Moderate ethanol ingestion and cardiovascular protection: From epidemiologic associations to cellular mechanisms

Abstract

While ethanol intake at high levels (3-4 or more drinks), either in acute (occasional binge drinking) or chronic (daily) settings, increases the risk for myocardial infarction and ischemic stroke, an inverse relationship between regular consumption of alcoholic beverages at light to moderate levels (1-2 drinks per day) and cardiovascular risk has been consistently noted in a large number of epidemiologic studies. Although initially attributed to polyphenolic antioxidants in red wine, subsequent work has established that the ethanol component contributes to the beneficial effects associated with moderate intake of alcoholic beverages regardless of type (red versus white wine, beer, spirits). Concerns have been raised with regard to interpretation of epidemiologic evidence for this association including heterogeneity of the reference groups examined in many studies, different lifestyles of moderate drinkers versus abstainers, and favorable risk profiles in moderate drinkers. However, better controlled epidemiologic studies and especially work conducted in animal models and cell culture systems have substantiated this association and clearly established a cause and effect relationship between alcohol consumption and reductions in tissue injury induced by ischemia/reperfusion (I/R), respectively. The aims of this review are to summarize the epidemiologic evidence supporting the effectiveness of ethanol ingestion in reducing the likelihood of adverse cardiovascular events such as myocardial infarction and ischemic stroke, even in patients with co-existing risk factors, to discuss the ideal quantities, drinking patterns, and types of alcoholic beverages that confer protective effects in the cardiovascular system, and to review the findings of recent experimental studies directed at uncovering the mechanisms that underlie the cardiovascular protective effects of antecedent ethanol ingestion. Mechanistic interrogation of the signaling pathways invoked by antecedent ethanol ingestion may point the way towards development of new therapeutic approaches that mimic the powerful protective effects of socially relevant alcohol intake to limit I/R injury, but minimize the negative psychosocial impact and pathologic outcomes that also accompany consumption of ethanol.

Regular Wine Consumption in Chronic Heart Failure

“…The dietary questionnaire used in the GISSI-HF trial did not distinguish between red and white wine, 2 beverages whose content in biologically active compounds may differ, although the differences in the cardiovascular effects of the 2 kinds of wine have been questioned. 49 For this reason, data from GISSI-HF cannot be easily compared with other populations with different types and patterns of alcohol consumption. In addition, the design of the clinical trial did not permit any causal relationship but only associations between patient-reported wine consumption and health status, which may be influenced by unreported confounding clinical variables.…”

Complex Association Between Alcohol Consumption and Myocardial Infarction

“…In brief, alcohol in moderation favorably affects reverse cholesterol transport, insulin sensitivity, abdominal obesity, systemic inflammation and oxidative stress, endothelial function, endogenous fibrinolysis, postprandial hypercoagulability, and platelet aggregation. 3,[8][9][10][11][12][13] These effects are in part of reasonable size and may well contribute to the health benefits of habitual moderate alcohol consumption regarding coronary heart disease (decrease of 29%), 2 diabetes mellitus (decrease of 30% to 40%), 3 and life span (decrease of 17% to 18% in total mortality). …”

“…1,14 In small intervention trials and on the basis of pathophysiologic considerations, wine surpassed other types of alcoholic beverages in terms of favorable short-term metabolic changes. 3,9,11,12 To date, epidemiologic research has not confirmed the superiority of wine over spirits. 2 However, it must be remembered that, in epidemiologic work, it is challenging, if possible at all, to disentangle effects of different types of beverages in mixed drinkers, and drinking behaviors allocated to 1 type of beverage only are usually driven by cultural and regional peculiarities.…”

“…Alcohol in excess produces an immediate rise in blood pressure, a short-lived oxidative and proinflammatory burst, impaired fibrinolysis, and temporary heart rhythm changes with enhanced oxygen demands. 3,[8][9][10][11][12][13] Briefly delayed, the platelet-rebound phenomenon creates a reversible procoagulant state and vulnerable period. Moreover, heavy drinking interferes with the absorption, metabolism, and action of several drugs used in cardiovascular prevention and may prompt irregular or delayed pill intake, which further amplifies risk.…”

Alcohol Flushing and Positive Ethanol Patch Test in Patients with Coronary Spastic Angina: Possible Role of Aldehyde Dehydrogenase 2 Polymorphisms

“…However, the sensitivity of EPT for CSA was not high in this study and we do not recommend this test for the screening and/or diagnosis of CSA. It is also to be noted that there may be some patients with CSA whose attack may be relieved by ingestion of small amounts of alcohol because small amounts of alcohol may enhance endothelial nitric oxide activity thereby leading to vasodilatation (25,26).…”