Date:
May 30, 2006
Promotors:
Prof. J.W.N. Akkerman, MD, PhD
Co-promotor:
Dr. A. van de Wiel, MD, PhD
Epidemiologic studies have shown an inverse relation between moderate alcohol consumption and the risk of coronary heart disease (CHD). Mortality as a function of alcohol consumption follows a U-shaped curve, reflecting a lower mortality at moderate alcohol consumption compared with abstinence or high alcohol intake. Consumption of (red) wine in France is thought to be the cause of the lower mortality of CHD in France in comparison with the United Kingdom, but this concept has been challenged. A meta-analysis showed a 32% decrease (95% confidence interval: 23– 41%) in CHD at low alcohol intake (<18 g/day, approximately 1.5 glass/day). A similar, although smaller, association (risk reduction: 22%; 95% confidence interval: 14 –30%) was found in studies on beer consumption. Although these epidemiological studies might be prone to confounding, they have raised considerable interest in the mechanisms behind the cardioprotection of alcohol and red wine. In contrast, rapid intake of large quantities of alcohol in a short period of time (binge drinking) is associated with increased mortality from all causes, including cardiovascular ones.
In this thesis we looked whether red wine and/or red wine polyphenolic compounds could inhibit ADP-induced platelet aggregation. They both inhibited platelet aggregation, but alcohol alone was not able to inhibit ADP-induced platelet aggregation in vitro. We also analysed adhesion of platelets to fibrinogen and collagen in a flow chamber. Alcohol, red wine and polyphenolic compounds were able to inhibit platelet adhesion to fibrinogen but not collagen. We found that the polyphenolic compounds were able to inhibit platelet endothelial cell adhesion molecule 1 (PECAM-1) and inhibit Ca2+-influx in platelets in vitro.
Secondly, we looked at healthy volunteers, who drank 6 glasses of an alcoholic beverage (red wine versus alcohol containing drink without polyphenols) in a 3-hour period (binge drinking). Ex vivo platelet ADP-induced platelet aggregation was markedly increased when consuming alcohol but not red wine. Acute alcohol consumption led to prolongation of the cardiac conduction velocities (PR and QTc-time).
In conclusion, the French Paradox claims lower mortality from CHD. But, this association is seriously confounded. Yet, certain ingredients of red wine, notably the polyphenolic compounds, are able to inhibit platelet aggregation and adhesion in vitro. Inhibition of PECAM-1 and a reduced Ca2+-influx in platelets were found. However, infrequent consumption of (large) quantities of alcohol (binge drinking) we associated with an increased platelet aggregation and a prolongation of cardiac conduction velocities. However, most people do not drink every day and people who do drink every day often don’t consume in moderation (the moderate drinker fiction)!