The Cardiovascular Protective Effect of Red Wine Alfredo C Cordova, MD, La Scienya M Jackson, MD, David W Berke-Schlessel, Bauer E Sumpio, MD, PhD Twenty-six years ago, St Legar and colleagues 1 first drew attention to the inverse relationship between red wine consumption and mortality from ischemic heart disease in 18 different European and American coun- tries. This report followed the observations of previ- ous investigators of the association between alcohol consumption and the low incidence of coronary ar- tery disease (CAD). 2-4 In 1992, Renaud and associ- ates 5 introduced the term French Paradox to under- score the low mortality rate from ischemic heart disease among people in France despite the high amount of saturated fats in their diet, 5-9 which is usu- ally associated with increased mortality from CAD. They attributed this unusual occurrence to red wine consumption based on the findings of the MONICA (MONItoring system for CArdiovascular disease) project, a worldwide program organized by the World Health Organization. Collaborating researchers from 21 countries studied more than 7 million men and women (35 to 64 years of age) from 37 mostly European popu- lations over a period of 10 years, from the mid-1980s to the mid-1990s. The investigators observed a lower mortality rate from CAD in France compared with that in the United Kingdom and the United States, despite the high consumption of saturated fats and similar serum cholesterol concentrations. In addition, other risk factors such as blood pressure, body mass index, and cigarette smoking were equivalent in France to what they were in other industrialized coun- tries ( Table 1). 10,11 Although France and Italy have halved their wine consumption from what it was in the 1960s, and now average 67 and 57 L/capita/year, respectively, these countries still have a much higher intake than the United Kingdom or the United States, where consumption is about 12 and 5 L/capita/year, respectively. 12 Within France, alcohol intake is mostly in the form of red wine. This is particularly true in the south (Toulouse), where CAD is at its lowest; in the north (Strasbourg, Lille), they consume less wine and more spirits, and have a higher incidence of CAD ( Table 1). Epidemiologic studies suggest that consumption of red wine at a level comparable to that of France (0.7 to 1.1 ounces of alcohol per day) can indeed reduce the risk of CAD 5 by preventing arteriosclerosis. Several reports postulate that this can be attributed to the French consumption of three times more wine. 9 But it is now widely accepted that regular, moderate intake of alcoholic beverages (1.1 to 1.8 ounces/day of alco- hol) can also decrease the risk of CAD by at least 40%. 5,13-16 Arteriosclerosis is the most significant condition contributing to the development of CAD. 17 The pro- cess of atherogenesis is believed to be accelerated by oxidation of low density lipoprotein (LDL). 18-23 Var- ious biologic effects can lead to the lipid peroxidation of LDL, such as the oxidation of LDL polyunsatu- rated lipid components with reactive nitrogen and oxygen species, and enzyme systems such as the nic- otinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, 15-lipoxygenase, cyto- chrome p450, and myeloperoxidase. 24 Accounting for nearly half the deaths in developed countries, 25 arte- riosclerosis has presented itself as a grave public health problem. There are a number of components of red wine that could have an effect on the cardiovascular system, pre- venting or delaying arteriosclerosis. Alcohol, which is present in up to 15% of the volume of red wine, is one of them. A number of epidemiologic studies have shown an inverse relationship between alcohol consumption and CAD. 13-16 For example, a prospective study 26,27 involving 51,529 men examined the relationship between alcohol consumption and risk of coronary disease among men without preexisting cardiovascular or cancer disorders. After a 12-year followup with food-frequency question- naires, the investigators concluded that the consump- This work was supported in part by an unrestricted grant from the North American Foundation for Limb Preservation. Received September 2, 2004; Revised October 22, 2004; Accepted October 22, 2004. From the Department of Vascular Surgery, Yale University School of Medi- cine, New Haven, CT. Correspondence address: Bauer E Sumpio, MD, Department of Surgery (Vascular Section),Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8062. 428 © 2005 by the American College of Surgeons ISSN 1072-7515/05/$30.00 Published by Elsevier Inc. doi:10.1016/j.jamcollsurg.2004.10.030