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Stroke. 1995;26:767-773

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(Stroke. 1995;26:767-773.)
© 1995 American Heart Association, Inc.

Articles

Alcohol Intake and the Risk of Cardiovascular Disease in Middle-Aged Japanese Men

Hiroyasu Iso, MD; Akihiko Kitamura, MD; Takashi Shimamoto, MD; Tomoko Sankai, MD; Yoshihiko Naito, MD; Shinichi Sato, MD; Masahiko Kiyama, MD; Minoru Iida, MD Yoshio Komachi, MD

From the Institute of Community Medicine, University of Tsukuba, Tsukuba (H.I., T. Shimamoto, T. Sankai); the Department of Epidemiology and Mass Examination, The Center for Adult Diseases, Osaka (A.K., Y.N., S.S., M.K., M.I.); and the Osaka Prefectural Institute of Public Health, Osaka (Y.K.); Japan.


*    Abstract
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 *Abstract
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 down arrowSubjects and Methods
 down arrowResults
 down arrowDiscussion
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Background and Purpose Understanding the effects of alcohol intake on stroke and other cardiovascular diseases is an important issue for public health.

Methods A 10.5-year prospective study of the relationship between alcohol intake and cardiovascular disease incidence was conducted in 2890 men, aged 40 to 69 years and free of a history of stroke and coronary heart disease, in three rural communities of Japan.

Results One hundred seventy-eight strokes (40 intracerebral hemorrhages, 18 subarachnoid hemorrhages, 104 nonhemorrhagic strokes, and 16 unclassified strokes), 34 coronary heart disease events, and 19 sudden unclassified deaths occurred. Drinkers of >=70 g/d ethanol had an approximately 2.5 times higher age-adjusted risk of all stroke than never-drinkers; the excess risk was more evident for hemorrhagic stroke than nonhemorrhagic stroke. When hypertension category, serum total cholesterol level, cigarette smoking, and diabetes mellitus were taken into account, these excess risks were reduced but remained significant for all stroke (2.0; 95% confidence interval, 1.3 to 3.1) and hemorrhagic stroke (3.4; 95% confidence interval, 1.2 to 9.2). A J-shaped relationship was suggested between alcohol intake and risk of nonhemorrhagic stroke; drinkers of <42 g/d ethanol had a slightly lower risk and heavy drinkers had a higher risk than never-drinkers. Current drinkers had a slightly lower risk of coronary heart disease than never-drinkers, although the risk difference was not statistically significant. The age-adjusted risk of sudden death was 10 times higher in heavy drinkers than never-drinkers, and the excess risk did not change when the covariates were controlled for. Total cardiovascular disease showed a similar pattern as did all stroke.

Conclusions Heavy drinking appeared to increase the risk of hemorrhagic stroke, in part due to hypertension, and to increase the risk of sudden death, which was probably due to drinking per se. Light or moderate alcohol consumption seemed to protect against nonhemorrhagic stroke and coronary heart disease.


Key Words: alcohol drinking • coronary heart disease • Japan • risk factors


*    Introduction
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 up arrowAbstract
 *Introduction
down arrowSubjects and Methods
 down arrowResults
 down arrowDiscussion
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Habitual drinking, either in social settings or at home, is common among Japanese middle-aged men.1 A 1980 national survey in Japan indicated that 47% of men aged 30 years and over were current daily drinkers, but only 4% of women were.2 The habit of frequent drinking in Japanese middle-aged men has drawn attention because evidence suggests that alcohol is an important risk factor for cardiovascular disease.3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Investigators consistently report that heavy drinking increases the risk of coronary heart disease3 4 5 and total mortality.4 5 6 7 However, evidence of an association between heavy drinking and stroke is sparse and less consistent. Several retrospective case-control studies showed an increased risk of stroke in relation to alcohol intoxication and heavy drinking.8 9 10 A follow-up study of Japanese male physicians6 showed a 70% increase in stroke deaths in heavy drinkers. However, a large prospective case-control study from the Kaiser Permanente Program showed no association for either stroke death or incidence.3 4

Data on the effect of moderate alcohol intake on cardiovascular disease has been available mostly from studies of whites and Japanese Americans. Moderate alcohol intake has been found to reduce the risk of coronary heart disease11 12 and to increase the risk of hemorrhagic stroke.13 14 Several prospective studies also have reported a lower risk of total stroke and nonhemorrhagic stroke associated with moderate alcohol consumption.14 15 16 17 18 Previous reports of Japanese cohorts19 20 21 22 23 were based on limited stratification of two or three drinking categories and did not explore carefully an effect of moderate alcohol intake on cardiovascular disease incidence.

Understanding the relation of alcohol intake to stroke and other cardiovascular diseases is important for the formulation of public health recommendations; Japan has both a high rate of heavy drinking in men and a very high stroke mortality rate.24 We used the data from a 10.5-year follow-up study of men in three rural Japanese populations with a wide range of alcohol intake to examine the relation of alcohol to the incidence of cardiovascular disease. The relation of alcohol intake to stroke type, determined primarily by computed tomography (CT), was examined because of suggestions that the alcohol-stroke relation may vary by stroke type.13 14 17 23


*    Subjects and Methods
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 up arrowAbstract
 up arrowIntroduction
 *Subjects and Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
The population surveyed included 2985 men aged 40 to 69 years who were examined between 1975 and 1979 in two northeast rural Japanese communities, Ikawa and Honjo, and between 1981 and 1985 in a central rural community, Kyowa. The overall participation rate was 65%. Persons with a history of stroke (n=75) or coronary heart disease (n=20) were excluded, and the data of 2890 men were used for the analyses (n=842 in Ikawa, 518 in Honjo, and 1530 in Kyowa). We did not examine the relation of alcohol intake to cardiovascular disease in women because only 6% of the 3908 female participants aged 40 to 69 years were current drinkers.

Subjects were followed up to determine cardiovascular disease end points occurring by the end of 1987 in Honjo and by the end of 1992 in other communities. Only 61 (2%) persons moved out of the communities during the follow-up, and 322 (11%) persons died. They were censored at the date of moving out or the date of death. The average follow-up for the participants was 10.5 years. Cardiovascular disease end points were ascertained through six sources25 : (1) national insurance claims, (2) reports by local physicians, (3) ambulance records, (4) death certificates, (5) reports by public health nurses and health volunteers, and (6) cardiovascular risk surveys. From death certificates, case subjects with underlying cause of death (International Classification of Diseases, 9th Revision: stroke, codes 430-438; coronary heart disease, codes 410-414, 428 and 429) were selected.

To validate the diagnosis, all living patients were visited or invited to complete risk-factor surveys. Study physicians obtained a medical history and a standard electrocardiogram (ECG) for coronary heart disease patients and a history and neurological examination from stroke patients. For deaths, histories were obtained from the families, and medical records were reviewed.

Stroke was defined as a focal neurological disorder with rapid onset that persists 24 hours or more. Thus, transient ischemic attack was not included. Determination of type of stroke (ie, intracerebral hemorrhage, subarachnoid hemorrhage, and nonhemorrhagic stroke) was done primarily by CT in a standardized way.26 Stroke cases that were diagnosed clinically but showed no lesion on CT were regarded as unclassified stroke. CT films were available for 72% of the stroke cases. Stroke cases without CT films were classified according to the clinical criteria27 based on Millikan's criteria.28

The criteria for coronary heart disease were modified from those of a World Health Organization expert committee.29 Painless types of coronary heart disease were not investigated because of difficulty with complete ascertainment. "Definite" myocardial infarction was indicated by typical chest pain (lasting for 30 minutes or longer) with the appearance of abnormal and persistent Q or QS waves, by changes in cardiac enzyme activity, or both. "Suspect" myocardial infarction was indicated by typical chest pain without positive ECG and enzyme activity findings. Angina pectoris was defined as repeated episodes of chest pain during effort, especially when walking, usually disappearing rapidly after the cessation of effort or by use of sublinguinal nitroglycerin. Definite or suspect myocardial infarction and angina pectoris were combined and presented as coronary heart disease. Unclassified sudden death was defined as death within 24 hours from the abrupt onset of symptoms that was unassociated with a previous diagnosis of coronary heart disease, stroke, or other identified causes of death. Using these standardized criteria, final diagnoses were made by a panel of three or four study physician-epidemiologists who were blinded to the data of the baseline examination.

Cardiovascular disease risk factors were measured at the baseline examinations when the men were first examined. An interviewer assessed usual weekly intake of alcohol in units of go (a Japanese traditional unit of volume corresponding to 28 g), which were converted to grams of ethanol per day. One go is 180 mL of sake, and it corresponds to one bottle (663 mL) of beer, two single shots (75 mL) of whisky, or two glasses (180 mL) of wine. Men who reported consuming 0.3 go or more per week were regarded as drinkers. Subjects were classified as never-drinkers, ex-drinkers, or current drinkers who averaged 1 to 20 g/d, 21 to 41 g/d, 42 to 69 g/d, or >=70 g/d of ethanol. Ex-drinkers were defined as abstainers for the past 3 months and over. Distribution of ethanol intake in the surveyed populations (Table 1Down) was somewhat higher than that in the 1990 national representative sample.30 Drinking status after 5 years in average from the baseline was examined for 65% of the participants. The proportions of men who remained in the same category of drinking status were 90% for never-drinkers, 63% for ex-drinkers, 39% for drinkers of 1 to 20 g/d ethanol, 36% for drinkers of 21 to 41 g/d ethanol, 58% for 42 to 69 g/d ethanol, and 60% for >=70 g/d ethanol. If drinkers of 1 to 20 g/d and of 21 to 41 g/d ethanol were combined, the respective proportion was 58%.


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  		Table 1. Age-Adjusted Incidence Rates of Cardiovascular Disease by Drinking Status in Men Aged 40-69 Years

We measured several potential confounders: serum total cholesterol level, blood pressure, body mass index, cigarette smoking, history of diabetes mellitus, hypertensive ophthalmoscopic changes, and ECG evidence of left ventricular hypertrophy. Serum total cholesterol level was measured by the Liebermann-Burchard direct method using the Autoanalyzer II (Technicon).31 The laboratory had been standardized by the Lipid Standardization Program, Centers for Disease Control and Prevention, Atlanta, Ga, and successfully met the criteria of precision and accuracy of cholesterol measurements.32 Blood pressures were measured by trained observers using standard mercury sphygmomanometers on the right arm of seated participants who had rested for 5 minutes.33 Hypertension was defined as systolic blood pressure of >=160 mm Hg, diastolic blood pressure of >=95 mm Hg, and/or current treatment with antihypertensive medication, while normotension was defined as systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg and no antihypertensive medication. Subjects with blood pressures between these categories were classified as having borderline hypertension. Height in stocking feet and weight in light clothing were measured. Body mass index was calculated as weight (kilograms) divided by the square of height (meters squared). An interview was conducted to ascertain the number of cigarettes smoked per day and use of medications for diabetes mellitus. Diabetes mellitus was defined as a fasting glucose level of 7.8 mmol/L or more, a nonfasting glucose level of 11.1 mmol/L or more, and/or use of medication for diabetes.

A color photograph of the right ocular fundus was taken and coded according to Scheie's classification.34 Hypertensive or arteriosclerotic changes of grades 2 or higher were regarded as a significant hypertensive change in the retinal arterioles. Reliable photographs for the grading were obtained for 90% of the participants. A resting ECG was obtained with the subject in the supine position and coded according to the Minnesota Codes, second version.29 We regarded Minnesota Codes 3-1 plus (4-1 to 4-3 or 5-1 to 5-3) as left ventricular hypertrophy.

Incidence rates per 1000 person-years were calculated according to the six categories of drinking status. Rates were adjusted for age by the direct method of standardization to the age distribution of the total cohort of 2890 men.

For statistical analyses, differences in age-adjusted mean values and the prevalence of potential confounding factors among six categories of drinking status were tested by ANCOVA and {chi}2 test, respectively. When the overall difference was significant (P<.05), comparison of confounding factors between never-drinkers and the other drinking categories was made using a t test or {chi}2 test. The relative risks and 95% confidence intervals (CI) relative to never-drinkers were calculated adjusting for age and other potential confounding factors using the Cox proportional hazards model. Potential confounding factors were the hypertension category (normotension, borderline hypertension, and hypertension), serum total cholesterol level (millimoles per liter), body mass index (kilograms divided by meters squared), cigarette smoking (number per day), a history of diabetes mellitus (yes versus no), hypertensive ophthalmoscopic changes (yes versus no), and left ventricular hypertrophy (yes versus no). Because the relationship between alcohol intake and cardiovascular disease was similar among the three populations sampled, we presented the results for the combined cohort.


*    Results
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 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
 *Results
down arrowDiscussion
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Mean±SD values of selected cardiovascular risk characteristics were 140±21 mm Hg for systolic and 83±12 mm Hg for diastolic blood pressures and 4.58±0.92 mmol/L for serum total cholesterol. During the 10.5-year follow-up, there were 178 strokes, 34 coronary heart disease events, and 19 unidentified sudden deaths. The total number of cardiovascular disease events was 225 because six case subjects suffered from both stroke and coronary heart disease. Among strokes, there were 40 intracerebral hemorrhages, 18 subarachnoid hemorrhages, 104 nonhemorrhagic strokes, and 16 unclassified strokes.

The age-adjusted incidence rate of stroke (per 1000 person-years) was 5.9 in the total population, which varied among the three populations (10.3 in Honjo, 5.9 in Ikawa, and 4.0 in Kyowa; difference, P<.001). The population difference in stroke incidence corresponded with a difference in the proportion of hypertensive subjects (43%, 38%, and 28%, respectively; P<.001).

Compared with that in never-drinkers, the age-adjusted incidence rate of all stroke was approximately 1.5 times higher in ex-drinkers and drinkers of 42 to 69 g/d ethanol and 2.5 times higher in drinkers of >=70 g/d (Table 1Up). The rate of stroke in the lighter drinkers did not differ so much from the rate in never-drinkers. For intracerebral hemorrhage, the three categories of drinkers of 1 to 69 g/d showed about two to three times higher risk, and drinkers of >=70 g/d showed seven times higher risk than never-drinkers. Although there was a small number of cases, an excess risk of subarachnoid hemorrhage was shown in drinkers of >=70 g/d. For nonhemorrhagic stroke, the rate was two times higher in drinkers of >=70 g/d and 30% lower in drinkers of 1 to 20 g/d than never-drinkers. Unclassified stroke, although a small number of cases, showed a similar pattern as nonhemorrhagic stroke. The rate of coronary heart disease was lower in current drinkers than never-drinkers, but a dose-response relation among current drinkers was not evident. The rate of sudden death was over 10 times higher in drinkers of >=70 g/d than in never-drinkers.

To examine confounders for alcohol-disease associations, mean age and age-adjusted values of selected risk factors at baseline were compared among drinking-status categories (Table 2Down). Compared with that in never-drinkers, mean age was 3 years older in ex-drinkers and 3 to 4 years younger in drinkers of >=42 g/d ethanol. Current drinkers showed higher systolic and diastolic blood pressure levels than never-drinkers, and there was a dose-response relationship between alcohol intake and blood pressure levels. The percentage of men on antihypertensive medication was 19% in ex-drinkers, 16% to 23% in current drinkers, and 10% in never-drinkers. The prevalence of hypertension was high in drinkers of >=70 g/d, intermediate in drinkers of <70 g/d, and ex-drinkers, and it was lowest in never-drinkers. Current drinkers had mean serum total cholesterol concentrations about 0.25 mmol/L (10 mg/dL) lower than those of never-drinkers. The prevalence of diabetes mellitus, although low across the drinking-status categories, was two or three times higher in current and ex-drinkers than in never-drinkers. Mean number of cigarettes was higher in drinkers of >=42 g/d than in never-drinkers. The prevalence of hypertensive ophthalmoscopic changes was two or three times higher in drinkers of >=21 g/d ethanol than in never-drinkers. Drinking status was not related to body mass index or left ventricular hypertrophy.


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  		Table 2. Age-Adjusted Mean Values or Prevalence (%) of Risk Factors at Baseline by Drinking Status in Men Aged 40-69 Years

Table 3Down presents the relative risk of cardiovascular disease relative to never-drinkers. The age-adjusted relative risk of all stroke was 2.7 for drinkers of >=70 g/d ethanol, and the relative risks for other categories of alcohol intake were not statistically significant. Adjusting for age, hypertensive status, serum total cholesterol level, and cigarette smoking, the relative risk for heavy drinkers was reduced to 1.9 but remained statistically significant. The age-adjusted relative risk of hemorrhagic stroke for heavy drinkers was 6.2, which was reduced to 3.4 with adjustment for covariates. The reduction of the adjusted relative risks was due mostly to the effect of hypertension. When only age and hypertension category were controlled for, the adjusted relative risk for heavy drinkers was 2.0 (95% CI, 1.2 to 3.2) for all stroke and 3.6 (95% CI, 1.3 to 9.8) for hemorrhagic stroke.


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  		Table 3. Relative Risk and 95% Confidence Interval of Cardiovascular Disease Incidence Relative to Never-Drinkers in Men Aged 40-69 Years

The age-adjusted relative risk of nonhemorrhagic stroke in heavy drinkers was 2.1, and the multivariate-adjusted relative risk was 1.7, which did not reach statistical significance (P=.12). The relative risk in ex-drinkers and drinkers of <42 g/d was <1.0, although it was not statistically significant. Thus, a J-shaped relation was suggested between alcohol intake and nonhemorrhagic stroke. Current drinkers had a relative risk of <1.0 for coronary heart disease, although it was not statistically significant. The age-adjusted risk of sudden death was 10 in heavy drinkers and remained largely unchanged after we controlled for the covariates. The relative risk of total cardiovascular disease was similar to that of all stroke.


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
 up arrowResults
 *Discussion
down arrowReferences
 
In our cohort of Japanese men, heavy drinking of >=70 g/d ethanol was associated with an elevated risk of all stroke incidence, in particular hemorrhagic stroke. Our results support previous findings of case-control studies in white men.8 9 10 The excess risk of stroke was much reduced when the hypertension category was taken into account, suggesting that hypertension was a strong mediator of a causal association between alcohol intake and stroke.35 A causal link between alcohol and hypertension is acceptable on the basis of many experimental, clinical, and epidemiological studies.36 In the present study, blood pressure levels and hypertension-related variables were strongly associated with alcohol intake. Ex-drinkers were more likely to be hypertensive than were light drinkers, as reflected by their higher usage of antihypertensive medication. We assume that treatment of hypertension triggered cessation of alcohol drinking, probably due to advice from physicians and other health professionals.

The present study also showed a 10-times higher risk of unclassified sudden death in heavy drinkers compared with never-drinkers. The excess risk did not change so much with adjustment for the covariates, which suggests that the excess risk was probably due to drinking per se or other unknown drinking-related factors. We assume that a considerable proportion of unclassified sudden deaths was due to heart disease. Underlying causes of death for the 19 cases of unclassified sudden death were coronary heart disease (n=6), heart failure or other heart disease (n=8), other acute cerebrovascular disease (n=3), and other causes (n=2). One of the plausible mechanisms for the excess risk of sudden death is cardiac arrhythmia occurring in the early stage of cardiomyopathy due to chronic heavy drinking.37 38 Another possible mechanism is ventricular arrhythmia due to subarachnoid hemorrhage, for which heavy drinkers had a higher risk.39

The results of the present study suggest an elevated risk of hemorrhagic stroke and a reduced risk of nonhemorrhagic stroke in men with light or moderate alcohol consumption. These alcohol-stroke relations are consistent with models of a linear relation with hemorrhagic stroke and a J-shaped relation with nonhemorrhagic stroke, reported by Camargo35 based on a systematic literature review. A linear relationship between alcohol intake and hemorrhagic stroke was reported from two prospective studies: one for men, the Honolulu Heart Study,13 and the other for women, the Nurses' Health Study.14 Both studies indicated that the linear relation was due mostly to the relation of alcohol to subarachnoid hemorrhage. For intracerebral hemorrhage, the slope of the positive association was smaller and not statistically significant.13 Mechanisms for the alcohol–hemorrhagic stroke relation are not fully understood except for an effect mediated by high blood pressure. It is possible that alcohol induces changes in hemostatic factors that increase the risk of hemorrhage in intracerebral arterioles. An experimental study of healthy volunteers demonstrated that ingestion of a moderate amount of alcohol prolonged bleeding time and reduced platelet aggregability.40 Alcohol also enhances fibrinolytic activity through increased secretion of plasminogen activator from endothelial cells.41

A J- or U-shaped association of alcohol intake with all stroke or nonhemorrhagic stroke has been found predominantly in white populations. A recent report of 32 years of follow-up in the Framingham Heart Study17 showed that, among men, moderate drinkers (<24 g/d ethanol) had a significantly lower incidence rate of stroke than heavy (>=24 g/d) or nondrinkers. A study of women showed a similar U-shaped relation, although it was not statistically significant.17 Prospective studies of men in Yugoslavia15 and in Albany16 both showed a significant U-shaped relation between alcohol consumption and all stroke deaths. The Nurses' Health Study,14 a prospective study of 87 526 American female nurses showed a U-shaped relation between alcohol intake and all stroke incidence, which was composed of a positive association with subarachnoid hemorrhage and an inverse association with nonhemorrhagic stroke. However, the Honolulu Heart Study,13 a prospective study of 7878 American Japanese men, showed a linear positive relation between alcohol intake and all stroke incidence because of a linear positive association with hemorrhagic stroke and a flat association with nonhemorrhagic stroke. A recent report of the Hisayama study,23 a prospective study of 1621 Japanese men and women, reported a nonsignificant linear positive relation of alcohol intake and hemorrhagic stroke and a nonsignificant J-shaped relation of alcohol intake and nonhemorrhagic stroke. In the Hisayama study, the categorization of alcohol intake was nondrinkers, drinkers of 1 to 34 g/d ethanol, and drinkers of >=34 g/d, and they did not differentiate between never-drinkers and ex-drinkers. The present study examined the effect of a wide range of alcohol drinking and found a J-shaped relation in Japanese men.

Potential mechanisms by which light or moderate alcohol intake could reduce the incidence of nonhemorrhagic stroke were addressed previously42 ; the mechanisms are similar for the case of coronary heart disease. Moderate alcohol consumption increases prostacyclin in vascular walls, a potential vasodilator and inhibitor of platelet aggregation, which prevents thrombus formation in cerebral and carotid arteries.43 Enhanced fibrinolysis via increased secretion of plasminogen activator from endothelial cells41 may be another potential mechanism. Elevated high-density lipoprotein cholesterol levels may protect against atheroma formation in cerebral and carotid arteries.44 Change in hemostatic variables such as reduced plasma fibrinogen45 may be another contributing factor. The increased risk of nonhemorrhagic stroke in heavy drinkers is explained by hypertension-induced atherosclerosis or arteriosclerosis,46 reduced cerebrovascular blood flow by spasm of cerebral arteries and arterioles,47 or by alteration of cerebral metabolism.48

There have been a number of prospective studies indicating that moderate alcohol consumption reduces the risk of coronary heart disease.12 The results of the present study do not conflict with previous reports, but the inverse relation was weak and not statistically significant, being based on a small number of cases. The low incidence of coronary heart disease was not surprising because serum total cholesterol level was much lower in the surveyed populations than in white populations.49 In our 6-year prospective investigation of 11 987 urban male employees aged 40 to 59 years, in whom the mean serum cholesterol level was higher at 5.04 mmol/L (195 mg/dL) and there were 83 subsequent coronary heart disease events, we observed a significant inverse association with alcohol intake.50 Mechanisms of the reduced risk of coronary heart disease may be similar to those of nonhemorrhagic stroke.41 43 44

Although a strength of the present study was the availability of CT examinations for stroke typing, a potential drawback was that 28% of stroke case subjects did not have CT examination data, necessitating the use of clinical criteria. We found no difference in the proportion of men with missing CT data between hemorrhagic and nonhemorrhagic stroke cases: 29% for hemorrhagic and 32% for nonhemorrhagic stroke. The validity of stroke diagnosis by the clinical criteria was tested by autopsy findings in our previous study51 : 90% of the cases diagnosed as hemorrhagic stroke and 75% of the cases diagnosed as nonhemorrhagic stroke were correctly diagnosed according to autopsy findings. Among the stroke cases with CT in the present study, all 25 cases diagnosed as hemorrhagic stroke by the clinical criteria were found to be hemorrhagic stroke by CT. On the other hand, 11 of the 88 cases (13%) diagnosed as nonhemorrhagic stroke by the clinical criteria were found to be hemorrhagic stroke by CT. All of the misdiagnosed cases showed a small hematoma without perforation to a ventricular system. The results suggest that clinical discrimination between hemorrhagic and nonhemorrhagic stroke was done well.

The relation between alcohol intake and total cardiovascular disease was similar to the relation for all stroke; stroke cases comprised 79% of the cardiovascular disease in the surveyed populations. Age-adjusted incidence rates were significantly higher in drinkers of >=42 g/d ethanol than in never-drinkers, whereas no excess risk was found in drinkers of <41 g/d. Therefore, according to results of this study in Japanese men, three drinks per day or fewer is recommended for current drinkers to prevent cardiovascular disease, which is similar to the recommendations for western populations.3 4 12 18 35


*    Acknowledgments
 
The authors thank Professor Aaron R. Folsom, University of Minnesota, for valuable advice on the manuscript.


*    Footnotes
 
Reprint requests to Hiroyasu Iso, MD, Institute of Community Medicine, University of Tsukuba 1-1-1, Tsukuba-shi, Ibaraki-ken, 305 Japan.

Received January 10, 1995; revision received February 14, 1995; accepted February 14, 1995.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
 up arrowResults
 up arrowDiscussion
 *References
 

  1. Nukada A. Backgrounds on rapid increase in alcohol consumption after World War II, and primary prevention of alcohol-related health problems [in Japanese]. Public Health. 1983;47:770-777.
  2. Ministry of Health and Welfare. National Survey of Circulatory Disorders 1980 [in Japanese, English summary]. Tokyo, Japan: Japan Heart Foundation; 1982:130-131
  3. Klatsky AL, Friedman GD, Siegelaub AB. Alcohol use and cardiovascular disease: the Kaiser-Permanente experience. Circulation. 1981;64(suppl III):32-40.
  4. Klatsky AL, Friedman GD, Siegelaub AB. Alcohol and mortality: a ten-year Kaiser-Permanente experience. Ann Intern Med. 1981;95:139-145.
  5. Dyer AR, Stamler J, Paul O, Lepper M, Shekelle RB, McKean H, Garside D. Alcohol consumption and 17-year mortality in the Chicago Western Electric Company Study. Prev Med. 1980;9:78-90. [Medline] [Order article via Infotrieve]
  6. Kono S, Ikeda M, Tokudome S, Nishizumi M, Kuratsune M. Alcohol and mortality: a cohort study of male Japanese physicians. Int J Epidemiol. 1986;15:527-532. [Abstract/Free Full Text]
  7. Marmot MG, Rose G, Shipley MJ, Thomas BJ. Alcohol and mortality: a U-shaped curve. Lancet. 1981;1:580-583. [Medline] [Order article via Infotrieve]
  8. Hillbom M, Kaste M. Does ethanol intoxication promote brain infarction in young adults? Lancet. 1978;2:1181-1183. [Medline] [Order article via Infotrieve]
  9. Hillbom M, Kaste M. Does alcohol intoxication precipitate aneurysmal subarachnoid hemorrhage? J Neurol Neurosurg Psychiatry. 1981;44:523-526. [Abstract]
  10. Gill JS, Zezulka AV, Shipley MJ, Gill SK, Beevers DG. Stroke and alcohol consumption. N Engl J Med. 1986;315:1041-1046. [Abstract]
  11. Yano K, Rhoads GG, Kagan A. Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii. N Engl J Med. 1977;297:405-409. [Abstract]
  12. Moore RD, Pearson TA. Moderate alcohol consumption and coronary artery disease: a review. Medicine. 1986;65:242-267. [Medline] [Order article via Infotrieve]
  13. Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic stroke: the Honolulu Heart Program. JAMA. 1986;255:2311-2314. [Abstract]
  14. Stampfer MJ, Golditz GA, Willett WC, Speizer FE, Henneken 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]
  15. Kozarevic DJ, Vojivodic N, Gordon T, Kaelber CT, McGee D, Zukel WJ. Drinking habits and death: the Yugoslavia Cardiovascular Disease Study. Int J Epidemiol. 1983;12:145-150. [Abstract/Free Full Text]
  16. Gordon T, Doyle JT. Drinking and mortality: the Albany Study. Am J Epidemiol. 1987;125:263-270. [Abstract/Free Full Text]
  17. Wolf PA, D'Agostino RB, Odell P, Belanger AJ, Hodges D, Kannel WB. Alcohol consumption as a risk factor for stroke: the Framingham Study. Ann Neurol. 1988;24:177. Abstract.
  18. Klatsky AL, Armstrong MA, Friedman GD. Alcohol use and subsequent cerebrovascular disease hospitalization. Stroke. 1989;20:741-746. [Abstract/Free Full Text]
  19. Tanaka H, Yutaka U, Hayashi M, Date C, Baba T, Yamashita H, Shoji H, Tanaka Y, Owada K, Detels R. Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke. 1982;13:62-73. [Abstract/Free Full Text]
  20. Tanaka H, Hayashi M, Data C, Imai K, Asada M, Shoji H, Okazaki K, Yamamoto H, Yoshikawa K, Shimada T, Lee SI. Epidemiologic studies of stroke in Shibata, a Japanese provincial city: preliminary report on risk factors for cerebral infarction. Stroke. 1985;16:773-780. [Abstract/Free Full Text]
  21. Kiyohara Y, Ueda K, Hasuo Y, Fujii I, Yanai T, Wada J, Kawano H, Shikata T, Omae T, Fujishima M. Hematocrit as a risk factor of cerebral infarction: long-term prospective population survey in a Japanese rural community. Stroke. 1986:17:687-692.
  22. Ueda K, Hasuo Y, Kiyohara Y, Wada J, Kawano H, Kato I, Fujii I, Yanai T, Omae T, Fujishima M. Intracerebral hemorrhage in a Japanese community, Hisayama: incidence, changing pattern during long-term follow-up, and related factors. Stroke. 1988:19:48-52.
  23. Omae T, Ueda K. Risk-factors of cerebral stroke in Japan: prospective epidemiological study in Hisayama community. In: Katsuki S, Ysubaki T, Toyokura, eds. Proceedings of the 12th World Congress of Neurology, Kyoto, Japan. Amsterdam, Netherlands: Excepta Medica; 1982:119-135.
  24. Pisa Z, Uemura K. Trends of mortality from ischaemic heart disease and other cardiovascular diseases in 27 countries, 1968-1977. World Health Stat Q. 1982;35:11-47. [Medline] [Order article via Infotrieve]
  25. Shimamoto T, Komachi Y, Inada H, Doi M, Iso H, Sato S, Kitamura A, Iida M, Konishi M, Nakanishi N, Terao A, Naito Y, Kojima S. Trends for coronary heart disease and stroke and their risk factors in Japan. Circulation. 1989;79:503-515. [Abstract/Free Full Text]
  26. Sankai T, Miagaki T, Iso H, Shimamoto T, Iida M, Tanigaki M, Naito Y, Sato S, Kiyama M, Kitamura A, Konishi M, Terao A, Doi M, Komachi Y. A population-based study of the proportion by type of stroke determined by computed tomography scan [in Japanese]. Jpn J Public Health. 1991;38:901-909.
  27. The Ministry of Education Study Group, Okinaka S, Chairman. Characteristics of Stroke in Japan and Standardized Criteria for Stroke Diagnosis[in Japanese]. Tokyo, Japan: The Ministry of Education; 1963.
  28. Millikan CH. A report by an ad hoc committee established by the Advisory Council for the National Institute of Neurological Disease and Blindness, Public Health Service: a classification and outline of cerebrovascular diseases. Neurology. 1958;8:393-433.
  29. Rose GA, Blackburn H. Cardiovascular Survey Methods. Geneva, Switzerland: World Health Organization; 1968.
  30. Ministry of Health and Welfare. National Survey of Circulatory Disorders, 1990 [in Japanese, English summary]. Osaka, Japan: Cardiovascular Disease Research Foundation; 1992:166.
  31. Manual of Laboratory Operations, Lipid Research Clinics Program: Lipid and Lipoprotein Analysis.Bethesda, MD, US Department of Health and Welfare Publication 1974;1:75-628.
  32. Nakamura M, Morita M, Yabuuchi E, Yukami M, Kuruma S, Kuritani C, Kanatsu Y, Nishiwaki E, Ueshima H, Iida M, Komachi Y. The evaluation and the results of cooperative cholesterol and triglyceride standardization program by WHO-CDC [in Japanese]. Rinsho Byori. 1982;30:325-332. [Medline] [Order article via Infotrieve]
  33. Kirkendall WM, Feinlieb M, Freis ED, Mark AL. Recommendations for human blood pressure determination by sphygmomanometers: subcommittee of the AHA Postgraduate Education Committee. Circulation. 1980;62:1146A-1155A.
  34. Scheie HG. Evaluation of ophthalmoscopic changes of hypertension and arteriosclerosis. Arch Ophthalmol. 1953;49:117-138.
  35. Camargo CA Jr. Moderate alcohol consumption and stroke. The epidemiologic evidence. Stroke. 1989;20:1611-1626. [Abstract/Free Full Text]
  36. Stokes GS. Hypertension and alcohol: is there a link? J Chronic Dis. 1982;35:759-762. [Medline] [Order article via Infotrieve]
  37. Ettinger PO, Wu CF, De La Cruz C, Weisse AB, Ahmed SS, Regan TJ. Arrhythmias and the "holiday heart": alcohol-associated cardiac rhythm disorders. Am Heart J. 1978;95:555-562. [Medline] [Order article via Infotrieve]
  38. Kramer K, Kuller L, Fisher R. The increasing mortality attributed to cirrhosis and fatty liver in Baltimore (1957-1966). Ann Intern Med. 1968;69:273-282.
  39. Estanol BV, Marin OSM. Cardiac arrhythmias and sudden death in subarachnoid hemorrhage. Stroke. 1975;6:382-386. [Abstract/Free Full Text]
  40. Elmer O, Goransson G, Zoucas E. Impairment of primary hemostasis and platelet function after alcohol ingestion in man. Hemostasis. 1984;14:223-228.
  41. Laug WE. Ethyl alcohol enhances plasminogen activator secretion by endothelial cells. JAMA. 1983;250:772-776. [Abstract]
  42. Gorelick PB. The status of alcohol as a risk factor for stroke. Stroke. 1989;20:1607-1610. [Free Full Text]
  43. Moncada S, Randomski NW. The problems and the promise of prostaglandin influences in atherogenesis. Ann N Y Acad Sci. 1985;454:121-130. [Medline] [Order article via Infotrieve]
  44. Castelli WP, Gordon T, Hjortland MC, Kagan A, Doyle JT, Hames CG, Hulley SB, Zukel WJ. Alcohol and blood lipids: the Cooperative Lipoprotein Phenotyping Study. Lancet. 1977;2:153-155. [Medline] [Order article via Infotrieve]
  45. Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet. 1987;2:986-988. [Medline] [Order article via Infotrieve]
  46. Russell RW. How does blood pressure cause stroke? Lancet. 1975;2:1283-1285. [Medline] [Order article via Infotrieve]
  47. Altura BM, Altura BT, Gebrewold A. Alcohol-induced spasms of cerebral blood vessels: relation to cerebrovascular accidents and sudden death. Science. 1983;220:331-333. [Abstract/Free Full Text]
  48. Rogers RL, Meyer JS, Shaw TG, Mortel KF. Reductions in regional cerebral blood flow associated with chronic consumption of alcohol. J Am Geriatr Soc. 1983;31:540-543. [Medline] [Order article via Infotrieve]
  49. Johnson CL, Rifkind BM, Sempos CT, Carroll MD, Bachorik PS, Briefel RR, Gordon DJ, Burt VL, Brown CD, Lippel K, Cleeman JI. Declining serum total cholesterol levels among US adults: the National Health and Nutrition Examination Surveys. JAMA. 1993;269:3002-3023. [Abstract]
  50. Komachi Y, Shimamoto T, Iso H, Iida M, Kitamura A, Konishi M, Iimura K, Tanaka H, Iida K, Doi M, Ozawa H. Alcohol and Health (2) Mortality and morbidity of cardiovascular disease [in Japanese]. Jpn J Public Health. 1992;39(suppl):435. Abstract.
  51. Ueshima H, Iida M, Shimamoto T, Konishi M, Tsujioka K, Tanigaki M, Nakanishi N, Ozawa H, Kojima S, Komachi Y. Multivariate analysis of risk factors for stroke: eight-year follow-up study of farming villages in Akita, Japan. Prev Med. 1980;9:722-740.[Medline] [Order article via Infotrieve]



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