Jurnal Stroke Saraf Reyjen
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1
Clinical Science
Alcohol and Acute Ischemic Stroke OnsetThe Stroke Onset Study
Elizabeth Mostofsky, MPH; Mary R. Burger, MD; Gottfried Schlaug, MD, PhD; Kenneth J. Mukamal. MD, MPH; Wayne D. Rosamond, PhD; Murray A. Mittleman, MD, DrPH
Background and Purpose Previous research suggests that regular heavy alcohol consumption increases the risk for ischemic stroke, whereas frequent light to moderate alcohol intake may decrease the risk. However, the risk of ischemic stroke associated with transient exposure to alcohol remains unclear. In this study. we used a case- crossover approach to test the hypothesis that alcohol consumption affects the acute risk of ischemic stroke, to determine the length of time between alcohol intake and the onset of symptoms (induction time) and to examine whether the risk varies by the type of alcohol.
Methods - In this multicenter study, we interviewed 390 patients (209 men. 181 women) between January 2001 and November 2006 (median 3 days after stroke). Alcohol consumption in the hour before stroke symptoms was compared with its expected frequency based on the usual frequency of alcohol consumption over the prior year.
Result0f the 390 patients. 248 (64%) reported alcohol consumption in the prior year. 104 within 24 hours and 14 within 1 hour of stroke onset. The relative risk of stroke in the hour after consuming alcohol was 2.3 (95% CI. 1.4 to 4.0:P0.002). The relative risks were similar for different types of alcoholic beverages and when the sample was restricted to those who were not simultaneously exposed to other potential triggers.
ConclusionsThe risk of stroke onset is transiently elevated in the hour after alcohol ingestion.
Moderate and high intakes of alcohol have been documented to have acute potentially deleterious physiological effects within hours after consumption, including impaired fibrinolysis and increased platelet activation, blood pressure, and heart rate. On the other hand, moderate consumption of alcohol has been associated with protective effects within hours, weeks, or years, including enhanced fibrinolytic activity, and improvements in lipid profile, inflammatory markers, flow-mediated vasodilatation, soluble vascular adhesion molecules, insulin sensitivity, and adipokinesis. However, only a few studies have examined the risk of ischemic stroke associated with transient exposure to alcohol.
In this study, we used a case crossover approach to test the hypothesis that alcohol consumption affects the acute risk of ischemic stroke, to determine the length of time between alcohol intake and the onset of symptoms (induction time), and to examine whether the risk varies by the type of alcohol.
Methods
Study PopulationThe Stroke onset Study was conducted in 3 medical centers (Beth Israel deaconess Medical center, Boston, Mass; University of North Carolina Hospitals. Chapel Hill, NC; Vancouver Island Health Authority, Victoria, British Columbia, Canada Between January 2001 and November 2006. 390 patients (209 men and 181 women) were interviewed a median of 3 days (range, 0 to 14 days) after sustaining an acute ischemic stroke. Research staff identified eligible patients by reviewing admission logs and charts of patients admitted to each hospitals stroke service. Additionally, patient with new onset of an acute neurological syndrome compatible with stroke were screened on admission to emergency departments. Presumed stroke etiology was classified using an abbreviated Trial of Org 10172 in Acute Stroke Treatment system.
Study personnel using standardized abstraction forms recorded data on demographics, medical history, and admission laboratory results. Eligible participants had a neurologist-confirmed diagnosis of acute ischemic stroke either by clinical diagnosis or appropriate imaging studies, were English-speaking, and free of dementia before the index event. Patients were excluded if they could not identify the time of onset of their stroke symptoms or if the treating clinician deemed them unable to complete the structured interview because they were cognitively impaired, had poor memory around the time of the stroke. experienced aphasia, or they were too ill to complete the structured interview that lasted 30 to 45 minutes Across all sites, 43% of patients with confirmed ischemic stroke met all inclusion criteria. of these, 83% agreed to participate 5.5% refused, and 12,5% were discharged from the hospital before the interviewers were able to approach them. The protocol was approved by the
HAL 2
Institutional Review Hoards ax each participating cernez and in
fanned consent was obtained from each paient
Interviewers used a structured questionnaire and asked patient to
report date and time of their first symptoms heralding their
stroke, Patients were asked if bey had consumed any alcoholic
beverage in the year before their stroke. Patcnrs who reponed any
alcohol consumption were aLso asked ro report the last time that they
had consumed an alcoholic beverage, their usual frequency of
alcohol consumption over the prior year. the usual number of
servings consumed each time they drank an alcoholic beverage, and
the types of alcohol consumed (beer, wine, or liquor). A serving size
of alcohol was definral as 12 ounces of beer, 4 ounces of wine, or 1,5
ounces of liquor straight or in a mixed drink. Patients were also
asked ro report the timing of their lass exposure to other potential
triggers and usual frequency of these factors over the prior year.
including caffeine, cigarette smoking, marijuana, cocaine, stress.
anger, and physical activity. Other information collectes! from the
interview included medication ase and symptoms on the day of the
strrtke
Reliability and Validity of the Questionnaire
The restretest reliability of she Stroke Onset Study questionnaire
was assessed in 25 patients who were renteniewerl up ro 6 days
after their initial interview. The intradass correlation for the usual
frequency of alcohol consumption was excellent (1)84), and these
was perfect agreement for reporting of any alcohol consumption
dunng the past year and daring each of the first 2 hours before stroke
onset f x1,0). In the subset of lilt subjects interviewed at Beth
israel Deaconess Medical Center who had highdensiry Irpoprotein
cholesterol levels measured at the time of hospitalization, rire partial
correlation between estimated alcohol consronption and high-density
lipoprotein cholesterol level adjusting for sex. age. rare, smoking,
education, and physical activity was 0,35 (P0.(X)3), comparable to
thai found in the Second National Health and Nutrition Examination
Survey.20
Study Design
The Stroke Onset Study used a easecross over sum design to assess
the change in risk of acute ischemic stroke onset during a brief
Hazard period after consumption of alcohol. In the case-crossover
design, control information for each patient is based on his or her
own past exposure experience, Self-matching eliminates confounding by risk factors that are constant within individuals over the
sampling period but differ between subjects. Alcohol use in the
hazard period, the 1-hour period immediately before the onset of
ischemic stroke symptoms, was compared with its expected frequency based on control data obtained from the patients. We used the
usual frequency of alcohol consumption over the year before stroke
to estimate its expected frequency in an avenge 1-hour period.
Statistical Analysis
Each patient in a casecrossover study forms his tr her own stratum
and titus is his tsr ber tiwn control.2m.22 The ratio of the observed
exposure frequency in the hazard period to the expected frequency
was used to calculate estimates of the rate ratio as a masure of
relative risk (KR) We multiplied the usual annual frequency nf
alcohol consumption by the hypothesized window of its physiolog
ical effect (I hour in the pnrnaiy analysis) ro estimare the amount of
person-time exposed to alcohol. The unexposed person-rime was
calculated by subtracting this value from the number of heurs in I
year. The data were analyzed using methods for cohen studies wnh
sparse data in each stratum.
To estimate the length of tizne floro alcohol consumption tri tIr
onset of isehemic stroke, RRs were calculated by comparing expo-
stat within different bypoehesized windows of its physiological
effect with the estimated person-rinse exposed ro alcohol in the
previous year. We conducted snatifted analyses to assess the effect
of drink type fbccr. wine, liquor), sex, age (2
senings of alcohol in the hour before stroke onset All reported
probability values are 2-sided.
Results
The characteristics of the Stroke Onset Study patients are
preaented in the Table. Of the 390 patients with acute
isehemie stroke, 248 (64%) reported that they had consumed
alcohol in the prior year (wine, n45; beer, n29; liquor,
n-32; >1 type, n-142). Compared with nondrinkers, sub
jects who reponed alcohol consumption were more likely to
be male and to have ever smoked cigarettes. Among the 248
subjects who drank alcohol in the prior year. 47 (12%)
reported drinking at least 1 serving of alcohol per day, 38
(10%) reponed drinking at least once per week, and 163
(66%) reported drinking al least oocc per month. The median
ftcqucncy of consumption among drinkers in the prior year
Table. Clinical Characteristics at tite Sfroke Onset
Study Population*
Age years
Ma
p
0.11
003
009
Nnndrlnkers
(n = 142)
69-- 137
66(47%)
56(39%)
63(44%)
23(16%l
31 (22%(
Alcohol Drinkers
(n 248)
6814.5
143(56%)
72 (29
t 22 (49% j
54(22%)
59(24%)
56(23%)
101 (41%)
0.68
Diabetes
Hypercholenlerotenta
Hypertension
AlrW librillatort
History of
I.e
39(27%) 028
45 (32%( 0.08
152(61%) 100(70%) 0.07
32 (13%) 22(15%) 0.48
0 19
0.14
0.77
0,15
066
0-31
36(15%)
41(17%)
29(12%)
11 (61w
2(1%)
67(29%)
46(20%)
57(25%)
60(26%)
14(10%)
32(23%)
18(13%)
31(13%)
5(2%)
44(37%)
21(18%)
24(20%)
32(26%)
Downloaded from Imp: stroke.ahajoonials.org by guest on September 4. 2013
HAL 3
Figure 1. lime of onset of stroke after an episode of alcohol
consumption. Each of the 3 hours before the onset of stroke
was assessed as independent hazard periods, and drinking dur
ng each hour was compared with that during the ccntrol
period. The error bs indicate the 95% confidence tinets. The
dashed line indicates the baseiwie risk,
was 2.0 times per week. Subjects reported that they typically
drank small amounts each time (median= I drink) and only
13 reported typically drinking 2>2 servings,
There were 169 subjects who reponed exposure dining the
week before stroke, 104 subjects drank alcohol within 24
hours of stroke onset, and 14 drank within I hour of stroke
onset. We found that within I hour after alcohol consump
ion, the risk of stroke onset was 2.3-fold higher (95% CL, 1.4
to 4.0; P=0.02) compared with periods of nonuse. The RR
was 1.6(95% Cl, 1.0 to 2.5; P0.05) in the second hour after
drinking and returned to baseline thereafter (Figure 1). By 24
hours, there was a 30% lower risk (RR-07, 95% CI, 0.5 to
0.9; P0.02).
Among the 14 participants who consumed alcohol in the
hour before stroke onset, 7 drank liquor. 5 drank beer, and 2
drank wine. The RR for alcohol consumption in the hour
before stroke onset was strongest for liquor and weakest for
wine, although the difference was not statistically significant
(P for interaction0.28; Figure 2). The RRs for alcohol
consunsptioii in the hour before stroke did not vary by sex.
age. smoking status, or stroke etiology (P for interne
tioo=0.62, 0.62, 0.12. and 0.43, respectively).
Among the 248 participants exposed to alcohol in the prior
year, 63 participants were exposed to other potential (riggers
in the hour before stroke onset. Of the 14 people exposed lo
alcohol in the hour before stroke onset. 4 were also exposed
to vigorous physical activity and I drank a caffeinated
bcvcragc. When we conducted an analysis excluding the 63
people exposed to any potential stroke trigger in the hour
before stroke onset, the results remained similar.
The mean usual frequency of alcohol consumption during
the past year was 4.42 times per week, similar to the mean
frequency of reported alcohol consumption during the past
week (4.23), In a sensitivity analysis using each patients
reported frequency of consumption in the past week as the
control information, the risk of ischcmic stroke onset was
3.3 -fold higher (95%. Cl, 1.2 ro 9.3; P=0.03) within 1 hour of
consuming at least I serving of alcohol compared with
periods with no alcohol intake. Excluding the I person who
reported drinking >2 servings of alcohol in the 2 hours
before stroke onset did not meaningfully alter the results.
Discussion
In this study, alcohol consumption was associated with a
transient increased risk of ischemic stroke in the subsequent
hour that was 2.3 times higher than the risk during periods
with no alcohol consumption. This finding is consistent with
previous research indicating an acute detrimental effect of
alcohol conaumphon.i7.hi The risk returned to baseline by 3
hours and there was a modestly lower risk by 24 hours.
Few studies have evaluated the role of alcohol ax a trigger
of ischemicw and hemorrhagic strnke. For instance,
Hiilbom et al5 found that moderate(l5l to 34X1 g)imd heavy
(>300 gj consumption of alcohol within the week before
stroke onset is associated with a significantly higher risk of
stroke With adjusted ORs of 3.6(95% Cl. 1.7 to 7.8) and 3.7
(95% CI, 1.6 to 117), respectively. Con.sisient with our data,
C,orelick et aP reported that after accounting for coexposures
including smoking, there was no statistically significant
increase in risk of isehemic stroke in the 24 hours after
alcohol consumption.
Previous studies on the acute effects of alcohol cohisump
tino indicate that heavy alcohol intake is associated with
impaired fihrinnlysis,2- increased platelet activation,4 and
increases in blood pressure and heart rate. Furthermore.
heavy consumption may acutely lead to dehydration, further
increasing the transient risk of stroke. However, such heavy
consumption was rare and unlikely to explain our findings.
Even moderate drinking may have acutely adverse cOisse
quenccs. [n a clinical trial of S healthy men, Hcndriks and
colleagues7 found that plasininogen activator inhibitor was
significantly higher after 40g of alcohol than water after 1.3.
and S hours but was not significantly different after 9 hours.
On the other hand, there is evidence that moderate drinking
may provide transient health imprnvemnenls.5 Short-
term randomized trials indicate that moderate alcohol con
sumption may have beneficial effects through changes in
flow-mediated vasodilat.a(ion within minutes to hours and
improvements in lipid profile.2 inflammatory markers,
soluble vascular adhesion molecules, and adipokin&-6
within weeks.
In contract to the evidence no acute effects of alcohol
consumption, there is consistent evidence that habitual heavy
alcohol consumption is associated with an increased risk of
ischcrnic2-> and hemorrhagic stroke!- However, the ev
idence regarding light to moderate consumption is mixed.
, -
..
i
iw.
Figure 2. Relative mba of stroke according to beverage type.
The error bas indicate the 95% confidence units. The dashed
line itsdicates the basehee nsk
I)ownloaded from littp simokcahaiur,,als org by guest on Septeniher 4,2013
HAL 4Although some studies reponed no association with ischctnic
or hcmotrhagic stroke,3 7recent comprehensive revicws6
indicate a decreased risk of ischemic stroke and a higher risk
of hemorrhagic stroke associated with light so moderate
consumption.
Integrating the .short-tenn effects obscncd here with other
studics on alcohol use and long-term risk is difficuls. Al
though speculative, it is possihle that the transiently increased
stroke risk from moderate alcohol consumption may he
outweighed hy the health benefits for the next 24 hours, hut
consuming multiple drinks at once may result in a sharp
increase in acute risk with potential increased long-tam risk
as well. Mukamal and colleagues7 found that, compared with
complete ahsaention from alcohol, light consumption (2 drinks per day is associated with an increasedrisk of isehcmie stroke. Our finding of an acute detrimentaleffect and a suggestion of a decreased risk over the 24-howperiod afta alcohol consumption seem consistent with thesefindings. Por example. one may hypothesize that over time,individuals who drink large amounts infrequently primarilyexperience the acute detrimental effect, whereas suhjects whodrink sinai] amounts frequently may still experience a transient increase in risk, hut this may he offset in part by thesuhsequeot reduction in risk that follows.There arc some limitations to our study. Because theeasecrossover design uses subjects as their own controls,there can he no confounding by risk factors that are stahleover time.7 Confounding by factors that change ova timewithin individuals can occur. However, excluding subjectsreporting other potential triggers in the hour before strokeonset did not materially alter the results. In an effort tomnini,nize reporting bias, efforts were made to ensure thepatients privacy during the interview. We used a standardized structured interview and patients were not informed ofthe duration of the hypothesized hazard period. Because mostof the participants drank small amounts of alcohol in the hourbefore stroke onset, we could not examine the acute effects ofdifferent doses of alcohol. We had limited power to evaluatethe effect of beverage type hecatise few participants wereexposed to each type. A larger study would help elucidatesuch effects. Finally, our results may not he generalizable topatients presenting with a severe or fatal stroke.SummaryIn conclusion, we found that the risk of ischemic stroke wastransiently elevated for 2 hours after drinking as little as Iserving of alcohol. The risk rapidly returned to baseline andwas modestly lower by 24 hours. When examined in thecontext of long-term studies of alcohol consumption, the netclinical impact on isehemie strokc risk appears to dcpcnd onthe frequency and quantity of alcohol consutnpton. Definitive evidence would require a long-term clinical trial, although auth a nial would he logistically difficult and isunlikely to he carried out in the near future.AcknowlcdgmcntsWe thank Cindy AicIlo for outstanding administrative assistancaSources of Fundinglisis work nc supponed hy an Established Investigator Grant(t)140219N) froto the Ainetican Heart Acsoeiasion, flattas, Tenc,and fl2-At007535-l t.Nonr.DisclosuresReferencesI Srank I, bterkwcn AC, Soleas (U. Tomnluoson (I. Monis RL Piano P,Notanus CE, Chas a, floras 1S Dose-related effects of rest wine andatcnhot on hemodynamies. sympathetic nerve activity, and annuldianteter. Am J Phnd tiran (in- Plis-dol. 2otat:294:t1605tjota.2. ICivinmem, It). 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