Medical/Scientific Council Comments
By 1992, the association between lowered risk of coronary artery disease (CAD) in particular, and atherosclerosis in general, and moderate alcohol consumption was well established. Several studies summarize that relationship. The position statement of the National Heart Foundation of Australia reviews the most common dietary factors (including alcohol) and their relationship to CAD. The article by Manson, et al. is a review of factors that might be helpful in reducing the risk of myocardial infarction. Their review includes comments about the quality of the research data as well as the magnitude of the impact of each intervention.
A number of studies during 1992 focused on refining our understanding of the relationship between alcohol consumption and CAD); specifically those that focused on the ways in which alcohol might protect against CAD. Interestingly, the bulk of those studies are beginning to provide compelling evidence that moderate alcohol consumption's cardioprotective effect is in part mediated by its impact on lipids such as high-density lipoprotein cholesterol. The biochemistry of blood lipids is a very complicated topic. For instance, fat in its many forms (e.g., cholesterol and triglycerides) is carried in the blood stream by a variety of proteins known as lipoproteins. Each of these lipoproteins has several subcomponents known as a apolipoprotein. From the point of view of the biochemist or molecular biologist who is concerned with mechanisms of atherosclerosis development, the implicated interrelationships are very important. From the point of view of the practicing physician and the patient, it is often only necessary to know the basics, such as the relationship between cholesterol, HDL, LDL, and CAD. Several studies address these questions, almost all of them arrive at same conclusion: 1) alcohol consumption affects the level of HDL cholesterol, 2) this is mediated by a very basic effect on apolipoprotein synthesis in the liver and 3) HDL elevation is responsible for only part of alcohol's cardioprotective effect. This latter point is important because several articles in this review suggest that alcohol's effect on blood clotting (as mediated through its effect on platelet function) may be a second, equally important mechanism by which alcohol protects against heart disease Another series of articles touches on the complicated set of interrelationships between alcohol, cardiovascular disease and other risk factors. For instance, several articles remind us that not all people are equally subject to the cardioprotective effects of alcohol. It appears that obesity diminishes this effect. This may be relevant to the article by Seppa, et al. which found no relationship between alcohol consumption and lipid values. This article stands out as an exception to nearly every other study that has been published in this area. It was suggested by R. A. Kreisberg in an editorial preceding the Seppa article in the archives of Internal Medicine, that the authors did not adequately control for other factors (such as exercise, body weight, smoking, and actual drinking during the two weeks prior to the measurement) in evaluating their findings.
On the other hand, the article by Razay, et al. finds that moderate alcohol consumption is associated with several improved cardiovascular risk factors among women, including higher levels of HI)L cholesterol, lower levels of total cholesterol, insulin and body weight. The study by Keenan, et al. further subdivides the interactions between alcohol and other cardiovascular risk factors. His study with black adults shows that waist-to-hip ratio (the lower the waist-to-hip ratio, the higher the risk of CAD) was related to socio-economic status, exercise and alcohol consumption in a variable pattern, depending upon the person's gender. Taken all together, these studies indicate that there is no single pathway to optimal cardiovascular health. It is modulated by a complicated interaction that includes gender, smoking, body weight, exercise, dietary intake of fat and intake of alcohol. Once again, the common caveat probably is the most important: moderation in all things.
Finally, several articles evaluate the physiology (as opposed to the biochemistry) of alcohol consumption. The article by Allison, et al. while limited in Its focus, indicates that alcohol does not acutely affect the body's response to immersion in very warm water. On the other hand, the several articles that deal with hypertension continue to show that increased levels of alcohol consumption (3 drinks or more per day) are associated with increased prevalence of hypertension. However, Shnall, et al. suggest the hypertensive effects of alcohol occur only in a stressful setting. Heavy drinking is also associated with increased risk of certain irregularities of heart rhythm, as indicated in the editorial by Koskinen. Both this article and the one by Maheswaran, et al. provide practical insights into simple ways to ameliorate these negative effects of excessive alcohol consumption.
Summaries
Blood Pressure
Ascherio, et al. studied the association between dietary intake, as reported by 30,681 men, and incidence of hypertension in a four-year prospective study. The authors reported a significant increase in risk of developing hypertension among men drinking over 30g of alcohol (2-3 drinks) compared with those who abstain. At levels of alcohol consumption less than 30g per day, there was no association between alcohol level and incidence of hypertension. The nutrients important in reducing risk of developing hypertension were dietary fiber, potassium, magnesium and calcium. After simultaneous adjustment for age, relative weight, alcohol consumption, physical activity, smoking, waist-to-hip ratio, only dietary fiber was still significantly and inversely associated with hypertension.
Ascherio A, et al. A prospective study of nutritional factors and hypertension among U.S. men., Circulation 1992; 86(5):1475-84.
Ekpo and colleagues studied a variety of correlates of blood pressure in 5200 people (43 82 men/8 18 women) living in an urban setting in the southeastern part of Nigeria. The overall prevalence of hypertension was 8. 1% (3.5 % for women and 8.9% for men). The prevalence of hypertension was higher in medium and heavy drinkers that in non-drinkers and light drinkers. Non-drinkers had - a prevalence of hypertension of 8.2 % compared to 4.4% for the lightest drinking group and 16% for the 2-3 pints/day consumers.
Ekpo EB, et al. Demographic, life style and anthropometric correlates of blood pressure of Nigerian urban civil servants, factory and plantation workers., Journal of Human Hypertension 1992; 6(4):275-80.
To investigate the time course of the effects of alcohol on blood pressure, Kawano, et al. examined 16 hypertensive Japanese men under standardized conditions. They found that a single moderate dose of alcohol (1 ml/kg of vodka) lowered the blood pressure in hypertensive patients who were habitual drinkers. This depressor effect was due to peripheral vasodilation and was accompanied by reflex tachycardia, an increase in cardiac output, and activation of the sympathetic nervous system. They suggest that the pressor effect of alcohol has been overestimated and the depressor effect has been underestimated by measuring only daytime blood pressure.
Kawano Y, et al. Acute depressor effect of alcohol in patients with essential hypertension., Hypertension 1992; 20(t):219-26.
Recognizing that advice to reduce alcohol is an important part of managing the treatment of hypertensive patients, Maheswaran, et al. evaluated the effectiveness of this advice in a randomized trial. Forty-one hypertensive males consuming more than 20 units per week (unit= 10g alcohol) were randomly~assigned either to a group that received counseling (10-15 minutes of simple advice) to reduce consumption or to a control group.
At the end of the 18 month study, the "advice" group had seduced consumption by 50% from an average consumption level of 60 u/w to 30, compared to no change in the control group. This reduction was accompanied by decreases in signs of liver injury and a fall in standing diastolic blood pressure. "The advice given in this study is a useful and practical form of treatment that is readily applicable in routine clinical practice."
Maheswaran R, et al. Effectiveness of advice to reduce alcohol consumption in hypertensive patients., Hypertension 1992; 19(1):79-84.
Schnall, et al. studied 264 men at 8 work sites to evaluate the relationship between job strain, alcohol and ambulatory blood pressure (AmBP). Among subjects not in high-strain jobs, alcohol had no apparent effect on AmBP at work. Instead, alcohol use and job strain interacted such that workers in high-strain jobs who drank regularly had significantly higher systolic AmBP at work.
Schnall PL, et al. Relation between job strain, alcohol and ambulatory blood pressure., Hypertension 1992; 19(5):488-94.
Ueshima, et al. used data from a 1980 national cardiovascular survey of Japan (4795 men/6102 women, age 30-94) to look at the effects of age and sex on the alcohol-blood pressure relationship. Level of drinking was defined as non-, ex-,, occasional or everyday drinker, and the authors note that the average everyday male drinker consumes 56g per day (5-6 drinks). They found that daily alcohol drinking was associated with an elevation in blood pressure in men of all ages and in young women.
Ueshima H, et al. Alcohol drinking and high blood pressure: Data from a 1980 national cardiovascular survey of Japan., Journal of Clinical Epidemiology 1992; 45(6):667-73.
Heart Rhythm
In an editorial, Koskinen and Kupari presented an overview of the effect of alcohol consumption on heart rhythm. The discussion included the circumstances under which alcohol might affect heart rhythm, possible mechanisms and management, including treatment with beta blockers, sedation, hydration and treatment of any potassium and magnesium depletion. They recommend questioning patients with unexplained tachyarrhythmias (rapid heart rates) about their drinking and treatment of underlying alcohol misuse. Since the effects of social drinking on clinically important arrhythmias have not been properly studied, they cautioned that advice to patients who are not alcoholics should be based on clinical judgement and on the understanding that the effects of alcohol on heart rhythm seen in heavy drinkers may not hold for social alcohol consumption.
Koskinen P and Kupari M, Alcohol and cardiac arrhythmias. (editorial), British Medical Journal 1992; 304(6839):1394-5
Lipids
Fruchart studied 334 men undergoing a routine health exam in Lille, France and correlated their drinking habits with a variety of blood lipid measures. HDL levels rose significantly with increased levels of drinking, as did apolipoprotein AII levels. Apolipoprotein AI levels were unaffected by different levels of drinking. The author concluded that the accumulation of HDL in drinkers is mainly accounted for by apolipoprotein particles that are less likely to be associated with an anti-atherogenic effect.
Fruchart JC, High-density lipoproteins particles, nutrition and arteriosclerosis., Bibl Nutr Dieta 1992; 49:66-78.
Hagiage, et al. attempted to answer the question of whether it might be commendable to preserve a small amount of alcohol in the dietary prescription of obese subjects who are already consuming alcohol. Seven healthy, young, obese men were compared with seven controls in two 14 day periods, the first in which they abstained from drinking alcohol and the second in which they were asked to drink three glasses (3 70 ml) of red wine in addition to their regular diet. Alcohol caused apolipoprotein (apo AI and apo AII) concentrations to increase in all controls by 12% to 16%, but not in obese subjects. HDL2 rose in controls, but not in obese subjects. HDL-triglyceride content normalized in obese subjects, however. These data show that the lipid responses to alcohol are significantly affected by obesity. The health implications of this are not yet known, but the authors conclude that "this study does not provide any argument in favor of a systematic exclusion of alcohol in dietary advice given to obese subjects."
Hagiage M, et al. Effect of a moderate alcohol intake on the lipoproteins of normotriglyceridemic obese subjects compared with normoponderal controls., Metabolism 1992; 41(8):856-61.
Langer, et al. used data from the Honolulu Heart Study, a study of 8006 men of Japanese descent, to explore possible biological pathways for the inverse association between alcohol consumption and CAD. The authors stated that their analysis model indicated about half of the observed protection against CAD is mediated by an increase of HDL. An additional 18% is attributable to the lowering of low-density lipoprotein (LDL) but it is counterbalanced by a 17% increase in risk due to increased systolic blood pressure. They concluded that "the consistency in findings across populations, along with the demonstration of reasonable biological pathways for this effect of alcohol, provides strong support for the hypothesis that- light-to-moderate alcohol intake is protective against heart disease in men."
Langer RD, et al. Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary artery disease., Circulation 1992; 85(3):910-15.
Since low levels of HDL are associated with atherosclerotic cardiovascular diseases, and since HDL is influenced by several factors under personal control (physical activity, obesity, cigarette smoking and alcohol consumption) Patsch, et al. investigated the potential mechanisms by which these environmental factors might affect HDL. Particularly they looked at either altering apolipoprotein A-I metabolism or through effects on plasma triglycerides. From their analysis of a cross-section of 7177 people from four different populations of middle-aged adults in the US in 1986-1989, they found that obesity and lack of physical activity lowered HDL by raising triglycerides, while alcohol use and smoking raised HDL by elevating apolipoprotein A-I. Greater body mass attenuated the association of alcohol use with elevated HDL cholesterol. They hypothesized that exercise and weight loss are more likely to have a greater public health impact than drinking or smoking cessation.
Patsch W, et al. The relation of high-density lipoprotein cholesterol and its subfractions to apolipoprotein A-l and fasting triglycerides: The role of environmental factors., American Journal of Epidemiology 1992; 136(5):546-557.
Seppa, et al. studied the serum lipid values in 380 men, including 184 controls (37 non-drinkers and 147 moderate drinkers), 90 heavy drinkers and 106 alcoholics to establish the effect of alcohol consumption on lipid values in middle-aged men. They found that serum levels of HDL cholesterol, apo A-I, and triglycerides tended to increase with alcohol consumption. While they found that the HDL/total cholesterol ratio values were significantly higher among alcoholics than among controls and heavy drinkers, they found no difference in this ratio among the non-drinkers, moderate or heavy drinkers.
Seppa K, et al. Moderate and heavy alcohol consumption have no favorable effect on lipid values., Archives of Internal Medicine 1992; 152:297-300.
Suh, et al. analyzed the alcohol consumption patterns of 11,688 men at high risk for developing coronary artery disease (CAD), but who had not yet developed the disease (the MRFIT study) during 7 years of observation. Their goal was to study the association between alcohol consumption and death from CAD and to determine the role played by HI)L cholesterol level. They found that those who drank more than two drinks per day were at the lowest risk of CAD (50% less risk than nondrinkers). They then conducted a statistical analysis of their data to control for the effect of HDL and found that the relationship diminished by 45%. They concluded that "this finding is strong evidence that HDL is a causal mechanism that explains, at least in part, the apparently beneficial effect of alcohol."
Suh I et al. Alcohol use and mortality from coronary artery disease: the role of high-density lipoprotein cholesterol., Annals of Internal Medicine 1992; 116(11):881-7.
Tao, et al. analyzed the measurements of serum total cholesterol (TC), HDL-cholesterol (HDL) and triglycerides (TG) in 4280 men and 4695 women aged 35-54 from urban and rural populations of Beijing and Guangzhou. Multiple regression analyses showed that body size was positively and independently related to TC, low- density lipoprotein cholesterol (LDL), TG and the ratio of TC toHDL(TC/HDL), and inversely related to HDL. Smoking was positively related in both sexes to TG and TC/HDL, and inversely related to HDL. Smoking was also positively related to TC and LDL in men. In men, alcohol was positively related to TC and HDL, and was inversely related to TG and TC/HDL. Heavy manual work was inversely related to TC, LDL, and TC/HDL in men, but not related to lipids in women. "Thus, for these Chinese population samples, despite their lower serum TC and body size, the correlates of serum lipids are similar to those in western populations."
Tao S, et al. Serum lipids and their correlates in Chinese Urban and Rural populations of Beijing and Guangzhou., International Journal of Epidemiology 1992; 21(5):893-903.
Miscellaneous
Allison, et al. immersed 6 healthy men in water at 40 C (104 F) after consuming 0, .27, or .54g of alcohol to test the hypothesis that alcohol consumption in low to moderate doses would alter thermoregulation and/or disrupt the normal relationship between physiological and psychophysical indexes of heat stress. These doses of alcohol were sufficient to achieve blood alcohol levels between .03 and .08 g/dl. Irrespective of the dose of alcohol, all of the measured responses during immersion were the same compared to drinking no alcohol, and suggest no adverse affect is associated with alcohol and warm water immersion in healthy young men. The findings in the study do not necessarily apply to women, older persons of either sex, or patients with significant cardiovascular limitations.
Allison TG et al. Thermoregulatory, cardiovascular, and psychophysical response to alcohol in men in 40~C water., Journal of Applied Physiology 1992; 72(6):2099-107.
Keenan, et al. investigated correlates of waist-to-hip ratio (a measure of body fat distribution which is positively correlated to diabetes, stroke, MI, and overall mortality) in a community sample of black adults in North Carolina. The data were collected from a sample of 1,784 black men and women between the ages of 25 and 30. Among men, there was a strong association between physical activity and lower waist-to-hip ratio. Other variables, including alcohol consumption, socio-economic status and smoking were not correlated with waist- to-hip ratio. Among women, measures of physical activity were not correlated with waist-to-hip ratio, but alcohol consumption and socio-economic status were. Women who drank one-to-six drinks per week had significantly higher waist-to-hip ratios than those who abstained. There was also a significant association between lower socio-economic status and higher waist-to-hip ratio. These results did not change after simultaneous control for age, body size, physical activity, alcohol consumption, socioeconomic status and smoking.
Keenan et al. Distribution and correlates of waist-to-hip ratio in black adults: The Pitt county study., American Journal of Epidemiology 1992; 13S;678-84.
Roine, et al. studied the cardiovascular response to 10 minutes of sauna bathing (ambient temperatures, 80- 90 C) in men who drank the equivalent of 1 litre of wine or 3.5 Iitres of beer just prior to the bathing. They compared those responses to those seen after drinking fruit juice There were no differences in physiologic responses seen with and without alcohol except that alcohol induced a significantly greater blood pressure drop (23 mm Hg for systolic pressure) and a greater serum cortisol rise compared to fruit juice. The authors concluded that sauna bathing, even in conjunction with an episode of heavy alcohol consumption did not induce heart rhythm irregularities, but it did induce a blood pressure drop that might be injurious to older people, especially those with pre-existing heart disease.
Roine R, et al. Alcohol and sauna bathing: effects on cardiac rhythm, blood pressure, and serum electrolyte and cortisol concentrations., Journal of Internal Medicine 1992; 231(4):333-8.
Myocardial Infarction
Jackson, et al. conducted a case-control study (278 male/60 female nonfatal MI patients vs. 458 male/266 female controls and 172 male/16 female coronary death cases vs.294 male/165 female controls) to investigate the relationship between both nonfatal myocardial infarction (heart attack) and coronary death and drinking during the previous 24 hours. They found that among people who drink alcohol at least once per month the risk of nonfatal MI and coronary death were consistently lower in those who had one or more drinks in the previous 24 hours. Since the reported findings suggested that part of the protective effect of alcohol in CAD risk may act acutely after a drinking episode, the authors proposed the mechanism may be reduced platelet function and/or lowered levels of fibrinogen, both of which are associated with reduced CAD risk.
Jackson R, Does recent alcohol consumption reduce the risk of acute myocardial infarction and coronary death in regular drinkers? American Journal of Epidemiology 1992; 136(7):81924.:
Manson, et al. conducted a review of the data on the various interventions that may reduce the risk of myocardial infarction. Noting that 1 in 3 deaths in the United States is from coronary artery disease, primarily MI, they suggested that a primary prevention that reduced MI by 20 percent would avert over 100, 000 deaths annually. They identified 9 interventions that have been found to lower the risk of MI to one degree or another.
The interventions reviewed are: smoking cessation, reduction in serum cholesterol, treatment of hypertension, exercise, maintenance of ideal body weight, maintenance of normoglycemia in diabetic patients, postmenopausal estrogen replacement therapy, mild to moderate alcohol consumption and prophylactic low- dose aspirin. For each intervention, the authors discussed the quality of the available data, achievable reductions in risk and the efficacy of the strategy. They concluded that alcohol is associated with a 25%-45% lowering of CAD risk, but that there are no data to indicate the efficacy of a strategy of prescribing drinking.
Manson et al. The primary prevention of myocardial infarction., New England Journal of Medicine 1992; 326(21):1406-15.
Razay, et al. evaluated 1048 women aged 25 to 69 years in Bristol, England. The study was controlled for body size, smoking habits and the use of oral contraceptives. The results showed that those women who consumed a moderate amount of alcohol (1 to 20g a day) had lower levels of triglycerides, cholesterol, insulin, and a lower body weight, with higher levels of HDL cholesterol than those women who were non-drinkers. Each of these conditions favor a reduced likelihood-of heart attacks or angina.
1 his study is remarkable because it was conducted with women and because the relationship between alcohol consumption and plasma concentrations of triglycerides and insulin found by the researchers "seems to be a new finding and might help to explain the U-shaped relation between alcohol consumption and cardiovascular mortality in women."
Razay G, et al. Alcohol consumption and its relation to cardiovascular risk factors in British women., British Medical Journal 1992; 304:80-3.
In a position statement on the nutrition policy for the National Heart Foundation of Australia, Shrapnel, et al. reviewed the literature on the links between diet and CAD. The key factors - saturated fatty acids, the n-6 polyunsaturated fatty acids, the n-3 polyunsaturated fatty acids, monounsaturated fatty acids, bans fatty acids, total fat, dietary cholesterol alcohol, sugar, sodium and potassium, overweight, and vegetarianism - are discussed in regard to their effect on cardiovascular health. The Foundation's position on alcohol consumption is as follows: "a high intake of alcohol increases blood pressure and serum triglyceride levels and increases mortality from cardiovascular disease. Light alcohol consumption reduces the risk of coronary artery disease."
Shrapnel et al. Diet and coronary artery disease., The Medical Journal of Australia 1992; 156 (supp):S9-S16.
Platelets
Renaud and de Lorgeril reviewed the literature to address the French paradox, the observation that the French have a high dietary intake of saturated fat (positively associated with CAD) and concentrations of serum cholesterol similar to those of the USA and UK, yet a low mortality from CAD similar to that of Japan or China. From their reexamination of previous study results, they hypothesized that moderate alcohol consumption protects from CAD through an anti-clotting mechanism rather than through an effect on atherosclerosis. For instance, they compared data from Wales to pilot studies conducted in France showing that platelet activity is lower in France. They concluded "it seems that consumption of alcohol is associated with inhibitory effects on atherosclerosis lesions in man and animals, but only at levels incompatible with a healthy life. At the moderate intake associated with the prevention of CAD, the mechanism of protection seems to be, at least partly, an anti-clotting effect (possibly a decrease in platelet activity)." They argued that this effect would account for the apparent rapid loss in cardioprotection with cessation of drinking.
Renaud S & de Lorgeril M, Wine, alcohol, platelets and the French paradox for coronary artery disease., The Lancet 1992; 339:1523.
Renaud, et al. examined dietary data from 1600 men (49-66 years old) from South Wales to look at the effect of alcohol consumption on platelet aggregation (blood clotting) using two different tests. Using one test, they found all levels of alcohol consumption decreased platelet aggregation. The other test did not show this effect but the authors suggest that this result may be an artifact of the timing of the blood sampling for the tests. They concluded that an inhibitory effect or certain aspects of platelet function seems to provide an additional pathway through which alcohol reduces the risk of CAD.
Renaud SC eta 1, Alcohol and platelet aggregation: the Caerphilly Prospective Heart Disease Study., American Journal of Clinical Nutrition 1992; 55:1012-17.