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(Stroke. 1997;28:26-30.)
© 1997 American Heart Association, Inc.

Articles

Lifestyle-Associated Risk Factors for Acute Brain Infarction Among Persons of Working Age

Helena Haapaniemi, MD; Matti Hillbom, MD Seppo Juvela, MD

the Department of Neurology, Oulu University Hospital (H.H., M.H.), and the Department of Neurosurgery, Helsinki University Hospital (S.J.), Finland.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose This study was designed to identify whether cigarette smoking, alcohol drinking, obesity, and use of oral contraceptives are independent risk factors for brain infarction among persons of working age.

Methods Health habits and previous diseases of 506 patients (366 men and 140 women aged 16 to 60 years) with acute first-ever symptomatic brain infarction were compared with those of 345 hospitalized control patients (219 men and 126 women) who did not differ from case subjects in respect to day of onset of symptoms or acuteness of disease onset. With the use of stepwise logistic regression, the variables for which the simultaneous risks of acute brain infarction were tested by sex were age, amount of alcohol consumed within 24 hours and 1 week before the illness, heavy drinking, smoking status, current smoking, cardiac disease, hypertension, diabetes, hyperlipemia, migraine, body mass index, and, in women, current use of oral contraceptives.

Results Intake of >40 g ethanol within the 24 hours preceding the onset of illness increased the risk for acute brain infarction both among men (P<.001) and women (P<.01) independently from other risk factors. Other significant independent risk factors for brain infarction among men were hypertension (P<.001), cardiac disease (P<.01), current smoking (P<.01), diabetes (P<.05), and history of migraine (P<.05) and among women, current use of oral contraceptives (P<.01) and current smoking (P<.05).

Conclusions Recent heavy drinking of alcohol, hypertension, cardiac disease, current smoking, diabetes, and history of migraine among men, and recent heavy drinking of alcohol, current use of oral contraceptives, and current smoking among women, seem to be independent risk factors for acute brain infarction.

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

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Ischemic brain infarction is a common and severely disabling disease. Hence, effective prevention is important, and all the risk factors, particularly those that are modifiable, should be known. Previous epidemiological studies have suggested several lifestyle-associated risk factors,^{1 2 3 4 5} among them cigarette smoking and heavy drinking of alcohol.

The role of alcohol as a risk factor for hemorrhagic stroke is well established. Heavy drinking seems at least to double the risk for spontaneous intracerebral hemorrhage, and it also increases the risk for subarachnoid hemorrhage.^{6 7 8 9} Many studies have shown a predominance of recent heavy drinkers among the cases stricken by hemorrhagic strokes.^{7 8 9 10 11} Hemorrhagic stroke risk usually shows a linear correlation with the extent of alcohol consumption.⁶ The relationship between alcohol consumption and ischemic stroke is less clear. Ischemic stroke shows a J- or U-shaped correlation.¹² The association between alcohol intake and the risk of ischemic stroke is complex and may depend on drinking habits. For example, regular light to moderate alcohol consumption seems to protect against the risk of ischemic stroke,^{12 13 14} whereas heavy drinking increases the risk.^{7 11 15}

This study was designed to evaluate the role of health habits such as cigarette smoking, alcohol drinking, obesity, and use of oral contraceptives as modifiable risk factors for brain infarction among persons of working age. To see whether these lifestyle-associated risk factors are independent risk factors for brain infarction, we tested them by taking into account age, hypertension, cardiac disease, diabetes, hyperlipemia, and migraine.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The study population consisted of 506 patients (140 women and 366 men aged between 16 and 60 years) with first-ever acute brain infarction who were admitted on an emergency basis to the Helsinki University Central Hospital and 345 control subjects (126 women and 219 men aged between 16 and 60 years) from the same hospital who were matched as a group with the brain-infarction patients by day of onset of symptoms and acuteness of disease onset. The control subjects were admitted to the emergency department because of acute appendicitis (n=143), nephrolithiasis (n=77), dyspnea (n=61), viral meningitis (n=38), and cholecystitis (n=26). According to the literature, none of these medical emergencies are considered to accumulate among heavy drinkers or teetotalers. These control subjects have previously been validated to be representative of the general population of the catchment area of our hospital in sex, age, recent alcohol drinking, and smoking habits.^{9 10 16}

This hospital has a defined catchment area: practically all the brain-infarction patients of this age group from the surrounding area are admitted into this hospital on an emergency basis without any selection. Consequently, the present study can be considered to be near population-based. Because patients with incomplete data were excluded, the sample represents 70% of all the consecutive brain-infarction patients of the age group admitted during the study period.

All the patients had clear clinical signs and symptoms of an acute brain infarction. CT scans of the head were performed for 91% of the patients on admission to exclude primary intracerebral hemorrhage and other brain disease except ischemic stroke. The head CT scan confirmed the location of the infarction in four fifths of the patients. The lesions of the remaining patients were not visible, mainly because of the brain stem location or the early timing of the investigation, but these subjects also had clinical signs and symptoms typical of an ischemic attack lasting for >24 hours that were verified at neurological examination; during a follow-up period from months to years, no other type of neurological disease (ie, brain tumor, etc) appeared.

The study protocol was approved by the institutional ethics committee, and informed consent was obtained before the interview was started. The data and permission for the study were given by a relative if the patient was too ill to cooperate. None of the case subjects, the relatives, or control subjects refused to participate in the study. The patients and the control subjects were personally interviewed according to a structured questionnaire. There were no differences in interview time and environment for the control and case patients. The questionnaire included questions as to the exact time of disease onset, the height and weight of the subjects, previous diseases and hospital visits, recent drug use including illicit drugs, recent and previous drinking of alcohol, and current and previous smoking status. To get more reliable data on use of alcohol, cigarettes, and illicit drugs, relatives and friends were interviewed when possible. We used the proxy data for alcohol consumption if a larger amount was reported by the proxy than the patient, since underestimation is more likely for alcohol intake than overestimation.¹⁷ Information was also collected from the medical records. Medical record data were used to check previous diseases and medications of the patients. The data proved to be useful to confirm the presence or absence of certain diseases, such as diabetes, hypertension, and hyperlipemia. We did not select the medical records. All the medical records of our own hospital were systematically examined, including those from other specialties. Sometimes it appeared that valuable information was also available from the medical records of other hospitals and general practitioners, but we did not systematically collect the medical records from other hospitals.

The body mass index (BMI), calculated as weight/(height)², was used as the index of relative weight. The patients were considered to be hypertensive if their blood pressure readings preceding the index stroke had repeatedly exceeded 160/95 mm Hg or if they were taking antihypertensive medication. Cardiac disease included current atrial fibrillation, current or previous myocardial infarction, heart failure of any cause, and other cardiac abnormalities that are conventionally considered cardiac sources of emboli.¹⁸ Minor cardiac abnormalities found on echocardiography (such as patent foramen ovale without evidence of paradoxical embolism, mitral valve prolapse, and spontaneous echo contrast) were not included. The occurrence of previously diagnosed diabetes and hyperlipemia (serum cholesterol >8 mmol/L) was recorded. These subjects were either taking medication or following a diet. Migraine was defined as a typical migrainous headache with or without aura in the patient's earlier history or immediately preceding the onset of brain infarction; thus, the cases of migrainous infarction were included.

The smokers were categorized into nonsmokers, former (regular) cigarette smokers who had quit at least 1 year ago, and current cigarette smokers, using 10 and 20 cigarettes per day as cutoff points. Recent drinking was recorded as grams of absolute ethanol (1 drink usually contains 12 g ethanol in Finland) consumed within the 24 hours and 1 week before the onset of the first symptoms, including possible prodromal symptoms. Heavy drinkers of alcohol included subjects whose recent mean weekly alcohol intake had regularly exceeded 300 g ethanol or who were problem drinkers. Both former and current problem drinkers were included as heavy drinkers. Problem drinking was assessed by using the short CAGE questionnaire.¹⁹ Two or more positive answers to the four CAGE questions^{9 10} suggest the presence of problem drinking (sensitivity and specificity, 80% to 90%).²⁰

The data were analyzed with biomedical data package statistical programs (BMDP Statistical Software Inc, University of California at Los Angeles, 1993). 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, which are expressed as mean±SD, were compared by Student's t test. The odds ratios (ORs) as estimates of multivariate relative risks and the 95% confidence intervals (CIs) before and after adjustment for possible confounding variables were calculated by logistic regression. The hypothesis testing and the estimation of the 95% CIs were performed using the standard error estimate for logistic coefficient estimates. With the use of stepwise logistic regression, the variables for which the simultaneous risks of brain infarction were tested by sex were age, amount of alcohol consumed within 24 hours before the illness, heavy drinking, smoking status, current smoking, cardiac disease (including myocardial infarction and current atrial fibrillation), hypertension, diabetes, hyperlipemia, migraine, BMI, and, in women, current use of oral contraceptives.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The 506 patients with complete data did not differ significantly from the rest of the patients (n=217; ie, those who were excluded because of incomplete data) by age (mean±SD, 48±10 versus 49±10), BMI (26±5 versus 26±5), platelet count on admission (242±87 versus 240±72), mean corpuscular volume (91±6 versus 90±5), or -glutamyltransferase (53±65 versus 49±87). Because the groups did not differ from each other by laboratory markers of alcohol consumption, it is unlikely that selection bias due to different drinking habits was introduced.

The frequencies of baseline characteristics and health habits of the case and control subjects by sex are shown in Table 1. The mean age of the case subjects was higher than that of the control subjects. Hypertension, diabetes, hyperlipemia, cardiac disease, myocardial infarction, and obesity were more common among the men with brain infarction than the control men, whereas the women with brain infarction differed from their controls in hypertension and more frequent use of oral contraceptives. Current heavy smoking and heavy drinking of alcohol were present more frequently among the men and women with brain infarction than among the control subjects. These two habits were also more prevalent among the men than the women.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics and Drinking and Smoking Habits by Sex in 506 Patients With Brain Infarction and 345 Control Subjects

Because heavy drinking of alcohol emerged as a prominent risk factor, we made further analyses to determine the associations between this and the other risk factors. No significant associations were found between heavy drinking and hypertension, cardiac disease, myocardial infarction, current atrial fibrillation, diabetes, and hyperlipemia. However, heavy drinking was significantly (P<.001) associated with smoking status (heavy drinkers were often heavy current smokers).

Recent light to moderate drinking (<40 g ethanol within 24 hours or <150 g ethanol within 1 week) before the illness did not seem to increase the risk for acute brain infarction, but heavier recent drinking increased the risk among both the men and the women. The amount of recently consumed alcohol that seemed to increase the risk was less among the women than the men.

Stepwise logistic regression showed that hypertension, amount of alcohol intake within 24 hours (>40 g ethanol), cardiac disease, current smoking, diabetes, and history of migraine were independent risk factors for brain infarction among men of working age. Relative risks of these risk factors after adjustment for age and all the other risk factors are shown in Table 2. Hyperlipemia and obesity were not found to be independent risk factors.

View this table: [in this window] [in a new window]   Table 2. Multivariate Relative Risks of Brain Infarction in Men

A corresponding stepwise logistic regression among women showed that current use of oral contraceptives, amount of alcohol intake within 24 hours (<40 g ethanol), and current smoking were independent risk factors (Table 3).

View this table: [in this window] [in a new window]   Table 3. Multivariate Relative Risks of Brain Infarction in Women

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The study was designed to evaluate the role of smoking status, drinking habits, use of oral contraceptives, and obesity as risk factors for brain infarction among persons of working age. We found that in both men and women, recent alcohol drinking and current smoking were independent risk factors. As expected, our data also showed that current use of oral contraceptives was an independent risk factor in women and that hypertension, cardiac disease, diabetes, and migraine were independent risk factors in men.

The increased risk of brain infarction from smoking and use of oral contraceptives is well established,⁵ but the role of alcohol drinking is contradictory. This probably results from the fact that very few studies have hitherto taken into account the great variability of drinking habits. The majority of the published epidemiological studies, for example, have categorized people dichotomously into alcohol drinkers and nondrinkers. These studies have suggested that drinkers as a group have an equal risk for brain infarction compared with nondrinkers. However, according to most of the studies, light to moderate drinkers are protected against ischemic stroke and heavy drinkers seem to run a slightly increased risk compared with nondrinkers. As suggested by Camargo,¹⁷ the effects of drinking habits should be thoroughly investigated before we conclude whether alcohol is a risk factor.

Establishing the role of all modifiable risk factors is highly important and forms the basis for a successful primary prevention strategy for ischemic stroke. We investigated recent drinking because binge drinking in particular could be a triggering factor, and we know that alcohol provokes different effects in the body depending on whether the acutely ingested dose is large or small. From the cardiovascular point of view, a large dose of alcohol could be harmful because it provokes rapid heart rate and sometimes cardiac arrhythmias during the following hangover. On the other hand, regular intake of small doses of alcohol may have a beneficial effect because alcohol may retard the development of cervicocerebral arterial atherosclerosis via several different mechanisms.^{13 14 21}

Previous investigations have shown that physical inactivity,^{3 22} which is often associated with obesity, and cigarette smoking^{2 3 23} are factors that increase the risk for ischemic stroke. On the other hand, vigorous exercise in early adulthood and lifelong continuation of exercise seem to protect against stroke in later life.⁴ Two of the above-mentioned studies also addressed recent drinking of alcohol.^{22 23} The first one²² did not observe an increased risk of stroke from recent regular alcohol drinking, possibly because the patient population had a median age of 66 years and elderly people are seldom heavy drinkers. The second study²³ detected an OR of 6.71 (95% CI, 1.68 to 26.8) for those subjects with first-ever stroke who had consumed >60 g alcohol per day during the preceding week compared with those who had not consumed alcohol, but the study did not separately address binge drinking. The investigators stated that the relative rarity of heavy consumption of alcohol means that alcohol is implicated in one in nine strokes at most. This agrees with a recent report²⁴ in which the population-attributable risk of stroke was calculated; the number of strokes (all types included) attributable to heavy alcohol consumption was one tenth of that attributable to hypertension and one third of that attributable to cigarette smoking.²⁴

Drinking habits have also shown an association with ischemic stroke mortality. A recent report showed that men who drank infrequently and those who were binge drinkers, as well as those who reported drinking for intoxication, had higher mortality than lifelong abstainers.²⁵ Previous studies have suggested that heavy drinkers will suffer brain infarction more often¹⁵ and at an earlier age²⁶ compared with other drinkers and abstainers.

Thus far, we do not know the mechanisms by which acute alcohol intake could precipitate ischemic stroke. Our observations do not automatically mean a causal relationship. However, several case reports have already addressed this question. A possible mechanism is cardiogenic embolism.^{27 28} Some case reports also suggest a direct association between alcohol abuse and traumatic carotid arterial dissection.²⁹

Mailed questionnaires cannot estimate alcohol drinking accurately. Forgetting and deliberate nonreporting are obvious.³⁰ Respondents usually report their drinking of alcohol as far lower than the reality. We tried to minimize this type of bias with as complete a collection of patients as possible and by matching the control subjects by sex, age, and acuteness of disease onset. All the subjects in this study agreed to participate, and the interviews were performed within 48 hours after admission to avoid recall bias. Alcohol consumption of the control subjects was calculated for a period preceding the first symptoms, including prodromal symptoms, of the disease to exclude the possible decreasing effect of prodromal symptoms on alcohol intake.

Alcohol consumption and cigarette smoking are more frequent in the city of Helsinki and its neighborhood than in other parts of Finland.¹⁶ This did not cause bias in the present study because the control subjects were from the same region. Recent alcohol consumption and current smoking in our hospital control subjects were similar to those in a randomly selected population control group having similar age and sex distributions.^{31 32}

The present study also showed that current use of oral contraceptives is an independent risk factor for ischemic brain infarction. Estrogen-containing oral contraceptives have been found to be associated with an increased risk in a dose-dependent way.^{33 34} Women using oral contraceptives seem to have a lower sensitivity to activated protein C, which could increase the risk for thrombosis.³⁵ Those women who are current users of oral contraceptives and have migraine have been shown to be prone to thrombotic stroke.³⁶ Smokers have been shown to have significant oral contraceptive–related procoagulant alterations in prothrombin time and fibrinogen antigen.³⁷ Finally, it has been suggested that smoking and use of oral contraceptives could predispose certain women to immunologic vasculopathy.³⁸

In conclusion, heavy drinking of alcohol, cigarette smoking, and use of oral contraceptives seem to be independent risk factors for ischemic stroke. It remains to be determined whether the number of ischemic strokes, particularly among persons of working age, can be decreased by targeting these common lifestyle factors.

	Acknowledgments

 
This study was supported by grants from the Oulu Medical Foundation, the Maire Taponen Foundation, and the Neurology Foundation (Dr Haapaniemi).

	Footnotes

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

Received July 2, 1996; revision received October 8, 1996; accepted October 9, 1996.

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