Commentary: Could abstinence from alcohol be hazardous to your health?

AL Klatsky

Kaiser Permanente Medical Center, 280 West MacArthur Boulevard, Oakland, CA D4611, USA. E-mail: hartmavn{at}pacbell.net

‘Those who cannot remember the past are condemned to repeat it.’

George Santayana 1905

William Heberden's classic description of angina pectoris in 17861 included: ‘Wine and spirituous liquors ... afford considerable relief’. This observation, plus the cutaneous facial vasodilatation often induced by alcohol, led to the presumption by some observers that alcohol was a coronary vasodilator.2,3 However, exercise ECG test data4,5 suggested only subjective symptomatic benefit and indicated no acute increase in myocardial oxygenation from alcohol. Thus, angina relief may be due to an anaesthetic effect of alcohol. Physiological studies do not convincingly establish a major immediate effect of alcohol upon coronary blood flow.6,7 In any case, angina is subjective, difficult to measure, and has been relatively little used as an endpoint in epidemiological studies of alcohol and coronary heart disease (CHD).

In the first half of the 20th century there were reports of an apparent inverse relationship between heavy alcohol consumption and atherosclerotic disease.811 Some speculated that premature deaths in alcoholics precluded development of CHD,12,13 but vascular benefit in cirrhotics from higher blood oestrogens or an effect on lipoprotein lipase was also suggested. In 1961 Stare14 wrote ‘Whatever the mechanism—cirrhosis is accompanied by a sparing of the vascular intima, especially of the coronary circulation’.

Preceding other reports of the J-shaped alcohol-mortality curve by half a century, Pearl described this relationship in a Baltimore, Maryland study of tuberculosis patients and controls.15 ‘Heavy/steady’ drinkers had the highest mortality; ‘abstainers’ were next; and ‘moderate’ drinkers had the lowest mortality. Pearl did not know that the favourable mortality of moderate drinkers was due to lower CHD risk and the study coincided with the US Prohibition era. He made the cautious interpretation that moderate drinking was ‘not harmful’. We scientists may not care to admit it, but cultural context often influences what research gets done and how it is interpreted. This is especially the case if, as with alcohol effects, the area of interest arouses strong feelings. Perhaps Pearl's major contribution was to realise the fallacy in comparing health risks of all drinkers to abstainers. Such comparison masks differences between the risks of heavy and light/moderate drinkers.

In the 1970s epidemiological studies began to appear which consistently show an inverse relationship between light-moderate alcohol drinking and either fatal or non-fatal CHD. With respect to moderate drinking and CHD, Dr Marmot's 1984 article,16 cites five case-control and seven longitudinal studies, plus two international comparisons and one time-trend report. A literature search through 1998 done for a meta-analysis17 uncovered no fewer than 196 articles on the subject.

Dr Marmot prefaces his discussion by mention of two difficulties. First, he discusses the ‘major problem’ of varying definitions of ‘heavy’ and ‘moderate’ drinking, with the suggestion that the boundary should be the imprecise level ‘above which alcohol-associated problems emerge’. In 2001 we still have a variety of definitions, although there is some consensus that 3+ drinks/day (36+ g of alcohol) may exceed the safe limit for men and less consensus that 2+ drinks/day (24+ g of alcohol) may exceed the safe limit for women. Second, he points out that the myocardial toxicity of chronic heavy drinking has nothing to do with the alcohol-CHD relationship. This disparity, plus other cardiovascular conditions related to heavy drinking (hypertension, arrhythmias, haemorrhagic stroke) still confounds reports using ‘cardiovascular’ and ‘coronary’ disease synonymously.

From here on, I shall adopt Dr Marmot's query-response format:

Does heavy alcohol consumption increase CHD risk?

The 1984 conclusion that the evidence is ‘not consistent’ remains accurate. Studies of alcoholics and problem drinkers show high CHD risk. Some population studies suggest the same situation, while other population studies of the entire usual drinking range show heavy drinkers at the same or lower CHD risk as non-drinkers. Studies of CHD mortality generally show a U-shaped or J-shaped alcohol-CHD relationship, with heavy drinkers at the same or higher risk than abstainers. Many studies of non-fatal CHD show an L-shaped graph, with heavy drinkers and light drinkers both at lower risk than abstainers.7 Non-fatal myocardial infarction (MI) may be a more reliable end-point than reported CHD deaths among heavy drinkers because death data may be confounded by erroneous diagnoses of cardiomyopathy or other conditions. Yet there is plausibility in higher risk of CHD among some heavy drinkers, because of alcohol's probable roles in hypertension, hypertriglyceridaemia, and genesis of arrythmias. These consequences can interact with unfavourable effects of binge-drinking patterns in many heavy drinkers.

The relationship of heavy drinking to CHD was one of the foci of a recent meta-analysis17 which indicated that CHD risk was increased in heavier drinkers. Of 196 articles screened, 51 (43 cohort studies and 8 case-control studies) met inclusion criteria. Most used CHD mortality or combined mortality/morbidity as end-points. The threshold for increased risk occurred at 89 g (approximately 7 standard drinks) per day. This is well above all usual definitions of moderate drinking and higher than Dr Marmot's estimate of 50 g of alcohol as the level of drinking no longer ‘safe’ for CHD.

Another recent meta-analysis18 led to the conclusion that five or more drinks per day ‘are not associated with a reduced risk of death and CHD’. That effort involved 8 cohort studies for assessment of CHD death and 12 cohort plus 2 case-control studies for assessment of non-fatal MI.

Does moderate alcohol consumption protect against CHD?

A consistent inverse empiric relationship in the studies reviewed in 1984 is robustly bolstered by a near-unanimous finding of lower CHD risk in the much larger number of studies now reported. Reviews6,7,1821 provide details, so there is no need for further elaboration here. Corrao et al.'s meta-analysis yielded an estimated risk reduction of 20% at 0–20 g (<=2 standard drinks) per day and some reduction of risk up to 72 g/day, or 6 standard drinks.17

Is the lower CHD risk due to factors other than alcohol?

As discussed in 1984, when reporting their alcohol intake some people ‘underestimate’, a polite euphemism for ‘lie’. While often mentioned as casting doubt upon the existence of the inverse alcohol-CHD relationship, it is difficult to plausibly explain how this phenomenon might spuriously produce the apparent protective effect of light drinking against CHD.

Controversy about protection persists in 2001 on the basis that correlates of abstinence and lighter drinking could explain the higher risk of abstainers. The so-called ‘sick-quitter’ hypothesis has been much debated. Forcefully advanced in 1988,22 this hypothesis suggested that the movement of people at high CHD risk, largely ex-drinkers, into the abstainer group could explain the U-shaped curve. A number of subsequent prospective population studies6,7,1821 separated lifelong abstainers from ex-drinkers and/or carefully controlled for baseline CHD risk; these showed lower CHD risk in light drinkers than in abstainers. Several studies were controlled for dietary habits and physical exercise. Various reports involve both sexes, multiple ethnic groups, populations with low and high CHD risk or small and large proportions of abstainers, people with and without diabetes, people without evident CHD and those with MI, smokers, ex-smokers and never smokers, and drinkers of wine, beer, or spirits. So it is worth repeating that ‘There may indeed be a complex of factors that could explain away the above findings. A simpler explanation is that moderate drinking is protective’.16

Proof of total independence from indirect explanations is best achieved by prospective controlled experiments. Observational data cannot control for all possible confounders. Since satisfactory experiments of alcohol drinking and CHD development may never be done, the prospective population studies are likely to be the best data we will ever have.

How might alcohol protect against CHD?

With no explanation evident, the first Kaiser Permanente report in 197423 offered protection as only one of several possible explanations for the lower CHD risk of drinkers. By 1984, data about plausible protective mechanisms had surfaced, including higher high density lipoprotein (HDL) cholesterol levels in drinkers and anti-thrombotic effects of alcohol.

The link via HDL (both HDL2 and HDL3) is now much more solidly established6,7,1821 and higher HDL seems to account for about 50% of the observed lower CHD risk in alcohol drinkers. Evidence for possible anti-thrombotic actions of alcohol has also grown, perhaps most convincingly with respect to lowered blood fibrinogen levels. An anti-thrombotic action of alcohol could partially account for the lower CHD risk at very light drinking levels (e.g. several drinks per week) seen in several of the epidemiological studies, but this protective mechanism is less established than the HDL cholesterol pathway. Evidence about other mechanisms, including decreased insulin resistance and myocardial ‘preconditioning’ in drinkers remains preliminary. Consideration of possible benefit from anti-anxiety or stress-reducing effects of alcohol has frequently been raised, but there are no convincing data to support this hypothesis.

The lack of evidence that one particular beverage type is more protective than others was considered a point favouring a role for alcohol itself in 1984. This issue has become more complicated over the ensuing 20 years. One major hypothesis is that non-alcoholic ingredients in red wine offer additional CHD protection to that of beer or spirits. Support for this hypothesis was found in ecologic studies as early as 1979.24 Reports of non-alcohol antioxidant phenolic compounds or anti-thrombotic substances in wine, especially red wine,6,7,1821 provide plausible biological explanations for extra CHD protection. However, prospective population studies show no consensus about the wine/liquor/beer issue.18,25,26 There is evidence of benefit from each beverage type. Most of the data about protective mechanisms deal with alcohol itself. Patterns of drinking and disparities in the traits of people who prefer wine, beer, or spirits are potential confounders, especially in the ecologic international comparison studies. This wine/liquor/beer question remains unresolved at this time. This is not an ‘either/or’ issue. Since it is likely that alcohol is protective, the true issue is probably the existence and magnitude of extra protection by specific beverages.

Is the negative association causal?

To my knowledge, Marmot's article was the first to apply epidemiological criteria of causality to the moderate drinking-CHD association. Using strength, dose-response, temporal sequence, consistency, independence, plausibility, and specificity, his conclusion was a qualified ‘yes’. In 2001 the data about consistency, independence, plausibility are more solid. Possibly fuelled by disappointing results in recent reports about CHD protection by oestrogenic hormones and vitamin E, the demand for a controlled experiment as proof for any causal association has also gained strength.27 It seems probable that debate about causality will long continue, but practical decisions about advice must often be made without certainty of knowledge.

What recommendations should be made?

Here, cultural context clearly influences attitudes. The need for great care is universally recognised. It is essential to avoid any inducement or even rationalization of heavy drinking. Much media dissemination about the possible CHD benefits of moderate alcohol drinking and of red wine, in particular, has occurred. This has resulted in increased red wine sales in the U.S., but it is not clear what, if any effect has occurred upon individual drinking habits. The general public is becoming increasingly sophisticated about health matters. Partially because of media presentation of conflicting reports, the public is also increasingly sceptical.

Risk of progression to problem drinking is the major health risk of moderate drinking. Other possible, but unproven, risks of moderate drinking include fetal alcohol syndrome, haemorrhagic stroke, large bowel cancer, and female breast cancer. The most troublesome data are those about moderate drinking and possible increased risk of breast cancer,27 especially since women <50 years of age are generally at very low CHD risk.

One widely used definition of a ‘safe limit’ is no more than two drinks per day for men or one per day for women, amounts associated with evidence of lower risk of CHD. Both the number and the size of drinks compromising the safe limit should always be specified. One thread which has emerged with increasing consistency in the medical literature is the need to individualize advice. Age, sex, family and personal history of drinking, and specific medical history all must be known to make a judgement about the individual risk benefit equation.2730 It is easier and more satisfactory for a knowledgeable health practitioner to advise his or her patient than to formulate rules for all. In the end, the responsibility to give wise and honest counsel falls upon the shoulders of the professional.

References

1 Heberden W. Some account of a disorder of the breast. Medical Transactions of the Royal College of Physicians, London. 1786;2:59–67.

2 White PD. Heart Disease. New York: Macmillan, 1931.

3 Levine SA. Clinical Heart Disease. 4th Edn. Philadelphia: Saunder, 1951.

4 Russek HI, Naegele CF, Regan FD. Alcohol in the treatment of angina pectoris. JAMA 1950;143:355–57.[ISI]

5 Orlando JF, Aronow WS, Cassidy J. Effect of ethanol on angina pectoris. Ann Intern Med 1976;842:652–55.

6 Renaud S, Criqui MH, Farchi G, Veenstra J. Alcohol drinking and coronary heart disease. In: Verschuren PM (ed.). Health Issues Related to Alcohol Consumption. Washington DC: ILSI Press, 1993, pp.43–80.

7 Klatsky AL. Epidemiology of coronary heart disease—influence of alcohol. Alcohol, Clin Exp Res 1994;18:88–96.[ISI][Medline]

8 Cabot RC. Relation of alcohol to arteriosclerosis. JAMA 1904;44: 774–75.

9 Leary T. Therapeutic value of alcohol, with special consideration of relations of alcohol to cholesterol, and thus to diabetes, to arteriosclerosis, and to gallstones. New Engl J Med 1931;205:231–42.

10 Wilens SL. Relationship of chronic alcoholism to atherosclerosis. JAMA 1947;135:1136–39.[ISI]

11 Parrish HM, Eberly AL Jr. Negative association of coronary atherosclerosis with liver cirrhosis and chronic alcoholism—a statistical fallacy. J Indiana State Med Assoc 1961;54:341–47.[ISI]

12 Ruebner BH, Miyai K, Abbey H. The low incidence of myocardial infarction in hepatic cirrhosis. A statistical artefact? Lancet 1961;ii: 1435–36.

13 Grant WC, Wasserman F, Rodensky PL, Thompson RB. The incidence of myocardial infarction in portal cirrhosis. Ann Inter Med 1959;51: 774–79.[ISI][Medline]

14 Stare F. Nutritional Review. 1961;19:37.

15 Pearl R. Alcohol & Longevity. New York: Knopf, 1926.

16 Marmot MG. Alcohol and coronary heart disease. Int J Epidemiol 1984; 13:160–67.[Abstract]

17 Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction 2000;95:1505–23.[ISI][Medline]

18 Cleophas TJ. Wine, beer and spirits and the risk of myocardial infarction: a systematic review. Biomed Pharmacother 1999;53:417–23.[ISI][Medline]

19 Klatsky AL. Cardiovascular effects of alcohol. Scientific American Science and Medicine 1995;2:28–37.

20 Alcohol and cardiovascular diseases. Paper presented at: Novartis Foundation Symposium 216, 1998; Chicester, England.

21 Paoletti R, Klatsky AL, Poli A, Zakhari S (eds). Moderate Alcohol Consumption and Cardiovascular Disease. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2000.

22 Shaper AG, Wannamethee G, Walker M. Alcohol and mortality in British men: Explaining the U-shaped curve. Lancet 1988;ii:1267–73.

23 Klatsky AL, Friedman GD, Siegelaub AB. Alcohol consumption before myocardial infarction: Results from the Kaiser-Permanente epidemiologic study of myocardial infarction. Ann Intern Med 1974;81:294–301.[ISI][Medline]

24 St Leger AS, Cochrane AL, Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet 1979;i:1017–20.

25 Rimm E, Klatsky AL, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: Is the effect due to beer, wine, or spirits? Br Med J 1996;312: 731–36.[Abstract/Free Full Text]

26 Klatsky AL, Armstrong MA, Friedman GD. Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization. Am J Cardiol 1997;80:416–20.[ISI][Medline]

27 Goldberg IJ, Mosca L, Piano MR, Fisher EA. Wine and your heart: A science advisory for healthcare professionals from the Nutrition Committee, Council on Epidemiology and Prevention, and Council on Cardiovascular Nursing of the American Heart Association. Circulation 2001;103:472–75.[Free Full Text]

28 Pearson TA, Terry P. What to advise patients about drinking alcohol. JAMA 1994;272:957–58.[Abstract]

29 Friedman GD, Klatsky AL. Is alcohol good for your health? [Editorial]. New Engl J Med 1993;329:1882–83.[Free Full Text]

30 Criqui MH, Golomb BA. Should patients with diabetes drink to their health? JAMA 1999;282:279–80.[Free Full Text]