowchartofpatientinclusion.SAHindicatessubarach-
SAH.11,12ThetimeofonsetofSAHwasdefinedasthetimeofthe
noidhemorrhage.*Criticallyillwithoutsufficientrecoveryfor
symptomsthatledtoreferral.Datawereobtainedontheactivitiesat
participation.†Transferredtoanotherhospitalbeforebeing
onset, demographics, medical and family history, and site of the
askedtoparticipate.
aneurysm.Forallpotentialtriggerfactors,patientswereaskedabout
exposureinthepastyear,usualfrequencyofexposure,andpresence
of exposure in the “hazard period.” The hazard periods were (SENS4B) are considered always exposed and more patients con-
D predefined according to the estimated duration of effect of each tributetotheRR.
ow potential trigger factor: 1 hour for coffee or cola consumption, The fraction of patients with SAH that can be attributed to a
nload sitmy,okteinmgp,eVraatlusarelvachmanangeeuv(eegr,,hseaauvnyaliuftsiengo,remaoctioolnds,ssheoxwuearl)a,catinvd- pcuarlatitceudlaarstrfioglgleorwfsa:ctpoorp,utlhaetiopno-pauttlraitbiounta-batlteribriustka(cid:1)blpererivsakl,eniscecaol-f
ed vigoroustoextremephysicalexercise(metabolicequivalentoftask exposure(RR(cid:2)1)/[prevalence of exposure(RR(cid:2)1)(cid:3)1].17 The
fro (cid:1)6);13 4 hours for cocaine, marijuana, and sildenafil use; and 24 prevalenceofexposureforeachfactorwascalculatedasthemean
hm hours for fever, a flu-like disease, and alcohol use. Patients were numberofexposuresperyearanddividedbytheannualnumber
ttp asked about exposure in the hazard period and for the last time of of hazard episodes.
://s exposurebeforeonsetofSAHtochecktheconsistencyofanswers
tro about exposure in the hazard period. If answers were inconsistent, Results
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e thenthedataofthatpatientwerenotusedinthemainanalysisofthat The characteristics of the 250 included patients (Figure) are
.a
ha particularfactor. given in Table 1. The activities reported in the medical
jo If patients were unable to complete the questionnaire during the
u records were similar for patients who were included in our
rn hospitalizationperiod,thentheywereaskedtobringthecompleted
als questionnaire to their first check-up. If patients forgot to bring it, studyandthosewhowerenot(datanotshown).Fiftypercent
.org thentheyreceivedacopyandwereaskedtoreturnitbypostalmail. of the surveys were completed within 3 weeks (range, 1
b/ day–34 weeks).
y
g Data Analysis Table2summarizestheexposuresandRRforallpotential
u
es The ratio of the observed exposure frequency in the hazard period triggerfactors.Coffeeconsumptionisusedasanexampleto
t on (beforetheonsetofSAH)andtheexpectedfrequencywasusedto explain the data presentation in detail; the analysis for all
A calculate relative risks (RR) with corresponding 95% CI.14,15 Ex-
p factorswasperformedinasimilarway.Forcoffeeconsump-
ril 1 poefcetxepdofsruerqeu.encieswerecalculatedwiththeusualannualfrequency tion, data were used from 197 patients. Fifty-three patients
3
, 2 Wecalculatedthatassumingatype1errorof5%,80%power,and gave incomplete answers (either on average exposure or the
0
1 anexposureinthehazardperiodof10%ofthepopulation,asample hazard period) or inconsistent data. Of the 197 patients who
7
size of 200 patients would be large enough to calculate RR of 2.2 providedconsistentdata,169patientshadconsumedcoffeein
with sufficient precision. To check the consistency of the results
the past year and 28 had not. Using the assumption of a
fromourmainanalysis,weperformed4sensitivityanalyses.First,
1-hour exposure period of coffee, none of the 169 patients
ananalysis(sensitivityanalysis[SENS]1)wasperformedusingonly
the yes-or-no question on exposure in the hazard period and wereall-daydrinkers(ie,(cid:1)24cups/day).Theriskofrupture
disregardingthequestionaboutlasttimeofexposure.Patientswho ofanIAwas1.7-times(95%CI,1.2–2.4)higherinthehour
were excluded from the main analysis because of inconsistent after drinking a cup of coffee compared with no coffee.
answersonexposureinhazardperiodandlasttimeofexposurewere
Similarly, we found elevated RR for drinking cola, nose-
nowincluded.Inasecondsensitivityanalysis,patientswithincon-
blowing, straining for defecation, startling, anger, sexual
sistent data were first assumed to be exposed in the hazard period
(SENS2A),andthenassumednottobeexposed(SENS2B).Assum- intercourse, and vigorous to extreme physical exercise (met-
ing6hoursofsleepandlessexposuretomosttriggers,ananalysis abolic equivalent of task (cid:1)6). In contrast, we found a
wasperformedmaximizingthenumberofexposedhoursto18hours decreasedRRforalltypesofalcohol.TheRRessentiallydid
perday,excludingpatientswhoseSAHoccurredbetweenmidnight
not change when comparing patients who completed the
and6:00AM(SENS3).
questionnaire before and after 6 weeks (data not shown).
Assuming a hazard period of 24 hours for alcohol, patients who
drink (cid:1)1 glass of alcohol per day are considered to be always SensitivityanalysesaregiveninTable3andSupplemental
exposed.Consideringtheirusualfrequency,thesepatientswilloften TableI(http://stroke.ahajournals.org).Inthesensitivityanal-
also report exposure in the hazard period. In the case-crossover ysis limited to the yes-or-no question on exposure in the
design, patients who report exposure in the hazard period and are
hazard period (SENS1), the RR increased for all triggers. In
consideredalwaysexposeddonotcontributetotheRR.16Therefore,
the sensitivity analysis in which patients with inconsistent
wechangedthehazardperiodforalcoholto6hours(SENS4A)and
2 hours (SENS4B). Now, only patients who drink (cid:1)4 glasses of data were considered exposed (SENS2A) or not exposed
alcohol per day (SENS4A) or (cid:1)12 glasses of alcohol per day (SENS2B)inthehazardperiod,allfactorsthatwerestatisti-
Vlak et al Triggers for Rupture of IA 3
Table1. BaselineCharacteristicsofthe250Patients Table2. RelativeRisksforPotentialTriggerFactorsfor
RuptureofIntracranialAneurysms
Characteristic Patients(n(cid:1)250)
Includedin Not
Men,n(%) 62(24.8)
Analysis(Always Exposed Noor
Meanage,y 54.7
Exposed,Exposed inPast Inconsistent
TimefromSAHtosurvey,n(%) RiskFactors* inHazardPeriod) Year Data RR(95%CI)
(cid:4)2wk 80(32.0) Caffeine
2–6wk 68(27.2) Coffee 169(0,48) 28 53 1.7(1.2–2.4)
(cid:1)6wk 102(40.8) Tea 100(0,6) 116 34 0.7(0.3–1.5)
Sitesymptomaticaneurysm,n(%) Cola 92(0,8) 135 23 3.4(1.5–7.9)
Anteriorcirculation 224(89.6) Alcohol
Posteriorcirculation 26(10.4) Alltypes 128(78,64) 52 70 0.2(0.1–0.2)
Cigarettesmoking,n(%) Beer 88(23,22) 143 19 0.2(0.1–0.4)
Never 53(20.8) Wine 139(62,51) 86 25 0.1(0.1–0.2)
Past 42(16.8) Liquor 76(14,15) 154 20 0.3(0.1–0.5)
Current(cid:4)20cigarettes/d 85(33.6) Smoking
Current(cid:1)20cigarettes/d 70(28.0) Cigarettes 119(24,80) 103 28 1.1(0.8–1.6)
D
ow Alcohol,n(%)§ Cigar 13(0,2) 230 7 1.0(0.2–5.6)
n
lo 0units/wk 52(21.6) Drugs
a
d
ed 1–12units/wk 143(59.3) Marijuana 6(0,2) 241 3 1.4(0.4–5.4)
fro (cid:1)12units/wk 46(19.1) Temperature
m
h Vigorousphysicalexercise,n(%)† Temperature 38(0,2) 199 13 2.9(0.6–14)
ttp://s (cid:1)3times/wk 51(23.2) change
tro (cid:4)3times/wk 72(32.7) Flu-likeillness 79(0,1) 134 37 2.4(0.3–16)
k
e.a Never 97(44.1) Valsalvamaneuver
h
ajo Medicalhistory,n(%) Sneezing 116(0,3) 34 100 0.5(0.2–1.3)
u
rn SAH 5(2.0) Coughing 88(0,7) 55 107 1.4(0.6–3.3)
a
ls.o Hypertension‡ 66(26.6) Nose-blowing 113(0,12) 49 88 2.4(1.3–4.5)
brg/ Heartdisease‡ 15(6.0) Strainingfor 87(0,5) 117 46 7.3(2.9–19)
y defecation
g Diabetes‡ 6(2.4)
ue Lifting(cid:5)50kg 23(0,0) 209 18 —
s Positivefamilyhistory,n(%)
t o Lifting(cid:5)25kg 69(0,2) 150 43 0.8(0.2–2.9)
n April 1 SAADHP‡K§D 112((04..48)) EmLoifttiionngs(cid:5)12.5kg 150(2,7) 65 56 0.7(0.4–1.4)
3 ADPKD indicates autosomal-dominant polycystic kidney disease; SAH,
, 20 subarachnoidhemorrhage. Startling 55(0,2) 148 47 23.3(4.2–128)
1
7 *Including anterior cerebral artery, anterior communicating artery, and Anger 66(0,2) 149 35 6.3(1.6–25)
pericallosalartery.
Sexualactivity
†Vigorousphysicalexercisewasdefinedasmetabolicequivalentoftask(cid:1)6;
Intercourse 113(0,8) 85 52 11.2(5.3–24)
12%missingdata.
‡(cid:4)5%missingdata. Masturbation 40(0,8) 155 55 5.9(0.8–42)
§Atleast1first-degreerelativewithSAH. Physicalexercise
MET(cid:1)6 115(0,11) 88 47 2.4(1.4–4.2)
callysignificantintheoriginalanalysisremainedsignificant
MET(cid:1)7 30(0,1) 177 43 3.5(0.5–25)
(Supplemental Table I).
Whenreducingthemaximumnumberofexposedhoursper CI indicates confidence interval; MET, metabolic equivalent of task; RR,
day to 18 hours (SENS3), the RR remained statistically relativerisk.
*NoRRcouldbecalculatedforcocaineuse,sildenafiluse,consumptionof
significant, except for liquor consumption and sneezing
RedBull®(RedBullGmbH,SantaMonica,CA)energydrinkbeverage,orfever
(SupplementalTableI).TheRRofbeer,wine,liquor,andall
becausenopatientswereexposedinthehazardperiod.
types of alcohol consumption in general remained (cid:4)1 when
thehazardperiodwas6hours(SENS4A),butnotwhenitwas
Discussion
2 hours (SENS4B; Table 3).
Our study shows that drinking coffee or cola, nose-blowing,
Population-Attributable Risk straining for defecation, startling, anger, sexual intercourse,
The population-attributable risks associated with trigger fac- andvigoroustoextremephysicalexercisewereallassociated
tors for SAH are shown in Table 4. Trigger factors that with the triggering of aneurysmal rupture. For drinking
contributed most to ruptures of IA were drinking coffee coffee, the population-attributable risk was (cid:5)10%; for all
(10.6%) and physical exercise (7.9%). other triggers, it was less.
4 Stroke July 2011
Table3. RelativeRisksWithHazardPeriodsof2,6,and24 biasregardingsmokingstatusbecauseitcomparestheexpo-
HoursforBeer,Wine,Liquor,andAllTypesofAlcohol sure to smoking in the hazard period with that in a control
period for the same patient.
AlcoholHazardPeriod
ImmediatelyaftertheSAH,patientsareseriouslyillanda
Risk 24-h 6-h 2-h considerable proportion never recovers. Inevitably, this has
Factor RR(95%CI) RR(95%CI) RR(95%CI) ledtosomelimitationsinourstudy.First,ithasresultedinan
Alltypes 0.2(0.1–0.2) 0.2(0.1–0.4) 0.9(0.5–1.6) interval between the SAH and completion of the question-
Beer 0.2(0.1–0.4) 0.1(0.0–0.6) 0.1(0.0–1.3) naire of (cid:5)2 weeks for two-thirds of the patients. The
Wine 0.1(0.1–0.2) 0.4(0.2–0.6) 1.1(0.6–2.1) retrospective assessment, the time lapse between SAH, and
completion of the questionnaire and specifically asking for
Liquor 0.3(0.1–0.5) 0.3(0.1–0.9) 1.3(0.4–4.5)
exposureinaprespecifiedperiodmayhaveledtorecallbias.
CIindicatesconfidenceinterval;RR,relativerisk.
Second, the inclusion of patients in relatively good clinical
condition could have led to survival bias if certain triggers
Previously, a case-crossover study on trigger factors for affect prognosis after SAH. However, we found no signifi-
SAH showed a 2.7-fold increase in the risk of aneurysmal cantdifferencebetweenactivitiesfromthemedicalrecordsof
rupture in the 2 hours after moderate to extreme physical patientswhowereincludedinourstudyandthosewhowere
exercise(metabolicequivalentoftask(cid:1)5),whichiscompa- not. Also, a previous study interviewing proxies for patients
rable with the RR of 2.4 we found.9 However, another withpooroutcomefoundnodifferenceinrisksafterexposure
D case-crossoverstudyshoweda15-foldincreaseofSAHinthe to physical exercise when using patient or proxy-derived
o
wn minutesaftervigoroustoextremeexercise(metabolicequiv- data.9Forothertriggerfactors,thishasnotbeeninvestigated.
loa alentoftask(cid:1)6).5Theriskofruptureispossiblythehighest A third limitation is the assumption of a 24-hour hazard
d
ed in the first 15 minutes and subsides in time thereafter. period for alcohol. Many patients who reported exposure in
fro A case-control study found an increased risk for SAH in thehazardperiodhadadailyintakeof(cid:1)1glassperdayand
m
h the initial 3 hours after cigarette smoking (odds ratio, 7.0; therefore did not contribute to the RR in the main analysis.
ttp://stro r9e5t%te CusI,e,3.a7n–d13n.1e)i.t6heWredfiodunadnonthoetrrigcagseer-incrgosesfofevcetrosftucdigya.9- Wreseulatsnablyyzuesdintghedifeffefreecnttohfaztahredsepepraiotidesntasndonfoouunrdpthriamtathrye
ke These contradicting results are probably explained by the risks of alcohol change according to the presumed exposure
.a
h differenceindesign.First,thecase-controlstudyusedcontrol time. Risks are higher soon after alcohol ingestion and
a
jou subjects from the general population, of which only 2% decrease thereafter. A previous case-crossover study also
rn
a harbor IA and are at risk for SAH.2 Second, patients with found a decreased risk of aneurysmal rupture during the
ls
.o SAH have a different risk factor profile than the general initial 2 hours after alcohol consumption, although this
rg
b/ population. There were twice as many subjects who smoked decrease was not statistically significant.9 The effects of
y
g heavilyintheSAHpopulationthaninthecontrolpopulation. dosage and time lapse since alcohol intake on acute risk of
u
es The higher proportion of subjects who smoke in the SAH SAH remain unclear and should be further investigated.
t on population 3 hours before SAH compared with the control Thestrengthsofourstudyaretheuseofthecase-crossover
A
p group may reflect the difference in smoking habits between design (no control selection bias), the inclusion of patients
ril 1 the 2 populations. In the case-crossover design, there is no with a proven aneurysmal SAH (no misclassification bias),
3
, 2 andtheinclusionofpatient-deriveddata(increasingreliabil-
0
1 ityandcompletenessofdata).Thelargenumberofincluded
7 Table4. RelativeRisks,Prevalence,andPopulation-
patients and consistency of the results in the sensitivity
AttributableRiskAssociatedWithTriggerFactorsforRupture
ofIntracranialAneurysms analyses support the robustness of our results.
Because blood pressure and intra-arterial pressure are
%of
directly related, an increase in blood pressure increases the
Population Prevalence
transmural pressure, which is a risk factor for aneurysmal
RiskFactor RR(95%CI) Exposed (%)* PAR(%)
rupture.18Severalofthefactorsweinvestigatedareknownto
Coffee 1.7(1.2–2.4) 88.1 17.5 10.6
cause a short-lasting and sudden increase in blood pres-
Cola 3.4(1.5–7.9) 42.8 1.5 3.5 sure.19–24 Our data support the view that a sudden and
Nose-blowing 2.4(1.3–4.5) 73.7 4.1 5.4 short-lasting increase in blood pressure caused by daily
Strain 7.3(2.9–19) 47.3 0.6 3.6 activities is a relevant pathophysiological pathway for aneu-
Startling 23.3(4.2–128) 29.2 0.1 2.7 rysmalrupture.Manyofthetriggerfactorswefoundconcern
lifestyle, which may have implications for patients with an
Anger 6.3(1.6–25) 33.5 0.2 1.3
unruptured IA or for SAH patients awaiting treatment.
Sexual 11.2(5.3–24) 59.1 0.4 4.3
Reducing caffeine consumption or treating constipated pa-
intercourse
tientswithunrupturedIAwithlaxativesmaylowertheriskof
Physical 2.4(1.4–4.2) 58.1 6.1 7.9
SAH. Although physical exercise has a triggering potential,
exercise†
wedonotadviserefrainingfromphysicalexercisebecauseit
CI indicates confidence interval; PAR, population-attributable risk; RR,
is also an important factor in lowering the risk of other
relativerisk.
*Percentofthepopulationthatisexposedinanygivenhour. cardiovascular diseases.25 Whether prescribing antihyperten-
†Metabolicequivalentoftask(cid:1)6. sive drugs to patients with unruptured IA is beneficial in
Vlak et al Triggers for Rupture of IA 5
termsofpreventinganeurysmalruptureandothercardiovas- smoking,andalcoholintheAustralasianCooperativeResearchonSub-
cular diseases should be studied in randomized trials. arachnoidHemorrhageStudy(ACROSS).Stroke.2003;34:1771–1776.
10. MaclureM.Thecase-crossoverdesign:amethodforstudyingtransient
effectsontheriskofacuteevents.AmJEpidemiol.1991;133:144–153.
Acknowledgments
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Sources of Funding resultsfromtheStrokeOnsetPilotStudy.Stroke.2001;32:366e–367e.
13. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ,
ThisstudywasfundedbytheJuliusCenterforHealthSciencesand
MullerJE.Triggeringofacutemyocardialinfarctionbyheavyphysical
Primary Care and the department of Neurology of the University
exertion.Protectionagainsttriggeringbyregularexertion.NEnglJMed.
MedicalCenterUtrecht.
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Disclosure
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e electrocardiogramduringmicturitionanddefecationinunrestrictedman.
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m unruptured intracranial aneurysms in relation to patient and aneurysm 20. LittlerWA,HonourAJ,SleightP.Directarterialpressure,heartrateand
http://strok 5. cFsJuhaNbanraenaurcaJrtRcoehl,rinKNsotueiicudksru:olhlasanuWermugApo,PdrKasryhtaecatdhoginema:tWertyaaJ.,-2paLn0ooa0pnl0uyg;lss6ait9tsri.e:o7tSnh6t8rWob–ka7Tes7.eJ2dr2..0Pc0ha7ys;3esi-8cc:a1ol4na0tcr4oti–lv1ist4yt1u0adn.yd. 21. e3Nbl2lueo1cro–mtdr3oi3npc1erae.nrsdMsiuoLrge,r:NaamiictrtdyitnuicerainnlLgre,vKhiueomwrpa.enElaucRro,JiVtuCaslp.ianJaNtaRuloterpH.r1.o9Cd9o9fF;f5ee3ert,:i8cl3.a1ff1–e98i7n34e9;.a4n0d:
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Trigger Factors and Their Attributable Risk for Rupture of Intracranial Aneurysms: A
Case-Crossover Study
Monique H.M. Vlak, Gabriel J.E. Rinkel, Paut Greebe, Johanna G. van der Bom and Ale Algra
D Stroke. published online May 5, 2011;
o
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lo Copyright © 2011 American Heart Association, Inc. All rights reserved.
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.a The online version of this article, along with updated information and services, is located on the
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ajo World Wide Web at:
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rn http://stroke.ahajournals.org/content/early/2011/05/05/STROKEAHA.110.606558
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b/ Data Supplement (unedited) at:
y
g http://stroke.ahajournals.org/content/suppl/2013/10/08/STROKEAHA.110.606558.DC1
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es http://stroke.ahajournals.org/content/suppl/2015/07/22/STROKEAHA.110.606558.DC2
t o http://stroke.ahajournals.org/content/suppl/2016/04/07/STROKEAHA.110.606558.DC3
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STROKE/2010/606558-R1

Supplemental material

1
Supplemental Table S1: Sensitivity analyses for trigger factors for rupture of intracranial aneurysms

SENS 1 SENS 2A SENS 2B SENS 3

Original Only y/n question Inconsistent data Inconsistent data Exposed time

Risk factor analysis on hazard period exposed not exposed max 18 hours

RR (95% CI) RR (95% CI) RR (95% CI) RR (95% CI) RR (95% CI)
Caffeine
Coffee 1.7 (1.2-2.4) 2.5 (1.8-3.3) 2.5 (1.9-3.4) 1.4 (1.0-2.0) 1.7 (1.2-3.1)
Cola 3.4 (1.5-7.9) 4.8 (2.3-9.9) 4.8 (2.3-9.9) 3.2 (1.4-7.4) 3.4 (1.5-7.9)
Alcohol
All types 0.2 (0.1-0.2) 0.1 (0.1-0.2) 0.1 (0.1-0.2) 1.1 (0.9-1.4) 0.6 (0.5-0.9)
Beer 0.2 (0.1-0.4) 0.2 (0.1-0.4) 0.2 (0.1-0.4) 0.2 (0.1-0.3) 0.5 (0.3-0.8)
Wine 0.1 (0.1-0.2) 0.2 (0.1-0.3) 0.2 (0.2-0.4) 0.1 (0.1-0.2) 0.6 (0.4-0.9)
Liquor 0.3 (0.1-0.5) 0.4 (0.2-0.7) 0.4 (0.2-0.7) 0.2 (0.1-0.5) 0.5 (0.2-1.0)
Valsalva
Maneuver
Nose blowing 2.4 (1.3-4.5) 3.4 (2.0-5.9) 3.4 (2.0-5.9) 2.3 (1.2-4.2) 1.3 (0.5-3.3)
Straining for 7.3 (2.9-19) 12.3 (5.7-26) 14.5 (6.9-31) 5.7 (2.3-14) 9.5 (3.2-28)
defecation
Emotions
Startling 23.3 (4.2-128) 35.2 (8.8-141) 35.2 (8.8-141) 23.3 (4.2-127) 14.2 (1.1-176)
Anger 6.3 (1.6-25) 18.6 (7.5-46) 18.6 (7.5-46) 4.8 (1.2-19) 8.6 (2.2-34)
Sexual intercourse 11.2 (5.3-24) 15.4 (8.1-29) 15.4 (8.1-29) 10.8 (5.2-22) 13.4 (6.0-30)
Physical exercise* 2.4 (1.4-4.2) 3.7 (2.4-5.8) 4.2 (2.8-6.4) 2.4 (1.4-4.2) 2.4 (1.4-4.2)

SENS indicates sensitivity analysis; RR, relative risk; *metabolic equivalent of task ≥6.
SENS 1: Only the yes/no question on exposure in the hazard period was used, the detailed question on last time of exposure was
disregarded; SENS 2A: In case of inconsistent data on exposure in the hazard period, patients were taken to be exposed in the
hazard period; SENS 2B: Identical to analysis 2A, but now inconsistent patients were taken not to be exposed in the hazard period;
SENS 3: Maximum exposure time 18 hours, assuming 6 hours of sleep for each patient.
2
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3(23)’2011 Эпидемиология и клиника
Триггерные факторы и связанный с ними риск разрыва аневризм
внутричерепных сосудов: перекрестное исследование
Источник. M.H.M. Vlak, G.J.E. Rinkel, P. Greebe, J.G. van der Bom, A. Algra. Trigger factors and their attributable
risk for rupture of intracranial aneurysms a case-crossover study. Stroke. 2011;42:6: 1878–1882
Дополнительная информация доступна on-line по адресу:
http://stroke.ahajournals.org/cgi/content/full/STROKEAHA.110.606558/DC1.
Utrecht Stroke Center, Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, the
Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands; Department of
Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
предпосылки и цель исследования. Данных о видах деятельности, провоцирующих разрыв аневризм внутричерепных сосудов,
недостаточно. Знание о триггерах разрыва аневризм внутричерепных сосудов способствует пониманию патофизиологии и разви-
тию стратегий профилактики. В связи с этим цель настоящего исследования заключалась в выявлении и количественной оценке про-
воцирующих факторов разрыва аневризм внутричерепных сосудов и получении представления о патофизиологии этого процесса.
методы. В течение 3-летнего периода провели опрос 250 пациентов с аневризматическим субарахноидальным кровоизлия-
нием с помощью структурированной анкеты, содержащей вопросы о воздействии 30 потенциальных провоцирующих факторов,
имевших место незадолго до развития кровоизлияния (период опасности), и об их обычной частоте и интенсивности воздействия.
Оценивали относительный риск (ОР) разрыва аневризмы после воздействия триггерных факторов с помощью перекрестного
исследования серии случаев для сравнения их влияния в период опасности с их обычной частотой воздействия. Кроме того,
рассчитали популяционно-обусловленные риски. Результаты. Восемь триггерных факторов увеличивали риск развития субарах-
ноидального кровоизлияния: употребление кофе (ОР=1,7; 95% доверительный интервал [ДИ] от 1,2 до 2,4), употребление кока-
колы (ОР=3,4, 95% ДИ от 1,5 до 7,9), чувство гнева (ОР=6,3, 95% ДИ от 4,6 до 25), чувство потрясения (ОР=23,3, 95% ДИ от 4,2
до 128), натуживание при дефекации (ОР=7,3, 95% ДИ от 2,9 до 19), половой акт (ОР=11,2; 95% ДИ от 5,3 до 24), высмаркивание
(ОР=2,4, 95% ДИ от 1,3 до 4,5) и интенсивные физические упражнения (ОР=2,4, 95% ДИ от 1,2 до 4,2). Высокие популяцион-
но-обусловленные риски обнаружили в отношении употребления кофе (10,6%) и интенсивных физических упражнений (7,9%).
Выводы. Выявили и количественно оценили 8 факторов, провоцирующих разрыв аневризмы. При воздействии всех триггеров
происходит внезапное и кратковременное повышение уровня артериального давления, которое, по всей вероятности, является
наиболее распространенной причиной разрыва аневризмы. Некоторые триггеры являются модифицируемыми, и в дальнейших
исследованиях необходимо оценить влияние снижения уровня воздействия этих факторов, а также мероприятий по профилак-
тике внезапного повышения уровня артериального давления на снижение риска разрыва аневризм внутричерепных сосудов
у пациентов с известным их наличием.
ключевые слова: внутричерепная аневризма (intracranial aneurysm), субарахноидальное кровоизлияние (subarachnoid hemorrhage),
факторы риска (risk factors), разрыв (rupture), предотвращение инсульта (stroke prevention)
Примерно у 2% населения встречаются аневризмы потенциально увеличивающих риск развития острых
внутричерепных сосудов (АВЧС), но лишь немногие состояний, таких как субарахноидальное кровоизли-
из АВЧС разрываются [1, 2]. В настоящее время, яние (САК), путем сравнения воздействия фактора
в связи с более широким использованием методов в период незадолго до события с обычной часто-
нейровизуализации, все больше аневризм выявляют той воздействия этого фактора на пациента [10].
случайно [3]. Понимание воздействия триггерных факторов и пато-
Риск разрыва АВЧС складывается из “хроничес- физиологии разрыва аневризмы помогает разраба-
ких” факторов риска, таких как женский пол, возраст тывать стратегии, направленные на снижение риска
и наличие артериальной гипертензии [4], и “триг- развития САК. В связи с этим цель настоящего иссле-
герных” факторов, которые фактически и приводят дования заключалась в выявлении и количественной
к разрыву. Такие виды деятельности, как физические оценке триггерных факторов разрыва АВЧС и опре-
упражнения, сексуальная активность, употребление делении характерных им рисков.
алкоголя, курение, эмоциональный стресс и проба
Вальсальвы часто предшествуют разрыву аневриз- ■ паЦиенТЫ и меТодЫ
мы [5–8], но количественную оценку триггерного
потенциала большинства факторов не проводили. дизайн и выборка исследования
Только физические упражнения были ассоциированы Провели исследование с перекрестным изучением
с повышенным риском разрыва аневризмы [5, 9]. серии случаев с участием пациентов с аневризмати-
Дизайн перекрестного исследования позволяет изу- ческим САК в возрасте 18 лет и старше, поступавших
чать влияние периодического воздействия факторов, в центр лечения инсульта в Утрехте. Письменное
информированное согласие на участие в иссле-
© American Heart Association, Inc., 2011 довании дали сами пациенты или их доверенные
Адрес для корреспонденции: Ale Algra, MD, PhD, Department of Neurology лица. Критерием наличия аневризматического САК
and Julius Center, University Medical Center Utrecht, Room STR 7.140,
была внезапная сильная головная боль или потеря
Mailbox STR 6.131, PO Box 85500, 3508 GA Utrecht, the Netherlands.
E-mail: [email protected] сознания с или без очаговой неврологической сим-
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