Background and Purpose The relationship between the pattern of alcohol intake and the risk of stroke is unclear, in particular the increased risk observed in abstainers and the possible protective effect of light to moderate drinking. For that reason, we examined in a large prospective study the role of alcohol consumption in the risk of a first major cerebrovascular event (stroke).
Methods We prospectively studied 7735 middle-aged men drawn from general practices in 24 British towns. With exclusion of those who had recall of physician diagnosis of ischemic heart disease or stroke, data were available for 7273 men all followed for 13.5 years, with 216 major stroke events (fatal and nonfatal).
Results Compared with occasional drinkers, nondrinkers (lifelong abstainers plus ex-drinkers) had an increased risk of stroke even after adjustment for age, lifestyle factors, and preexisting cardiovascular disease (relative risk [RR]=1.6; 95% CI, 1.0 to 2.7). All regular weekend drinkers (1 to 2, 3 to 6, and >6 drinks/d) and daily 1 to 2 and 3 to 6 drinkers showed no significant difference in adjusted risk of stroke compared with occasional drinkers. Heavy drinkers (daily >6 drinks) showed significantly increased risk evident within the first 8 years of follow-up only (RR=1.9; 95% CI, 1.0 to 3.5); however, this finding was attenuated after additional adjustment for systolic blood pressure (RR=1.5; 95% CI, 0.8 to 2.7). Information obtained 5 years after screening was used to separate lifelong abstainers and ex-drinkers. On subsequent 8.5 years of follow-up, both groups showed similar increased risk (RR=1.5) compared with occasional drinkers, but the risk in ex-drinkers was reduced after adjustment for lifestyle factors and cardiovascular disease status (RR=1.2). Lifelong abstainers, however, showed an increase in risk after adjustment of 1.8 (95% CI, 0.7 to 4.6).
Conclusions Heavy drinking is associated with an increased risk of total stroke that is largely mediated through blood pressure. The apparent increased risk seen in lifelong abstainers but not in ex-drinkers or occasional drinkers is unexplained but is unlikely to be attributed to abstinence from alcohol. There is no convincing evidence that light or moderate drinking is beneficial for stroke risk compared with occasional drinking.
Light-to-moderate alcohol consumption has been associated with a lower risk of coronary heart disease,1 2 3 although it is not necessarily associated with a lower risk of all cardiovascular mortality or total mortality.3 4 5 The association between alcohol intake and the risk of stroke has been less well documented. The studies that had examined this relationship have been reviewed,6 7 and although heavy drinking has been associated with an increased risk, the effects of light-to-moderate drinking and of abstention have not been clearly established. Several epidemiological studies have suggested that light or moderate drinking may be protective against stroke and that abstainers are at increased risk.6 7 8 9 10 However, few of these studies have differentiated between lifelong abstainers and ex-drinkers. Most studies grouped subjects on the basis of their weekly alcohol intake, but there is increasing interest in the possible influence of day-to-day patterns of consumption. Our earlier report on risk factors for stroke in middle-aged British men was based on weekly intake of alcohol and 8 years of follow-up11 ; in that study, lifelong abstainers and ex-drinkers were not separated. The purpose of the present study was to examine the more detailed patterns of drinking in relationship to risk of stroke in a major prospective study of cardiovascular disease in middle-aged men and in particular to determine the risk of stroke separately in lifelong abstainers and ex-drinkers.
Subjects and Methods
The British Regional Heart Study is a prospective study of cardiovascular disease involving 7735 men, aged 40 to 59 years, selected from the age-sex registers of one group general practice in each of 24 towns in England, Wales, and Scotland and initially examined from 1978 through 1980. The criteria for selecting the town, the general practice, and the subjects as well as the methods of data collection have been reported previously.12 Research nurses administered to each man a standard questionnaire (Q1) that included questions on smoking habits, alcohol intake, and medical history. Several physical measurements were made, and blood samples (nonfasting) were taken for measurement of biochemical and hematological variables. Classification methods for smoking status, body mass index, occupation (social class), and physical activity have been reported previously.12 13 The London School of Hygiene sphygmomanometer was used to measure blood pressure twice in succession with the subject seated and the arm supported on a cushion. The mean of the two readings was used, and all readings have been adjusted for observer variation in each town.14
Five years after the initial examination (1983 through 1985), a postal questionnaire (Q5) similar to the one administered at initial screening was sent to all surviving men, and detailed information was obtained on medical history, changes in smoking and drinking behaviors, and changes in other risk factors. Ninety-eight percent of the survivors responded (7275 men).
Alcohol consumption was recorded at initial screening (Q1) with the use of questions on frequency, quantity, and type that were similar to those used in the 1978 General Household Survey.15 The men were questioned about frequency (none, occasional, weekend, or daily) and quantity (1 to 2, 3 to 6, or >6 drinks/day) of alcohol intake, resulting in eight drinking categories: nondrinkers, occasional drinkers (special occasion or 1 to 2 drinks/month), weekend drinkers (1 to 2, 3 to 6, or >6 drinks/d), and daily drinkers, men drinking daily or on most days (1 to 2, 3 to 6, or >6 drinks/d).16 These categories were the only choices provided. It should be noted that the “>6 drinks/d” category is an open-ended one. One UK unit of alcohol (one drink) is defined as half a pint of beer, a single measure of spirits, or a glass of wine (approximately 8 to 10 g alcohol). Heavy drinking refers to those drinking >6 drinks daily or on most days. No history of previous drinking was requested at Q1, and at this stage it was not possible to separate nondrinkers into lifelong abstainers and ex-drinkers. Twenty-five biochemical and hematological measurements on a single blood sample taken at the time the questionnaire was completed indicated that the reported levels of alcohol consumption were valid on a group basis.17 The occasional drinker group is used as the baseline group because the nondrinker group is a small, heterogeneous group unsuitable for this purpose.18
Classification of Drinking Behavior
Five years after the initial screening, because we had become aware of the many adverse characteristics of the nondrinking group and the need to separate ex-drinkers from lifelong abstainers,19 the men were asked about their past drinking habits in addition to questions on their current alcohol consumption (Q5). Complete information on alcohol consumption at both Q1 and Q5 was obtained from 7166 men.
Tables 1⇓ and 2⇓ and the Figure⇓ are based on the classification of alcohol intake of men at Q1. Nondrinkers include ex-drinkers and lifelong abstainers. In Table 3⇓, classification is based on the combined information obtained at Q1 and Q5 (numbers in parentheses are actual classifications): (1) lifelong abstainers—men who were nondrinkers at Q1 and Q5 and who claimed at Q5 that they had never been drinkers; (2) ex-drinkers—nondrinkers at Q1 and Q5 who at Q5 reported previous drinking and nondrinkers at Q5 who were occasional or regular drinkers at Q1; (3) occasional drinkers—those who reported occasional drinking at Q5, unless they were heavy drinkers (daily >6 drinks) at Q1 (see 10 below); (4 to 6) weekend drinkers—1 to 2, 3 to 6, and >6 drinks at Q5 unless they were daily drinkers of >6 drinks at Q1 (see 10 below); (7 to 8) daily drinkers—1 to 2 and 3 to 6 drinks/d at Q5 unless they were daily drinkers of >6 drinks/d at Q1 (see 10 below); (9) heavy drinkers—daily >6 drinks/d at Q5; and (10) ex–heavy drinkers—men who reported drinking >6 drinks/d on a daily basis at Q1 and were no longer heavy drinkers at Q5.
Preexisting Ischemic Heart Disease and Stroke
At both Q1 and Q5 men were asked whether a doctor had ever told them that they had angina or myocardial infarction (heart attack, coronary thrombosis), stroke, or a number of other disorders. The WHO (Rose) chest pain questionnaire20 was administered to all men at the initial examination and a three-orthogonal lead ECG was recorded at rest. Men with evidence of IHD were defined as those with a recall of a diagnosis of angina or heart attack made by a doctor, with a response on WHO (Rose) chest pain questionnaire suggesting angina or possible myocardial infarction, or with ECG evidence of definite or possible myocardial ischemia or myocardial infarction. Evidence of a previous stroke was determined by the subject’s recall of such a diagnosis made by a doctor. There were 52 such men in the study at Q1. Information on prevalence of IHD as measured by WHO (Rose) chest pain questionnaire and recall of physician diagnosis was also provided at Q5.
All men, whether or not they showed evidence of IHD at initial examination, were followed for all cause mortality and for cardiovascular morbidity for a period of 13.5 years from the initial screening, which was performed from January 1978 through July 1980.21 Follow-up was possible for 99% of the cohort. In the analysis concerning lifelong abstainers (Table 3⇑) stroke events are based on 8.5 years of follow-up for each man from the Q5. Information on death was collected through the established “tagging” procedures provided by the National Health Service registers in Southport (England and Wales) and Edinburgh (Scotland). Nonfatal stroke events were those that produced a neurological deficit that was present for more than 24 hours. Evidence regarding such episodes was obtained by reports from general practitioners, from personal questionnaires sent to surviving subjects at Q5, and by semiannual reviews of the patients’ notes made through the end of the study period. Fatal stroke episodes were those coded on the death certificate to International Classification of Diseases (ICD) codes 430 through 438. All death certificates in which it appeared that coding to stroke was not appropriate, or in which stroke was not the attributed code when it might have been, were explored by correspondence with the certifying doctor and the hospital concerned. No information on the type of stroke was available.
The Cox proportional-hazards model was used to assess the independent contributions of alcohol intake to the risk of stroke and to obtain the relative risks adjusted for age and the other risk factors.22 Alcohol was fitted as a categorical variable. Age, blood cholesterol level, and systolic blood pressure were fitted as continuous variables. Smoking (5 levels), physical activity (6 levels), social class (3 groups), diabetes mellitus (yes/no), and preexisting IHD on questionnaire/ECG (yes/no) were also fitted as categorical variables. The validity of the proportional-hazards assumption was assessed by fitting a time-dependent interaction variable x=x(t) with the levels of alcohol where x(t)=log(t).23 The tests for trend over time in the proportional-hazards ratio were not statistically significant for any category of alcohol intake. There was no evidence that the proportional-hazards assumption was violated.
During the follow-up period of 13.5 years, there were 250 major stroke events (59 fatal and 191 nonfatal) in the 7729 men with available information on alcohol consumption at Q1. Because of the strong influence that physician diagnosis of ischemic heart disease/stroke has on drinking behavior,24 we have excluded from analysis all men with recall of ischemic heart disease or stroke at screening (n=456 men; 34 cases; a rate of 7 cases/1000 person-years). In the 7273 men with no previously diagnosed IHD or stroke there were 216 major stroke events (50 fatal and 166 nonfatal events) representing a rate of 2.3/1000 person-years.
Table 1⇑ shows the rate per 1000 person-years and age-adjusted relative risk of stroke in the eight alcohol categories at screening (Q1). Nondrinkers, weekend >6 drinks/d drinkers, and daily drinkers of >6 drinks/d all showed increased relative risk compared with occasional drinkers (P=.06, P=.05, and P=.03, respectively). Daily 3 to 6 and weekend 3 to 6 drinks/d drinkers showed slightly but nonsignificantly lower risk than occasional drinkers. The weekend 1 to 2 drinker group showed the lowest relative risk of stroke and this was of marginal significance (P=.06). Within the weekend drinker group, risk tended to increase with increasing intake of alcohol (test for trend P<.001). Since alcohol intake is associated with many of the factors known to be associated with stroke, such as age, smoking, social class, physical activity, diabetes mellitus, preexisting IHD, and systolic blood pressure, we have examined the relationship, adjusting for these potential confounders and excluding systolic blood pressure. No adjustments were made initially for systolic blood pressure because it may be a mechanism by which alcohol exerts its influence on risk of stroke.
Adjustments for these factors reduced the increased risk seen in weekend >6 and daily >6 drinkers; the latter although elevated was no longer statistically significant. Since daily 1 to 2 drinkers had the most favorable profile of risk,16 adjustment increased the risk in this group. Within the weekend drinker group risk of stroke still tended to increase with increasing intake (test for trend P=.06). The risk in nondrinkers remained elevated and was of marginal significance (P=.08).
Alcohol Intake and Systolic Blood Pressure
The increasing risk of stroke with increasing intake of alcohol in the weekend drinkers and the elevated risk in daily heavy drinkers largely reflects the patterns seen between alcohol and systolic blood pressure. The Figure⇑ shows the mean systolic blood pressure according to the eight categories of alcohol intake adjusted for age and then also for body mass index, social class, smoking, physical activity, preexisting IHD, and diabetes mellitus. In both weekend and daily drinkers there was a significant increase in systolic blood pressure with increasing alcohol intake (tests for trends P=.007 and P<.0001, respectively). Compared with occasional drinkers, adjusted systolic blood pressure was significantly elevated in weekend >6 (P=.0003) and daily >6 drinkers (P<.0001) and to a lesser degree in daily 3 to 6 drinkers (P=.09). Weekend >6 drinkers showed significantly higher age-adjusted mean systolic blood pressures than daily 3 to 6 drinkers (P<.001), but this difference was much attenuated after adjustment (P=.20). In Table 1⇑ additional adjustment for systolic blood pressure further reduced the risk in weekend >6 and daily >6 drinkers.
Duration of Follow-up
We have shown that middle-aged British men tend to reduce their intake with increasing age and that although about 25% of heavy drinkers were still drinking >6 drinks/d, about half of those who reported daily >6 drinking at Q1 were daily 3 to 6 drinkers at Q5.24 Elevated blood pressure is also known to decrease on reduction of alcohol intake.25 26 We have therefore looked at the relationship between alcohol intake at screening and risk of stroke in the first 8 years (111 cases) and in the subsequent 5.5 years (105 cases), with the time division being selected to achieve an adequate number of stroke cases in each time period (Table 2⇑). The effects of heavy drinking on risk of stroke were only evident in the earlier follow-up period. Further adjustment for systolic blood pressure substantially reduced the significantly elevated risk in heavy daily drinkers from 1.9 (95% CI=1.0 to 3.5) to 1.5 (95% CI=0.8 to 2.7), suggesting that the increased risk is largely mediated by systolic blood pressure. The increased risk associated with nondrinking status was seen in both periods of follow-up, although it was not statistically significant in either presumably because of the smaller number of cases involved in each separate period.
To separate lifelong abstainers from ex-drinkers, information on past drinking habits was obtained at Q5. Of the 7273 men with no history of IHD or stroke at Q1, 6802 men provided complete information on drinking behavior at Q5. Of these, 353 men had experienced a heart attack or stroke or had recall of a physician diagnosis of angina between Q1 and Q5 and have been excluded from the analysis, leaving 6449 men. During the 8.5-year follow-up in these men, there were 132 major stroke events, representing a rate of 3.5/1000 person-years. The men were classified primarily on the basis of their reported alcohol intake at Q5 (see “Subjects and Methods”). Since heavy daily drinkers at Q1 showed significantly increased risk of stroke over an 8-year follow-up, heavy daily drinkers at Q1 who did not report drinking heavily at Q5 formed a separate group. Thus, 10 groups were used: lifelong abstainers, ex-drinkers, occasional, weekend 1 to 2, weekend 3 to 6, weekend >6, daily 1 to 2, daily 3 to 6, current heavy drinkers (daily >6), and ex–heavy drinkers (daily >6 at Q1).
Table 3⇑ shows the stroke rate per 1000 person-years and age-adjusted relative risk for the 10 groups. Both current heavy drinkers and ex–heavy drinkers showed increased relative risk compared with occasional drinkers and other regular drinkers, although these differences were not statistically significant presumably because of the small numbers involved. To a lesser extent, lifelong abstainers and ex-drinkers also showed an increased risk of stroke. Of all the other drinking categories, only weekend 1 to 2 drinkers showed lower risk of stroke than occasional drinkers, although this was not statistically significant. These findings are similar to those seen for the first 8-year follow-up with the use of the Q1 classification (Table 2⇑).
Adjustment for Risk Factor Status at Q5
Adjustments for physical activity were based on measures at Q1 because data were not available at Q5. Adjustments for preexisting IHD were based on preexisting IHD at Q1 (ECG/questionnaire) and on newly reported angina on the WHO (Rose) chest pain questionnaire at Q5 in men who did not have recall of a physician diagnosis of angina. Adjustments for smoking and diabetes were based on smoking status at Q5 and recall of diabetes at either Q1 or Q5. Adjustment for the potential confounders reduced the increased risk in ex-drinkers and increased the risk seen in lifelong abstainers, although the difference in risk between lifelong abstainers and occasional drinkers was still not significant (P=.24). Current heavy drinkers still showed some increased risk, although the difference from occasional drinkers was not statistically significant (P=.28). Ex–heavy drinkers showed slightly lower risk than continuing heavy drinkers. Only weekend 1 to 2 drinkers showed lower (but nonsignificant) risk than occasional drinkers (P=.27).
For those concerned with the effects of weekly intake of alcohol on risk of stroke, we have grouped the regular non–heavy drinkers on the basis of their estimated average weekly intake into “light” drinkers (1 to 15 drinks/wk) comprising weekend 1 to 2, weekend 3 to 6, and daily 1 to 2 and “moderate” drinkers (16 to 42 drinks/wk) comprising weekend >6 and daily 3 to 6.27 Light and moderate drinkers showed virtually the same adjusted relative risk of stroke as occasional drinkers (RR=1.0; 95% CI, 0.7 to 1.5 and RR=0.9; 95% CI, 0.5 to 1.6, respectively).
Several epidemiological studies have suggested a U-shaped association between alcohol and stroke,6 7 8 9 10 but the epidemiological evidence linking light to moderate drinking to ischemic stroke is unclear. It has been suggested that the differences between studies may be due to combining different types of stroke, the use of nondrinkers (undifferentiated) as a comparison group, or the possibility that the health effects of light to moderate drinking may depend on differing drinking patterns despite similar average weekly consumption.7 It has also been argued that case-control studies may be subject to methodological bias in selection of controls, and it has been shown that the effects of alcohol consumption on risk of stroke vary according to the control groups selected.28
In this study of middle-aged men in which occasional drinkers were used as the reference group, nondrinkers as a group (lifelong abstainers and ex-drinkers) showed significantly increased risk of total stroke even after adjustment for smoking, social class, physical activity, diabetes mellitus, and preexisting IHD (Table 1⇑). There was no significant difference in risk of stroke between daily 1 to 2 and daily 3 to 6 drinkers and all weekend drinkers (1 to 2, 3 to 6, or >6 drinks/d) compared with occasional drinkers. The lowest risk was seen in weekend 1 to 2 drinkers, but the difference was not statistically significant. Heavy daily drinkers (>6 drinks/d) showed a significantly increased age-adjusted risk of stroke (RR=1.6), which was attenuated after adjustment and although increased (RR=1.4) was not statistically significant over the total 13.5-year follow-up.
Light or Moderate Drinking
In this study, these broad categories include all subjects other than nondrinkers (lifelong abstainers and ex-drinkers), heavy drinkers, and ex–heavy drinkers. On a weekly intake basis, light and moderate drinking groups at Q5 have the same relative risks of stroke as occasional drinkers. In those studies that have shown a beneficial effect of light to moderate drinking on risk of stroke, the use of nondrinkers as a baseline comparison will not unexpectedly result in an apparently reduced risk in these two categories.6 7 8 9 10 When we examined the drinking categories in detail, with no broad grouping, the component categories of light or moderate drinking showed no significant differences in risk from occasional drinking at both Q1 and Q5 or any pattern of dose response that might have suggested a protective effect from regular drinking. Although we had no available information on type of stroke, about 85% of strokes in adults in Great Britain are due to cerebral thrombosis and infarction, with only about 15% attributable to intracerebral or subarachnoid hemorrhage.29 Thus, the pattern of relationship seen is likely to reflect the relationship with ischemic stroke.
It is unlikely that the findings in this study are due to misclassification of self-reported alcohol intake because the alcohol groups have been validated against 25 biochemical/hematological variables.17 Although the alcohol information at Q5 was from postal questionnaires only, the high degree of validity recorded for self-reported alcohol intake30 suggests that the data are comparable with those recorded at Q1. Occasional drinkers are likely to include some periodic heavy drinkers (binge drinkers) who have been shown to have an increased risk of stroke,31 32 and inclusion of these subjects might increase the risk seen in occasional drinkers. It is also unlikely that the lack of beneficial effect in the daily 3 to 6 drinkers is due to inclusion of men drinking up to 6 drinks within this group because we have shown that moderate drinkers (weekend >6 and daily 3 to 6 combined) have a significantly decreased risk of coronary heart disease compared with occasional drinkers.3 In addition, daily 1 to 2 drinkers showed no decreased risk of stroke. Thus, when contrasted with occasional drinkers, there is no convincing evidence from this study that light or moderate drinking is protective against stroke.
In most studies that show increased risk in nondrinkers, there has been no separation of lifelong abstainers and ex-drinkers. In the studies that have separated these categories, some have found increased risk in lifelong abstainers,8 33 while others have not.31 34 In a recent prospective study of alcohol consumption in the elderly, there was no evidence of a protective effect of regular drinking on risk of ischemic stroke compared with lifelong abstainers.31 Ex-drinkers, on the other hand, showed significantly increased risk after adjustment for age and smoking. No adjustments were made for disease status in this group. Similar findings were seen in a Japanese study, with lifelong abstainers showing the lowest risk.34 In the present British study, when lifelong abstainers and ex-drinkers were separated, both showed similar increased age-adjusted risk of stroke despite the fact that lifelong abstainers have very low rates of smoking. Further adjustment for smoking and other risk factors as well as cardiovascular disease status increased the risk in lifelong abstainers, although the finding was still not statistically significant possibly due to the small numbers. The increased risk in ex-drinkers was reduced, and these men showed risk similar to occasional drinkers after adjustment. Our findings are similar to those of a British (Newcastle upon Tyne) case-control study that reported increased risk in lifelong abstainers (odds ratio=2.36) but not in ex-drinkers compared with regular drinkers.8
The differences found among studies in the risk of stroke in lifelong abstainers may be due to the different characteristics of lifelong abstainers in differing populations. The reasons for lifelong abstainers having an apparently increased risk of stroke are difficult to conceive in terms of the risk factor status of this group. Overall these men showed levels of risk factors and physical disorder similar to occasional drinkers, although they have slightly higher rates of regular medication.18 The number of lifelong abstainers in our study is small, but if the increased risk is real, the finding that occasional drinkers and regular non–heavy drinkers as well as ex-drinkers do not differ significantly in the risk of stroke (Table 3⇑), ie, the absence of any dose-response effect, makes it seem unlikely that the reason why lifelong abstainers have an apparently increased risk of stroke is because of their abstinence from alcohol.
Although there is a general consensus that heavy drinking is associated with increased risk of stroke, and in particular hemorrhagic stroke, several prospective studies have found no increased risk of total stroke or ischemic stroke in heavy drinkers.1 6 7 We have observed a modest but nonsignificant increased risk of stroke in heavy drinkers during the total follow-up period. When the patterns of drinking were examined by duration of follow-up, the increase in risk of total stroke in heavy daily drinkers was clearly evident in the shorter follow-up period (8 years) and not in the subsequent 5.5 years. This is consistent with the known reduction in alcohol intake in heavy drinkers over time in this cohort and in middle-aged men in general.24 The increased risk of total stroke in heavy drinkers was attenuated after adjustment for systolic blood pressure, suggesting that the effect of heavy drinking on risk of stroke is acute and largely mediated by elevated systolic blood pressure. Given that men tend to reduce their intake during the course of follow-up and that the effect may be acute, the long-term effect of alcohol on risk of stroke judged on the basis of one assessment in time is unlikely to represent the true effect and is likely to attenuate with longer follow-up as seen in this study. This may explain the lack of association seen between heavy drinking and risk of stroke in many long-term prospective studies.
The Joint Working Party of the Royal Colleges35 concluded that alcohol consumption is not associated with an increase in risk of overall stroke except at quite high levels (>5 UK units/d), and our findings are consistent with this conclusion. A recent major review indicates that there is no consensus regarding the possible decreased risk of ischemic stroke with light to moderate levels of alcohol intake.7 Our findings do not provide any convincing evidence that light to moderate drinking is beneficial for risk of overall stroke compared with occasional drinking. The apparent increase in risk of stroke seen in lifelong abstainers but not in ex-drinkers or occasional drinkers remains unexplained but is unlikely to be due to lack of alcohol.
Selected Abbreviations and Acronyms
|IHD||=||ischemic heart disease|
|Q1||=||initial screening questionnaire|
|WHO||=||World Health Organization|
The British Regional Heart Study is a British Heart Foundation Research Group and receives support from The Stroke Association and The Department of Health. Dr Wannamethee is a British Heart Foundation Research Fellow.
- Received December 27, 1995.
- Revision received February 19, 1996.
- Accepted March 5, 1996.
- Copyright © 1996 by American Heart Association
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