Original Article
Alcohol Consumption and Mortality among Middle-Aged and Elderly U.S. Adults
N Engl J Med 1997; 337:1705-1714December 11, 1997
- Abstract
Background
Alcohol consumption has both adverse and beneficial effects on survival. We examined the balance of these in a large prospective 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-specific death rates and rates of death from all causes across categories of base-line alcohol consumption, adjusting for other risk factors, and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years.
Results
Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) 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 overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk.
Conclusions
In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco.
Media in This Article
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.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.Article Activity
- Article
Men and women who drink alcoholic beverages regularly have, in comparison with abstainers, higher death rates from injuries,1,2 violence,2 suicide,2 poisoning,3 cirrhosis,4 certain cancers,5 and possibly hemorrhagic stroke,6,7 but lower death rates from coronary heart disease and thrombotic stroke.8-27 The net balance of risks and benefits is likely to differ in different age groups and populations. Examining this balance in a particular population requires large epidemiologic studies that have information on all causes of death and include sufficient numbers of people and deaths to estimate risks reliably within subgroups defined according to age, sex, and tobacco use.
We calculated death rates according to self-reported alcohol consumption in half a million U.S. adults 30 years old or older who provided information on alcohol consumption, smoking, and other behavior in 1982 and who were followed prospectively through 1991. We had three aims: to quantify the relation between drinking at base line and specific causes of death thought to be increased or decreased by the consumption of alcohol, while controlling for smoking5,13; to determine how age, sex, and background risk of cardiovascular disease modify the relation of drinking to total mortality; and to compare alcohol and cigarette smoking as risk factors for death in middle age.
Methods
Study Population
The Cancer Prevention Study II is a nationwide prospective mortality study of nearly 1.2 million U.S. adults, 30 years old or older, that was begun in 1982. At the request of an American Cancer Society volunteer, each enrollee completed a confidential, four-page mailed questionnaire on his or her alcohol and tobacco use, diet, and other factors potentially affecting mortality. The present analyses include approximately 490,000 people (251,420 women and 238,206 men) who at enrollment reported either not drinking or currently drinking alcohol and who provided complete information on smoking (Table 1Table 1
Numbers of Subjects and Deaths in the Analysis of Alcohol Consumption in the Cancer Prevention Study II, 1982–1991.).28,29 The mean age was 56 years (range, 30 to 104). Because the study subjects were recruited by American Cancer Society volunteers, they were also more likely than the general U.S. population to be college-educated, married, middle-class, and white (Table 2Table 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.).28 Deaths were ascertained from the month of enrollment until December 1991 through personal inquiries by the volunteers in September 1984, 1986, and 1988, and then through linkage with the National Death Index.30 By September 1988, 2 percent of the subjects had been lost to follow-up and another 0.2 percent could not be followed further because data were insufficient for linkage. By 1991, 12 percent were known to have died. Death certificates were obtained for 98 percent, and from these the underlying cause of death was coded according to the International Classification of 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 you usually drink a day, and for how many years?” Beer, wine, and spirits were assessed separately. People who reported changing their drinking habits in the past 10 years were asked about previous consumption. We defined as nondrinkers people who explicitly recorded zero for current consumption of any alcoholic beverage and zero or blank for previous drinking. We defined as “less than daily” drinkers those who reported drinking any alcoholic beverage less than daily but at least three times per week. People who reported drinking at least 1 drink a day were classified on the basis of the sum of their reported current consumption of all three types of alcoholic beverages, from “1 daily” to “>6 daily.” People who indicated alcohol consumption but did not quantify it were excluded from the analyses, as were people for whom all questions about alcohol were left blank (Table 1). Consumption levels were grouped into three categories in analyses of specific causes of death and into five categories for broader combinations of causes. Each drink was assumed to contain, on average, 12 g of alcohol.
Stability of Alcohol Consumption
Of the 490,000 subjects, 98,000 also completed a more detailed dietary questionnaire in 1992 that included similar questions on alcohol. In this subgroup, 95 percent of the nondrinkers in 1982 continued to abstain or drink less often than twice weekly, and 78 percent of the current drinkers in 1982 remained within the same or an adjacent (usually lower) consumption category. Furthermore, among 47,000 people who were excluded from our analyses because of missing 1982 data but who responded in 1992, 82 percent reported drinking less often than weekly (suggesting that a blank 1982 answer usually, but not always, indicated no regular alcohol consumption).
Alcohol and Specific Causes of Death
We expected death rates from certain conditions to increase with alcohol consumption13: cirrhosis of the liver (ICD-9 code 571; grouped with 67 deaths from alcoholic psychosis and dependence, codes 291 and 303); alcohol-related cancers (those of the oral cavity, pharynx, esophagus, liver, and larynx, but excluding the salivary glands and nasopharynx; codes 141, 143, 144, 145, 146, 148, 149, 150, 155, and 161); accidents and other external causes (codes E800 to E999); and possibly breast cancer in women (code 174), cancer of the colon or rectum (codes 153 and 154),5 pneumonia (codes 480 to 487),13 and hemorrhagic stroke (codes 430 to 432). Decreased mortality was expected from coronary heart disease (codes 410 to 414), total stroke (codes 430 to 438), and possibly “other circulatory conditions” combined (codes 390 to 405, 415 to 429, and 449 to 459). No association was expected with all “other cancers” or “other causes of death.”
The subjects who reported preexisting illness in 1982 were excluded from some analyses but not from others. No exclusions for preexisting disease have been made in Table 1 and Table 2 and Figure 1Figure 1
Rates of Death from All Causes, All Cardiovascular Diseases, and Alcohol-Augmented Conditions from 1982 to 1991, According to Base-Line Alcohol Consumption. and Figure 2Figure 2Estimated 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.. In Table 3Table 3
Number of Deaths and Multivariate-Adjusted Death Rates According to Cause of Death and Alcohol Consumption among Men., Table 4Table 4
Number of Deaths and Multivariate-Adjusted Death Rates According to Cause of Death and Alcohol Consumption among Women. and Table 5Table 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., people with cirrhosis or cancer (except nonmelanoma skin cancer) at base line have been excluded. The relation between drinking and mortality from coronary heart disease differed in subjects with and without prevalent 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 and Table 5.Statistical Analysis
We estimated the relative risks and 95 percent confidence intervals by Cox proportional-hazards analyses,32 comparing mortality at each level of base-line drinking with that in abstainers, with adjustment for certain other risk factors. All models were stratified according to exact age at enrollment and race and were adjusted for education, body-mass index, smoking, a crude index of fat consumption,33 and the use or nonuse of estrogen-replacement therapy in women. Analyses of mortality from cardiovascular causes were also adjusted for marital status, any current aspirin use (vs. none), current employment (yes or no), blue-collar employment (yes or no), and physical activity. Analyses of mortality from breast cancer controlled for family history of breast cancer in mother or sister, total number of sisters, age at menarche, age at first birth, age at menopause, oral-contraceptive use or nonuse, and presence or absence of breast cysts. Analyses of deaths due to other cancers controlled for vegetable consumption.33
Multivariate-adjusted death rates were then derived by multiplying the adjusted relative risk at each level of drinking by the age-standardized death rate in nondrinkers. Variances of the log relative risks were calculated,34 and the square roots of these, multiplied by the corresponding death rates, gave the standard errors of those rates.
The probabilities of death between the ages of 35 and 69 years among drinkers and smokers were estimated as follows. First, we calculated the relative risk of death from all causes at these ages for six combinations of drinking (yes or no) and cigarette 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 (representing the death rate among nondrinkers) so that the weighted average of the six rates equaled the U.S. death rate per 100,000 people 35 through 69 years old in 1990 for a uniform age distribution.36 The corresponding probability of death at ages 35 to 69 then equaled 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 cigarettes at the time of enrollment increased with the frequency of alcohol consumption, from 22 percent of men and women reporting less than one drink daily to 37 percent of those who consumed four or more drinks daily. The drinkers also reported eating more vegetables than did abstainers, but this may have been an artifact of more complete reporting of both beverage and food consumption by some subjects. People excluded from the alcohol analyses because of blank answers in 1982 resembled abstainers demographically but were somewhat older and less likely to have completed high school or to be employed (Table 2).
Specific Causes of Death
Alcohol consumption was associated with increased rates of death from cirrhosis and alcoholism and from cancers of the mouth, esophagus, pharynx, larynx, and liver combined (Table 3 and Table 4). The death rates from these conditions were three to seven times as high among both men and women who reported at least four drinks daily as among nondrinkers. For men but not for women, mortality from external causes (mostly unintentional injuries and suicide) was 30 percent higher among those drinking at this level than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6) (Table 3). The rate of death from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6) (Table 4).
In contrast, the rates of death from all cardiovascular diseases combined were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers. The largest reduction, in both absolute and relative terms, occurred in mortality from coronary heart disease among drinkers who, at enrollment, had reported heart disease, stroke, or some other indication of preexisting risk of cardiovascular disease (Table 3 and Table 4). This subgroup contained one third of all the people in the study but contributed nearly three quarters of all deaths from cardiovascular causes.
We found no consistent relation between alcohol consumption and 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 rates among subjects excluded from the analyses because of missing data on alcohol consumption, whose mortality patterns were consistent with most but not all of them being nondrinkers, are not shown.
Combined Causes of Death
Figure 1 illustrates how death rates from all alcohol-augmented conditions (cirrhosis and alcoholism, alcohol-related cancers, breast cancer in women, and external causes) compare, at various levels of drinking, with those from all cardiovascular diseases. Overall, cardiovascular causes accounted for 45 percent and 37 percent of all deaths among men and women, respectively, whereas the alcohol-augmented conditions accounted for 7 percent of all deaths among men and 15 percent among women. The percentage of deaths due to cardiovascular diseases decreased as alcohol consumption increased.
The rates of death from all causes were lowest among both men and women who reported one drink daily; the rates were about 20 percent below those of nondrinkers (Figure 1). Above one drink per day, the overall death rate among drinkers increased, although the shape of the dose–response relation with alcohol consumption varied substantially in different subgroups of the population.
Table 5 illustrates how age and background risk of cardiovascular disease influence the relation between drinking and mortality from all causes. For men and women 30 to 59 years old who were at low risk for cardiovascular disease, the rates of death from all causes among those reporting four or more daily drinks exceeded the rates among nondrinkers (J-shaped pattern). In the two subgroups at intermediate risk for cardiovascular disease (30 to 59 years old with cardiovascular risk factors and 60 to 79 years old without cardiovascular risk factors), the rates of death from all causes among persons reporting four or more drinks daily nearly equaled those of nondrinkers (U-shaped pattern). In the subgroup at highest risk for cardiovascular disease (60 to 79 years old with preexisting risk factors), the rates of death from all causes among drinkers remained significantly below those among nondrinkers, even for subjects reporting four or more drinks daily (L-shaped pattern).
In Figure 1, which includes people of all ages, with or without cardiovascular risk factors, the U-shaped relation between alcohol consumption and mortality from all causes represents the average dose–response relation in the study population. Although most of the 20 percent reduction in rates of death from all causes among daily drinkers was attributable to lower mortality from cardiovascular causes, other nonneoplastic conditions, which are classified with “other causes” of death in Table 3 and Table 4, also contributed. Similarly, although most of the increase in the overall death rates associated with heavier drinking 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 between the ages of 35 and 69, whereas moderate alcohol consumption was associated with a small reduction in risk (Figure 2). Thus, for death in middle age, the benefits of moderate alcohol consumption are much smaller than the hazards of tobacco use.
Discussion
This prospective study of 490,000 people and 46,000 deaths has three main findings about alcohol consumption and mortality from all causes. First, those who consumed up to one or two drinks of alcohol daily had lower overall mortality rates than nondrinkers. Similar findings have been reported previously.10,13,22 An important caveat is that the subjects in all these studies were largely middle-aged and elderly middle-class people. These studies excluded or underrepresented certain high-risk groups, such as adolescents, young adults, binge drinkers or very heavy drinkers, members of groups with lower socioeconomic status, and population groups in which deaths from accidents, violence, and other external causes outnumber deaths from cardiovascular causes.
Second, the balance of adverse and beneficial effects of drinking on mortality from all causes depends not only on the amount of alcohol consumed but also on age and background cardiovascular risk. In most subgroups, the rates of death from all causes were lowest among people who reported one drink of alcohol daily. With heavier consumption, the rate of death from all causes followed 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 among low-risk men and women 30 to 59 years old is similar to the pattern reported among men 40 to 59 years old in a previous American Cancer Society study.10 Differences in age and background risk of cardiovascular disease can help explain apparent inconsistencies among previous epidemiologic studies with respect to mortality from all causes at higher levels of drinking. Because overall death rates are a weighted average of the rates for specific causes of death, the relative importance of alcohol-augmented (mostly injury-related) deaths as compared with deaths from cardiovascular disease influences the relation between alcohol consumption and total mortality. At one extreme are men 18 to 29 years old, an age group not included in our study. A study of Swedish military recruits found a linear increase in rates of death from all causes (mostly from accidents, violence, and suicide) with greater alcohol consumption.2 Among U.S. men 15 to 29 years old, deaths from injuries and other external causes predominate, accounting for 75 percent of all deaths, as compared with 4 percent from cardiovascular conditions.35 The reverse is true among men 60 or more, for whom external causes account for 3 percent of deaths and circulatory conditions for over 45 percent.
Our third point is that drinking alcohol does not compensate for the large increase in risk produced by smoking. Whereas moderate alcohol consumption slightly reduces the risk of death between the ages of 35 and 69 years, cigarette smoking approximately doubles this risk. The analyses in Figure 2 adjust for the higher prevalence and intensity of smoking among drinkers, but not for the slightly heavier drinking by smokers than by nonsmokers. Furthermore, such calculations consider only mortality and disregard consequences to people other than the drinker. Nevertheless, despite the catastrophic harm that alcohol can cause,3 Figure 2 illustrates the more usual slight protective effects of moderate alcohol consumption on mortality among middle-aged and elderly adults.
The strengths of this study include its large size, the ability to control for tobacco smoking, the exclusion of former drinkers from the reference group (which minimized bias due to cessation because of illness caused by alcohol), and the availability of the responses to a repeated questionnaire that helped to assess the stability of drinking behavior in this population. Its limitations include the difficulty of quantifying alcohol consumption by self-report, the low prevalence of heavy drinking, the lack of information on sporadic binge drinking (and hence on its hazards), and the exclusion of those who left the alcohol questions blank in 1982. (Few of these people, however, were heavy drinkers whose exclusion might have biased our results, given their demographic characteristics and mortality and the infrequency of regular drinking among those who completed the second questionnaire in 1992.)
An unexpected finding was the lower mortality among drinkers than among nondrinkers from the aggregate of the causes we had originally postulated would be unrelated to drinking. A similar reduction was found in a study of British doctors.13 This reduction, which was more evident among men than among women, needs further investigation.
Several consensus groups37,38 have concluded that moderate alcohol consumption reduces the overall risk of cardiovascular disease, but it is not known how long moderate alcohol consumption must continue for this benefit to occur. Alcohol consumption beginning in middle age might suffice, while averting much of the risk of accidents and cancer associated with drinking. However, many factors influence alcohol consumption besides knowledge of the potential health hazards or benefits for the drinker, and the implications of the present findings for social policy are beyond the scope of this paper.
The authors alone are responsible for the views expressed in this article.
We are indebted to Ms. Audrey Earles for preparing many drafts of the manuscript, and to Drs. Peter Anderson and Neil Collishaw for 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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