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(Stroke. 1995;26:40-45.)
© 1995 American Heart Association, Inc.

Articles

Recent Alcohol Consumption, Cigarette Smoking, and Cerebral Infarction in Young Adults

Presented in part at the First International Stroke Congress, Kyoto, Japan, October 15-19, 1989, and at the 20th International Congress of Internal Medicine, Stockholm, Sweden, June 17-21, 1990.

Matti Hillbom, MD; Helena Haapaniemi, MD; Seppo Juvela, MD; Heikki Palomäki, MD; Heikki Numminen, MD Markku Kaste, MD

From the Departments of Neurology (H.P., M.K.) and Neurosurgery (S.J.), Helsinki University Hospital, and the Department of Neurology (M.H., H.H., H.N., Oulu University Hospital, Finland.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose The role of recent heavy drinking of alcohol as a risk factor for ischemic brain infarction is unclear. We investigated this problem in young adults, in whom even a thorough workup often fails to reveal any predisposing factor.

Methods This was a hospital-based case-control study comprising 75 consecutive subjects aged 16 to 40 years with first-ever ischemic brain infarction and 133 control subjects from the same hospital who were group-matched with the case patients for age, sex, day of the onset of symptoms, and acuteness of disease onset.

Results Multiple logistic regression analysis showed that alcohol intake exceeding 40 g of ethanol within the 24 hours preceding disease onset was a significant independent risk factor for brain infarction among both men (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.8 to 20.3) and women (OR, 7.8; 95% CI, 1.0 to 60.8). Cigarette smoking was not found to be an independent risk factor in the model, whereas among men arterial hypertension was (OR, 6.2; 95% CI, 1.5 to 24.7).

Conclusions We conclude that very recent alcohol drinking, particularly drinking for intoxication, may trigger the onset of brain infarction in young adults and that there might be a variety of mechanisms behind this effect.

Key Words: alcohol drinking • cerebral infarction • cigarette smoking • risk factors • young adults

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Cigarette smoking, hypertension, and alcohol drinking are considered to be risk factors for stroke.¹ Smoking increases the risk for cerebral infarction^{2 3 4 5} and aneurysmal subarachnoid hemorrhage,^{2 3 6 7 8} while hypertension increases the risk for cerebral infarction and primary intracerebral hemorrhage.^{1 7 8 9} Some studies suggest that smoking is not a risk factor for cerebral hemorrhage.^{3 10} According to recent studies, hypertension may increase the risk for subarachnoid hemorrhage.^{6 7 8} The risk, however, remains insignificant after adjustment for alcohol drinking and cigarette smoking.^{7 8}

The role of alcohol as a risk factor for stroke is less clear. Primary intracerebral hemorrhage is strongly associated with heavy alcohol consumption^{9 11 12 13 14} and recent heavy drinking seems to precipitate subarachnoid hemorrhage,^{7 8} but the data on the relationship between alcohol consumption and ischemic stroke risk are contradictory.^{5 14 15 16 17 18 19 20 21 22 23 24}

Although heavy drinking is associated with an increased risk for cerebral infarction,^{14 19 20} habitual light to moderate daily alcohol consumption diminishes the risk for occlusive atherothrombotic cerebrovascular disease,^{12 16 17 18} in agreement with the well-known preventive effect of daily alcohol consumption on the development of atherosclerosis. Accordingly, current weekly alcohol consumption was not found to be an independent risk factor for cerebral infarction in middle-aged and elderly patients, among whom occlusive atherothrombotic cerebrovascular disease is common.²⁵ However, young adults and the effects of recent alcohol intake were not investigated.

Because age, sex, and different drinking habits should be taken into account when evaluating the role of alcohol, we designed a study to demonstrate the role of recent heavy, moderate, and light drinking and of current heavy, moderate, and light cigarette smoking, as well as former smoking and problem drinking, as risk factors for ischemic cerebral infarction in young adults. Hypertension, cardiac disease, diabetes, obesity, migraine, use of oral contraceptives, and hyperlipemia were considered confounding factors. We hypothesized that acute alcohol consumption may carry an increased risk for ischemic brain infarction in young adults.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The study series comprised 75 consecutive patients with first-ever ischemic cerebral infarction aged 16 to 40 years who were admitted into the Helsinki University Hospital and 133 control subjects from the same hospital who were matched as a group with the infarction patients for age, sex, day of the onset of symptoms, and acuteness of the disease. None of the subjects refused to participate. The study protocol was approved by the institutional ethical committee of our center.

Both the infarction and the control groups were recruited during a period of 5 years and were from the same population encompassing the city of Helsinki and its suburbs. We included also those patients who were in poor health at admission. Because alcohol consumption is closely associated with holidays in Finland, we selected the control subjects in such a way that they had symptom onsets equally often during holidays and weekends (32%) and working days (62%) as had the patients with brain infarction.

The control subjects were admitted into the emergency unit because of acute appendicitis (n=72), acute viral meningitis (n=21), or acute attacks of dyspnea (n=16), nephrolithiasis (n=16), and cholecystitis (n=8). According to the literature, none of these emergencies is significantly associated with alcohol use. The lower prevalence of gallstone disease among current drinkers seems to be confined to those in a postcholecystectomy state,²⁶ and no such patients were included in the present study.

Computed tomography (CT) scans of the head were obtained in the acute phase to exclude primary intracerebral hemorrhage. The CT scan confirmed the location of the infarction in 72% of the patients. The lesions in the rest of the patients could not be visualized, mainly because of a brain stem location or the early timing of the investigation. Twenty-six patients had solitary hemispheric infarctions. Six of them (6/75, 8%) died soon after admission. Thirteen patients had multiple, five had cerebellar, and seven had brain stem infarctions. Solitary lacunes were not detected. Aortocervical or selective cervicocerebral angiographies were performed on 46 patients, and pathological results were found in 20 (43%), including occlusions (n=8), atherosclerotic lesions (n=4), carotid arterial dissections (n=3), incompletely developed vertebral arteries (n=3), and cerebral arterial vasculitis (n=2). Cardiological investigations showed 11 subjects as having a potential cardiac source of embolism. We did not exclude any of the patients with pathological abnormalities from the analyses.

All 75 subjects, apart from 7 with brain infarction who were dysphasic or moribund, were personally interviewed within 48 hours after admission by a trained interviewer; there were no differences in interview time and environment for the control and case subjects. Data on the remaining 7 patients were obtained by interviewing their relatives and friends. A structured questionnaire was verbally administered by the interviewer; it included questions on previous diseases and lifestyle factors. The possible relationship between lifestyle factors and stroke was not mentioned, but dummy questions about drinking and eating habits were included. Questions about previous drinking habits and illicit drug use were also asked, but only one drug abuser was identified. Toxicological screens for drugs were not performed because drug abuse is not common in Finland. Recent drinking was recorded as grams of absolute ethanol (one drink usually contains 12 g of ethanol in Finland) consumed within the 24 hours and 1 week before the onset of the first symptoms, including possible prodromal symptoms. Cigarette smoking and problem drinking were assessed as recently described elsewhere.^{8 27} The category of current cigarette smokers included subjects who had been smoking within the past year. Problem drinking was assessed using the short CAGE questionnaire (Have you ever felt you should Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever had a drink first thing in the morning to steady your nerves and to get rid of a hangover [Eye-opener]?).²⁷ If the subject gave at least two positive answers to the four CAGE questions,⁸ he or she was considered to be or have been a problem drinker.

Information on all patients was also systematically collected from the medical records of other hospitals and general practitioners to check diseases, medications, and blood pressure values of the patients. The subjects were considered to be hypertensive if their blood pressure readings before the index admission had repeatedly exceeded 160 mm Hg systolic or 95 mm Hg diastolic or if they were on antihypertensive medication. Cardiac disease included atrial fibrillation, previously diagnosed myocardial infarction, heart failure, and other cardiac abnormalities that are conventionally considered cardiac sources of emboli. The occurrence of previously diagnosed diabetes, hyperlipemia, and migraine were recorded. Relative weight was determined by using the body mass index (weight/[height]²). -Glutamyltransferase (GGT) and mean corpuscular volume (MCV) were used as laboratory markers of major alcohol consumption, although they are not very sensitive.²⁸ Like alcohol, cigarette smoking elevates MCV; diabetes, obesity, and use of certain drugs are associated with elevated GGT values.²⁸

The data were analyzed by the biomedical data package statistical programs (BMDP).²⁹ The categorical variables were compared using Fisher's exact two-tailed test, the Pearson ² test, or the test for linear trend. The continuous variables were compared using the Mann-Whitney U test, Student's t test, or Spearman's rank correlation coefficients (r_s) as appropriate. The odds ratio (OR) with 95% confidence intervals (CIs) was used as an estimate of the relative risk. The relative risks before (univariate) and after (multivariate) adjustment for possible confounding variables were calculated by multiple logistic regression separately in men and women. Hypothesis testing and the estimation of the 95% CI were performed using the standard error estimate for the logistic coefficient estimates.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The baseline characteristics of all subjects are shown in Table 1. The age and body mass index distributions between the case and control subjects were similar. The frequencies of hypertension, cardiac disease, diabetes, and hyperlipemia were not significantly different among the female case and control subjects, but history of migraine (P<.05) and current use of oral contraceptives (P<.05) were; male subjects with brain infarction were more likely to have a history of arterial hypertension (OR, 4.9; 95% CI, 1.5 to 14.8; P<.01) and cardiac disease (OR, 8.3; 95% CI, 1.7 to 41.0; P<.01) as well as diabetes (P<.05) and migraine (P<.05) compared with the control subjects. Cardiac disease was significantly (P<.01) associated with hypertension.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics by Sex in 75 Patients With Acute Brain Infarction and in 133 Control Subjects

The crude data on recent alcohol drinking, problem drinking, and cigarette smoking are shown in Table 2. Drinking within the 24 hours preceding the disease onset was heavier and more frequent among both the male (P<.001) and female case patients (P<.05) than the control subjects. Alcohol consumption within the week before the disease onset, however, was not significantly more abundant. Problem drinking was more frequent among the male infarction patients than among the male control subjects (4 patients lacked the CAGE data), whereas smoking status did not significantly differ between the case and control subjects. The ORs for brain infarction were 3.0 (95% CI, 1.3 to 6.8; P<.05) and 1.4 (0.3 to 7.0) among the male and female problem drinkers, and 1.4 (0.7 to 3.0) and 2.1 (0.1 to 4.0) among the male and female current smokers, respectively.

View this table: [in this window] [in a new window]   Table 2. Alcohol Consumption and Smoking by Sex in 75 Patients With Acute Brain Infarction and in 133 Control Subjects

Risk factors that were significantly associated were smoking status, the 24-hour alcohol intake, and problem drinking. Smoking status, as shown in Table 2, was associated with the amount of alcohol consumed within the 24 hours before disease onset (r_s=.168, P<.05). We also observed that the greater the 24-hour alcohol intake, the more often the subject was a problem drinker (r_s=.371, P<.001). Yet, half of the subjects with a 24-hour alcohol intake exceeding 120 g were not problem drinkers.

To confirm the interview data, we took blood samples for laboratory markers of alcohol consumption. The amount of alcohol consumed within 24 hours correlated clearly (r_s=.426, P<.01) with GGT values but not significantly with MCV values (r_s=.065). Weekly alcohol consumption correlated with both GGT (r_s=.493, P<.01) and MCV (r_s=.150, P<.05) values. The corresponding correlation coefficients between these laboratory markers of alcohol consumption and problem drinking were r_s=.315, P<.01, for GGT and r_s=.289, P<.01, for MCV. Heavy recent alcohol intake was the factor that was most significantly associated with the increased GGT values as well as with the elevated MCV values of the study population. In men, the mean values of MCV (91.2±4.6 versus 89.4±3.9, P<.05) and GGT (73±102 versus 29±18, P<.05) were significantly higher in the case than in the control subjects; high values were found in both groups if the amount of alcohol intake during the preceding week had exceeded 300 g of ethanol, a level suggesting heavy drinking. Heavy drinking was infrequent among women. MCV and GGT values were not significantly different between the case and control subjects.

Using stepwise logistic regression, the variables for which the simultaneous risk of brain infarction was tested by sex were body mass index, hypertension, cardiac disease, diabetes, hyperlipemia, migraine, smoking status, current use of oral contraceptives, problem drinking, and the amount of alcohol consumed within the 24 hours and 1 week before the illness. The univariate and multivariate statistics for the significant variables are shown in Tables 3 and 4.

View this table: [in this window] [in a new window]   Table 3. Odds Ratios and 95% Confidence Intervals of Brain Infarction in Men

View this table: [in this window] [in a new window]   Table 4. Odds Ratios and 95% Confidence Intervals of Brain Infarction in Women

Among the men, the significant risk factors for brain infarction were a history of hypertension (P<.01), the amount of alcohol consumed within the 24 hours before the onset of illness (P<.01), and a history of migraine (P<.05). Diabetes and lipid disorders were quite infrequent among both the index patients and the control subjects, and they were not accommodated by the model, probably because the series was too small. Cases of cardiac disease were more frequent, but these patients often had hypertension (P=.0054); hypertension therefore replaced cardiac disease in the model as a significant risk factor. By contrast, recent alcohol consumption was not associated with a history of hypertension, and it remained as a significant independent risk factor even after adjustment for hypertension and age. Likewise, hypertension proved to be a significant independent risk factor after adjustment for recent alcohol consumption and age.

Problem drinking and recent drinking expressed in terms of the 1-week ethanol intake did not remain as significant risk factors in the model, most likely because these two parameters were strongly associated with the 24-hour ethanol intake.

Smoking was tested separately using current smoking and the number of cigarettes per day. As expected according to the univariate analysis, smoking status did not appear in the model as a significant risk factor, although the number of smokers was relatively high.

Among the women, the significant risk factors for brain infarction according to univariate analysis were the amount of alcohol consumed within the 24 hours before the onset of illness (P<.05), history of migraine (P<.05), and current use of oral contraceptives (P=.05). After adjustment for potential confounding factors, only the 24-hour alcohol intake remained as an independent risk factor (Table 4).

However, because the number of women in this study was rather small, we tested our hypothesis by expanding the population to include women aged 41 to 50 years (data not shown). After this enlargement of the material, we had 51 case and 83 control women, and current cigarette smoking replaced recent alcohol intake as an independent risk factor in the model.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We found recent alcohol intake to be an independent risk factor for ischemic brain infarction in young men and women in whom overt cardiac disease, atherosclerosis, and arterial hypertension, which are the common risk factors in older people, have a lesser impact. Interestingly, although cigarette smoking is a very common habit among young adults and is associated with alcohol drinking,³⁰ neither current smoking nor the number of cigarettes smoked daily appeared to be an independent risk factor for brain infarction among men and women aged 40 years or less. Accordingly, cigarette smoking did not seem to be a significant risk factor for brain infarction in young people, as it is in older people. This observation suggests that the deleterious effect of cigarette smoking is due mainly to the enhanced development of atherosclerotic lesions in the arterial vessel walls, an effect that is dependent on the amount and duration of smoking.

Several studies have indicated a positive relationship between habitual heavy drinking including alcoholism and ischemic stroke.^{14 19 31} Many authors believe that alcohol consumption may play a role in human health long before severe alcohol dependence has developed. Everyday experience, case histories,^{32 33 34} and case series^{19 35 36} have suggested that even occasional drinking and binge drinking could be provoking factors for ischemic cerebral infarction. Binge drinking has been defined as alcohol consumption that markedly exceeds the normal average daily intake by the subject, particularly consumption for intoxication. Binge drinking can start from various levels of daily alcohol consumption, even from a level of zero, and it is therefore more accurate to speak of "acute" alcohol intake instead of binge drinking.

One controlled study of acute alcohol ingestion as a risk factor for ischemic stroke has been published previously.³⁷ Subjects with nonatherosclerotic strokes were excluded from that study, and the investigators found that among middle-aged and elderly people recent alcohol intake before the onset of stroke was not an independent risk factor, while both hypertension and smoking were. The apparent association between recent alcohol intake and the onset of brain infarction was confounded by the association of alcohol consumption with smoking. The authors concluded that the more marked effects of hypertension and smoking in older subjects may prevent the detection of any effect ascribable to alcohol and suggested that their findings might not necessarily hold true for young adults. In fact, the significance of recent alcohol intake as a stroke-provoking risk factor could be difficult to prove because of the great variety of risk factors and the diversity of the pathogenetic mechanisms leading to cerebral ischemia. Another way to test the hypothesis is to investigate whether brain infarction relapses are more frequent among heavy drinkers than among patients who are infrequent and light drinkers. In fact, a recent report suggests that alcohol abuse may be a determinant of ischemic stroke recurrence.³⁸

To our knowledge, the present case-control study is the first to suggest that recent alcohol intake is in fact a triggering factor for brain infarction in young adults. The validity of this observation depends on whether there is any bias in the selection of both the case patients and the control subjects. It should be emphasized here that the subjects of this study were consecutively selected and that none were chosen or excluded because of their drinking habits. Our hospital admits all young adults with acute stroke and other acute emergencies from the catchment area without any selection. The subjects were interviewed with similar intensity and according to a structured protocol, and they came from the same region into the same hospital. Accordingly, we consider referral and ascertainment bias very unlikely. Berksonian bias was also avoided because the patients did not have any concurrent major health problems.

To control for hospital control bias, we compared afterward the data on our control subjects with data on randomly selected population control groups.^{39 40 41} Our control subjects were not different in terms of hypertension,⁴¹ MCV and GGT values,³⁹ number of problem drinkers,⁴⁰ or weekly alcohol intake⁴⁰ from the population control subjects that were recruited during the same time from the same catchment area. Accordingly, our control subjects represent well the average population of the city of Helsinki at that time.

The elevated levels of the laboratory markers of alcohol consumption in our index case patients strongly support our observation. Particularly, among men with brain infarction, elevated GGT levels were associated with recent binge drinking, whereas elevated MCV values were associated with problem drinking. Our interview data were based on both recall of recent drinking and the CAGE questionnaire. Recall bias is possible, but the observed significant correlations between the laboratory markers of alcohol consumption and the interview data indicate that it was not a major problem.

Our conclusion on the role of recent alcohol intake as a triggering factor for brain infarction in young adults should, however, be taken with caution because the number of subjects was rather small, and there might be confounding factors that were not included in our analyses. Thus far, we do not know the mechanisms by which acute alcohol intake could precipitate ischemic stroke. Neither do we know whether acute alcohol intake could precipitate stroke in middle-aged and elderly people, among whom acute heavy drinking is less frequent.

Finally, bias could have resulted from the control subjects having reduced their drinking in the prodrome of their acute illnesses. However, such a bias is unlikely (see Table 2); for example, 12% of the male control subjects reported having consumed >40 g of ethanol within 24 hours before disease onset, although an estimate of only 8% was suggested by their reported weekly intake.

The difficulty of choosing control subjects for case-control studies designed to evaluate the stroke risk due to alcohol consumption has been recently emphasized.⁴² Different relative risks were obtained by using population and hospital control subjects. However, it is important to pay equal attention to the selection of index cases as to that of control subjects. This will be illustrated by comparing the present data with the data of the above-mentioned study.

The frequency of problem drinking in the study of Ben-Shlomo et al⁴² was almost the same among the case and control subjects. Subjects who were CAGE-positive accounted for 17% of their cases and for 14% to 16% of subjects in their different control groups. In the present study, 15% of the control group but 28% of the infarction patients (men and women together) were problem drinkers. The difference between the two studies could be explained by age, as the subjects of the previous study⁴² were older. However, CAGE positiveness is expected to increase along with age because it includes both former and present problem drinking. On the other hand, in many countries young adults drink more than middle-aged people; therefore, the prevalence of heavy drinkers but not necessarily that of problem drinkers decreases along with age, as heavy drinkers tend to die at an earlier age.

An association of recent alcohol intake with the onset of ischemic brain infarction does not automatically mean that there is a causal relationship. Alcohol consumption and the following intoxication may bring about possibly significant consequential activities. Among these we should mention hazardous behavior, which might lead to a trauma in the vertebral and carotid arterial walls. Strenuous exertion, fights, and falls are common among intoxicated young people. Accordingly, the relation of traumatic arterial dissections to recent alcohol ingestion should be elucidated. Other mechanisms include the actions of alcohol on heart rate and blood pressure. Hyperdynamic circulation, cardiac arrhythmias, and spontaneous Valsalva maneuvers commonly occur during heavy intoxication and the following hangover. These phenomena, when precipitated by alcohol ingestion and possibly alcohol-induced sleep apneas, may be dangerous for subjects having some hidden or known cardiac or other vascular abnormality predisposing to embolism. Therefore, patients with cardiac abnormalities increasing the risk of embolic stroke should not be excluded,²³ but rather studied separately, when we evaluate the mechanisms by which alcohol ingestion might increase the risk.

Several mechanisms, ranging from alcohol-induced changes in platelet function and hemocoagulation to cerebral arterial vasoconstriction,⁴³ have already been suggested to mediate the alcohol-associated risk for stroke, but thus far there is no clinical evidence to indicate that any such effect of alcohol might be responsible for the association. Further clinical studies are needed to elucidate the mechanisms by which alcohol intoxication triggers the onset of brain infarction.

In conclusion, our present study indicates that there is an association between very recent alcohol intake and the onset of ischemic cerebral infarction. This can be seen in young adults. We have no proof that habitual daily alcohol consumption could prevent the risk. Problem drinkers, if not at a higher risk, might be equally prone to cerebral accidents as occasional heavy drinkers.

	Acknowledgments

 
This study was supported in part by grants from the Yrjö Jahnsson Foundation (Drs Numminen, Hillbom, and Kaste) and the Alcohol Research Foundation, Finland (Dr Hillbom).

	Footnotes

 
Reprint requests to M. Hillbom, MD, Department of Neurology, Oulu University Hospital, FIN-90220 Oulu, Finland.

Received June 27, 1994; revision received September 12, 1994; accepted September 30, 1994.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Shaper AG, Phillips AN, Pocock SJ, Walker M, MacFarlane PW. Risk factors for stroke in middle aged British men. Br Med J. 1991;302:1111-1115.
2. Colditz GA, Bonita R, Stampfer MJ, Willett WC, Rosner B, Speizer FE, Hennekens CH. Cigarette smoking and risk of stroke in middle-aged women. N Engl J Med. 1988;318:937-941. [Abstract]
3. Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. Br Med J. 1989;298:789-794.
4. Donnan GA, McNeill JJ, Adena MA, Doyle AE, O'Malley HM, Neill GC. Smoking as a risk factor for cerebral ischaemia. Lancet. 1989;2:643-647. [Medline] [Order article via Infotrieve]
5. Harmsen P, Rosengren A, Tsipogianni A, Wilhelmsen L. Risk factors for stroke in middle-aged men in Göteborg, Sweden. Stroke. 1990;21:223-229. [Abstract/Free Full Text]
6. Bonita R. Cigarette smoking, hypertension, and the risk of subarachnoid hemorrhage: a population-based case-control study. Stroke. 1986;17:831-835. [Abstract/Free Full Text]
7. Longstreth WT Jr, Nelson LM, Koepsell TD, van Belle G. Cigarette smoking, alcohol use, and subarachnoid hemorrhage. Stroke. 1992;23:1242-1249. [Abstract/Free Full Text]
8. Juvela S, Hillbom M, Numminen H, Koskinen P. Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid hemorrhage. Stroke. 1993;24:639-646. [Abstract/Free Full Text]
9. Calendre L, Arnal C, Fernandez Ortega J, Bermejo F, Felgeroso B, del Sir T, Vallejo A. Risk factors for spontaneous cerebral hematomas. Case-control study. Stroke. 1986;17:1126-1128. [Abstract/Free Full Text]
10. Fogelholm R, Murros K. Cigarette smoking and risk of primary intracerebral hemorrhage: a population-based case-control study. Acta Neurol Scand. 1993;87:367-370. [Medline] [Order article via Infotrieve]
11. Weisberg L. Alcoholic intracerebral hemorrhage. Stroke. 1988;19:1565-1569. [Abstract/Free Full Text]
12. Klatsky AL, Armstrong MA, Friedman GD. Alcohol use and subsequent cerebrovascular disease hospitalizations. Stroke. 1989;20:741-746. [Abstract/Free Full Text]
13. Monforte R, Estruch R, Graus F, Nicolas JM, Urbano-Marquez A. High ethanol consumption as risk factor for intracerebral hemorrhage in young and middle-aged people. Stroke. 1990;21:1529-1532. [Abstract/Free Full Text]
14. Gill JS, Shipley MJ, Tsementzis SA, Hornby RS, Gill SK, Hitchcock ER, Beevers DG. Alcohol consumption: a risk factor for hemorrhagic and non-hemorrhagic stroke. Am J Med. 1991;90:489-497. [Medline] [Order article via Infotrieve]
15. Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med. 1988;319:267-273. [Abstract]
16. Rodgers H, Aitken PD, French JM, Curless RH, Bates D, James OFW. Alcohol and stroke: a case-control study of drinking habits past and present. Stroke. 1993;24:1473-1477. [Abstract/Free Full Text]
17. Bogousslavsky J, Van Melle G, Despland PA, Regli F. Alcohol consumption and carotid atherosclerosis in the Lausanne stroke registry. Stroke. 1990;21:715-720. [Abstract/Free Full Text]
18. Palomäki H, Kaste M, Raininko R, Salonen O, Juvela S, Sarna S. Risk factors for cervical atherosclerosis in patients with transient ischemic attack or minor ischemic stroke. Stroke. 1993;24:970-975. [Abstract/Free Full Text]
19. Hillbom M, Kaste M. Ethanol intoxication: a risk factor for ischemic brain infarction. Stroke. 1983;14:694-699. [Abstract/Free Full Text]
20. Gill JS, Zezulka AV, Shipley MJ, Gill SK, Beevers DG. Stroke and alcohol consumption. N Engl J Med. 1986;315:1041-1046. [Abstract]
21. Gill JS, Shipley MJ, Hornby RH, Gill SK, Beevers DG. A community case-control study of alcohol consumption in stroke. Int J Epidemiol. 1988;17:542-547. [Abstract/Free Full Text]
22. Boysen G, Nyboe J, Appleyard M, Soelberg Sörensen P, Boas J, Somnier F, Jensen G, Schnohr P. Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke. 1988;19:1345-1353. [Abstract/Free Full Text]
23. Henrich JB, Horwitz RI. Evidence against the association between al- cohol use and ischemic stroke risk. Arch Intern Med. 1989;149:1413-1416. [Abstract]
24. Ellekjär EF, Wyller TB, Sverre JM, Holmen J. Lifestyle factors and risk of cerebral infarction. Stroke. 1992;23:829-834. [Abstract/Free Full Text]
25. Gorelick PB, Rodin MB, Langenberg B, Hier DB, Costigan J. Weekly alcohol consumption, cigarette smoking, and the risk of ischemic stroke: results of a case-control study at three urban medical centers in Chicago, Illinois. Neurology. 1989;39:339-343. [Abstract/Free Full Text]
26. Kono S, Shinchi K, Ikeda N, Yanai F, Imanishi K. Prevalence of gallstone disease in relation to smoking, alcohol use, obesity, and glucose tolerance: a study of self-defense officials in Japan. Am J Epidemiol. 1992;136:787-794. [Abstract/Free Full Text]
27. Mayfield D, McLeod G, Hall P. The CAGE questionnaire: validation of a new alcoholism screening instrument. Am J Psychiatry. 1974;131:1121-1123. [Abstract/Free Full Text]
28. Papoz L, Warnet J-M, Pequignot G, Eschwege E, Claude JR, Schwartz D. Alcohol consumption in a healthy population: relationship to gamma-glutamyl transferase activity and mean corpuscular volume. JAMA. 1981;245:1748-1751. [Abstract]
29. Dixon WJ, ed. BMDP Statistical Software. Berkeley, Calif: University of California Press; 1988.
30. Keil U, Chambless L, Filipiak B, Härtel U. Alcohol and blood pressure and its interaction with smoking and other behavioural variables: results from the MONICA Augsburg Survey 1984-1985. J Hypertens. 1991;9:491-498. [Medline] [Order article via Infotrieve]
31. Marini C, Carolei A, Roberts RS, Prencipe M, Gandolfo C, Inzitari D, Landi G, de Zanche L, Scoditti U, Fieschi C, and the National Research Council Study Group. Focal cerebral ischemia in young adults: a collaborative case-control study. Neuroepidemiology. 1993;12:70-81. [Medline] [Order article via Infotrieve]
32. Wilkins MR, Kendall MJ. Stroke affecting young men after alcoholic binges. Br Med J. 1985;291:1342.
33. Hess DC, Sethi KD, Nichols FT. Carotid dissection: a new false localising sign. J Neurol Neurosurg Psychiatry. 1990;53:804-805. [Medline] [Order article via Infotrieve]
34. Gras P, Abdoul Karim A, Grosmaire N, Borsotti JP, Giroud M, Blettery B, Dumas R. Embolies cerebrales multiples au cours d'une intoxication alcoolique aigue: un cas anatomo-pathologique. Rev Neurol. 1992;148:215-217. [Medline] [Order article via Infotrieve]
35. Hillbom M, Kaste M. Does ethanol intoxication promote brain infarction in young adults? Lancet. 1978;2:1181-1183. [Medline] [Order article via Infotrieve]
36. Carolei A, Marini C, Ferranti E, Frontoni M, Prencipe M, Fieschi C, and the National Research Council Study Group. A prospective study of cerebral ischemia in the young: analysis of pathogenic determinants. Stroke. 1993;24:362-367. [Abstract/Free Full Text]
37. Gorelick PB, Rodin MB, Langenberg P, Hier DB, Costigan J, Gomez I, Spontak S. Is acute alcohol ingestion a risk factor for ischemic stroke? Results of a controlled study in middle-aged and elderly stroke patients at three urban medical centers. Stroke. 1987;18:359-364. [Abstract/Free Full Text]
38. Sacco RL, Shi T, Zamanillo MC, Kargman DE. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the Northern Manhattan Stroke Study. Neurology. 1994;44:626-634. [Abstract/Free Full Text]
39. Koskinen P, Kupari M, Leinonen H. Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age. Am J Cardiol. 1990;66:954-958. [Medline] [Order article via Infotrieve]
40. Kupari M, Koskinen P. Time of onset of supraventricular tachyarrhythmia in relation to alcohol consumption. Am J Cardiol. 1991;67:718-722. [Medline] [Order article via Infotrieve]
41. Salomaa V, Tuomilehto J, Nissinen A, Korhonen HJ, Vartiainen E, Kartovaara L, Puska P. The development of hypertension care in Finland from 1982 to 1987. J Hypertens. 1989;7:837-844. [Medline] [Order article via Infotrieve]
42. Ben-Shlomo Y, Markowe H, Shipley M, Marmot MG. Stroke risk from alcohol using different control groups. Stroke. 1992;23:1093-1098. [Abstract/Free Full Text]
43. Altura BM, Altura BT. Alcohol, the cerebral circulation and strokes. Alcohol. 1984;1:325-331.[Medline] [Order article via Infotrieve]

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