Do known cardiovascular risk factors mediate the effect of alcohol on cardiovascular disease?

The association between alcohol intake and atherosclerotic cardiovascular disease (CVD) in epidemiological studies is consistent and shows some protection from CVD at consumption levels of one to two drinks per day, but a sharp increase in CVD associated with three or more drinks per day. Analyses of potential mediators of effects of alcohol on CVD show that it increases high density lipoprotein (HDL) cholesterol levels and favourably influences thrombotic factors, especially fibrinogen, and also fibrinolytic factors. Some evidence also suggests moderate alcohol consumption may reduce insulin resistance. However, studies also show an adverse effect of alcohol, particularly at higher doses, on blood pressure (leading to hypertension) and directly on the myocardium (leading to arrhythmias and myocardiopathy). Statistical modelling of the alcohol-CVD relationship is consistent in several studies, with a protective pathway via elevated HDL cholesterol and an adverse pathway through elevated blood pressure. Other possible mediators influenced by alcohol have not yet been examined in this type of analysis. The French Paradox has led to speculation that wine is the only protective alcoholic beverage for CVD, or at least that it has a stronger effect. Multiple non-ethanol components of wine have been studied in the laboratory and have been shown to have antioxidant or anticoagulant effects. Although wine does appear more protective in ecological studies, studies within cohorts show similar effects across alcoholic beverages, suggesting confounding in ecological studies by diet, lifestyle, or other variables. The key component of alcoholic beverages thus appears to be ethanol, consistent with the known potent effects of ethanol on HDL cholesterol and thrombotic factors. The upswing in CVD risk with three or more drinks per day is sharp and emphasizes that benefit from alcohol is limited to moderate consumption only. This upswing also cautions against any public health recommendation to drink alcohol, since many persons will not or cannot limit their intake to moderate levels.