Alcohol Consumption and Mortality among Middle-Aged and Elderly U.S. Adults
Michael J. Thun, M.D., Richard Peto, F.R.S., Alan D. Lopez, Ph.D., Jane H. Monaco, M.S., S. Jane Henley, B.A., Clark W. Heath, M.D., and Richard Doll, F.R.S.
Background Alcohol consumption has both adverse and beneficialeffects on survival. We examined the balance of these in a largeprospective study of mortality among U.S. adults.
Methods Of 490,000 men and women (mean age, 56 years; range,30 to 104) who reported their alcohol and tobacco use in 1982,46,000 died during nine years of follow-up. We compared cause-specificdeath rates and rates of death from all causes across categoriesof base-line alcohol consumption, adjusting for other risk factors,and related drinking and smoking habits to the cumulative probabilityof dying between the ages of 35 and 69 years.
Results Causes of death associated with drinking were cirrhosisand alcoholism; cancers of the mouth, esophagus, pharynx, larynx,and liver combined; breast cancer in women; and injuries andother external causes in men. The mortality from breast cancerwas 30 percent higher among women reporting at least one drinkdaily than among nondrinkers (relative risk, 1.3; 95 percentconfidence interval, 1.1 to 1.6). The rates of death from allcardiovascular diseases were 30 to 40 percent lower among men(relative risk, 0.7; 95 percent confidence interval, 0.7 to0.8) and women (relative risk, 0.6; 95 percent confidence interval,0.6 to 0.7) reporting at least one drink daily than among nondrinkers,with little relation to the level of consumption. The overalldeath rates were lowest among men and women reporting aboutone drink daily. Mortality from all causes increased with heavierdrinking, particularly among adults under age 60 with lowerrisk of cardiovascular disease. Alcohol consumption was associatedwith a small reduction in the overall risk of death in middleage (ages 35 to 69), whereas smoking approximately doubled thisrisk.
Conclusions In this middle-aged and elderly population, moderatealcohol consumption slightly reduced overall mortality. Thebenefit depended in part on age and background cardiovascularrisk and was far smaller than the large increase in risk producedby tobacco.
Men and women who drink alcoholic beverages regularly have,in comparison with abstainers, higher death rates from injuries,1,2violence,2 suicide,2 poisoning,3 cirrhosis,4 certain cancers,5and possibly hemorrhagic stroke,6,7 but lower death rates fromcoronary heart disease and thrombotic stroke.8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27The net balance of risks and benefits is likely to differ indifferent age groups and populations. Examining this balancein a particular population requires large epidemiologic studiesthat have information on all causes of death and include sufficientnumbers of people and deaths to estimate risks reliably withinsubgroups defined according to age, sex, and tobacco use.
We calculated death rates according to self-reported alcoholconsumption in half a million U.S. adults 30 years old or olderwho provided information on alcohol consumption, smoking, andother behavior in 1982 and who were followed prospectively through1991. We had three aims: to quantify the relation between drinkingat base line and specific causes of death thought to be increasedor decreased by the consumption of alcohol, while controllingfor smoking5,13; to determine how age, sex, and background riskof cardiovascular disease modify the relation of drinking tototal mortality; and to compare alcohol and cigarette smokingas risk factors for death in middle age.
Methods
Study Population
The Cancer Prevention Study II is a nationwide prospective mortalitystudy of nearly 1.2 million U.S. adults, 30 years old or older,that was begun in 1982. At the request of an American CancerSociety volunteer, each enrollee completed a confidential, four-pagemailed questionnaire on his or her alcohol and tobacco use,diet, and other factors potentially affecting mortality. Thepresent analyses include approximately 490,000 people (251,420women and 238,206 men) who at enrollment reported either notdrinking or currently drinking alcohol and who provided completeinformation on smoking (Table 1).28,29 The mean age was 56 years(range, 30 to 104). Because the study subjects were recruitedby American Cancer Society volunteers, they were also more likelythan the general U.S. population to be college-educated, married,middle-class, and white (Table 2).28
Table 2. Demographic Characteristics of Persons in the Cancer Prevention Study II Who in 1982 Reported Current Alcohol Drinking, No Current Drinking, or No Information on Alcohol Consumption.
Deaths were ascertained from the month of enrollment until December1991 through personal inquiries by the volunteers in September1984, 1986, and 1988, and then through linkage with the NationalDeath Index.30 By September 1988, 2 percent of the subjectshad been lost to follow-up and another 0.2 percent could notbe followed further because data were insufficient for linkage.By 1991, 12 percent were known to have died. Death certificateswere obtained for 98 percent, and from these the underlyingcause of death was coded according to the International Classificationof Diseases, Ninth Revision (ICD-9).31
Alcohol Consumption
Current alcohol consumption in 1982 was assessed by the question"How many cups, glasses, or drinks of these beverages do youusually drink a day, and for how many years?" Beer, wine, andspirits were assessed separately. People who reported changingtheir drinking habits in the past 10 years were asked aboutprevious consumption. We defined as nondrinkers people who explicitlyrecorded zero for current consumption of any alcoholic beverageand zero or blank for previous drinking. We defined as "lessthan daily" drinkers those who reported drinking any alcoholicbeverage less than daily but at least three times per week.People who reported drinking at least 1 drink a day were classifiedon the basis of the sum of their reported current consumptionof all three types of alcoholic beverages, from "1 daily" to">6 daily." People who indicated alcohol consumption butdid not quantify it were excluded from the analyses, as werepeople for whom all questions about alcohol were left blank(Table 1). Consumption levels were grouped into three categoriesin analyses of specific causes of death and into five categoriesfor broader combinations of causes. Each drink was assumed tocontain, on average, 12 g of alcohol.
Stability of Alcohol Consumption
Of the 490,000 subjects, 98,000 also completed a more detaileddietary questionnaire in 1992 that included similar questionson alcohol. In this subgroup, 95 percent of the nondrinkersin 1982 continued to abstain or drink less often than twiceweekly, and 78 percent of the current drinkers in 1982 remainedwithin the same or an adjacent (usually lower) consumption category.Furthermore, among 47,000 people who were excluded from ouranalyses because of missing 1982 data but who responded in 1992,82 percent reported drinking less often than weekly (suggestingthat a blank 1982 answer usually, but not always, indicatedno regular alcohol consumption).
Alcohol and Specific Causes of Death
We expected death rates from certain conditions to increasewith alcohol consumption13: cirrhosis of the liver (ICD-9 code571; grouped with 67 deaths from alcoholic psychosis and dependence,codes 291 and 303); alcohol-related cancers (those of the oralcavity, pharynx, esophagus, liver, and larynx, but excludingthe salivary glands and nasopharynx; codes 141, 143, 144, 145,146, 148, 149, 150, 155, and 161); accidents and other externalcauses (codes E800 to E999); and possibly breast cancer in women(code 174), cancer of the colon or rectum (codes 153 and 154),5pneumonia (codes 480 to 487),13 and hemorrhagic stroke (codes430 to 432). Decreased mortality was expected from coronaryheart disease (codes 410 to 414), total stroke (codes 430 to438), and possibly "other circulatory conditions" combined (codes390 to 405, 415 to 429, and 449 to 459). No association wasexpected with all "other cancers" or "other causes of death."
The subjects who reported preexisting illness in 1982 were excludedfrom some analyses but not from others. No exclusions for preexistingdisease have been made in Table 1 and Table 2 and Figure 1 andFigure 2. In Table 3, Table 4 and Table 5, people with cirrhosisor cancer (except nonmelanoma skin cancer) at base line havebeen excluded. The relation between drinking and mortality fromcoronary heart disease differed in subjects with and withoutprevalent vascular conditions (prior heart attack, hypertension,medications for these conditions, stroke, or diabetes mellitus),and the two are presented separately in Table 3, Table 4 andTable 5.
Figure 1. Rates of Death from All Causes, All Cardiovascular Diseases, and Alcohol-Augmented Conditions from 1982 to 1991, According to Base-Line Alcohol Consumption.
Alcohol-augmented conditions are cirrhosis and alcoholism, alcohol-related cancers, breast cancer in women, and injuries and other external causes. "Less than daily" alcohol consumption was defined as drinking three or more times per week but less than one drink per day. The numbers in parentheses are the standard errors of the rates of death from all causes.
Figure 2. Estimated Probability of Death from Any Cause in the General U.S. Population from 35 to 69 Years of Age for Four Combinations of Alcohol Consumption and Smoking.
The probabilities projected for the general U.S. population are based on relative risks calculated in this study, combined with prevalence and mortality data for the U.S. population in 1990. They reflect the smoking of approximately one pack of cigarettes per day by smokers and consumption of approximately one to two drinks per day by those who reported drinking alcohol in 1982.
Table 5. Number of Deaths and Multivariate-Adjusted Death Rates from All Causes among Men and Women According to Base-Line Alcohol Consumption, Age, and Background Risk of Cardiovascular Disease.
Statistical Analysis
We estimated the relative risks and 95 percent confidence intervalsby Cox proportional-hazards analyses,32 comparing mortalityat each level of base-line drinking with that in abstainers,with adjustment for certain other risk factors. All models werestratified according to exact age at enrollment and race andwere adjusted for education, body-mass index, smoking, a crudeindex of fat consumption,33 and the use or nonuse of estrogen-replacementtherapy in women. Analyses of mortality from cardiovascularcauses were also adjusted for marital status, any current aspirinuse (vs. none), current employment (yes or no), blue-collaremployment (yes or no), and physical activity. Analyses of mortalityfrom breast cancer controlled for family history of breast cancerin mother or sister, total number of sisters, age at menarche,age at first birth, age at menopause, oral-contraceptive useor nonuse, and presence or absence of breast cysts. Analysesof deaths due to other cancers controlled for vegetable consumption.33
Multivariate-adjusted death rates were then derived by multiplyingthe adjusted relative risk at each level of drinking by theage-standardized death rate in nondrinkers. Variances of thelog relative risks were calculated,34 and the square roots ofthese, multiplied by the corresponding death rates, gave thestandard errors of those rates.
The probabilities of death between the ages of 35 and 69 yearsamong drinkers and smokers were estimated as follows. First,we calculated the relative risk of death from all causes atthese ages for six combinations of drinking (yes or no) andcigarette smoking (currently, formerly, or never) in our cohort.We then multiplied these rates by the proportion of the U.S.population in this category in 199035 and by a constant (representingthe death rate among nondrinkers) so that the weighted averageof the six rates equaled the U.S. death rate per 100,000 people35 through 69 years old in 1990 for a uniform age distribution.36The corresponding probability of death at ages 35 to 69 thenequaled 1 – exp [–35 (death rate per 100,000)].
Results
Demographic Characteristics
As compared with nondrinkers, drinkers were more likely to smoke,to have graduated from high school, and to be Catholic (Table 2).Among the drinkers, the percentage who smoked cigarettesat the time of enrollment increased with the frequency of alcoholconsumption, from 22 percent of men and women reporting lessthan one drink daily to 37 percent of those who consumed fouror more drinks daily. The drinkers also reported eating morevegetables than did abstainers, but this may have been an artifactof more complete reporting of both beverage and food consumptionby some subjects. People excluded from the alcohol analysesbecause of blank answers in 1982 resembled abstainers demographicallybut were somewhat older and less likely to have completed highschool or to be employed (Table 2).
Specific Causes of Death
Alcohol consumption was associated with increased rates of deathfrom cirrhosis and alcoholism and from cancers of the mouth,esophagus, pharynx, larynx, and liver combined (Table 3 andTable 4). The death rates from these conditions were three toseven times as high among both men and women who reported atleast four drinks daily as among nondrinkers. For men but notfor women, mortality from external causes (mostly unintentionalinjuries and suicide) was 30 percent higher among those drinkingat this level than among nondrinkers (relative risk, 1.3; 95percent confidence interval, 1.1 to 1.6) (Table 3). The rateof death from breast cancer was 30 percent higher among womenreporting at least one drink daily than among nondrinkers (relativerisk, 1.3; 95 percent confidence interval, 1.1 to 1.6) (Table 4).
In contrast, the rates of death from all cardiovascular diseasescombined were 30 to 40 percent lower among men (relative risk,0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relativerisk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reportingat least one drink daily than among nondrinkers. The largestreduction, in both absolute and relative terms, occurred inmortality from coronary heart disease among drinkers who, atenrollment, had reported heart disease, stroke, or some otherindication of preexisting risk of cardiovascular disease (Table 3and Table 4). This subgroup contained one third of all thepeople in the study but contributed nearly three quarters ofall deaths from cardiovascular causes.
We found no consistent relation between alcohol consumptionand rates of death from colorectal cancer (Table 3 and Table 4),colon or rectal cancer separately, hemorrhagic stroke, pneumonia,or all respiratory diseases (data not shown). The death ratesamong subjects excluded from the analyses because of missingdata on alcohol consumption, whose mortality patterns were consistentwith most but not all of them being nondrinkers, are not shown.
Combined Causes of Death
Figure 1 illustrates how death rates from all alcohol-augmentedconditions (cirrhosis and alcoholism, alcohol-related cancers,breast cancer in women, and external causes) compare, at variouslevels of drinking, with those from all cardiovascular diseases.Overall, cardiovascular causes accounted for 45 percent and37 percent of all deaths among men and women, respectively,whereas the alcohol-augmented conditions accounted for 7 percentof all deaths among men and 15 percent among women. The percentageof deaths due to cardiovascular diseases decreased as alcoholconsumption increased.
The rates of death from all causes were lowest among both menand women who reported one drink daily; the rates were about20 percent below those of nondrinkers (Figure 1). Above onedrink per day, the overall death rate among drinkers increased,although the shape of the dose–response relation withalcohol consumption varied substantially in different subgroupsof the population.
Table 5 illustrates how age and background risk of cardiovasculardisease influence the relation between drinking and mortalityfrom all causes. For men and women 30 to 59 years old who wereat low risk for cardiovascular disease, the rates of death fromall causes among those reporting four or more daily drinks exceededthe rates among nondrinkers (J-shaped pattern). In the two subgroupsat intermediate risk for cardiovascular disease (30 to 59 yearsold with cardiovascular risk factors and 60 to 79 years oldwithout cardiovascular risk factors), the rates of death fromall causes among persons reporting four or more drinks dailynearly equaled those of nondrinkers (U-shaped pattern). In thesubgroup at highest risk for cardiovascular disease (60 to 79years old with preexisting risk factors), the rates of deathfrom all causes among drinkers remained significantly belowthose among nondrinkers, even for subjects reporting four ormore drinks daily (L-shaped pattern).
In Figure 1, which includes people of all ages, with or withoutcardiovascular risk factors, the U-shaped relation between alcoholconsumption and mortality from all causes represents the averagedose–response relation in the study population. Althoughmost of the 20 percent reduction in rates of death from allcauses among daily drinkers was attributable to lower mortalityfrom cardiovascular causes, other nonneoplastic conditions,which are classified with "other causes" of death in Table 3and Table 4, also contributed. Similarly, although most of theincrease in the overall death rates associated with heavierdrinking arose from the conditions we designated as alcohol-augmented,some resulted from "all other cancers" and "all other causes"(Table 3 and Table 4).
Comparison between Alcohol and Tobacco
Continued smoking approximately doubled the risk of death betweenthe ages of 35 and 69, whereas moderate alcohol consumptionwas associated with a small reduction in risk (Figure 2). Thus,for death in middle age, the benefits of moderate alcohol consumptionare much smaller than the hazards of tobacco use.
Discussion
This prospective study of 490,000 people and 46,000 deaths hasthree main findings about alcohol consumption and mortalityfrom all causes. First, those who consumed up to one or twodrinks of alcohol daily had lower overall mortality rates thannondrinkers. Similar findings have been reported previously.10,13,22An important caveat is that the subjects in all these studieswere largely middle-aged and elderly middle-class people. Thesestudies excluded or underrepresented certain high-risk groups,such as adolescents, young adults, binge drinkers or very heavydrinkers, members of groups with lower socioeconomic status,and population groups in which deaths from accidents, violence,and other external causes outnumber deaths from cardiovascularcauses.
Second, the balance of adverse and beneficial effects of drinkingon mortality from all causes depends not only on the amountof alcohol consumed but also on age and background cardiovascularrisk. In most subgroups, the rates of death from all causeswere lowest among people who reported one drink of alcohol daily.With heavier consumption, the rate of death from all causesfollowed a J-, U-, or L-shaped pattern in subgroups at low,intermediate, or high risk of cardiovascular disease, respectively(Table 5). The J-shaped configuration that we observed amonglow-risk men and women 30 to 59 years old is similar to thepattern reported among men 40 to 59 years old in a previousAmerican Cancer Society study.10 Differences in age and backgroundrisk of cardiovascular disease can help explain apparent inconsistenciesamong previous epidemiologic studies with respect to mortalityfrom all causes at higher levels of drinking. Because overalldeath rates are a weighted average of the rates for specificcauses of death, the relative importance of alcohol-augmented(mostly injury-related) deaths as compared with deaths fromcardiovascular disease influences the relation between alcoholconsumption and total mortality. At one extreme are men 18 to29 years old, an age group not included in our study. A studyof Swedish military recruits found a linear increase in ratesof death from all causes (mostly from accidents, violence, andsuicide) with greater alcohol consumption.2 Among U.S. men 15to 29 years old, deaths from injuries and other external causespredominate, accounting for 75 percent of all deaths, as comparedwith 4 percent from cardiovascular conditions.35 The reverseis true among men 60 or more, for whom external causes accountfor 3 percent of deaths and circulatory conditions for over45 percent.
Our third point is that drinking alcohol does not compensatefor the large increase in risk produced by smoking. Whereasmoderate alcohol consumption slightly reduces the risk of deathbetween the ages of 35 and 69 years, cigarette smoking approximatelydoubles this risk. The analyses in Figure 2 adjust for the higherprevalence and intensity of smoking among drinkers, but notfor the slightly heavier drinking by smokers than by nonsmokers.Furthermore, such calculations consider only mortality and disregardconsequences to people other than the drinker. Nevertheless,despite the catastrophic harm that alcohol can cause,3Figure 2illustrates the more usual slight protective effects of moderatealcohol consumption on mortality among middle-aged and elderlyadults.
The strengths of this study include its large size, the abilityto control for tobacco smoking, the exclusion of former drinkersfrom the reference group (which minimized bias due to cessationbecause of illness caused by alcohol), and the availabilityof the responses to a repeated questionnaire that helped toassess the stability of drinking behavior in this population.Its limitations include the difficulty of quantifying alcoholconsumption by self-report, the low prevalence of heavy drinking,the lack of information on sporadic binge drinking (and henceon its hazards), and the exclusion of those who left the alcoholquestions blank in 1982. (Few of these people, however, wereheavy drinkers whose exclusion might have biased our results,given their demographic characteristics and mortality and theinfrequency of regular drinking among those who completed thesecond questionnaire in 1992.)
An unexpected finding was the lower mortality among drinkersthan among nondrinkers from the aggregate of the causes we hadoriginally postulated would be unrelated to drinking. A similarreduction was found in a study of British doctors.13 This reduction,which was more evident among men than among women, needs furtherinvestigation.
Several consensus groups37,38 have concluded that moderate alcoholconsumption reduces the overall risk of cardiovascular disease,but it is not known how long moderate alcohol consumption mustcontinue for this benefit to occur. Alcohol consumption beginningin middle age might suffice, while averting much of the riskof accidents and cancer associated with drinking. However, manyfactors influence alcohol consumption besides knowledge of thepotential health hazards or benefits for the drinker, and theimplications of the present findings for social policy are beyondthe scope of this paper.
The authors alone are responsible for the views expressed inthis article.
We are indebted to Ms. Audrey Earles for preparing many draftsof the manuscript, and to Drs. Peter Anderson and Neil Collishawfor their review and comments.
Source Information
From Epidemiology and Surveillance Research, American Cancer Society, Atlanta (M.J.T., J.H.M., S.J.H., C.W.H.); the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, England (R.P., R.D.); and the Programme on Substance Abuse, World Health Organization, Geneva (A.D.L.).
Address reprint requests to Dr. Thun at Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Rd., NE, Atlanta, GA 30329-4251.
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