Moderate alcohol intake is associated with survival in the elderly: the Dubbo Study

In elderly people, some of this benefit from moderate alcohol intake may be negated by mortality from other causes.⁹ In a prospective study of men and women aged 65 years and over in the United States (Established Populations for Epidemiologic Studies of the Elderly), alcohol intake under 21 drinks/week was associated with a 30%-40% lower all-causes mortality in two cohorts, but with no influence in a third cohort.¹⁰ In Australian men and women aged 60 years and over with 77 months' follow-up, the intake of 1-7 drinks/week was associated with a 22%-25% reduction in all-causes mortality, although this reduction did not achieve statistical significance.¹¹ We have examined the relationship between alcohol intake and survival in this Australian cohort during a more extended follow-up of 116 months. We present the results and include an economic analysis of moderate alcohol intake.

Dubbo Study
The Dubbo Study is an ongoing prospective examination of cardiovascular and other diseases in an elderly Australian cohort first examined in 1988-89. All non-institutionalised residents of Dubbo, New South Wales, born before 1930 were eligible; participation rate was 73% (1235 men and 1570 women). Methods and measures have already been described in detail.^12,13 The baseline examinations comprised demographic, psychosocial and standard cardiovascular risk assessments, including examination of fasting blood samples.

Alcohol usage
Questions on alcohol usage were those asked in the National Heart Foundation Risk Factor Prevalence Study,¹⁴ and yielded an approximation of usual alcohol intake coded as zero, 1-7, 8-14, 15-28 and more than 28 drinks/week (referring to a standard drink containing 10 g of alcohol). Specific intakes of beer, wine and spirits were not separately sought, but subjects were asked whether they normally drank beer or not, allowing a separation of drinking behaviour into beer and "other".

Survival analysis
Outcomes from August 1988 to 31 December 1998 were included in the analysis, a median 116 months' follow-up. Hospitalisation and death records were monitored continuously, and postal surveys were conducted every two years to confirm vital status. The survey in 1997 successfully traced more than 98% of surviving participants. Records were coded according to the International classification of diseases, ninth revision, clinical modification (ICD-9-CM).

The independent contribution of any risk factor to mortality was examined in a Cox proportional hazards model. Point estimates and 95% CIs for the relative hazard of death were calculated from the regression coefficients (presented as hazard ratio, a measure of relative risk). The models included categories of alcohol intake as described above, and, where relevant, a categorical term describing whether a subject normally drank beer or "other" (ie, wine/spirits). The proportional hazards model assumes constant relative hazard over the length of follow-up. This assumption was confirmed for each model by a plot of log-minus-log survival, demonstrating parallel curves over all categories of alcohol intake. Statistical analyses were conducted using SPSS for Windows NT.¹⁵

Economic analysis
A weighted alcohol acquisition cost per week using the midpoint of the intake ranges was calculated for each alcohol intake stratum and for each sex using 1999 Dubbo club prices. Individuals were assumed to remain in their initial consumption strata over the whole time period. Survival curve data from the Cox model were used to calculate total expenditure on alcohol, as well as survival benefit for each stratum of intake. An incremental analysis (difference in cost/difference in benefit) was conducted using the no-alcohol-consumption stratum as the reference. This yielded an estimate of the gross cost per life-year gained. Although the study collects hospitalisation records, hospitalisation costs were not available and a net cost per life-year gained could not be estimated.

Ethical approval
The study was approved by the institutional ethics committees at St Vincent's Hospital, Sydney, the University of New South Wales and the Australian National University. All participants gave informed, written consent.

Pattern of alcohol intake
The pattern of alcohol intake and its clinical associations have been fully documented in an earlier report.¹¹ The pattern of alcohol intake, by quantity and type, is shown in Box 1. On a day when alcohol was consumed, 40% of all men and 45% of all women took one or two drinks, 23% and 7% took three or four drinks, and 15% and 1%, respectively, took five or more drinks.

All-causes mortality
Death occurred in 450 men (36%) and 392 women (25%). Consumption of more than 14 drinks/week was uncommon. Hence, where relevant, the use of alcohol has been grouped into zero use and any use.

Alcohol intake: Age-specific all-causes mortality by alcohol intake is presented in Box 2. Alcohol use in men appeared to be associated with reduced mortality up to age 74 years, but not beyond. In women, its use was associated with reduced mortality in all groups older than 64 years.

Predictors of all-causes mortality: The independent contribution of alcohol to all-causes mortality was explored in men 60-74 years and in all women in proportional hazards models which adjusted for the presence of major demographic, psychosocial and cardiovascular variables at study entry. The significant predictors of all-causes mortality are summarised in Box 3. (Alcohol intake was not a significant predictor of mortality in men aged more than 74 years.) Any alcohol intake was significantly associated with reduced all-causes mortality in both sexes.

Quantity or type of alcohol intake: The relationship between quantity or type of alcohol intake and all-causes mortality in the proportional hazards model is presented in Box 3. The risk of mortality was significantly reduced at all levels of alcohol intake, except in women taking 15-28 drinks/week (representing only 3% of women in the study). A similar degree of reduction in all-causes mortality was observed at all levels of alcohol intake. The protection observed was broadly similar in those using beer versus wine/spirits, although this only reached statistical significance for beer consumption.

Pattern of alcohol intake: In a subsequent model, the quantity of alcohol consumed per week was replaced by a variable denoting the usual number of drinks taken on a given day, a measure of the pattern of drinking. Using zero intake as the reference group, the hazard ratio in men with a consumption of one or two drinks on a given day was 0.64 (95% CI, 0.46-0.89), with three or four drinks 0.68 (95% CI, 0.47-0.98), and with five or more drinks 0.69 (95% CI, 0.45-1.06). The corresponding hazard ratios in women were 0.74 (95% CI, 0.59-0.93), 0.68 (95% CI, 0.38-1.22) and 1.38 (95% CI, 0.58-3.29) (there were only 17 women in this group).

Hazard curves: The hazard curves calculated from the proportional hazards models in men and women are presented in Box 4. By the end of almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, than their counterparts taking no alcohol.

Specific causes of death: Cardiovascular death (ie, CHD and stroke) was reduced from 20/100 (95% CI, 14-26) in non-drinkers to 11/100 (95% CI, 9-13) in men taking any alcohol. The corresponding reduction in cardiovascular death in women was from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). Deaths attributed to any cancer were unchanged in men (6/100 [95% CI, 3-9] versus 7/100 [95% CI, 5-9]) and in women (4/100 [95% CI, 2-6] versus 5/100 [95% CI, 3-7]).

Gross cost for alcohol per life-year gained
From the number of life-years added to survival for each quantity of intake, we have estimated the gross cost for alcohol per life-year gained. In men 60-74 years and in women 60 years and over taking 1-28 drinks/week, the respective costs were $13 000 and $31 000 per life-year gained. Since much of the benefit from alcohol intake was observed at a moderate intake of only 1-7 drinks/week, the respective costs at this intake were $5700 and $19 000 per life-year gained.

Not all studies have documented an association between all-causes mortality and alcohol intake.^16,17 The reduction in CHD and stroke mortality associated with alcohol use we observed is consistent with findings of previous reports,^8,18,19 as well as those of recent reports in large middle-aged cohorts from the United States.^4,5,20 These data are gradually causing health authorities to reconsider public policy on moderate alcohol intake, say 1-7 drinks/week, in the prevention of future morbidity and mortality.²¹ Studies in younger populations indicate a "U"- or "J"-shaped relationship between alcohol intake and all-causes mortality.² This has not been a general finding in the elderly, possibly because these cohorts contain an excess of "healthy survivors".¹⁰ It is surprising that we could find no relationship between alcohol intake and mortality in men aged over 74 years, but it is plausible that very elderly men lose the benefit of alcohol intake because they become subject to competing causes of mortality.⁹

There is a potential for misclassification of alcohol intake between zero and low intake because of under-reporting. This would diminish any apparent relative benefit of alcohol intake on all-causes mortality. Hence, our statistically significant findings may represent a minimum estimate of the benefit of moderate alcohol intake. We have demonstrated essentially a "threshold effect" between alcohol intake and all-causes mortality in either sex. Protection does not improve greatly as alcohol intake increases further (Box 3). Thus, under-reporting would then have less impact on our findings. This threshold effect is important, particularly if we were to move to a public health position of suggesting that abstainers should begin to imbibe!

The economic findings take no account of any changes in healthcare costs arising downstream through the benefits or otherwise of alcohol intake. What we regard as an acceptable cost per life-year gained is arbitrary, but it is informative to compare our calculated costs with, for example, recently published gross costs for the use of simvastatin in patients with established CHD, with survival increased by around 20%.²² Assuming such patients receive lifetime therapy with simvastatin from their mid-50s, the gross cost per life-year gained in the UK population would be £5100 (or about $13 000). Although one is comparing unrelated "therapy", moderate alcohol intake, at least in older men, may turn out to be a popular and cost-effective means of improving survival which does not require government subsidy!

The relative merits of wine versus other forms of alcohol consumption remain controversial. Data from France⁶ and Denmark⁷ highlight specific benefits of wine, and this has generated a new research effort to identify which components of wine, apart from alcohol, may be the most beneficial. Antioxidants are among the most prominent suggestions.²³ Others consider that alcohol in any form gives protection against cardiovascular disease,⁸ largely through its effect in raising high density lipoprotein (HDL) cholesterol levels.¹¹ In Dubbo, the quantity of alcohol intake was highly correlated with HDL cholesterol (r = 0.32, P < 0.001 and r = 0.23, P < 0.001 in men and women, respectively). Other suggested mechanisms for cardiovascular protection include favourable effects of alcohol on thrombotic and fibrinolytic pathways, reduced insulin resistance and improved endothelial function through increased nitric oxide production.⁵ Alcohol may also influence survival in ways which currently defy measurement: regular alcohol intake may reflect a special lifestyle integrated with less tangible factors.²¹

Although excess alcohol intake is undoubtedly toxic to the central nervous system, recent studies suggest that a moderate intake may reduce the risk of dementia. In a study of elderly French people 65 years and over, appropriately from Bordeaux, the rate of hospitalisation for dementia in non-drinkers over three years was 4.9/100, but only 3.9/100 in those taking any alcohol (with a more striking effect on the risk of Alzheimer's disease).²⁴ During 116 months' follow-up in the Dubbo population, the respective rates of hospitalisation for dementia were 4.3/100 and 2.5/100 (P < 0.01). It is premature to promote the use of alcohol for prevention of dementia, but the 21st century may witness a completely new role for alcohol in health.

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Faculty of Health, University of Western Sydney MacArthur, Sydney, NSW.
John McCallum, DPhil, Professor and Dean.

Department of Social Medicine, Hebrew University - Hadassah Hospital, Jerusalem, Israel.
Yechiel Friedlander, PhD, Associate Professor in Epidemiology.

Pfizer Pty Ltd, Sydney, NSW.
Michael Ortiz, PhD, Health Outcomes Manager.

Reprints will not be available from the authors.
Correspondence: Professor L A Simons, Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW 2010.
l.simonsATnotes.med.unsw.edu.au

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