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while the HDL3 cholesterol subfraction, was decreased in girls only and curiously, together with Low Density Lipoprotein (LDL) cholesterol eubfraetion. These results are not consistent enough to permit a definite conclusion inasmuch as other parameters ApoAl, ApoB or better LpA1, LpB are now considered to be better correlated with atherosclerosis risk. Further research work is necessary to evaluate effects of ETS on lipidic fractions, alli the more so as in active smokers, variations of HDL subfractions are not very significant either [341. , PLttelets Passive smoking increases platelet aggregation and produces a desquamation effect on endothelial cells of a similar magnitude to thatt observed in active smoking [48]. Davis [48] , thinks that even a small increase in plasma nicotine concentration may release catecholamines. Polycyclic Aromatic Hydrocarbon. (PAHs) Although PAHs are potentially very harmful because of their carcinogenic effect on the lungs, bladder and heart through formation of adducts, it is questionable whether they are actually playing a role in the case of ETS: Indeed, the amounts thus absorbed are so small compared on the hand to those of an active smoker who inhales from 75 to 150 times more, according to Scherer [46]i (table 3) and on the other hand to amounts contributed by the environment (50) as in the case of benzene which brings about ten times more. Grimmer [50] has demonstrated that sidestream smoke (SS) contains ten times more PAHs (Benzo(a)pyrene for instance) than mainstream smoke (MS). 99 % of these PAHs, however, occur in the particulate phase whereas a non-smoker is only exposed to the vapour phase [46].. When recapitulating available evidence on ETS generated stimuli in the body, it appears that increases in nicotine and CoHb levels are so low that only very low variations can be expected from direct actions or cathecholamine releasing mechanisms. Effects on lipids are just about significant. Effects on platelet aggregation seem to be a more promising avenue of research as platelets influence both the slowly developing atherosclerosis process and more important still, the rapidly developing phase of thrombus formation preceding a cardiac incident. OOtaC:[.iJS[OIVS About 10 epidemiologic studies conducted in different countries have concluded that ETS exposure accounts for about 30% risk increase of CHD mortality. Because of the many factors, some of which have only been recently discovered„ that play a role in the development of CHD, a number of these studies have not been properly designed even if some (Svendsen, Garland, He-Hole) have controlled for age, race, weight, hypertension~ altoholl consumption, exercise and total serum cholesterol. Many other 439

factors need to be considered: diabetes, heredity or associated lipidic factors, Apo Al, Apo B, Lp Al, Lp(a), platelet factors, diet (antioxidizing factors,; vit E, vit C, selenium) etc... In addition to those, should of course be listed' all the confounding factors currently found in ETS epidemiologic studies and generally connected with exposure assessment (intensity,, duration ). As in the case of lung cancer, it is now certain that active smoking increases the risk of fatal CHD: the risk is supposed to be about 2.0 (Framingham) but may vary from 1.6 to 2.0 for a cigarette smoker but from 1.08 to 1.40 only for a pipe smoker (Surgeon General Report) [54]. Some of the most import'ant' action mechanisms of mainstream smoke by means of nicotine, CO (CoHb); platelet aggregation are now fairly well known. However, its action on coronary atherosclerosis remains unexplained as available evidence is inconsistent and even contradictory. The fact that CHD risk decreases rapidly after cessation or diminution of smoking [51]I may indicate that effects of smoking are more severe on thrombosis [52] or infarction than on coronary atherosclerosis. As far as ETS action is concerned, increases in plasma nicotine and CoHb levels are extremely low compared to those in active amoking (1 % for the former, 20 % for the latter). The physiobiochemical effects actually observed on an exposed non-smoker are real: HDL and HDL2 are decreased and platelet aggregation increased, they indicate that the role of ETS in CHD incidence is biologically plausible. It is, however, unrealistic, given our present knowledge, to suggest new mechanisms, inspired for instance by animal experimentation and which would not first apply to active smoking. Indeed, an~ active smoker is also a passive smoker who inhales his own smoke as well as that of others. Therefore, the magnitude of risk in an ETS exposed non-smoker is bound to be very small compared to that of an active smoker. This risk has certainly been overestimated' in some studies: a scientist s common sense is baffle& when relative risk estimates of ETS exposure are equal or even higher than those of active smoking (Garland; Gillis, Svensen, Hole). Is a smoker more intoucated by ETS than by mainstream smoke ? This suggests that mean RR of CHD due to ETS~ exposure calculated from available epidemiologic studies, has probably been overestimated as at the moment it cannot be explained by physiobiochemical changes caused by ETS in the body. Among the mechanisms suggested by Glantz„ CoHb (at 1 %) and P.A.H. (PS/S = 1/100)~ incidence is unconvincing. However, action on platelet aggregation is more likely. Reversibility of action suggests thatt incidence is stronger on thrombosis process than on coronary atherosclerosis development. Therefore, Well's [ill] extrapolation to the North American population leading to a very high CHD mortality due to ETS appears to be questionable even though he maintains it against critiques [55]. A number of very carefully conducted studies will be necessary before correct risk assessment and satisfactory physiobiochemical interpretation can be achieved. 440

r I 1lEI7EFa7%X:Es 1 S 1 1. Hirayama T., Lung cancer in Japan+ Effects of nutrition and passive smoking. In: Lttng Cancer> Causes and Prevention, Mizell M. and Correa P., New York, Verlag Chemie International, 175-195 (1984): Gillis C.R.,, Hole D.J., Hawthorne V.M. and Boyle P.,, The effect of environment tobacco smoke in two urban communities in the west of Scotland., Eur. J. ftesp: Du., 65 (sup- n' 133), 121-126 (1984): 3. Garland C., Barrett-Connor E., Suarez L.,, Criqui M,H. and Wingard D.L., Effects of passive smoking on ischemic heart disease mortality of non smokers. Am, J. Epidemiol., 121, 645•650 (1985). 4. Lee P.N., Chamberlain J. and Alderson M.R:, Relhtionship of passive smoking to risk of lung cancer and other smoking associated diseases. Br. J. Cancer, b4, 97-105 (1986). 5. Helsing K.J., Sandier D.P., Comstock G.W. and Chee E., Heart disease mortality in non smokers living with smokers. Am., J. Epidemiol:, 127, 915-922 (1988). 6:, He Y., Women's passive smoking and coronary heart disease. Chung-Hua-Yu-Fang-l- Hsueh-Tsa-Chin, 23;,19-22 (1989):, 7. Humble C., Croft J:, Gerber A., Casper M., Hames C. and Tyroler H., Passive smoker and twenty year cardiovascular disease mortality among non smoking wives in Evans Country Georgia.,Am. J. Public. Health, 80, 599-601 (1990):, 8': Butler T:, The relationship of passive smoking to various health outeomes among Seventh-Day Adventists in California (abstract). Seventh World Conference on Tbbaceo and health, p 316 (1990). 9: Svendsen ICH., Kuller L.H. and Neaton J'.D.,, Effects of passive smoking in the multiple risk factor, intervention trial. Am. J: Epidemiol., 126, 783-795 (1987). 10. Hole D., Gillis C.,, Chopra C. and Hawthorne V., Passive smoking and cardiorespiratory health in a general population in the west of Scotland. Br. Med. J:, 299, 423d27 (1989). 11. Judson Wells A., An estimate of' adult mortality in the United States from passive smoking. Environ. Int-,14, 249-265 (1988)h 12. Glantz SA and Parmley W.W., Passive smoking and Heart disease. Epidemiology, Physiology and Biochemistry Ci'rculation, 83(1) (1991). 13. Selt¢er C:,, Framingham Study data and established wisdom about, cigarette smoking andd coronary disease. Joarnal of Clin. Epid., 42(8); 743-750 (1989): 14. Kannel W.B., Importance of hypertension as a major risk factor in cardiovascular disease in hypertension. In: Hypertension, Physiopathology and Treatment„Genest J., Koi.v E: and Kuched 0. (eds), New York, McGraw Hill'y,p. 888-910 (1977). 15: Puchois P., Kandousei A., Fievet P., Fburrier J.L., Bertrand'. M,, Koren E. and FrucharC J.C., Apolipoprotein Al containing lipoproteins in coronary artery disease., Atherosclerosis, 68, 35 (1987)j 161 Alaupovic P., Mc Conathy W.J.,, Fesmire J., Tavella M., and Bard M.J., Profiles of' apolipoproteins and apoliproteins B-containing lipoproteins particules in dyslipoproteinemias. Clin. Chem.,,34, 13-27 (1988): 17: Mezdour H., Parra H.J., Aguie-Aguie G. and Fruchart J.C:, La lipoproteine (a): un marqueur additionnel de Tatheroselerose. Ann. Biol: Clin., 48, 139-153 (1990). 18. Dejager S:, Cohen R. an& Bruckert E.,, Het6rog6neitE des lipoprotbines de basse deneitE (LDL) et atherosclErose: Ann. Biol. Clin., 48, 154-160',(1990L 19. Goldstein J:L., Ho Y'.IC, Basu S.K and Brown M.S., Binding site on macrophages that mediates uptake and degradation ox scetylated low density lipoprotein; producing massive cholesterol deposition. Proc. Natt. Acad. Sti. USA, 76, 333-337 (1979)j 20. Sparrow C.P., Parthasarathy S. and Steinberg D., A macrophage receptor that recognizes oxidized: low density lipoprotein but not acetylated low density lipoprotein. J. Biol: Chem.,,264„2599-2604 (Q989). 441

21. Steinberg D., Parthasarathy S., Carew T.E., Khoo J.C. and Wilztum J.L., Modifications of low-density lipoprotein that increase its atherogenecity. NETM„ 520, 915-924 (1989):. 22. Stocker F.B. and Ames B.N., Mtiorydant defenses and lipid peroxydation in human blood plasma. Proc. NatC Arod. Sti. USA, 85, 9748-9752 (1988). 23. Garrity RG., The role of monoeyte in atherogenesis. Am. J. PathoL, 108, 181 (1981). 24. Agel'N.M., Ball RY., Waldman H.,and Mitchinson M.J., Monocytic origin of foam cells in human atherosclerosis plaque. Atherosclerosis, 63, 265-271 (1984). 25. Heldin C.H. and Westermark B., Platelet derive growth factor three isoforms and~ two receptor types. Trends Genet.,6, 108 (1989). 26. Thyberg J., Hedin U., Sjblund M., Palmberg L. and Bottger B.A., Regulation of differentiated properties of arterial smooth muscle cells. Ateroscleroaia, 10, 966 (1990). 27. Sahmiti G., Hankowit= J; and Kovacs E.M.,, Cellular processes im atherogenesis:: potential targets of Ca«t channel blockers. Atherosclerosiu, 88, 109-132 (1991). 28: Beiech J.I.F:, Chopra M. and Hutchinson S., Free radicali pathology in chronic arterial disease. Frec-Rodie. Biol. Med:, 8, 375378 (1989): 29. Jusaa F., Trevisan 1S. lnad C{rogfi V., Serum selenium and eoronary fieart' disense risk factors in southern Italian men. Atherosclerosis, 87, 129-134 (1991). 30. Downey H.F., Williams Jr, Yonekura S., Wanataben N: and Lawrence M,E., Dominant 1Role of circulating catecholamines in the myocardial contractile response to intravenous nicotine. J. Cardiouase_ Pharrnacol., 12, b8-64 (1988). 3L Sers}.baum A., Bellet S., Dickstein E.R and Feinberg L.J.,, Effect of cigarette smoking and nicotine on serum free fatty acids. Based on a study in the human subject and the experimental animal. Circ. Rts., O, 631 (1961). 32. Mjos O.D.. Lipid effects of smoking. Am. Heart. J.,,115,272(1988). 33. Moffatt R.J:,, Effects of cessation of smoking on serum lipids and high-density lipoprotein-cholesterol. Atherosclerosis, 74, 85 (1988). 34. ]Iintt6ri M., Koskinen P., Manninen V., Tenkanen L. and Kuttunen J.K, Life.atyle determinants of HDL2 and HDL3 cholesterol levels in a hypercholesterolemic male population. Atheroselerosi.,,87, 1-8 (1991). 35. Grignani G., Gamba G. and: Ascari~ E., Cigarette smoking effect on platelet fonction. Thwmb. Xoemost:, 37, 442 (1977): 36. Renaud S:,,Blache D., Dumont E., Thevenorr C:,, Wiasendauger T:, Platelet fonction after cigarette smoking in relation to nicotine and carbon monoxide. Clin. Pharmacol: TAer.,,36, 389 (1984): 37. Imaizumi T.A, Satch K., Yoshida H., Kawamura Y., Hiramoto M. and Takamatsu S., Effect of cigarette smoking on the levels of pletelet' activating factor-like lipid(s) in plasma lipoproteina. Atherosclerosis, 87„47.55 (1991). 38. Pittilo RM., Mackie I.J., Rowles P.M., Machin S.J. and Woolf N., Effects of cigarette smoking on the ultraattucture of rat thoracic aorte andi it4 ability to produce prostaryelin. Thromb. Haemostas.,, 48, 173 (1982). 39., Reinders J., Brinkman H., Mourik J.V: an& de Groot P., Cigarette smoke impairs endothelial cell prostacyclin production. Atherosclerosis, 6, 15 (1986). 40. Sherratt A.J., Culpepper B.T. and Lubawy W.C.,, Alterations in prostacyclin and thromboxane formation following chronique exposure to high on low nicotine cigarettes in rats. Artery, 14, 216 (1987). 41. Effeney D.J., Proatacyclin production by the heart effect of nicotine and carbon monoride., J. Vaac. Surg., b„237 (1987): 42. Revis N:W., Bull IL, Laurie D. and Schiller C.A., The effectiveness of chemical carcinogens to induce atherosclerosis in the white carneau pigeon. Tozieology; 32, 215-227 (1984). 43. Randerath E., Ivlittal D. and Randerath IC, Tissue distribut6on of covalent DNA damage in mice treated dermally with cigarette "tar': preference for Lung and Heart DNA. Careinogentsis, 9(1), 75-80 (1988).

44., Me Cord J.M., Oxygen-derived free radical in post ischaemic tissue injury. N. Engl. J. Med.,313, 159=163 (1985). 45,, Bekh4.J.F., Chopra M, and Hutchinson,S:, Free radical pathology in chronic arterial disease. Free Radic. Biol. Med., 8, 375-378 (1989): 46, Scherer G., Conze C., Meyerinck L., Sarss M., and Adlkofer F., Importance of exposure to gaseous and particulate phase components of tabacco smoke in active and passive smokers. Int. Arch. Occup. Env. Health, 62, 459-466 (1990). 47. Moakowitz W.B., Michael Mosteller M.D., Richard P.D. and Schieken M., Lipoprotein and oxygen transport alterations in passive smoking preadolescent children: the MCV twin study. Circulation, 81, 586-592 (1990): 48:, Davis J., Shelton L, Vvanatabe I., and Arnold J!, Passive smoking affects endothelium and platelets. Arch. Intern., Med.,,149; 386-389 (1989). 49:, Jarvis M.J. an&Russel M:A.H.,, Mesurement and estimation of smoke dosage to non- smokers from environmental tobacco smoke. Eur. J. Respir. Dis., 65 (suppl!133), 68- 75 (1984). 50: Adkofer F., Sherer G., Conze C, Angerer Ji and Lehnert G.,,Signifiance of exposure to benzene and other toxic compounds through environmental tobacco smoke. J: Canerr- Res. Clin. Oneot.,116„591598 (1990) j 51. Grimmer G., Naujack ACW. and Dettbarn G., Gaschromatoraphic determination of polycyclic aromatic hydrocarbons, aza-arenes, aromatic amines in the particle and vapor phase of mainstream and sid'estream of cigarettes. Toxicology letters, 35, 117- 124 (1987). 52. Robertson D., Tseng C.J. and Appalsamy M., Smoking and mechanism of cardiovascular controll Am: Heart. J.,115„258 (1988): 53. Fitzgerald GA., Oates J.Ak and Nowak J.,, Cigarette smoking and hemostatic function. Am: Heart. J.,11b, 26T(1988). 54. Benowitz N.L:, Clinical pharmacology of nicotine. Annual. Review of Medecine, 37; 21-32 (1986L 55. Department Health Human Services, The health consequences of smoking: cardiovascular disease: in a report of the surgeon general Rockville Maryland' USA USPHS (1983)j 56. Judson Wells A, An estimate of adult mortality in United States from passive smoking a reponse to criticism. Environ. Int.,,16, 187-196 (Q990):. 57: Brown M.S. and Goldstein J.L., Lipoprotein metabolism in the macrophages: Implications for cholesterol deposition in atherosclerosis. Ann. Review. Biochem., 52, 223-263' (1983 ): 443