(Stroke. 1996;27:1033-1039.)
© 1996 American Heart Association, Inc.
Articles |
From the Department of Public Health, Royal Free Hospital School of Medicine, Rowland Hill St, London NW3 2PF, UK.
Correspondence to Dr S. Goya Wannamethee, Department of Public Health, Royal Free Hospital School of Medicine, Rowland Hill St, London NW3 2PF, United Kingdom.
| Abstract |
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Methods We prospectively studied 7735 middle-aged men drawn from general practices in 24 British towns. With exclusion of those who had recall of physician diagnosis of ischemic heart disease or stroke, data were available for 7273 men all followed for 13.5 years, with 216 major stroke events (fatal and nonfatal).
Results Compared with occasional drinkers, nondrinkers (lifelong abstainers plus ex-drinkers) had an increased risk of stroke even after adjustment for age, lifestyle factors, and preexisting cardiovascular disease (relative risk [RR]=1.6; 95% CI, 1.0 to 2.7). All regular weekend drinkers (1 to 2, 3 to 6, and >6 drinks/d) and daily 1 to 2 and 3 to 6 drinkers showed no significant difference in adjusted risk of stroke compared with occasional drinkers. Heavy drinkers (daily >6 drinks) showed significantly increased risk evident within the first 8 years of follow-up only (RR=1.9; 95% CI, 1.0 to 3.5); however, this finding was attenuated after additional adjustment for systolic blood pressure (RR=1.5; 95% CI, 0.8 to 2.7). Information obtained 5 years after screening was used to separate lifelong abstainers and ex-drinkers. On subsequent 8.5 years of follow-up, both groups showed similar increased risk (RR=1.5) compared with occasional drinkers, but the risk in ex-drinkers was reduced after adjustment for lifestyle factors and cardiovascular disease status (RR=1.2). Lifelong abstainers, however, showed an increase in risk after adjustment of 1.8 (95% CI, 0.7 to 4.6).
Conclusions Heavy drinking is associated with an increased risk of total stroke that is largely mediated through blood pressure. The apparent increased risk seen in lifelong abstainers but not in ex-drinkers or occasional drinkers is unexplained but is unlikely to be attributed to abstinence from alcohol. There is no convincing evidence that light or moderate drinking is beneficial for stroke risk compared with occasional drinking.
Key Words: alcohol drinking risk factors Great Britain stroke
| Introduction |
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| Subjects and Methods |
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Fifth-Year Questionnaire
Five years after the initial examination (1983 through 1985), a
postal questionnaire (Q5) similar to the one administered at initial
screening was sent to all surviving men, and detailed information was
obtained on medical history, changes in smoking and drinking behaviors,
and changes in other risk factors. Ninety-eight percent of the
survivors responded (7275 men).
Alcohol Intake
Alcohol consumption was recorded at initial screening (Q1)
with the use of questions on frequency, quantity, and type that were
similar to those used in the 1978 General Household
Survey.15 The men were questioned about frequency (none,
occasional, weekend, or daily) and quantity (1 to 2, 3 to 6, or >6
drinks/day) of alcohol intake, resulting in eight drinking categories:
nondrinkers, occasional drinkers (special occasion or 1 to 2
drinks/month), weekend drinkers (1 to 2, 3 to 6, or >6 drinks/d), and
daily drinkers, men drinking daily or on most days (1 to 2, 3 to 6, or
>6 drinks/d).16 These categories were the only choices
provided. It should be noted that the ">6 drinks/d" category is
an open-ended one. One UK unit of alcohol (one drink) is defined as
half a pint of beer, a single measure of spirits, or a glass of wine
(approximately 8 to 10 g alcohol). Heavy drinking refers to those
drinking >6 drinks daily or on most days. No history of previous
drinking was requested at Q1, and at this stage it was not possible to
separate nondrinkers into lifelong abstainers and ex-drinkers.
Twenty-five biochemical and hematological measurements on a single
blood sample taken at the time the questionnaire was completed
indicated that the reported levels of alcohol consumption were valid on
a group basis.17 The occasional drinker group is used as
the baseline group because the nondrinker group is a small,
heterogeneous group unsuitable for this
purpose.18
Classification of Drinking Behavior
Five years after the initial screening, because we had become
aware of the many adverse characteristics of the nondrinking group and
the need to separate ex-drinkers from lifelong
abstainers,19 the men were asked about their past drinking
habits in addition to questions on their current alcohol consumption
(Q5). Complete information on alcohol consumption at both Q1 and Q5 was
obtained from 7166 men.
Tables 1
and 2
and the
Figure
are based on the classification of alcohol intake
of men at Q1. Nondrinkers include ex-drinkers and lifelong
abstainers. In Table 3
, classification is based on the
combined information obtained at Q1 and Q5 (numbers in parentheses are
actual classifications): (1) lifelong abstainersmen who were
nondrinkers at Q1 and Q5 and who claimed at Q5 that they had never been
drinkers; (2) ex-drinkersnondrinkers at Q1 and Q5 who at Q5
reported previous drinking and nondrinkers at Q5 who were occasional or
regular drinkers at Q1; (3) occasional drinkersthose who reported
occasional drinking at Q5, unless they were heavy drinkers (daily >6
drinks) at Q1 (see 10 below); (4 to 6) weekend drinkers1 to 2, 3 to
6, and >6 drinks at Q5 unless they were daily drinkers of >6 drinks
at Q1 (see 10 below); (7 to 8) daily drinkers1 to 2 and 3 to 6
drinks/d at Q5 unless they were daily drinkers of >6 drinks/d at Q1
(see 10 below); (9) heavy drinkersdaily >6 drinks/d at Q5; and
(10) exheavy drinkersmen who reported drinking >6 drinks/d
on a daily basis at Q1 and were no longer heavy drinkers at Q5.
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Preexisting Ischemic Heart Disease and Stroke
At both Q1 and Q5 men were asked whether a doctor had ever told
them that they had angina or myocardial infarction (heart attack,
coronary thrombosis), stroke, or a number of other disorders.
The WHO (Rose) chest pain questionnaire20 was administered
to all men at the initial examination and a three-orthogonal lead
ECG was recorded at rest. Men with evidence of IHD were defined as
those with a recall of a diagnosis of angina or heart attack made by a
doctor, with a response on WHO (Rose) chest pain questionnaire
suggesting angina or possible myocardial infarction, or with ECG
evidence of definite or possible myocardial ischemia or
myocardial infarction. Evidence of a previous stroke was
determined by the subject's recall of such a diagnosis made by a
doctor. There were 52 such men in the study at Q1. Information on
prevalence of IHD as measured by WHO (Rose) chest pain questionnaire
and recall of physician diagnosis was also provided at Q5.
Follow-up
All men, whether or not they showed evidence of IHD at initial
examination, were followed for all cause mortality and for
cardiovascular morbidity for a period of 13.5 years
from the initial screening, which was performed from January 1978
through July 1980.21 Follow-up was possible for 99%
of the cohort. In the analysis concerning lifelong abstainers
(Table 3
) stroke events are based on 8.5 years of follow-up for
each man from the Q5. Information on death was collected through the
established "tagging" procedures provided by the National Health
Service registers in Southport (England and Wales) and Edinburgh
(Scotland). Nonfatal stroke events were those that produced a
neurological deficit that was present for more than 24 hours.
Evidence regarding such episodes was obtained by reports from general
practitioners, from personal questionnaires sent to
surviving subjects at Q5, and by semiannual reviews of the patients'
notes made through the end of the study period. Fatal stroke episodes
were those coded on the death certificate to International
Classification of Diseases (ICD) codes 430 through 438. All death
certificates in which it appeared that coding to stroke was not
appropriate, or in which stroke was not the attributed code when it
might have been, were explored by correspondence with the certifying
doctor and the hospital concerned. No information on the type of stroke
was available.
Statistical Methods
The Cox proportional-hazards model was used to assess the
independent contributions of alcohol intake to the risk of stroke and
to obtain the relative risks adjusted for age and the other risk
factors.22 Alcohol was fitted as a categorical
variable. Age, blood cholesterol level, and
systolic blood pressure were fitted as continuous
variables. Smoking (5 levels), physical activity (6 levels), social
class (3 groups), diabetes mellitus (yes/no), and preexisting IHD on
questionnaire/ECG (yes/no) were also fitted as categorical
variables. The validity of the proportional-hazards assumption
was assessed by fitting a time-dependent interaction variable
x=x(t) with the levels of alcohol where
x(t)=log(t).23 The tests for trend over time in
the proportional-hazards ratio were not statistically significant
for any category of alcohol intake. There was no evidence that the
proportional-hazards assumption was violated.
| Results |
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Table 1
shows the rate per 1000 person-years and age-adjusted
relative risk of stroke in the eight alcohol categories at screening
(Q1). Nondrinkers, weekend >6 drinks/d drinkers, and daily drinkers of
>6 drinks/d all showed increased relative risk compared with
occasional drinkers (P=.06, P=.05, and
P=.03, respectively). Daily 3 to 6 and weekend 3 to 6
drinks/d drinkers showed slightly but nonsignificantly lower risk than
occasional drinkers. The weekend 1 to 2 drinker group showed the lowest
relative risk of stroke and this was of marginal significance
(P=.06). Within the weekend drinker group, risk tended to
increase with increasing intake of alcohol (test for trend
P<.001). Since alcohol intake is associated with many of
the factors known to be associated with stroke, such as age, smoking,
social class, physical activity, diabetes mellitus, preexisting IHD,
and systolic blood pressure, we have examined the relationship,
adjusting for these potential confounders and excluding
systolic blood pressure. No adjustments were made initially for
systolic blood pressure because it may be a mechanism by which
alcohol exerts its influence on risk of stroke.
Adjustments for these factors reduced the increased risk seen in weekend >6 and daily >6 drinkers; the latter although elevated was no longer statistically significant. Since daily 1 to 2 drinkers had the most favorable profile of risk,16 adjustment increased the risk in this group. Within the weekend drinker group risk of stroke still tended to increase with increasing intake (test for trend P=.06). The risk in nondrinkers remained elevated and was of marginal significance (P=.08).
Alcohol Intake and Systolic Blood Pressure
The increasing risk of stroke with increasing intake of alcohol in
the weekend drinkers and the elevated risk in daily heavy drinkers
largely reflects the patterns seen between alcohol and systolic
blood pressure. The Figure
shows the mean systolic blood
pressure according to the eight categories of alcohol intake adjusted
for age and then also for body mass index, social class, smoking,
physical activity, preexisting IHD, and diabetes mellitus. In both
weekend and daily drinkers there was a significant increase in
systolic blood pressure with increasing alcohol intake (tests
for trends P=.007 and P<.0001, respectively).
Compared with occasional drinkers, adjusted systolic blood
pressure was significantly elevated in weekend >6 (P=.0003)
and daily >6 drinkers (P<.0001) and to a lesser degree in
daily 3 to 6 drinkers (P=.09). Weekend >6 drinkers showed
significantly higher age-adjusted mean systolic blood
pressures than daily 3 to 6 drinkers (P<.001), but this
difference was much attenuated after adjustment (P=.20). In
Table 1
additional adjustment for systolic blood pressure
further reduced the risk in weekend >6 and daily >6 drinkers.
Duration of Follow-up
We have shown that middle-aged British men tend to reduce
their intake with increasing age and that although about 25% of heavy
drinkers were still drinking >6 drinks/d, about half of those who
reported daily >6 drinking at Q1 were daily 3 to 6 drinkers at
Q5.24 Elevated blood pressure is also known to decrease on
reduction of alcohol intake.25 26 We have therefore looked
at the relationship between alcohol intake at screening and risk of
stroke in the first 8 years (111 cases) and in the subsequent 5.5 years
(105 cases), with the time division being selected to achieve an
adequate number of stroke cases in each time period (Table 2
). The
effects of heavy drinking on risk of stroke were only evident in the
earlier follow-up period. Further adjustment for systolic
blood pressure substantially reduced the significantly elevated risk in
heavy daily drinkers from 1.9 (95% CI=1.0 to 3.5) to 1.5 (95% CI=0.8
to 2.7), suggesting that the increased risk is largely mediated by
systolic blood pressure. The increased risk associated with
nondrinking status was seen in both periods of follow-up, although
it was not statistically significant in either presumably because of
the smaller number of cases involved in each separate period.
Nondrinkers
To separate lifelong abstainers from ex-drinkers, information
on past drinking habits was obtained at Q5. Of the 7273 men with no
history of IHD or stroke at Q1, 6802 men provided complete information
on drinking behavior at Q5. Of these, 353 men had experienced a heart
attack or stroke or had recall of a physician diagnosis of angina
between Q1 and Q5 and have been excluded from the analysis,
leaving 6449 men. During the 8.5-year follow-up in these men, there
were 132 major stroke events, representing a rate of
3.5/1000 person-years. The men were classified primarily on the
basis of their reported alcohol intake at Q5 (see "Subjects and
Methods"). Since heavy daily drinkers at Q1 showed significantly
increased risk of stroke over an 8-year follow-up, heavy
daily drinkers at Q1 who did not report drinking heavily at Q5 formed a
separate group. Thus, 10 groups were used: lifelong abstainers,
ex-drinkers, occasional, weekend 1 to 2, weekend 3 to 6, weekend
>6, daily 1 to 2, daily 3 to 6, current heavy drinkers (daily >6),
and exheavy drinkers (daily >6 at Q1).
Table 3
shows the stroke rate per 1000 person-years and
age-adjusted relative risk for the 10 groups. Both current heavy
drinkers and exheavy drinkers showed increased relative risk
compared with occasional drinkers and other regular drinkers, although
these differences were not statistically significant presumably because
of the small numbers involved. To a lesser extent, lifelong abstainers
and ex-drinkers also showed an increased risk of stroke. Of all the
other drinking categories, only weekend 1 to 2 drinkers showed lower
risk of stroke than occasional drinkers, although this was not
statistically significant. These findings are similar to those seen for
the first 8-year follow-up with the use of the Q1 classification
(Table 2
).
Adjustment for Risk Factor Status at Q5
Adjustments for physical activity were based on measures at Q1
because data were not available at Q5. Adjustments for preexisting IHD
were based on preexisting IHD at Q1 (ECG/questionnaire) and on newly
reported angina on the WHO (Rose) chest pain questionnaire at Q5 in men
who did not have recall of a physician diagnosis of angina. Adjustments
for smoking and diabetes were based on smoking status at Q5 and recall
of diabetes at either Q1 or Q5. Adjustment for the potential
confounders reduced the increased risk in ex-drinkers and increased
the risk seen in lifelong abstainers, although the difference in risk
between lifelong abstainers and occasional drinkers was still not
significant (P=.24). Current heavy drinkers still showed
some increased risk, although the difference from occasional drinkers
was not statistically significant (P=.28). Exheavy
drinkers showed slightly lower risk than continuing heavy drinkers.
Only weekend 1 to 2 drinkers showed lower (but nonsignificant) risk
than occasional drinkers (P=.27).
For those concerned with the effects of weekly intake of alcohol on risk of stroke, we have grouped the regular nonheavy drinkers on the basis of their estimated average weekly intake into "light" drinkers (1 to 15 drinks/wk) comprising weekend 1 to 2, weekend 3 to 6, and daily 1 to 2 and "moderate" drinkers (16 to 42 drinks/wk) comprising weekend >6 and daily 3 to 6.27 Light and moderate drinkers showed virtually the same adjusted relative risk of stroke as occasional drinkers (RR=1.0; 95% CI, 0.7 to 1.5 and RR=0.9; 95% CI, 0.5 to 1.6, respectively).
| Discussion |
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In this study of middle-aged men in which occasional drinkers were
used as the reference group, nondrinkers as a group (lifelong
abstainers and ex-drinkers) showed significantly increased risk of
total stroke even after adjustment for smoking, social class, physical
activity, diabetes mellitus, and preexisting IHD (Table 1
). There was
no significant difference in risk of stroke between daily 1 to 2 and
daily 3 to 6 drinkers and all weekend drinkers (1 to 2, 3 to 6, or >6
drinks/d) compared with occasional drinkers. The lowest risk was seen
in weekend 1 to 2 drinkers, but the difference was not statistically
significant. Heavy daily drinkers (>6 drinks/d) showed a significantly
increased age-adjusted risk of stroke (RR=1.6), which was
attenuated after adjustment and although increased (RR=1.4) was not
statistically significant over the total 13.5-year follow-up.
Light or Moderate Drinking
In this study, these broad categories include all subjects other
than nondrinkers (lifelong abstainers and ex-drinkers), heavy
drinkers, and exheavy drinkers. On a weekly intake basis, light
and moderate drinking groups at Q5 have the same relative risks of
stroke as occasional drinkers. In those studies that have shown a
beneficial effect of light to moderate drinking on risk of stroke, the
use of nondrinkers as a baseline comparison will not unexpectedly
result in an apparently reduced risk in these two
categories.6 7 8 9 10 When we examined the drinking categories
in detail, with no broad grouping, the component categories of light or
moderate drinking showed no significant differences in risk from
occasional drinking at both Q1 and Q5 or any pattern of dose response
that might have suggested a protective effect from regular drinking.
Although we had no available information on type of stroke, about 85%
of strokes in adults in Great Britain are due to cerebral thrombosis
and infarction, with only about 15% attributable to
intracerebral or subarachnoid
hemorrhage.29 Thus, the pattern of relationship
seen is likely to reflect the relationship with ischemic
stroke.
It is unlikely that the findings in this study are due to misclassification of self-reported alcohol intake because the alcohol groups have been validated against 25 biochemical/hematological variables.17 Although the alcohol information at Q5 was from postal questionnaires only, the high degree of validity recorded for self-reported alcohol intake30 suggests that the data are comparable with those recorded at Q1. Occasional drinkers are likely to include some periodic heavy drinkers (binge drinkers) who have been shown to have an increased risk of stroke,31 32 and inclusion of these subjects might increase the risk seen in occasional drinkers. It is also unlikely that the lack of beneficial effect in the daily 3 to 6 drinkers is due to inclusion of men drinking up to 6 drinks within this group because we have shown that moderate drinkers (weekend >6 and daily 3 to 6 combined) have a significantly decreased risk of coronary heart disease compared with occasional drinkers.3 In addition, daily 1 to 2 drinkers showed no decreased risk of stroke. Thus, when contrasted with occasional drinkers, there is no convincing evidence from this study that light or moderate drinking is protective against stroke.
Lifelong Abstainers
In most studies that show increased risk in nondrinkers, there has
been no separation of lifelong abstainers and ex-drinkers. In the
studies that have separated these categories, some have found increased
risk in lifelong abstainers,8 33 while others have
not.31 34 In a recent prospective study of alcohol
consumption in the elderly, there was no evidence of a protective
effect of regular drinking on risk of ischemic stroke compared
with lifelong abstainers.31 Ex-drinkers, on the other
hand, showed significantly increased risk after adjustment for age and
smoking. No adjustments were made for disease status in this group.
Similar findings were seen in a Japanese study, with lifelong
abstainers showing the lowest risk.34 In the present
British study, when lifelong abstainers and ex-drinkers were
separated, both showed similar increased age-adjusted risk of
stroke despite the fact that lifelong abstainers have very low rates of
smoking. Further adjustment for smoking and other risk factors as well
as cardiovascular disease status increased the risk in
lifelong abstainers, although the finding was still not statistically
significant possibly due to the small numbers. The increased risk in
ex-drinkers was reduced, and these men showed risk similar to
occasional drinkers after adjustment. Our findings are similar to those
of a British (Newcastle upon Tyne) case-control study that reported
increased risk in lifelong abstainers (odds ratio=2.36) but not in
ex-drinkers compared with regular drinkers.8
The differences found among studies in the risk of stroke in lifelong
abstainers may be due to the different characteristics of lifelong
abstainers in differing populations. The reasons for lifelong
abstainers having an apparently increased risk of stroke are difficult
to conceive in terms of the risk factor status of this group. Overall
these men showed levels of risk factors and physical disorder similar
to occasional drinkers, although they have slightly higher rates of
regular medication.18 The number of lifelong abstainers in
our study is small, but if the increased risk is real, the finding that
occasional drinkers and regular nonheavy drinkers as well as
ex-drinkers do not differ significantly in the risk of stroke
(Table 3
), ie, the absence of any dose-response effect, makes it
seem unlikely that the reason why lifelong abstainers have an
apparently increased risk of stroke is because of their abstinence from
alcohol.
Heavy Drinkers
Although there is a general consensus that heavy drinking is
associated with increased risk of stroke, and in particular hemorrhagic
stroke, several prospective studies have found no increased risk of
total stroke or ischemic stroke in heavy
drinkers.1 6 7 We have observed a modest but
nonsignificant increased risk of stroke in heavy drinkers during the
total follow-up period. When the patterns of drinking were examined
by duration of follow-up, the increase in risk of total stroke in
heavy daily drinkers was clearly evident in the shorter follow-up
period (8 years) and not in the subsequent 5.5 years. This is
consistent with the known reduction in alcohol intake in heavy
drinkers over time in this cohort and in middle-aged men in
general.24 The increased risk of total stroke in heavy
drinkers was attenuated after adjustment for systolic blood
pressure, suggesting that the effect of heavy drinking on risk of
stroke is acute and largely mediated by elevated systolic blood
pressure. Given that men tend to reduce their intake during the course
of follow-up and that the effect may be acute, the long-term
effect of alcohol on risk of stroke judged on the basis of one
assessment in time is unlikely to represent the true effect and
is likely to attenuate with longer follow-up as seen in this study.
This may explain the lack of association seen between heavy drinking
and risk of stroke in many long-term prospective studies.
Conclusions
The Joint Working Party of the Royal Colleges35
concluded that alcohol consumption is not associated with an increase
in risk of overall stroke except at quite high levels (>5 UK units/d),
and our findings are consistent with this conclusion. A recent
major review indicates that there is no consensus regarding the
possible decreased risk of ischemic stroke with light to
moderate levels of alcohol intake.7 Our findings do not
provide any convincing evidence that light to moderate drinking is
beneficial for risk of overall stroke compared with occasional
drinking. The apparent increase in risk of stroke seen in lifelong
abstainers but not in ex-drinkers or occasional drinkers remains
unexplained but is unlikely to be due to lack of alcohol.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received December 27, 1995; revision received February 19, 1996; accepted March 5, 1996.
| References |
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M. Hillbom, H. Numminen, and S. Juvela Recent Heavy Drinking of Alcohol and Embolic Stroke Stroke, November 1, 1999; 30 (11): 2307 - 2312. [Abstract] [Full Text] [PDF] |
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M. C. Reid, D. A. Fiellin, and P. G. O'Connor Hazardous and Harmful Alcohol Consumption in Primary Care Arch Intern Med, August 9, 1999; 159(15): 1681 - 1689. [Abstract] [Full Text] [PDF] |
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C. L Hart, G. D. Smith, D. J Hole, and V. M Hawthorne Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years of follow up BMJ, June 26, 1999; 318(7200): 1725 - 1729. [Abstract] [Full Text] |
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R. L. Sacco, M. Elkind, B. Boden-Albala, I-F. Lin, D. E. Kargman, W. A. Hauser, S. Shea, and M. C. Paik The Protective Effect of Moderate Alcohol Consumption on Ischemic Stroke JAMA, January 6, 1999; 281(1): 53 - 60. [Abstract] [Full Text] [PDF] |
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S. G. Wannamethee, A. G. Shaper, M. Walker, and S. Ebrahim Lifestyle and 15-Year Survival Free of Heart Attack, Stroke, and Diabetes in Middle-aged British Men Arch Intern Med, December 1, 1998; 158(22): 2433 - 2440. [Abstract] [Full Text] [PDF] |
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T. Truelsen, M. Gronbæk, P. Schnohr, and G. Boysen Intake of Beer, Wine, and Spirits and Risk of Stroke : The Copenhagen City Heart Study Stroke, December 1, 1998; 29(12): 2467 - 2472. [Abstract] [Full Text] [PDF] |
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A. E. Kunst, M. del Rios, F. Groenhof, and J. P. Mackenbach Socioeconomic Inequalities in Stroke Mortality Among Middle-Aged Men : An International Overview Stroke, November 1, 1998; 29(11): 2285 - 2291. [Abstract] [Full Text] [PDF] |
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R. X. You, J. J. McNeil, H. M. O'Malley, S. M. Davis, A. G. Thrift, and G. A. Donnan Risk Factors for Stroke Due to Cerebral Infarction in Young Adults Stroke, October 1, 1997; 28(10): 1913 - 1918. [Abstract] [Full Text] |
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