Alcohol and coronary artery disease

International Journal of Cardiology 44 (1994) 157-162

Alcohol and coronary artery disease Sushi1 K. Ahlawat*t, Department

(Received

of Medicine.

S.B. Siwach

Medical College, Rohtak, India

6 May 1993; revision

accepted

20 December

1993)

Abstract

Alcohol affects the heart and circulation in several ways. Chronic alcohol consumption can be associated with a variety of cardiovascular disorders, ranging from hypertension and stroke to heart failure and sudden death. At the same time an inverse correlation has been found between moderate drinking and incidence of coronary artery disease, perhaps due to its favourable effects on lipoprotein levels. Reports on acute effects of alcohol on coronary circulation, which may be of great significance in patients with pre-existing heart disease, have been contradictory. However, clinical studies have demonstrated an adverse effect of acute alcohol intake in low to moderate doses on coronary supply-demand relation in patients with angina pectoris. Considering the overall health hazard of alcohol consumption, a recommendation that patients increase their alcohol intake or that they start to drink if they do not already would probably be unjustifiable. Key words: Ethyl alcohol; Coronary artery disease

description by Heberden. However, now it is increasingly being recognised as a health hazard. However, there are still many who believe ‘A tot a day keeps disease away’. Chronic ethanol abuse can be associated with a variety of cardiovascular disorders, ranging from hypertension and stroke to heart failure and sudden death. Over the past two decades important influences on the cardiovascular system have been either rediscovered or observed for the first time. While many individuals addicted to ethanol have subclinical abnormalities of the heart [ 1.21,

1. Introduction

Ethyl alcohol has been imbibed, abused, admired and deplored since the beginning of the recorded history. Opinions and traditions of the past often cloud the discussion of this subject. In the Middle Ages, when the Arabs introduced it to Europe, it was held to be a remedy for practically all diseases as indicated by the term whisky (Gaelic, Urquebaugh meaning ‘water of life’). Reports of using alcohol in the treatment of angina pectoris have been available ever since its * Corresponding author, 3-D. Evershine Apartments, TPresent address:

Department

of Medicine,

R.M.L.

Vikaspuri, Hospital.

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New Delhi I10018,

New Delhi, India.

Ltd. All rights reserved

India.

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somewhat less than a majority develop symptomatic cardiac problems. These include heart failure [3] and arrhythmias [4,5]. In addition to supraventricular arrhythmias that often normalize spontaneously, there is an increased incidence of sudden death that peaks at about 50 years of age in the alcoholic population [6,7]. A significant degree of blood pressure elevation occurs in individuals who abuse alcohol. This appears to be transient and is normalised in most individuals during abstinence [8]. The increased incidence of hemorrhagic and non-hemorrhagic stroke in middle age also appear to decline when alcohol abuse is interrupted [9]. A preventive effect of mild to moderate drinking on coronary artery disease is, at present, equivocal [ 10,111. 2. Epidemiologic studies A series of epidemiologic investigations have suggested that low to moderate ethanol intake reduces the risk of coronary heart disease [ 12- 171. A study of more than 50 000 men [lo] supported the view that moderate alcohol consumption (30-50 g/day) reduces the risk of coronary heart disease (95% CI for relative risk, 0.35-0.79). This protective effect of alcohol is seen in men and women [l 11, in the elderly 1181, in smokers and non-smokers [10,19] and also applies to total mortality [ll]. However, the risk increases at high levels of alcohol consumption [ 191.A U-shaped relationship has been observed between alcohol consumption and cardiovascular and total mortality [20,21]. Heavy drinkers have an increased risk of death compared with moderate drinkers but moderate drinkers have a lower mortality than abstainers. Abstainers include people who have stopped drinking because of ill health (‘sick quitters’) and people who are at higher risk for other reasons. Most authorities now accept the existence of the U-shaped curve relating the intake of alcohol to the instance of cardiovascular disease. What has been debated is whether this is a consequence of a protective effect of alcohol. Several case-control studies, including that of Jackson et al. [22] have shown that moderate drinkers of alcohol have a lower risk of coronary heart disease compared with non-drinkers. A re-

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view of prospective studies in 1991 showed similarly that with the exception of the Alameda county study, all studies found a lower rate of coronary heart disease in moderate drinkers than abstainers [23]. The studies did not show uniformly that heavy drinkers have a higher risk of cardiovascular disease than moderate drinkers. The Ushaped curve describing the link of alcohol with risk of death comes from the higher rate of death from various other causes in heavy drinkers. 3. Main issues Reviews of studies relating alcohol to cardiovascular disease have shown consistent findings in diverse populations [20,24]. However, one of the criticisms levelled at many of the studies is that non-drinkers will include people who have given up drinking because they were unwell. These people would be expected to have an increased rate of diseases and thus, may account for high mortality observed amongst non-drinkers. Recent studies [22,25,26] have, however, found an increased incidence of coronary heart disease in those who were never drinkers and former drinkers compared with moderate drinkers. Another argument raised is that abstainers may have a greater burden of ill health than moderate drinkers, regardless of their previous drinking patterns. In the most recent report, moderate alcohol consumption was associated with lower mortality from coronary heart disease, even in the half of the population remaining after anyone who had one of 17 indicators of the cardiovascular illness or risk factors [25] was excluded. In another study, after excluding the men who were classified as sick at enrolment (33%) an increased incidence of coronary heart disease among the healthy remainder in non-drinkers compared with moderate drinkers was clear [27]. Data collected on alcohol intake are often more limited than in a dedicated alcohol study. The methods of assessing alcohol consumption varied widely in different studies. This seems to have had little effect on the results for risk of coronary heart disease as has been seen in the American Cancer Society Study [27].

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3.1. Possible mechanism of cardio-protective effect of alcohol

Moderate consumption is associated with increased concentration of high density lipoprotein cholesterol [28]. However, it is now known that the effect of alcohol on high density lipoprotein cholesterol can explain only half the protection against coronary heart disease afforded by alcohol [29]. Alcohol ingestion or infusion inhibits platelet aggregability in man [30], and it has also been shown in rats [31]. Of course, the dose-related effect of alcohol on platelet does not exclude additional beneficial effects on other haemostatic factors such as fibrinogen and fibrinolytic activity [32]. Thus, at the moderate intake associated with prevention of coronary heart disease, the mechanism of protection seems to be, at least partly, a haemostatic effect, possibly a decrease in platelet reactivity [33]. There is no clear evidence that one type of alcoholic beverage is more protective than another although the international study by Ceger et al. [34] showed a stronger correlation with wine. Recently, it has been found that the alcohol content of wine may not be the sole explanation for the protective effect, and that phenolic compounds may have an important role [35]. 3.2. Alcohol and hypertension It is well known that alcohol is associated with increased blood pressure [36-391. This effect is greater in heavy drinkers [40]. A strong positive correlation between blood pressure and coronary heart disease is also well documented [41,43]. Given these facts, we might hypothesize that one effect of alcohol is to promote coronary heart disease by increasing blood pressure; on the other hand, several epidemiological studies [ 12- 171have shown light to moderate alcohol consumption to have a net protective effect on the incidence of coronary heart disease. In a cohort of men of Japanese descent followed in the Honolulu Heart Programme, it was found about half of the observed protection against coronary heart disease afforded by moderate alcohol consumption is mediated by an increase in high density lipoprotein cholesterol. An additional 18% of this protection is attributable to a decrease in low density lipoprotein cholesterol, but it is counterbalanced by a 17%

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increase in risk due to increased systolic blood pressure [29]. A similar result has previously been published using data from the Lipid Research Clinic study [44]. The explanation for the residual 50% benefit attributable to alcohol is unknown but may include interference with thrombosis. Thus, overall, alcohol provides some protection against coronary heart disease. This effect, however, is the sum of multiple components, some of which may be protective (e.g. increased high density lipoprotein cholesterol and decreased low density lipoprotein cholesterol) and some of which may increase coronary heart disease risk (e.g. SBP). 4. Experimental data Controlled experimental and clinical observations on the effects of alcohol on coronary blood flow are contradictory. Some experimental studies [45-471 have reported a decrease in coronary blood flow. In an experimental study Hayes and Bove [48] demonstrated ethanol-induced coronary artery vasoconstriction in dogs. However, they did not study the effect on resistance arterioles in the myocardium, which really maintain the perfusion pressure required to supply the ischaemic myocardium through collaterals. Altura et al. [49], in an isolated canine coronary artery study, reported that ethanol produced coronary artery vasospasm. At the same time they demonstrated that acetaldehyde, which is the major metabolite of ethanol, produced relaxation in coronary basal tone. Since both substances with opposite actions will exist in the body simultaneously, the net result in vivo cannot be predicted from such in vitro studies. However, the bulk of the evidence suggests that ethanol increases coronary blood flow and decreases coronary vascular resistance [50-551. Although these observations have been made largely on the basis of experimental studies on animals, in humans, two investigations on coronary blood flow by using rubidium technique have found no significant change in coronary blood flow in normal individuals [56,57]. Gould et al. [57] found an increase in coronary blood flow by measuring the myocardial clearance of rubidium in patients with coronary artery disease 20 min after ingestion of 90 ml of Canadian Club whiskey.

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4.1. Acute effects of alcohol in coronary artery disease

In view of the concept that alcohol is a coronary vasodilator, it has frequently been recommended, or at least permitted, in the treatment of angina pectoris in the past [58,59]. However, recent clinical studies have demonstrated that angina and abnormal EKG response to exercise are not favourably affected by ingestion of ethanol [60-621. Further it has been observed that myocardial ischaemia might even occur sooner and with exaggerated ST segment depression [62]. This paradoxical effect could possibly be due to adverse effect of ethanol on myocardial the demand-supply relation in the ischaemic myocardium. Recently, in an experimental model simulating fixed partial coronary obstruction (commonly seen in patients with coronary artery disease), Friedman [63] demonstrated the phenomenon of coronary steal with ethanol. He postulated that worsening of angina by alcohol intake in patients with atheromatous heart disease is possibly due to the phenomenon of coronary steal produced by ethanol. However, myocardial perfusion studies are required to document the direct effect of ethanol on coronary perfusion in patients with coronary artery disease. Thus, acute and transient effects of a bout of alcohol intake on cardiac performance and coronary circulation are clearly of significance in patients with coronary artery disease. Worsening of myocardial ischaemia produced by ethanol ingestion could prove hazardous to patients with angina pectoris since they may not experience the ischaemic pain under the influence of alcohol and thus, may indulge in activity for longer, which may lead to unfavourable consequences. Moreover, acute alcohol injection has been reported to provoke variant angina by a few workers [64,65]. Similarly, in patients with recent or old myocardial infarction a transient myocardial depressant effect of alcohol intake in low to moderate dose may lead to compromised LV performance [66]. In view of the negative ionotropic effect of acute alcohol intake in low to moderate doses in patients with coronary artery disease and its adverse effect on the coronary supply-demand relation in ischaemit heart, it seems unjustifed to recommend social drinking to patients with any form of

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ischaemic heart disease. On the other hand, there is substantial body of evidence in the literature to support the hypothesis that a small intake of alcohol confers some protection against ischaemic heart disease. This observation raises an important question in the mind of the physician/cardiologist: should one recommend a daily drink as a major preventive measure for the most common cause of death? The determining point is that those with a high alcohol intake are associated with increased overall mortality. Moreover, alcohol ingestion also leads to direct and indirect health hazards. Until we know more about the metabolism and behavioural effects of alcohol intake and its linkage to atherosclerosis, it hardly seems appropriate to recommend alcohol in the interests of health. 5. References 1

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