Follow up study of moderate alcohol intake and mortality among middle aged men in Shanghai, China

Introduction

In prospective cohort studies conducted in Western populations men and women who drink light to moderate amounts of alcohol have been found to have lower overall death rates than either non-drinkers or heavy drinkers.1 2 3 4 5 6 7 8 9 10 11 The observed protective effect of drinking on overall mortality is largely due to a reduced risk of fatal ischaemic heart disease, which accounts for roughly one third of all deaths in such populations. High consumption of wine has been suggested to be responsible for the low risk of ischaemic heart disease in France,12 and recent findings from a prospective study in Copenhagen support this hypothesis; drinking wine but not beer or spirits was found to be associated with reduced overall mortality in Danish people.13 On the other hand, several studies reported no differential effects of wine and other types of alcoholic beverages on risk of death.11 12 13 14 15 16 17 In a recent review of the relation between specific types of alcoholic drink and risk of coronary heart disease, Rimm et al concluded that there is no evidence that wine offers any more protection against ischaemic heart disease than beer or spirits.18

We examined prospectively the relation between alcohol consumption and mortality in a large cohort of middle aged Chinese men in Shanghai, China. In this cohort, ischaemic heart disease accounts for only about 9% of all deaths19 and grape wine is a minor source of alcohol among those who drink regularly. Therefore, our study population is a valuable one to evaluate further the relation between moderate alcohol intake and mortality.

Subjects and methods

Between January 1986 and September 1989 we invited all eligible male residents of four small, geographically defined communities from a wide area of the city of Shanghai to participate in a prospective, epidemiological study of diet and cancer. The men had to be aged 45-64 years and have no history of cancer. At recruitment we interviewed each subject using a structured questionnaire which included level of education, usual occupation, adult height and usual adult weight, history of tobacco and alcohol use, current diet, and medical history.

We asked each participant whether he had ever drunk alcoholic beverages at least once a week for six months or more. If the answer was yes, he was asked to provide the age at which he started to drink regularly and the usual amount of consumption of beer, wine, and spirits separately. If the subject was a former drinker the age at which he stopped drinking was recorded. One drink was defined as 360 g of beer (12.6 g of ethanol), 103 g of wine (12.3 g of ethanol), or 30 g of spirits (12.9 g of ethanol).20

Details of the follow up procedures for this cohort have been described.21 We routinely reviewed death certificates and cancer reports from the population-based Shanghai Cancer Registry, and all surviving members of the cohort were contacted each year.

For each man, years of follow up were counted from the date of recruitment to 28 February 1995 or the date of death or loss to follow up, whichever occurred first. Overall mortality was calculated according to various categories of alcohol consumption. Because of the small number of former drinkers in the study population, former and current drinkers could not be analysed separately. All rates were adjusted for age by using the person-year distribution of the entire cohort as the internal standard.

We used the Poisson regression method to examine the relation between alcohol consumption at recruitment and subsequent risk of death.22 Relative risks and their corresponding 95% confidence intervals were calculated for various categories of drinkers in reference to lifelong non-drinkers. Two statistical models were used to examine whether the observed relation between alcohol intake and mortality was specific to the type of drink consumed (beer, wine, or spirits). Model one examines the relation between a specific type of alcoholic drink and overall mortality while controlling for the consumption of the other two types (a covariate representing the total ethanol intake for the latter was added to the list of confounding variables). Model two tests for possible association between mortality and a specific type of alcoholic drink after adjusting for total ethanol intake (a covariate representing total ethanol intake was added to the list of confounding variables). Therefore, if the putative U shaped relation between alcohol intake and mortality is independent of type of drink consumed, model one will yield similar U shaped curves for beer, wine, and spirits while model two will show no additional association with beer, wine, or spirits after total alcohol intake has been taken into consideration. The other confounding variables adjusted for in the various regression models were age, cigarette smoking, and level of education.

We used the proportional hazards regression method to test for a curvilinear relation between alcohol intake and total mortality (linear and quadratic terms for number of drinks per week were included in the regression model).23 All quoted P values are two sided. Relative risks with two sided P values under 0.05 were considered to be significantly different from 1.0.

Results

During the three year recruitment period 18 244 men enrolled in the study, and to date only 108 have been lost to follow up. At recruitment, 57% (10 471) of cohort members had never drunk alcoholic beverages regularly, 41% (7390) were current drinkers, and the remaining 2% (383) were former drinkers (table 1). Drinking was closely and positively associated with cigarette smoking and moderately related to age (positively) and level of education (negatively) (data not shown).

As of 28 February 1995, the cohort had been followed up for 122 300 person-years (an average of 6.7 years of follow up per man). During the follow up 1198 of the men had died (980/100 000 person-years). There were 498 deaths from cancer, 269 deaths from stroke, and 104 deaths from ischaemic heart disease. We attempted to review the medical records of all cancer cases and deaths. Sixty per cent (298) of the deaths from cancer were confirmed histopathologically, including 93% (27) of deaths from colorectal cancer, 88% (80) from stomach cancer, 81% (26) from upper aerodigestive tract cancer, 67% (98) from lung cancer, and 13% (13) from liver cancer; 97% of the remaining cancer cases showed raised α fetoprotein concentrations or a positive liver scan, or both, at diagnosis.

Of the men who died from stroke, 85% (229) had been admitted to hospital before dying; no evidence of medical care immediately before death was established for 9% (24) of these patients. The comparable figures, respectively, were 82% (85) and 13% (13) for ischaemic heart disease, 84% (59) and 11% (8) for chronic bronchitis and emphysema, and 94% (33) and 3% (1) for hepatic cirrhosis.

Discussion

We found that Chinese men who consumed no more than 14 drinks a week had a significant 19% reduction in overall mortality relative to lifelong non-drinkers. The observed association was not explicable by confounding factors such as cigarette smoking, dietary intake, level of education, and age. In agreement with findings in Western populations,1 2 3 4 5 6 16 17 we observed a significant 36% reduction in mortality from ischaemic heart disease among light to moderate drinkers relative to lifelong non-drinkers. However, the protective effect of moderate drinking on total mortality in Shanghai men was not restricted to ischaemic heart disease, which accounts for only 9% of total deaths.

Bias is unlikely to explain the observed associations. The prospective study design precluded recall bias. A structured questionnaire was used to administer the interviews to ensure that all subjects were asked identical questions. We were also able to separate former drinkers from lifelong non-drinkers and thus eliminated the potential bias that former drinkers might have an increased risk of death and account for the raised mortality.24 Another proposed argument to explain the relatively high mortality among abstainers is that such individuals carry a greater “burden of ill health” due to lifelong health problems than light to moderate drinkers, regardless of their previous drinking status.25 We excluded all subjects with a history of potentially life threatening illnesses and no change in the results was observed. Our results also were unaffected by duration of follow up, supporting the notion that other unidentified bias is not likely to be responsible for the observed association.

There is evidence that the collected information is reasonably reliable. Diseases reported to be positively associated with heavy alcohol intake in Western populations (upper aerodigestive cancer, liver cirrhosis, and injury/accident) showed similar associations in our study. It is also important to note that loss to follow up was negligible (only 108 out of 18 244 subjects). Finally, it is unlikely that the observed associations between cause-specific mortality and alcohol intake were due to misclassification of cause of death. In 82% of cases cause of death was medically confirmed immediately before death, and exclusion of those without such confirmation did not affect the association between light to moderate alcohol intake and cause-specific mortality.

An ecological study suggested that high consumption of wine might be responsible for the lower risk of ischaemic heart disease in France.12 Recent findings from a prospective study in Copenhagen have shown that wine drinkers had a 50% reduction in mortality relative to non-drinkers.13 In the same study, beer drinking was not related to mortality and spirit consumption increased the risk.13 However, several studies have reported no differential effects of wine relative to other types of alcoholic beverages on mortality.11 14 15 16 17 Rimm et al recently concluded that much of the benefit is from alcohol rather than other components of each type of drink.18 We did not separate the grape wine from other wines drunk by Chinese, but data from a case-control study of nasopharyngeal carcinoma that we conducted in Shanghai in the late 1980s indicate that few Chinese men drink grape wine regularly. Among male controls in that study, only 6% of wine drinkers drank grape wine; the rest of them drank only rice wine (unpublished data). Our data did not show that intake of wine was more beneficial in reducing risk of death than consumption of beer or spirits.

In summary, light drinking was associated with a 19% reduction in overall mortality in middle aged men in Shanghai. This protective effect was not restricted to any specific type of alcoholic drink. There was also a 36% reduction in risk of death from ischaemic heart disease among light to moderate drinkers and significant increases in risks of cancer of the upper aerodigestive tract, stroke, and hepatic cirrhosis among heavy drinkers.

We thank X-L Wang, Y-L Zhang, and J-R Cheng of the Shanghai Cancer Institute for their help in data collection and management, the staff at the Shanghai Cancer Registry for their help in verifying cancer diagnosis, and Kazuko Arakawa of the University of Southern California for her help in data management and analysis.