Atherosclerosis, 80 (1990) 255-256 Elsevier Scientific Publishers Ireland,
ATHERO
255 Ltd.
04423
Letter
to the Editors
Linoleic acid, platelet aggregation and myocardial infarction Dear Editors, The results of Lewis and Taylor [l] indicating that platelet aggregation to ADP is increased by a high intake of both saturated and n - 6 polyunsaturated (linoleic acid) fat in 10 monkeys studied for 30 months confirm the results we reported a few years ago in man. We observed first that, by comparing within France and Great Britain farmers of high-risk and low-risk areas (MoselleVar in France, West-East in Scotland) for coronary heart disease (CHD), there was, in high risk areas a higher response of platelets to aggregation induced by both thrombin and ADP [2-51 related to a higher intake of satured fat. Moreover, when the diet of 50 Moselle farmers was changed for one year, in such a way that the P/S ratio was enhanced from 0.32 to approx. 1, we obtained a significant decrease in the response of platelets to thrombin aggregation, but a significant increase in the response to ADP [6]. It was only a P/S ratio from 0.6 to 0.8 that was able to decrease in subsequent studies, all the platelet aggregation tests to the level observed in Var [6]. Consequently, increasing markedly the intake of n - 6 polyunsaturated fat “is a question of some concern” since such a diet, as emphasized by Lewis and Taylor [l] may increase the predisposition to thrombosis, i.e., to myocardial infarction (MI). The close relationship between ADP aggregation and MI has been demonstated recently in the Caerphilly prospective collaborative heart study on more than 2000 men (45-69 years). In this study, the response of platelets to ADP in whole blood [7] and in platelet rich plasma (unpublished results) is highly significantly increased in the prevalent cases of MI. The Caerphilly study also indicates that the association between MI and ADP aggregation is independent of that between total and HDL-cholesterol. Concerning the relationship between a high intake of linoleic acid and thrombosis, most of the 0021-9150/90/$03.50
6 1990 Elsevier Scientific
Publishers
Ireland,
intervention trials either primary [8] or secondary [9] with P/S ratio of 1.5 or above did not decrease the mortality rate from CHD. In the only intervention which has been completely successful in that connection [lo], the investigators decreased the intake of saturated fat without increasing that of polyunsaturated. The initial goal was to obtain a P/S ratio of 1, but a subsequent reevaluation of the diet used indicates that the P/S ratio was not higher than 0.7 [ll]. As to the mechanism involved in the possible untoward effects of a high n - 6 polyunsaturated diet, studies in monkeys [l] as well as our own studies in man, suggest that a P/S ratio higher than 1, even if it decreases successfully serum cholesterol, will increase the reactivity of platelets to ADP. This phenomenon, at least in women taking hormonal contraceptives [12], appears to be related to the formation of lipid peroxides that can be blocked by antioxidants, in vitro [13] as well as in vivo in women [12]. The observations mentioned above are concordant with the hypothesis that the efficient diet to prevent CHD, in addition to being decreased in saturated fat (below 10% of calories), should also be moderate in linoleic acid in such a way that the P/S ratio does not exceed 0.7. This is the type of P/S ratio and saturated fat intake occurring in the two populations documented to have the greatest life expectancy, i.e., Japanese in Japan (P/S = 0.7 with a substantial intake of n - 3 fatty acids) [14] and Crete (P/S = 0.4) [15]. References Lewis, J.C. and Taylor, R.G., Effects of varying dietary fatty acid ratios on plasma lipids and platelet function in the African green monkey, Atherosclerosis. 77 (1989) 167. Renaud, S., Dumont, E., Godsey, F.. Suplisson, A. and Thevenon, C., Platelet functions in relation to dietary fats in farmers from two regions of France. Thromb. Haemost.. 40 (1979) 518. Ltd
256 3 Renaud, S., Morazain, R., Godsey, F., Dumont, E., Symington, I.S., Gillanders, E.M. and O’Brien, J.R., Platelet functions in relation to diet and serum lipids in British farmers, Br. Heart J., 46 (1981) 562. 4 Renaud, S., Dumont, E., Baudier, F., Ortchanian, E. and Symington, I.S., Effect of smoking and dietary saturated fats on platelet functions in Scottish farmers, Cardiovasc. Res., 19 (1985) 155. 5 Renaud, S., Morazain, R., Godsey, F., Dumont, E., Thevenon, C., Martin, J.L. and Mendy, F., Nutrients platelet function and composition in nine groups of French and British farmers, Atherosclerosis, 60 (1986) 37. 6 Renaud, S., Godsey, F., Dumont, E., Thevenon, C., Ortchanian, E. and Martin, J.L., Influence of long-term diet modification on platelet function and composition in Moselle farmers, Am. J. Clin. Nutr., 43 (1986) 136. 7 Elwood, P.C., Beswick, A.D., Sharp, D.S., Yarnell, J.W.G. and Renaud, S. Ischaemic heart disease and whole blood aggregation: The Caerphilly collaborative heart disease study, submitted for publication. 8 Fran@ I.D., Dawson, E.A., Ashman, P.L., Gatewast, L.C., Bartsch, G.E., Kuba, K. and Brewer, E.R., Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota coronary survey, Arteriosclerosis, 9 (1989) 129.
INSERM U. 63, II au. du Doyen Lepine, F-69500 Bron (France) (Received 13 July, 1989) (Revised, received 4 September, (Accepted 17 October, 1989)
1989)
9 Renaud, S. and de Lorgeril, M., Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention, J. Intern. Med., 225 (Suppl. 1) (1989) 39. 10 Hjermann, I., Holme, I. and Leren, P., Oslo study diet and antismoking trial. Results after 102 months, Am. J. Med., 80 (Suppl. 2A) (1986) 7. 11 Hjermann, I., Dietary prevention of coronary heart disease. In: Somogy J.C., Renaud, S. and Astier-Dumas (Eds.), Emerging problems in human nutrition, Biblthca Nutr Dieta, 40 (1987) 28. 12 Renaud, S., Ciavatti, M., Perrot, L., Berthezene, F., Dargent, D. and Condamin, P., Influence of vitamin E administration on platelet functions in hormonal contraceptive users, Contraception, 36 (1987) 347. 13 Ciavatti, M., Blache, D. and Renaud, S., Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis, Arteriosclerosis, 9 (1989) 84. 14 Ohno, Y., Health development in Japan: determinants, implications and perspectives, World Health Stat., 38 (1985) 176. 15 Blackburn, H., The low risk coronary male, Am. J. Cardiol., 48 (1986) 161.
S. Renaud
ATHERO
255 Ltd.
04423
Letter
to the Editors
Linoleic acid, platelet aggregation and myocardial infarction Dear Editors, The results of Lewis and Taylor [l] indicating that platelet aggregation to ADP is increased by a high intake of both saturated and n - 6 polyunsaturated (linoleic acid) fat in 10 monkeys studied for 30 months confirm the results we reported a few years ago in man. We observed first that, by comparing within France and Great Britain farmers of high-risk and low-risk areas (MoselleVar in France, West-East in Scotland) for coronary heart disease (CHD), there was, in high risk areas a higher response of platelets to aggregation induced by both thrombin and ADP [2-51 related to a higher intake of satured fat. Moreover, when the diet of 50 Moselle farmers was changed for one year, in such a way that the P/S ratio was enhanced from 0.32 to approx. 1, we obtained a significant decrease in the response of platelets to thrombin aggregation, but a significant increase in the response to ADP [6]. It was only a P/S ratio from 0.6 to 0.8 that was able to decrease in subsequent studies, all the platelet aggregation tests to the level observed in Var [6]. Consequently, increasing markedly the intake of n - 6 polyunsaturated fat “is a question of some concern” since such a diet, as emphasized by Lewis and Taylor [l] may increase the predisposition to thrombosis, i.e., to myocardial infarction (MI). The close relationship between ADP aggregation and MI has been demonstated recently in the Caerphilly prospective collaborative heart study on more than 2000 men (45-69 years). In this study, the response of platelets to ADP in whole blood [7] and in platelet rich plasma (unpublished results) is highly significantly increased in the prevalent cases of MI. The Caerphilly study also indicates that the association between MI and ADP aggregation is independent of that between total and HDL-cholesterol. Concerning the relationship between a high intake of linoleic acid and thrombosis, most of the 0021-9150/90/$03.50
6 1990 Elsevier Scientific
Publishers
Ireland,
intervention trials either primary [8] or secondary [9] with P/S ratio of 1.5 or above did not decrease the mortality rate from CHD. In the only intervention which has been completely successful in that connection [lo], the investigators decreased the intake of saturated fat without increasing that of polyunsaturated. The initial goal was to obtain a P/S ratio of 1, but a subsequent reevaluation of the diet used indicates that the P/S ratio was not higher than 0.7 [ll]. As to the mechanism involved in the possible untoward effects of a high n - 6 polyunsaturated diet, studies in monkeys [l] as well as our own studies in man, suggest that a P/S ratio higher than 1, even if it decreases successfully serum cholesterol, will increase the reactivity of platelets to ADP. This phenomenon, at least in women taking hormonal contraceptives [12], appears to be related to the formation of lipid peroxides that can be blocked by antioxidants, in vitro [13] as well as in vivo in women [12]. The observations mentioned above are concordant with the hypothesis that the efficient diet to prevent CHD, in addition to being decreased in saturated fat (below 10% of calories), should also be moderate in linoleic acid in such a way that the P/S ratio does not exceed 0.7. This is the type of P/S ratio and saturated fat intake occurring in the two populations documented to have the greatest life expectancy, i.e., Japanese in Japan (P/S = 0.7 with a substantial intake of n - 3 fatty acids) [14] and Crete (P/S = 0.4) [15]. References Lewis, J.C. and Taylor, R.G., Effects of varying dietary fatty acid ratios on plasma lipids and platelet function in the African green monkey, Atherosclerosis. 77 (1989) 167. Renaud, S., Dumont, E., Godsey, F.. Suplisson, A. and Thevenon, C., Platelet functions in relation to dietary fats in farmers from two regions of France. Thromb. Haemost.. 40 (1979) 518. Ltd
256 3 Renaud, S., Morazain, R., Godsey, F., Dumont, E., Symington, I.S., Gillanders, E.M. and O’Brien, J.R., Platelet functions in relation to diet and serum lipids in British farmers, Br. Heart J., 46 (1981) 562. 4 Renaud, S., Dumont, E., Baudier, F., Ortchanian, E. and Symington, I.S., Effect of smoking and dietary saturated fats on platelet functions in Scottish farmers, Cardiovasc. Res., 19 (1985) 155. 5 Renaud, S., Morazain, R., Godsey, F., Dumont, E., Thevenon, C., Martin, J.L. and Mendy, F., Nutrients platelet function and composition in nine groups of French and British farmers, Atherosclerosis, 60 (1986) 37. 6 Renaud, S., Godsey, F., Dumont, E., Thevenon, C., Ortchanian, E. and Martin, J.L., Influence of long-term diet modification on platelet function and composition in Moselle farmers, Am. J. Clin. Nutr., 43 (1986) 136. 7 Elwood, P.C., Beswick, A.D., Sharp, D.S., Yarnell, J.W.G. and Renaud, S. Ischaemic heart disease and whole blood aggregation: The Caerphilly collaborative heart disease study, submitted for publication. 8 Fran@ I.D., Dawson, E.A., Ashman, P.L., Gatewast, L.C., Bartsch, G.E., Kuba, K. and Brewer, E.R., Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota coronary survey, Arteriosclerosis, 9 (1989) 129.
INSERM U. 63, II au. du Doyen Lepine, F-69500 Bron (France) (Received 13 July, 1989) (Revised, received 4 September, (Accepted 17 October, 1989)
1989)
9 Renaud, S. and de Lorgeril, M., Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention, J. Intern. Med., 225 (Suppl. 1) (1989) 39. 10 Hjermann, I., Holme, I. and Leren, P., Oslo study diet and antismoking trial. Results after 102 months, Am. J. Med., 80 (Suppl. 2A) (1986) 7. 11 Hjermann, I., Dietary prevention of coronary heart disease. In: Somogy J.C., Renaud, S. and Astier-Dumas (Eds.), Emerging problems in human nutrition, Biblthca Nutr Dieta, 40 (1987) 28. 12 Renaud, S., Ciavatti, M., Perrot, L., Berthezene, F., Dargent, D. and Condamin, P., Influence of vitamin E administration on platelet functions in hormonal contraceptive users, Contraception, 36 (1987) 347. 13 Ciavatti, M., Blache, D. and Renaud, S., Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis, Arteriosclerosis, 9 (1989) 84. 14 Ohno, Y., Health development in Japan: determinants, implications and perspectives, World Health Stat., 38 (1985) 176. 15 Blackburn, H., The low risk coronary male, Am. J. Cardiol., 48 (1986) 161.
S. Renaud
