Abstract
The data on two questions are reviewed: does heavy alcohol intake increase the risk of coronary heart disease (CHD)? And, is moderate intake protective? Identified alcoholics and problem drinkers have an increased risk of CHD, and in Britain there is a correlation among 22 towns, between the proportion of heavy drinkers in a town and CHD mortality. Of seven longitudinal studies reviewed, one shows heavy drinkers to have an increased CHD incidence. An inverse association between alcohol consumption and CHD mortality is seen in international comparisons and in time trends in the USA. Of six case-control studies reviewed from England and the USA, all show an inverse association between CHD and alcohol consumption which persists after control for other risk factors. Longitudinal studies, in Japanese-Americans, white American men and women, British civil servants, Puerto Ricans, Yugoslavs and Australians, all show moderate drinkers to have a lower CHD risk than abstainers. Abstainers are likely to differ from moderate drinkers in a number of ways. To date it has not proved possible to show that any of these differences account for the higher CHD risk of abstainers. The apparent protective effect is not large (RR = 0.5) but the consistency of the association and the existence of plausible mechanisms increase the likelihood that the negative association is causal. However, if alcohol intake were to increase in the population the social and medical consequences would be large. An increased intake is therefore not recommended as a community measure for CHD prevention.
Revised 1 August 1983
Medical and political discussions of the health effects of alcohol should give prominence to the individual and social damage caused by alcohol.1 In the interests of public health, it is right that any discussion should begin and end with these problems. In the middle, however, perhaps a small place may be reserved for continued exploration of why moderate drinkers appear to have a lower mortality risk, and particularly a lower incidence of coronary heart disease (CHD), than abstainers. Is the association causal? That is, do moderate amounts of alcohol exert a protective effect?
As suggested recently, non-drinkers may include a number of ex-drinkers who gave up because of ill-health.2 Hence a high mortality would not be surprising. This is plausible, but other evidence suggests different reasons for the CHD advantage of moderate drinkers. I should like to consider the evidence on two questions: does heavy alcohol consumption increase the risk of CHD and does moderate consumption protect against it?
A major problem concerns the varying definitions of heavy and moderate. There is agreement that daily consumption of more than 80 g of ethanol is heavy.3 This is the amount of alcohol contained in five pints of beer, or a bottle of table wine, or one third of a bottle of spirits (Table 1). However, others would put the dividing line between moderate and heavy at a lower level than this.4 Presumably an appropriate way to define heavy is the level above which alcohol-associated problems emerge; but this is a complex subject since alcohol is associated with a wide range of medical and social problems. The question considered here relates only to coronary heart disease.
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Does heavy alcohol consumption increase CHD risk?
Heavy alcohol consumption is related to increased total mortality, but the evidence for a relationship with cardiovascular mortality or morbidity is not consistent.
International comparisons
As will be seen below, international comparisons show a negative association between alcohol consumption and CHD mortality. Figures for the proportion of heavy, moderate and light drinkers in different countries are not readily available.
Regional comparisons
In the Regional Heart Study of 22 towns in Great Britain Shaper and colleagues show a positive correlation between the proportion of heavy drinkers in a town and mortality from CHD.6 These data do not relate to individuals; they examine one group characteristicheavy drinkingand relate it to anotherCHD mortality.
Studies of alcoholics or problem drinkers
Several studies on institutionalized alcoholics (e.g. by Sundby in Norway7) show them to have a high total mortality and an excess from cardiovascular disease. The generalizability of these results is uncertain as institutionalized alcoholics are likely to differ in many respects from heavy drinkers in the general population.
Two studies in industry of non-institutionalized men whose drinking interfered with their work, in the Du Pont company8 and in Chicago,9 showed these problem drinkers to have an increased risk of dying from cardiovascular disease. The relative risk was 2.3 for CHD in Du Pont, and 4.0 in Chicago. In Chicago, making adjustments for age, smoking and other risk factors reduced the mortality ratio a little, but it was still elevated.9
In Sweden, Wilhemsen et al. took registration with the Swedish Temperance Board as an indicator of heavy alcohol consumption and found an increased rate of non-fatal CHD and of sudden cardiac death, independent of blood pressure and smoking.10
Alcohol consumption and CHD
Other studies have concentrated not on problem drinkers or alcoholics but on actual alcohol consumption; almost all have shown heavy drinkers to have either a lower or the same risk of CHD as non-drinkers. Apparently the only exceptions are one study from Chicago that showed a non-significant excess mortality11 and a twin study that showed an excess of angina pectoris.12
Does moderate alcohol protect against CHD?
International comparisons
St Leger and colleagues13 compared CHD mortality in 18 developed countries with alcohol consumption and found a significant negative correlation. The strongest association was with wine and this was independent of cigarette consumption, dietary intake and gross national product. It is unlikely that this correlation could all be due to differences in diagnosis. Such analyses are always weakened by the absence of age-sex-social class specific consumption figures and cannot by themselves settle causal questions.
These data are consistent with a protective effect of moderate alcohol consumptionbut give little clue to what moderate means. From other data,14 we know that in France, a country with a low rate of CHD, the mean yearly alcohol consumption of people aged 15 and over is 22.3 litres. This corresponds to the startling figure of 49 g alcohol per adult per day, or approximately six drinks per day. Presumably these figures are not adjusted for sales to visitors and they may overstate consumption. Nevertheless, a high proportion of the French population exceed any definition of moderate drinking.
Time trends
Laporte and colleagues15 studying death rates in 20 countries, two years later than St Leger, confirmed the negative association between wine and CHD mortality. They then examined time trends in the USA of CHD mortality 195075, and found a negative association with alcohol consumption. This negative association was strongest for beer. In an exploratory way, without prior hypothesis, they examined the relation between CHD mortality and alcohol consumption a variable number of years previously. The correlation was strongest with a lag time of five years. For total alcohol the correlation was 0.73, and for beer the correlation was 0.94. This leads to speculation that increases in alcohol consumption may have contributed to the decline in CHD in the USA, although other factors have changed at the same time.
Case-control studies
The results of five studies comparing CHD cases with non-cases are summarized in Table 2, alcohol intake being determined before the CHD event in the study by Klatsky,19 but after it in the other studies. They included studies of men and women in the USA and men in England. None suggests that heavy intake is harmful. The studies by Stason et al.16 and Klatsky et al.19 find a lower relative risk associated with heavy intake. The others are consistent with a lower relative risk for moderate drinkers compared to non-drinkers.
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Yano et al., in the study of Japanese-Americans,21 did find that ex-drinkers had a higher mortality than life-time abstainers, but life-time abstainers had a higher mortality than current drinkers.
As a different approach to this question, in the Whitehall Study,27 we analysed separately the 10-year all-cause mortality of men who were unhealthy at entry into the study (history of diabetes, symptoms of cardiovascular or chronic respira-tory disease, or taking any medication), and compared them with the supposedly healthy remainder. In both the healthy and the unhealthy groups mortality was higher in non-drinkers.
(b) Could inaccuracies in alcohol history lead to the observed results?
Alcohol histories are notoriously inaccurate, although when they have been compared with biochemical measures of the effects of alcohol the correlation has been found to be high enough for some purposes. Simple inaccuracies would blur true associations and therefore could not account for the observed results; neither could underreporting by heavy drinkers unless they declared themselves to be total abstainers. Two of the studies, in Hawaii21 and San Francisco,19 found an inverse dose-response relationship (higher alcohol-lower CHD). It seems unlikely that denial of drinking could per se account for this association.
(c) Non-drinkers may differ in other ways that put them at higher risk.
Most of the studies reviewed above controlled for major known coronary risk factors, particularly smoking, and the negative association between CHD and alcohol was independent of these. It remains a possibility that non-drinkers may differ from moderate drinkers in other ways that put them at high risk, e.g., personality type, or diet. One recent study found drinkers in the upper moderate range (2549 g alcohol) but not lower moderate range (124 g alcohol) to differ in nutrient intake from non-drinkers. But differences in fat intake were small and inconsistent for men and women.28
To account for the above findings one would have to postulate that this factor X was more common in abstainers and non-abstainers in Yugoslavs, in Puerto Ricans, in Japanese-Americans, and in the other populations studies, and in men and women. This factor X would have to be more common in countries with lower than countries with higher alcohol consumption, and would have to have changed in frequency in the USA in the opposite way to alcohol consumption, increasing in the late 1940s and 1950s and declining again in the 1960s and 1970s.
There may indeed be a complex of factors that could explain away the above findings. A simpler explanation is that moderate drinking is protective.
How might alcohol protect against CHD?
Type of alcohol
If one type of alcohol beverage were more strongly protective against CHD, this would make it more likely that it was not alcohol per se. The findings on this point do not, at the moment, implicate one type of drink over another. St Leger et al.13 found the inverse association between countries to be strongest with wine, but Laporte et al. found the inverse association with time trends in the USA to be strongest with beer.15 In three studies18,21,23 different types of alcoholic drinks were all shown to be more or less equally associated with lower CHD risk. The other studies did not distinguish type of alcoholic drink. Nevertheless, it remains a possibility that components of alcoholic drink other than ethanol are responsible for a protective effect.
Possible mechanisms
Atheroma
There is not general agreement, but there have been reports of less atheroma in alcoholics at autopsy.15 In general these were studies of heavy, not moderate drinkers.
One study of patients undergoing coronary angiography29 found significantly lower occlusive scores in moderate than in non-drinkers. Such studies are difficult to interpret because of the biased selection of patients.
Lipids
Several studies have shown HDL cholesterol levels to be higher in moderate drinkers15,30 and high levels of HDL cholesterol are associated with lower CHD risk. However, the fraction associated with lower CHD risk is HDL2, whereas alcohol may increase the HDL3 fraction, although this has not been definitely established.
Thrombosis
Alcohol in large amounts can produce thrombocytopaenia and decreased platelet aggregation. Meade has reported that drinkers have lower fibrinogen levels and higher fibrinolytic activity than non-drinkers.31 These effects could protect against CHD.
Is the negative association causal?
There is some evidence of an increased risk of CHD in heavy drinkers. This is not a crucial public health question, however, as there is sufficient evidence of the hazards of heavy drinking to make it undesirable, regardless of a possible relation with CHD.
The evidence that moderate alcohol consumption may be protective may be assessed in relation to the formal criteria for a causal association.
Strength
The relative risk for moderated alcohol consumption is of the order of 0.5. It is quite conceivable that some third factor(s) may account for an observed association of this order of strength.
Dose-response
An inverse dose-response relationship has not been found consistently, possibly due to inaccuracies in determining alcohol consumption. Whatever the reason, this is a weakness in the current evidence.
Temporal sequence
A number of studies have established that non-drinking preceded the onset of CHD.
Consistency
One of the strongest arguments in favour of causality is that the inverse association with alcohol has been found in several different populations, in case-control and longitudinal studies, in international comparisons and in analyses of mortality time trends. Each of these types of study has its own weaknesses. Consistent findings from such varied sources make it more likely that moderate alcohol consumption is protective.
Independence
Where studied, the association between non-drinking and CHD has been found to be independent of other major cardiac risk factors.
Plausibility
The effect of alcohol on HDL cholesterol offers a plausible mechanism (or did so, until recent doubts arose on the relevance of the HDL fraction influenced by alcohol), as does the effect on haemostasis.
Specificity
There is some evidence that deaths from other causes may be commoner in non-drinkers, but not to the same extent as cardiovascular disease,24 and this has been found less consistently.
In summary, the evidence is far from complete; but it does point towards a protective effect of moderate alcohol consumption. If there is a level of alcohol which is no longer safe for CHD, it is probably in excess of six drinks per day (approx 50 g alcohol). If the apparent protective effect is due to confounding variables, they have yet to be identified.
What recommendations should be made?
If, as an interim judgement, we assume that the protective effect of moderate alcohol consumption is likely to be causal, two further aspects must be considered in making recommendations: what is the upper limit of moderate and what are the likely effects of recommending moderate alcohol intake?
The figure from the Whitehall study shows a U-shaped relationship of mortality to alcohol; we took 34 g alcohol per day (about four drinks) as the start of our heavy category of consumption. It is difficult to know at precisely what level of alcohol consumption the non-CVD mortality starts to increase, but data from other studies show blood pressure to be higher with four drinks (or even less) per day.
The Royal College of Psychiatrists has recommended32 a maximum limit of twice this amount (about eight drinks per day), but this seems to be too high. There is an association between the mean level of alcohol consumption of a community and the proportion of problem drinkers,14 and anything that encourages an increase in average consumption is likely to lead to disastrous consequences in a minority, as well as to more widespread social costs and an increase in road accidents. These considerations, linked with the fact that the role of moderate intake in protecting against CHD is not certain, lead the author to agree with the conclusion of the recent WHO Expert Committee on the Prevention of CHD: Increased alcohol intake is not recommended as a preventive measure in CHD, either in populations or in individuals.
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I should like to thank Professor Geoffrey Rose for his valuable comments. Research support was received from the British Heart Foundation.
Notes
* Reprinted from International Journal of Epidemiology 1984;13:16067.
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
a Current address: International Centre for Health and Society, Department of Epidemiology and Public Health, University College London, 119 Torrington Place, London WC1E 6BT, UK. E-mail: m.marmot{at}ucl.ac.uk
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