Objective To summarise quantitatively the association between moderate alcohol intake and biological markers of risk of coronary heart disease and to predict how these changes would lower the risk.

Design Meta-analysis of all experimental studies that assessed the effects of moderate alcohol intake on concentrations of high density lipoprotein cholesterol, apolipoprotein A I, fibrinogen, triglycerides, and other biological markers previously found to be associated with risk of coronary heart disease.

Participants Men and women free of previous chronic disease and who were not dependent on alcohol. Studies were included in which biomarkers were assessed before and alter participants consumed up to 100 g of alcohol a day.

Interventions Alcohol as ethanol, beer, wine, or spirits.

Main outcome measures Changes in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, Lp(a) lipoprotein, triglycerides, tissue type plasminogen activator activity, tissue type plasminogen activator antigen, insulin, and glucose after consuming an experimental dose of alcohol for 1 to 9 weeks; a shorter period was accepted for studies of change in concentrations of fibrinogen, factor Vii, von Willebrand factor, tissue type plasminogen activator activity, and tissue type plasminogen activator antigen.

Results 61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease.

Conclusions Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors.

Introduction

The inverse association between moderate alcohol intake and coronary heart disease is documented in over 40 prospective studies in diverse populations.[1-5] Men and women who consume one to three drinks a day have a 10% to 40% lower risk of coronary heart disease than those who abstain. In most large studies risk of coronary heart disease decreases in a downward linear fashion with alcohol intake up to three drinks a day.[6-9] This reduction is generally attributed to the beneficial effects of alcohol on lipids and haemostatic factors.[5 10-13]

Over 75 experimental studies have examined the effects of alcohol intake on lipids, haemostatic factors, vitamins, glucose, insulin, and lipid peroxidation.[10 w1-w55] However, only a few epidemiological studies have simultaneously examined the relation between alcohol intake, biochemical variables, and subsequent risk of coronary heart disease.[w56-w61] From these studies it is estimated that half of the beneficial effect of moderate alcohol intake is due to increased high density lipoprotein cholesterol concentrations. This calculation may, however, be an underestimate because it does not take into account measurement error in the assessment of average alcohol intake or biological variability in high density lipoprotein cholesterol concentrations. In several of these studies potential confounding by other lifestyle factors–for example, diet, obesity, and physical activity–was also not considered. Furthermore, other biochemical variables, such as fibrinogen, triglycerides, von Willebrand factor, and insulin, were not examined in these simultaneous models.

We quantitatively summarised the effects of alcohol on a variety of biomarkers from experimental studies using standard meta-analysis methods, and we projected the impact of those changes on risk of coronary heart disease using data from published studies relating biomarker concentrations to coronary heart disease.

Methods

We searched Medline for all experimental studies of alcohol (ethanol) in humans published in English between 1965 and 1998. We supplemented our search by examining citations in review articles,[1 3 14 15] the proceedings of meetings and symposia, and the Journal of the Alcohol Beverage Medical Research Foundation and Alcohol Research–journals that track alcohol related research. We restricted our search to studies in individuals without diagnosed coronary heart disease, diabetes, or alcohol dependence. We included only those studies that assessed biomarkers consistently modified by alcohol and related to risk of coronary heart disease. For lipid factors we included only studies with an intervention period of at least seven days; shorter intervals seem to have little or no effect. We included all studies of coagulation and thrombolytic factors because effects have been documented within hours after consumption of alcohol. Although we describe studies of lipid peroxidation and platelet aggregation we did not include these in our quantitative analyses because these assays were not comparable across studies owing to major differences in methodology. Furthermore, most were assessed with in vitro assays, which have not consistently been linked to risk of coronary heart disease.