Intake of Beer, Wine, and Spirits and Risk of Stroke

The Copenhagen City Heart Study

Thomas Truelsen, MD; Morten Grønbæk, MD, PhD; Peter Schnohr, MD; Gudrun Boysen, DMSc

Background and Purpose—Alcohol consumption has been associated with a protective effect on risk of ischemic stroke.
There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic
that has gained only little attention in stroke research.
Methods—Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years,
participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and
health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were
analyzed by means of multiple Poisson regression.
Results—We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted
for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke
compared with no wine intake (monthly: relative risk [RR], 0.83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45
to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for
confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR,
0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke.
Conclusions—The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the
wine in addition to ethanol are responsible for the protective effect on risk of stroke. (Stroke. 1998;29:2467-2472.)
Key Words: alcohol n cerebrovascular disorders n epidemiology

S everal epidemiological studies have found that moderate

alcohol consumption is associated with a decreased risk
In the present study we examined the influence of alcohol
intake and the different types of alcohol on risk of first-ever
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of coronary heart disease.1 The association between alcohol
and stroke is less well described, although many of the
biological mechanisms suggested to influence the risk of
cardiac disease are likely to influence the risk of ischemic
stroke as well. Established risk factors for stroke such as
systolic blood pressure and HDL are modified by the intake
of alcohol.2–5 Furthermore, alcohol consumption leads to an
increased tissue insulin sensitivity and has an antithrombotic
effect on the coagulation system.6,7 In contrast to studies of
ischemic heart disease, stroke studies are often hampered by
the fact that the general definition of stroke includes both
ischemic and hemorrhagic insults. Alcohol may be associated
with a lower risk of cerebral ischemia, while it could cause an
increased risk of intracranial hemorrhages.8
Beer, wine, and spirits may have different effects on the
risk of cardiovascular disease, indicating that compounds
other than ethanol may be of importance.9,10 Particularly, an
additional beneficial effect of wine consumption has gained
attention and has been suggested as one of many possible
explanation of the “French paradox”: a low incidence of
cardiovascular disease in the French population despite an
unfavorable exposure to known cardiovascular risk factors.11
stroke in a large Danish prospective cohort study.
Subjects and Methods
Population
The Copenhagen City Heart Study was initiated in 1976 and included
19 698 persons living in Østerbro and Nørrebro in Copenhagen, Den-
mark. The participants were randomly chosen within age and sex strata
and invited by letter to 3 health examinations held in 1976 –1978,
1981–1983, and 1991–1994. Less than 2% of the population was of
nonwhite origin. There were 371 persons who died before the exami-
nation, and of the remaining 19 327 people, there were 5104 (26.4%)
nonresponders and 14 223 (73.6%) responders, in all age groups. During
the 16-year follow-up period, data were available for 13 329 eligible
subjects aged 45 to 84 years. A total of 55 persons (0.04%) were lost to
follow-up; of these, 53 were due to immigration, and there was no
information regarding the other 2 persons. A detailed description of the
examinations has previously been published.12
Alcohol
The participants were asked in multiple choice form whether they
drank beer (bottles), wine (glasses), or spirits (units). The choices
were “never/hardly ever,” “monthly,” “weekly,” or “daily.” Infor-
mation for each person regarding intake of beer, wine, and spirits
was entered into the model simultaneously.

Received June 25, 1998; final revision received August 18, 1998; accepted September 7, 1998.
From the Danish Epidemiology Science Center at the Institute of Preventive Medicine, Copenhagen University Hospital (T.T., M.G.); The Copenhagen
City Heart Study (M.G., P.S.); and Department of Neurology, Bispebjerg University Hospital (G.B.), Copenhagen, Denmark.
Correspondence to Thomas Truelsen, MD, Institute of Preventive Medicine, Kommunehospitalet, DK-1399 Copenhagen K, Denmark. E-mail truelsen@
ipm.hosp.dk
© 1998 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

2467
 2468 Intake of Beer, Wine, and Spirits and Risk of Stroke

TABLE 1. Baseline Characteristics 1976 –1978 According to Weekly Alcohol Consumption

Units per Week

,1 1–7 8 –14 15–21 22– 41 $42

Proportion of study sample 23.3% 36.8% 20.1% 7.4% 7.5% 4.9%
Mean age, y 56.4 52.8 53.1 52.9 52.1 51.5
Proportion men 20.1% 29.6% 65.9% 77.2% 86.4% 92.6%
Current smoking 54.8% 61.8% 65.4% 72.2% 75.5% 81.2%
Education ,8 y 64.1% 47.4% 41.0% 41.2% 47.8% 54.0%
Physical activity in leisure time 79.7% 74.7% 70.7% 72.4% 71.1% 73.4%
,4 h/wk
Cholesterol .8 mmol/L 9.8% 7.0% 6.3% 6.1% 5.1% 6.2%
Antihypertensive treatment 17.7% 13.5% 10.3% 9.6% 7.8% 8.5%
Mean systolic blood 139.3 135.6 138.6 138.8 141.2 141.5
pressure, mm Hg
Mean triglycerides, mmol/L 1.7 1.6 1.8 2.0 2.1 2.5
Body mass index, kg/m2 25.6 24.9 25.2 25.2 25.9 26.7
Diabetes mellitus 2.8% 1.5% 1.7% 2.2% 1.6% 2.4%

The subjects were then classified according to the total weekly intake of
alcohol: ,1 beverage; 1 to 7 beverages; 8 to 14 beverages; 15 to 21
beverages; 22 to 41 beverages; and $42 beverages. One bottle of beer
contains 12 g of alcohol, and this was considered the average for the other
types of drinks. Abstinence due to treatment with drugs (disulfiram) was
noted, and those subjects were excluded from the study (n516).
Covariates
The following variables were assumed to confound the analyses: smoking
(never smokers; ex-smokers; 1 to 10, 11 to 20, and .20 cigarettes per day);
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without history of symptoms. Unspecified stroke relates to a patient for
whom no information of stroke subtype was available.
The follow-up period was 16 years (from January 1, 1977, to
December 31, 1992). We used data from participants aged 45 to 84
years and who attended the initial study examination; the present
analyses are therefore based on 6067 men and 7262 women. The age
reduction was applied because most strokes occurred in this age
group, because very young people may differ in respect to suscep-
tibility to alcohol,16 and to diminish uncertainty about the reliability
of stroke diagnoses among very old persons.17

sex (men and women); monthly income in 1976 to 1978 (monthly income
in 1976–1978 (,4000, 4000 to 10 000, and .10 000 Danish crowns,
which is approximately equivalent to ,666, 666 to 1667, and .1667 US
dollars for exchange rates in 1977); physical activity in leisure time (almost
completely physically passive or light physical activity ,2 h/wk, light
physical activity 2 to 4 h/wk, light physical activity .4 h/wk or more
exhausting physical activity 2 to 4 h/wk, and exhausting physical activity
.4 h/wk or regular hard training); educational level (education ,8, 8 to 11,
or .11 years); presence of diabetes mellitus (yes or no); cholesterol (,8
and .8 mmol/L)13; triglycerides in millimoles per liter; and body mass
index (,20, 20 to 24, $25 and ,30, and $30 kg/m2). Systolic blood
pressure (millimeters of mercury) was regarded as a possible effect mediator
of alcohol.
Outcome
Information about prior stroke (hospitalized as well as nonhospital-
ized events) was obtained at the health examinations. Furthermore,
the Danish National Patient Register and the Central Death Register
were used to provide information about all persons with regard to
stroke hospitalization and death. The International Classification of
Diseases, codes 430 to 438 (8th revision), was used to identify
persons who had had a stroke. The World Health Organization
definition of stroke was used for validation: an acute disturbance of
focal or global cerebral function with symptoms lasting .24 hours or
leading to death with presumably no reasons other than of vascular
origin.14 Subjects who suffered a stroke before the beginning of the
study period were excluded from the analyses. This investigation is
based on data of risk of first-ever stroke, thus excluding 178 persons
who had had a stroke before the start of the study.
To distinguish between ischemic infarction, intracerebral hemor-
rhages, and subarachnoid hemorrhages, either CT or MR scan, autopsy,
spinal fluid examination, or operation description was necessary. If a
scan did not visualize an infarction but the person had symptoms that
met the criteria of the stroke definition, a diagnosis of ischemic
infarction was made.15 The diagnosis of stroke was not applied in cases
in which a scan had revealed signs of prior cerebrovascular disease but
Statistical Analyses
The data were analyzed by means of multiple Poisson regression
analysis,18,19 and the statistical software package STATA was used.20
Tests for linearity of variables and interactions were based on log
likelihood ratio tests at the 5% level. Although income was considered
a potential confounder, the variable was omitted in the final analyses
because it had no statistical effect in the present set of analyses.
Adjustment for age was done by 4-year lexis groups,19a ie, a subject
contributed to the age effect only with the years within the relevant age
strata and was included in the following age group when that was
reached. This implies that a person reaching the age limits within the
time frame of this study could be included or excluded. The incidence
was assumed to be constant within each 4-year age interval.
Results
During the 16 years of follow-up of 13 329 eligible persons, 833
strokes occurred: 442 (53%) unspecified, 310 (37%) ischemic
infarctions, 47 (6%) intracerebral hemorrhages, and 34 (4%) sub-
arachnoid hemorrhages. There were 346 events (42%) among
women and 487 (58%) among men. One hundred fifty-nine (19%)
of the stroke patients died within the initial 28 days.
Alcohol
There was a high proportion of men in the groups consuming
high amounts of alcohol, and the proportion of smokers
increased with higher alcohol consumption (Table 1). The
proportion of subjects with cholesterol levels .8 mmol/L fell
with a high alcohol intake, as did the proportion of subjects
receiving antihypertensive treatment. Both mean concentra-
tion of triglycerides and mean systolic blood pressure were
highest in the groups with high intake of alcohol (Table 1).
 Truelsen et al December 1998 2469

TABLE 2. Weekly Alcohol Consumption and Risk of Stroke

Complete Complete
Simple Complete Adjustment Adjustment Including
No. of Units Adjustment* Adjustment† Excluding SBP ICH and SAH
,1 (212/197) 1.33 (1.10–1.62) 1.18 (0.96–1.44) 1.17 (0.96–1.43) 1.12 (0.93–1.36)
1–7 (260/229) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
8–14 (164/150) 0.97 (0.79–1.20) 1.00 (0.81–1.25) 1.02 (0.82–1.26) 0.97 (0.79–1.19)
15–21 (71/64) 1.01 (0.76–1.35) 1.03 (0.77–1.38) 1.02 (0.76–1.37) 1.02 (0.78–1.35)
22–41 (65/55) 0.89 (0.65–1.21) 0.92 (0.68–1.26) 0.93 (0.68–1.26) 0.96 (0.72–1.28)
$42 (61/57) 1.56 (1.15–2.23) 1.33 (0.96–1.82) 1.35 (0.99–1.86) 1.29 (0.95–1.75)
SBP indicates systolic blood pressure; ICH, intracerebral hemorrhage; and SAH, subarachnoid hemorrhage.
Parentheses in column 2 show the number of total stroke events and of stroke events excluding ICH and SAH. Other
parentheses show 95% CIs.
*Adjusted for age, sex, and smoking.
†Adjusted for age, sex, smoking, body mass index, physical activity in leisure time, SBP, cholesterol,
antihypertensive treatment, triglycerides, education, and diabetes mellitus.

In analyses adjusted for age, sex, and smoking, subjects
drinking ,1 unit of alcohol per week had a significantly
higher risk of stroke compared with the reference group of
subjects drinking 1 to 7 units per week (relative risk [RR],
1.33; 95% CI, 1.10 to 1.62) (Table 2). Subjects who drank
$42 units per week also had an increased risk of stroke (RR,
1.56; 95% CI, 1.15 to 2.23). There were no statistically
significant differences between the intermediate consumption
groups and light drinkers. The increased risk in the low- and
high-consumption groups indicates a U-shaped relation.
After complete adjustment for confounding factors, the risk
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subjects reporting a daily consumption of wine (P50.06).
Intake of neither beer nor spirits was associated with risk of
stroke. Exclusion of systolic blood pressure in the model had
only a modest effect and did not change the overall results.
Inclusion of intracerebral hemorrhage and subarachnoid hem-
orrhage did not alter the estimates substantially. The differ-
ences between the various frequency groups could be ex-
pressed as linear, with the RR (95% CI) for beer, wine, and
spirits being 1.03 (0.96 to 1.11), 0.85 (0.77 to 0.94), and 0.99
(0.91 to 1.08), respectively. There was no interaction between
sex and wine consumption (x250.004, 1 df ; P50.95), wine

of stroke was statistically insignificant between the reference
group and the other groups. However, the estimates did not
change substantially; only the CIs became wider, and thus the
U-shaped relation remained. Exclusion of systolic blood
pressure increased the risk slightly in the high-consumption
group. Inclusion of subarachnoid hemorrhage and intracere-
bral hemorrhage had a modest effect on the results, with a
tendency of altering the RR estimates toward the value of 1.
First-order interaction between alcohol consumption and sex
was statistically insignificant (x253.14, 5 df ; P50.68).
Beer, Wine, or Spirits
Men drank beer and spirits more often than women, whereas
there was no difference between the sexes in regard to intake
of wine (Table 3). There was a low proportion of persons
reporting a frequent consumption of wine who had had ,8
years of education. There were no differences between the
groups with regard to body mass index, mean concentration
of triglycerides, proportion with cholesterol concentration
.8 mmol/L, and physical activity in leisure time (not shown).
The effect of drinking beer, wine, and spirits on risk of stroke
varied among the 3 types of alcohol (Table 4). In simple adjusted
analyses, subjects who drank wine had a statistically significant
decreased risk of stroke in all 3 frequency groups compared with
subjects who never/hardly ever drank wine. In contrast, no
statistically significant effect of drinking either beer or spirits
was found in either of the frequency groups.
After complete adjustment for confounding factors, sub-
jects who drank wine weekly had a significantly lower risk of
stroke, while the difference was marginally significant for
and beer intake (x250.232, 3 df ; P50.97), or intake of wine
and spirits (x252.766, 3 df ; P50.43).
Discussion
Our analyses suggest, in accordance with other studies, that
there is a beneficial effect of intake of a small amount of
alcohol on risk of stroke. In addition, we have found that this
effect is strongest among wine drinkers, since subjects who
drank wine had a lower risk of stroke than subjects who never
drank wine. The risk of stroke among wine drinkers was not
influenced by beer or spirits consumption.
The sampling procedures of the study population ensured
that a representative proportion of the Copenhagen popula-
tion was selected for the investigation. All data on exposure
were collected before the end points occurred, precluding
recall bias. Validation of stroke events was possible for all
participants regardless of socioeconomic status, thereby
avoiding selection bias of the case ascertainment. Nonfatal
nonhospitalized stroke events were detected at the health
examinations. Therefore, it is likely that only few events were
missed in the analyses. Any such nuisance would lead to a
lower estimated RR, and the results are therefore to be
considered conservative estimates of the true risk differences.
Alcohol consumption was self-reported, which may raise
questions regarding the validity of the data. It is possible that the
true alcohol consumption was underreported, especially among
heavy drinkers.21 In case of underreporting, the true higher risk
in the group with high alcohol consumption would relate to an
even higher alcohol consumption. Similarly, for the wine results,
 2470 Intake of Beer, Wine, and Spirits and Risk of Stroke

TABLE 3. Baseline Characteristics According to Consumption of Beer,

Wine, and Spirits
Consumption of Alcohol

Never/Hardly
Ever Monthly Weekly Daily
Beer
Proportion of study sample 35.4% 23.0% 19.9% 21.6%
Mean age, y (6SD) 54.9 (10.4) 52.7 (10.7) 52.0 (10.8) 54.0 (10.5)
Proportion men 20.9% 36.7% 57.2% 84.6%
Current smoking 56.7% 62.1% 66.7% 74.2%
Mean units of alcohol per 2.3 (6.2) 4.5 (5.1) 11.0 (5.8) 28.9 (19.6)
week (6SD)
Education ,8 y 56.2% 46.8% 39.8% 52.5%
Antihypertensive treatment 17.0% 12.1% 10.4% 9.2%
Diabetes mellitus 2.6% 1.3% 1.3% 2.2%
Mean systolic blood 137.6 (22.4) 135.6 (21.3) 137.8 (21.3) 141.4 (20.9)
pressure, mm Hg (6SD)
Wine
Proportion of study sample 42.1% 38.6% 14.9% 4.5%
Mean age, y (6SD) 55.6 (10.4) 52.4 (10.6) 51.2 (10.6) 54.1 (10.7)
Proportion men 45.5% 44.9% 47.4% 43.7%
Current smoking 65.4% 62.8% 61.2% 62.1%
Mean units of alcohol per 8.4 (15.8) 8.8 (12.0) 15.1 (11.7) 25.9 (18.6)
week (6SD)
Education ,8 y 64.7% 44.6% 29.6% 23.9%
Antihypertensive treatment 14.9% 11.6% 10.9% 12.4%
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Diabetes mellitus 2.8% 1.6% 0.7% 1.4%

Mean systolic blood 139.9 (22.3) 136.4 (21.2) 136.5 (20.4) 139.2 (23.0)
pressure, mm Hg (6SD)
Spirits
Proportion of study sample 47.9% 33.4% 12.6% 6.1%
Mean age, y (6SD) 54.0 (10.7) 52.1 (10.5) 53.6 (10.2) 58.5 (10.2)
Proportion men 36.1% 50.5% 59.3% 63.8%
Current smoking 60.4% 65.5% 68.2% 70.3%
Mean units of alcohol per 5.6 (11.4) 10.3 (11.8) 18.5 (14.2) 30.7 (24.13)
week (6SD)
Education ,8 y 56.6% 43.7% 42.5% 46.3%
Antihypertensive treatment 14.0% 11.3% 11.0% 16.1%
Diabetes mellitus 2.1% 1.6% 1.4% 3.5%
Mean systolic blood 138.0 (22.4) 136.4 (20.8) 139.6 (20.9) 143.2 (21.8)
pressure, mm Hg (6SD)

underreporting would consequently reflect that daily wine con-
sumption is beneficial and not only weekly wine intake.
The validity of self-reported alcohol intake in a simple
questionnaire, like the one used in this study, has been
compared with a more detailed dietary interview, and there
was only little or no systematic variation for the 3 types of
alcoholic beverages.22 Therefore, it is unlikely that bias in
alcohol reporting is responsible for the findings of differences
in risk of stroke among drinkers of beer, wine, and spirits.
Information regarding diet, a potential confounder,23 has not been
obtained in the Copenhagen City Heart Study. If differences in diet
could explain the results between the 4 wine groups, it would
require that drinking wine was directly associated with a beneficial
intake of food ingredients, independently from potential confound-
ers already controlled for. Furthermore, diet should be quite strongly
inversely related to risk of stroke. We consider that to be an unlikely
explanation for the results.
Other studies have addressed the question of a relation
between alcohol consumption and stroke in different set-
tings.24 There are discrepancies in the statistical strength of
the results; some studies found a protective effect of moderate
alcohol consumption,8,25–29 whereas other authors concluded
that there was no effect.30 High alcohol consumption may be
associated with an increased risk of stroke, and, as in our
study, there is evidence that at least some of this effect is
mediated through systolic blood pressure.4,5,8 Furthermore,
 Truelsen et al December 1998 2471

TABLE 4. Intake of Beer, Wine, and Spirits and Risk of Stroke

No. of Strokes Complete Adjustment
(Total/Excluding ICH Complete Adjustment Including ICH and
Type of Alcohol and SAH) Simple Adjustment* Complete Adjustment† Excluding SBP SAH
Beer
Never/hardly ever (286/261) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference)
Monthly (158/137) 0.89 (0.72–1.10) 0.95 (0.75–1.20) 0.95 (0.75–1.199) 0.97 (0.78–1.21)
Weekly (152/139) 1.01 (0.81–1.27) 1.09 (0.85–1.39) 1.12 (0.88–1.42) 1.06 (0.84–1.34)
Daily (237/215) 1.08 (0.87–1.33) 1.11 (0.89–1.39) 1.12 (0.90–1.41) 1.10 (0.89–1.36)
Wine
Never/hardly ever (432/399) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference)
Monthly (288/252) 0.83 (0.69–0.98) 0.84 (0.70–1.02) 0.85 (0.70–1.02) 0.88 (0.74–1.06)
Weekly (79 /72) 0.59 (0.45–0.77) 0.66 (0.50–0.88) 0.67 (0.50–0.89) 0.66 (0.50–0.86)
Daily (34 /29) 0.70 (0.46–1.00) 0.68 (0.45–1.02) 0.74 (0.50–1.11) 0.70 (0.48–1.03)
Spirits
Never/hardly ever (404/369) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1.00 (Reference)
Monthly (254/227) 0.98 (0.81–1.18) 0.99 (0.81–1.21) 0.98 (0.81–1.20) 1.00 (0.82–1.20)
Weekly (103 /93) 0.98 (0.77–1.26) 0.97 (0.74–1.24) 0.96 (0.74–1.24) 0.99 (0.77–1.27)
Daily (72 /63) 1.01 (0.77–1.33) 0.91 (0.68–1.22) 0.93 (0.70–1.25) 0.97 (0.74–1.28)
ICH indicates intracerebral hemorrhage; SAH, subarachnoid hemorrhage; and SBP; systolic blood pressure.
*Adjusted for age, sex, and smoking, including intake of beer, wine, and spirits simultaneously.
†Adjusted for age, sex, smoking, body mass index, physical activity in leisure time, SBP, cholesterol, antihypertensive treatment, triglycerides,
education, and diabetes mellitus, including intake of beer, wine, and spirits simultaneously.

high alcohol consumption has been associated with an in- hemorrhagic strokes support a differential effect of intake of
creased risk of hemorrhagic stroke.31 Our study confirms alcoholic beverages on risk of ischemic and hemorrhagic
these findings, but the effect of alcohol consumption was strokes, they are presumably too low.
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significant only in analyses controlling for age, sex, and
smoking. When lifestyle factors were entered into the model,
the association between alcohol intake and stroke was atten-
uated, and the nonsignificant results are likely merely to
reflect the powerful confounding effect of these covariates
rather than a lack of power. It is possible that the inconsis-
tency in the literature on the effect of alcohol on cerebrovas-
cular disease is partly due to differences in adjustment for
some of the lifestyle factors.
Alcohol is purported to influence risk of stroke through an action
on the coagulation system and/or atherogenesis similar for both
sexes. There were few women in the high-consumption groups and
consequently few stroke events (one in the highest-consumption
group and 3 in the second highest group). Therefore, the results in
these alcohol categories are largely based on stroke events that
occurred in men. In the other groups and in the analyses for beer,
wine, and spirits, a sufficient number of stroke events in both men
and women indicated that there were no differences between
analyses stratified by sex or grouped.
The follow-up period covers the period in which neuroimag-
ing was introduced as a routine diagnostic tool in Danish
hospitals, which is reflected by a relatively high proportion of
unspecified strokes in this study. Our stroke diagnosis was based
on clinical signs, and neuroimaging had no or little effect.32 A
large proportion of unspecified strokes may explain the modest
effect of exclusion of hemorrhagic stroke in this investigation.
Although a vast majority of these strokes can be expected to be
of ischemic origin, '10% may have been hemorrhagic. The
possible misclassification will lead to a negation of the differ-
ence. Therefore, although the results in the analyses excluding
A few authors have discussed whether the effect of alcohol
on risk of cardiovascular disease depends on the type of
alcohol ingested.9,33,34 We found that weekly and daily
consumption of wine was associated with lower risk of
stroke. Furthermore, the relation could be explained as a
linear relationship that was statistically significant, indicating
a dose-response effect. There was no interaction between
wine consumption and intake of beer and spirits, and there-
fore the protective effect on risk of stroke is solely connected
with intake of wine and not with a certain amount of alcohol.
In a recent correlation study from Spain, it was found that low
wine consumption, together with sedentary lifestyle, was
associated with increased cerebrovascular death.35 In the
Nurse’s Health Study,8 which included women aged 34 to 59
years, consumption of wine was also associated with a
reduced risk of stroke, but the investigation was based on
relatively few events (66 ischemic strokes, 12 intracerebral
hemorrhages, 28 subarachnoid hemorrhages, and 14 unclas-
sified). Wine contains flavonoids and tannins, which are
components presumed to prevent cardiovascular disease; this
may be a possible explanation of the apparent protective
effect in this study.36 –38 On the other hand, it has been
suggested that the beneficial effect of wine consumption is
merely related to drinking pattern. Wine may be consumed
with meals to a greater extent than beer and spirits; the latter
2 may be consumed more irregularly throughout the day.
These differences in “timing” may be important. In a recent
study, intake of alcohol was shown to reduce potential
atherogenic postprandial alterations of the blood.39
 2472 Intake of Beer, Wine, and Spirits and Risk of Stroke
Our data do not allow discrimination between ex-drinkers
and life-long abstainers in the reference groups. The lower
risk of stroke found among subjects reporting a weekly
consumption of wine could be due to a higher risk among
ex-drinkers. However, our reference groups are composed of
people who reported a low alcohol consumption rather than
people who are teetotalers, which reduces this problem
considerably. Furthermore, in a large study it was found that
ex-drinkers had higher risk of mortality from cardiovascular
and coronary artery diseases in unadjusted analyses but not in
analyses adjusted for age, sex, race, body mass index, marital
status, and education.40 In this study we have adjusted for
additional confounding factors, and if ex-drinkers should bias
the results, it was to be expected that in addition to wine
consumption, intake of beer and spirits would also have been
associated with a reduced risk of stroke, which was not found.
Our data indicate that intake of wine is associated with
lower risk of stroke. We cannot determine whether these
results are due to components in wine in addition to ethanol
or whether this is an effect due to intake of ethanol with
meals. Whatever the biological mechanism may be, the
consistency of the results, the lack of obvious biases, and the
biological plausibility suggest that there may be a beneficial
effect of intake of wine on risk of stroke.
Acknowledgments
This study was supported by funds from Direktør Werner Richter og
Hustrus Legat, the Danish National Board of Health, and Copenha-
gen University. The Copenhagen City Heart Study was funded by the
Danish Heart Foundation. We are grateful to G. Jensen, J. Nyboe,
Downloaded from http://ahajournals.org by on July 6, 2022
and A.T. Hansen, who, together with P. Schnohr, initiated and
conducted the Copenhagen City Heart Study. We acknowledge M.
Appleyard for her support and assistance.
References
1. Maclure M. Demonstration of deductive meta-analysis: ethanol intake
and risk of myocardial infarction. Epidemiol Rev. 1993;15:328 –351.
2. Lieber CS. Metabolism and metabolic effects of alcohol. Med Clin North
Am. 1984;68:3–33.
3. Gaziano JM, Buring JE, Breslow JL, Goldhaber SZ, Rosner B,
Vandenburgh M, Willett W, Hennekens CH. Moderate alcohol intake,
increased levels of HDL and its subfractions, and decreased risk of
myocardial infarction. N Engl J Med. 1993;329:1829 –1834.
4. Gordon T, Kannel WB. Drinking and its relation to smoking, BP, blood
lipids and uric acid. Arch Intern Med. 1983;143:1366 –1374.
5. Witteman JC, Willett WC, Stampfer MJ, Colditz GA, Kok FJ, Sacks FM,
Speizer FE, Rosner B, Hennekens CH. Relation of moderate alcohol con-
sumption and risk of systemic hypertension in women. Am J Cardiol. 1990;
65:633–637.
6. Facchini F, Chen YD, Reaven GM. Light to moderate alcohol intake is asso-
ciated with enhanced insulin sensitivity. Diabetes Care. 1994;17:115–119.
7. Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The
red wine phenolics trans-resveratrol and quercetin block human platelet
aggregation and eicosanoid synthesis: implications for protection against
coronary heart disease. Clin Chim Acta. 1995;235:207–219.
8. Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A
prospective study of moderate alcohol consumption and the risk of cor-
onary disease and stroke in women. N Engl J Med. 1988;319:267–273.
9. Grønbæk M, Deis A, Sørensen TIA, Becker U, Schnohr P, Jensen G.
Mortality associated with moderate intakes of wine, beer, or spirits. BMJ.
1995;310:1165–1169.
10. Rimm EB, Klatsky AL, Brobbee D, Stampfer MJ. Moderate alcohol
consumption and reduced risk of coronary heart disease: is the effect due
to beer, wine, or spirits? BMJ. 1996;312:731–736.
11. Renaud S, Lorgeril M. Wine, alcohol, platelets, and the French paradox
for coronary heart disease. Lancet. 1992;339:1523–1526.
12. Appleyard M, Hansen T, Schnohr P, Jensen G, Nyboe J. The Copenhagen
City Heart Study: Østerbroundersøgelsen: a book of tables with data from
the first examination (1976-78) and a five year follow-up (1981-83).
Scand J Soc Med. 1989;170(suppl 41):1–160.
13. Lindenstrøm E, Boysen G, Nyboe J. Influence of total cholesterol, high
density lipoprotein cholesterol and triglycerides on risk of cerebro-
vascular disease. BMJ. 1994;1994:11–15.
14. WHO MONICA Project Investigators. The World Health Organization
MONICA Project (Monitoring Trends and Determinants in Cardiovascu-
lar Disease). J Clin Epidemiol. 1988;41:105–114.
15. Lindgren A, Norrving B, Rudling O, Johansson B. Comparison of clinical and
neuroradiological findings in first-ever stroke. Stroke. 1994;25:1371–1377.
16. Klatsky AL, Armstrong MA, Friedman GD. Alcohol and mortality. Ann
Intern Med. 1992;117:646 – 654.
17. Bonita R, Broad JB, Anderson NE, Beaglehole R. Approaches to the problems
of measuring the incidence of stroke. Int J Epidemiol. 1995;24:535–542.
18. Grønbæk M, Deis A, Sørensen TIA, Becker U, Borch-Johnsen K, Müller
C, Schnohr P, Jensen G. Influence of sex, age, body mass index, and
smoking on alcohol intake and mortality. BMJ. 1994;308:302–306.
19. McCullagh P, Nelder JA. Generalized Linear Models. New York, NY:
Chapman and Hall; 1983.
19a.Clayton D, Hills M. Statistical Models in Epidemiology. New York, NY:
Oxford University Press; 1993.
20. Statistical Software, Release 5.0. College Station, Tex: Stata Corp; 1997.
21. Poikolainen K. Underestimation of recalled alcohol intake in relation to
actual consumption. Br J Add. 1985;80:215–216.
22. Grønbæk M, Heitman BL. Validity of self-reported intakes of wine, beer,
and spirits in population studies. Eur J Clin Nutr. 1996;50:487– 490.
23. Gillman MW, Cupples LA, Gagnon D, Posner BM, Ellison RC, Castelli
WP, Wolf PA. Protective effect of fruit and vegetables on development of
stroke in men. JAMA. 1995;273:1113–1117.
24. Camargo CA. Case-control and cohort studies of moderate alcohol con-
sumption and stroke. Clin Chim Acta. 1996;246:107–119.
25. Boffetta P, Garfinkel L. Alcohol drinking and mortality among men enrolled in
an American Cancer Society prospective study. Epidemiology. 1990;1:342–348.
26. Klatsky AL, Armstrong MA, Friedman GD. Alcohol use and subsequent
cerebrovascular disease hospitalizations. Stroke. 1989;20:741–746.
27. KiyoharaY, Kato I, Iwamoto H, Nakayama K, Fujishima M. The impact
of alcohol and hypertension on stroke incidence in a general Japanese
population. Stroke. 1995;26:368 –372.
28. Palomäki H, Kaste M. Regular light-to-moderate intake of alcohol and the
risk of ischemic stroke. Stroke. 1993;24:1828 –1832.
29. Rodgers H, Aitken PD, French J, Curless RH, Bates D, James OFW.
Alcohol and stroke. Stroke. 1993;24:1473–1477.
30. Wannamethee SG, Shaper AG. Patterns of alcohol intake and risk of
stroke in middle-aged British men. Stroke. 1996;27:1033–1039.
31. Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic
stroke. JAMA. 1986;297:519 –522.
32. Truelsen T, Prescott E, Grønbæk M, Schnohr P, Boysen G. Trends in
stroke incidence. Stroke. 1997;28:1903–1907.
33. Klatsky AL, Armstrong MA. Alcoholic beverage choice and risk of
coronary artery disease mortality: do red wine drinkers fare best? Am J
Cardiol. 1986;58:710 –714.
34. Klatsky AL, Armstrong MA, Friedman GD. Red wine, white wine,
liquor, beer, and risk for coronary artery disease hospitalization. Am J
Cardiol. 1997;80:416 – 420.
35. Artalejo FR, Guallar-Castillón P, Gutiérrez F, Banegas JR, Calero JR.
Socioeconomic level, sedentary lifestyle, and wine consumption as
possible explanations for geographic distribution of cerebrovascular
disease in Spain. Stroke. 1997;28:922–928.
36. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary
antioxidant flavonoids and risk of coronary heart disease. Lancet. 1993;
342:1007–1011.
37. Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of
oxidation of human low-density lipoprotein by phenolic substances in red
wine. Lancet. 1993;341:454 – 457.
38. Caarnacini A, Arfelli G. Selected nutritional components of wine.
Alcologia. 1994;6:41– 49.
39. Locher R, Suter PM, Vetter W. Ethanol suppresses smooth muscle cell
proliferation in the postprandial state: a new antiatherosclerotic
mechanism of ethanol? Am J Clin Nutr. 1998;67:338 –341.
40. Klatsky AL, Armstrong MA, Friedman GD. Risk of cardiovascular mor-
tality in alcohol drinkers, ex-drinkers and nondrinkers. Am J Cardiol.
1990;66:1237–1242.