Southwestern Internal Medicine Conference
In Vino Veritas: Alcohol and Heart Disease

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ABSTRACT

Numerous epidemiological studies, numbering nearly 100, have documented an inverse association between alcohol consumption and vascular risk. The preponderance of evidence supports an independent beneficial effect of mild-to-moderate alcoholic beverage consumption on risk of coronary heart disease (CHD). However, it is important to remember that observational data cannot prove causation; unmeasured or incompletely controlled confounding factors cannot be excluded. That said, most authorities now attribute a causal role to the relationship: moderate alcohol consumption reduces the risk of CHD, and current research centers on the mechanistic underpinnings and whether patterns of drinking are important. Here, I review the association between alcohol use and CHD risk, explore putative mechanisms, and make recommendations.

Section snippets

Historical Perspective

Today, alcohol is viewed variably as a social menace, party tool, sophisticated social lubricant, or enjoyable medicine. For the vast majority of the past 10,000 years, however, alcohol was viewed very differently. Indeed, for most of that time, alcoholic beverages may have been the only safe liquid to drink.1

Ethanol is a by-product of the energy-producing metabolism of sugar by yeast. As such, accidental ingestion of ethanol in "spoiled" foods has undoubtedly occurred for millennia; indeed, at

Early Suggestions of Health Benefits

References to wine and beer as medicines are commonplace in ancient texts, such as the Bible and records from Egypt and ancient Babylon. Hippocrates recommended wine as remedy for a host of ailments, and alcohol as medicine was taught at the Alexandrian School of Medicine.

In the early part of the 20th century, the potential impact of alcohol consumption on coronary heart disease (CHD) was proposed. Pathologists noted that the large arteries of people who died of alcoholic liver cirrhosis were

Epidemiologic Evidence of Association

Numerous epidemiologic studies, numbering nearly 100, have documented an inverse association between alcohol consumption and vascular risk. All-cause mortality has typically been depicted as a J-shaped function, where risk of CHD is lower at moderate levels of consumption and risk of cancer and cirrhosis are elevated at high levels of consumption.

As one example, in the recently published Health Professional Follow-up Study, patterns of alcohol consumption were followed for 12 years in 38,077

Meta-Analyses

Given the large number of studies documenting an inverse association between consumption of alcoholic beverages and rates of CHD mortality and total mortality, recent work has emphasized meta-analytic approaches. Several large meta-analyses, incorporating many thousands of subjects, have been reported examining the relationship between alcohol consumption and heart disease. Caution is warranted, however, as interpreting these data can be difficult if poorly controlled studies are included or if

Dementia

In a recent report from the Cardiovascular Health Study, Mukamal et al16 described an inverse relationship between alcohol consumption and risk of dementia. Compared with nondrinkers, the adjusted odds ratio for dementia among those whose weekly alcohol consumption was one to six drinks was 0.46 (95% CI, 0.27-0.77).16 A typical J-shaped relationship was observed with increased risk noted at high levels of consumption. Intriguingly, the relations between alcohol use and both Alzheimer disease

Epidemiologic Evidence: Association versus Causation

At present, there is virtual unanimity regarding the inverse association between moderate consumption of alcohol and CHD. Indeed, most authorities attribute a causal role to the relationship: moderate alcohol consumption reduces risk of CHD. Current research, then, centers on the mechanistic underpinnings of this salutary effect and whether patterns of drinking are important. It is essential, however, to discuss briefly how epidemiologic associations may (or may not) be used to infer

Biologic Actions

The sequelae of alcohol use can be divided into three inter-relating phenomena: intoxication, dependence, and direct biologic actions (Figure 6). The interplay among these actions ultimately evokes a complex pattern of biologic and clinical phenotypes.21 The biologic actions can be divided into several categories (Table 2). In an attempt to quantify the "strength" of evidence supporting each proposed mechanism, I have utilized a standard ranking system (Class I-III),f

Diminished Atherogenesis

Studies conducted in animal models have yielded conflicting results. In two studies, addition of alcohol to the diets of atherosclerosis-prone mice decreased atherosclerosis. Dai and coworkers41 fed low-density lipoprotein receptor knockout mice an atherogenic liquid diet containing different amounts of alcohol (5%, 2.5%, 0% ethanol). These investigators reported a 70% reduction in fatty lesion size in the proximal aorta in mice fed 5% alcohol for 6 weeks. Lesion size in the group fed 2.5%

Genetic Predispositions

In a case-control study based on data from the prospective Physicians' Health Study, Hines et al20 examined the relationship between CHD and a polymorphism in the gene coding for alcohol dehydrogenase type 3 (ADH3). They studied a common polymorphism in ADH3 that alters the maximal velocity of ethanol oxidation (γ1, 2.5-fold increased rate relative to γ2) in relation to alcohol consumption. Among men who were homozygous for the γ1 allele (fast oxidizers), those who consumed at least one drink

Does It Matter What One Drinks?

With the observation that HDL levels are no higher in France than elsewhere, a search for other possible explanations ensued. Wine intake, in particular, was suggested as a possible explanation in one report.6 However, this assertion has not withstood careful scrutiny.

It is difficult for epidemiologic studies to tease out whether different types of alcoholic beverage differ in beneficial properties. A large Danish study of 13,000 people followed for 12 years suggested that wine drinkers have

Does It Matter How One Drinks?

Recent investigation has focused on patterns of alcohol consumption. It has been known for some time that episodic binge consumption is linked to adverse cardiovascular events.53 Only recently, however, have studies rigorously controlled for potential confounders, such as average volume and duration of consumption. Numerous recent studies have documented a protective effect for daily light-to-moderate consumption, but no benefit, or even detrimental effects, for people whose drinking patterns

Clinical Implications

When considering clinical implications, an obvious distinction must be made between light-to-moderate alcohol consumption and heavy consumption. Whereas a number of beneficial effects are associated with light-to-moderate consumption (Table 3), there are no benefits associated with heavy drinking (Table 4).

Both low-to-moderate consumption and heavy consumption are associated with risk. In the case of moderate alcohol use, the potential for abuse is important, especially in individuals with

Societal Impact

It is estimated that alcohol contributes to 100,000 deaths in the United States annually, making it the third leading cause of preventable mortality, after smoking and conditions related to poor diet and sedentary lifestyle. Heavy consumption of alcohol is dangerous to both the drinker and those around him or her (Table 4).55 Numerous sequelae are associated with this pattern of alcohol use, and patients who consume heavily should be urged to abstain.

Highlighting the enormous impact of

Recommendations

Policy changes or recommendations to patients regarding alcohol consumption must take into account the complexity of the metabolic, physiologic, and psychological effects of alcohol. The potential risks and benefits of alcohol consumption should be evaluated on a case-by-case basis. A balanced message should be tailored to the specifics of each individual. For those in whom alcohol consumption imposes increased risk, such as people with family or personal histories of alcoholism or preexisting

Conclusion

The preponderance of evidence supports an independent beneficial effect of alcoholic beverage consumption on risk of CHD. However, it is important to remember that observational data cannot prove causation; unmeasured or incompletely controlled confounding factors cannot be excluded. That said, the consistency of the relationship across numerous cohorts and hundreds of thousands of subjects demonstrate that light-to-moderate alcohol consumption can be considered part of a healthy lifestyle for

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    This work was supported by grants from the Donald W. Reynolds Cardiovascular Clinical Research Center and the NIH (HL-03908).

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    Copyright © 2005 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.