Tobacco Documents Online

OTH E R PEOPLE'S TOBACCO SMOKE i ~ Edited by A. K. Armitage Ch,p~ '7. C.c A.k. Arw,~~w9e Galen Press 0

First published in 1991 by Galen Press, 54, Westwood Road, Beverley, E. Yorks, HU17 8EJ Printed and bound by Clifford Ward & Company (Bridlington) Limited 55a West Street, Bridlington, East Yorkshire, YO1S 3DZ Artwork by B.A. Press, 2-4 Newbegin, Lairgate, Beverlcy, North Humberside, HU17 8EG © Galen Press 1991 All rights reserved British Library Cataloguing in Publication Data Other people's tobacco smoke 1. Health. Effects of Tobacco Smoking I. Armitage, A. K. 613.85 ISBN 0-9508726-1-X

{ E r, u I 7. Environmental Tobacco Smoke and Coronary Heart Disease A. K. Armitage* 1. What is coronary heart disease? Before considering whether exposure of the non-smoker to ETS represents a health risk, let us highlight, briefly and simply, some of the basic physiology, anatomy and pathology of importance to an understanding of coronary heart disease (CHD). This type of heart disease, also known as ischaemic heart disease, has been at the centre of public health interest for 25 years because it is the leading cause of death in many countries, including the UK and the USA. The heart is a blood-filled bag of' muscle, which contracts and relaxes roughly 70, tirnes a minute to pump blood around the body. It has a remarkable capacity to adapt its performance throughout life, according to the needs of the body, by varying its rate and strength of beat. As one of the most active tissues in the body, the heart muscle needs a good supply of oxygen to function efficiently. This supply is not obtained from the bloo& which is pumped through the chambers of the heart, but from blood pumped through the coronary arteries. These arteries branch off from the main artery(aorta) as it leaves the lieartand they then divide into a network of smaller branches which fan out all over the surface of the heart. Over a period of many years,,the walls of the coronary arteries gradually 'fur up' with fatty deposits known as atheroma. This condition, when severe„istoronary heart disease, the clinical manifestations of whichappear in two forms - angina and heart attack. If the narrowing of the coronaryy arteries is very gradual (as it usually is) then the first sign of trouble may only be notice& when the heart has to work harder than usual. For example, during brisk exercise, the heart muscle may fail to receive an adequate supply of oxygenated blood and chest pains (angina) may result. The symptoms are generally relieved by resting for a few minutes. A heart' *Dr Alin Mmitage is a Consultant Phartnacologisr.?oxicologist„ formerly Director of Toxicology at Haz.itton Laboratories Europe and Head of Pharmacology ar the Tobacco Researcb Council iLabontories.

OTHER PEOPLE'S TOBACCO SMOKE attack, on the other hand, occurs when there is a sudden~ and severe blockage of one of the coronary arteries, so that the blood supply to part of the heart muscle is not merely reduced, but cut off. The blockage is usually caused' by a blood clot forming in an artery already severely affected by fatty atheroma and is known as a coronary thrombosis. The part of the heart muscle affected is severely damaged (myocardial infarction) causing the prolonged pain that is the most common symptom of a heart attack. Sometimes the blockage is so severe that the heart stops beating in a coordinated manner and circulation of blood to all the tissues of'the bodyy effectively stops. Unless the heart starts beating normally within a feww minutes, the person will die. 2. What causes coronary heart disease? Death rates from CHD vary widely from country to country. For example, in 1984 the figures for the age group 55-641were in excess of 800 per 100,000 in Northern Ireland, Scotland and Finland'and less than 100 per 100,000 in Japan. Research workers are still trying to discover exactly what it is in our everyday lives that increases the risk of heart attack and angina. It seems certain that there is no singlp cause; the major risk factors are usually said to be high blood' pressure, high levels of cholesterol in ~ ttie blood' and cigarette smoking. In addition, diabetes,, lack of exercise an& a-generally aggressive work temperament (so-called Type A behaviour) are all considered to contribute to the multifactorial atherogenic process (Kannel, 1981). 3. Active cigarette smoking and coronary heart disease It has been reported that male cigarette smokers, but not pipe and cigarr smokers, have consistently higher overall death rates than non-smokers from CHD in many, but not all, Western societies. The size of the risk is claimed to be dependent on age and daily consumption of cigarettes, being greater in men under 50 years of age than in older men. The various epidemiology studies consider mortality ratios in slightly different age ranges. For men aged `around 50', the reported mortality ratios are some 2-3 times greater than those of non-smokers. In men age& 60 and above, however, when death from heart attacks is in any case more prevalent, the mortality ratios are consistently lower, around 1.5 (Surgeon GcneralPs Report, 1983). I!n female smokers, the reported association between cigarette smoking and CHD is much weaker. Several studies indicate that cigarette smoking may occasionally precipitate anginal pain in some patients or reduce exercise tolerance in others. In others, the frequency and severity of atheroma of the coronary arteries at post mortem were greater in smokers than in non-smokers. (For specific references, see Royal College of' Physicians, Reports 1-4, on Smoking and Health, 1962, 1971, 1977, 1i983.). 110

CORONARY HEART DISEASE On an acute basis, the act of cigarette smoking causes a marked increase in hean rate, an increase in cardiac output and a relatively smaller increase in blood pressure. The effects arc due to absorption of nicotine into the bloodstream, increase with dcgree of inhalation, and in healthy subjects are perfectly normal and harmless. In subjects who have already had a heart attack and suffered a myocardial infarction, however, a fall in cardiac output may occur. It follows that such subjects who can readily be identified should not smoke cigarettes (Pentecost and Shillingford, 1964). Although the public healt;h4obby frequently claims a causal relationship between active cigarette smoking and CHD it should not be forgotten that the disease is a common affliction among non-smokers. Furthermore, there is much evidence that is not wholly consistent with a claim of' causation (Seltzer, 1980, 1981). One notable objection is lack of proof of the mechanisms by which cigarette smoking may accclerate development of CHD and precipitate death. Nicotine and' carbon monoxide have been implicated atone time or another, but the reasons have been theoretical and emotional, rather than strictly factual.. The possibilities have been fully discussed by Wynder et al. (1976); while Cohen and Roe (1981) ~ elegantly summarised the actions of nicotine that might play a role in ~ cardiovascular disease. In the opinion of the present author, however, it is misleading to state that cigarette smoking, nicotine and carbon monoxide may cause CHD. A similar claim for eating is just as reasonable! After al14 our restricted diet in World War II and for the rest of the 1940s had a favourable effect on CHD death statistics. 4. ETS and coronary heart disease The foregoing summary concerning active cigarette smoking and CHD provides the basis for comparing the role of ETS. On this subject, there are relatively few relevant published data, which is reflected in the fact that cardiovascular diseases occupied only two of the 359 pages of the recent Surgeon General's report, The Health Consequences of lnvoluntary Smoking. (1986), and did not feature in any of the 16 paragraphs concerned with exposure to ETS of the 4th Report of the Independent Committee on Smoking and Health (1988). S. Dosimetry The concentration of ETS to which an individual is exposed depends on: • Type and number of cigarettes burned' • Volume of room • Ventilation rate • Proximity of burning cigarette The effective dose for an exposed individual is the dynamic integration of concentration in various environments and the time the individual spends in

OTHER PEOPLE'S TOBACCO ~SMOKE these environments. These considerations highlight the difficulty of assessing accurate d'osage under 'real life' conditions, which is one major weakness of most, if not all, ETS epidemiology studies. It is possible to measure the concentration of specific components in ~ETS, and the two most common marker substances are nicotine and carbon monoxide. In~a recent study (Kirk a al., 1988), large differences were shown to exist according to the environmental circumstances - for example, travel, leisure, work, home. The concentration of nicotine varied from non-detectable to a maximum of the order of 400 micrograms per cubic metre (mean approximately 15 micrograms per cubic metre); for carbon monoxide the range was 0-30 parts per million with a mean~concentration of around 2.5 parts per million. With an individual exposed to ETS, there is normal breathing of diluted sidestream smoke (SS) and exhaled mainstream smoke (MS)from active smokers. This contrasts with the situation obtaining for the active cigarette smoker, who takes a puff of neat smoke into the mouth and then inhales it. Under these circumstances, the concentration of' nicotine and carbon monoxid'e to which the alveolar membranes of the lung are exposed is of a totally different order of magnitude - perhaps as much as 1000 times. On theoretical consideration, therefore, the dice are heavily loaded against significant absorption of nicotine and carbon monoxide, and indeed any other putative cardiovascular toxins like nitrogen dioxide. The theory is borne outlin practice because cotinine level5 in blood, saliva and urine, which are often used as a measurement of nicotine absorption of non-smokers exposed to-ETS, are approximately 1% of those measured in active smokers Qarvis et al:, 1984). Blood carboxyhaemoglobin levels (COHb) have been measured in non-smokers exposed to ETS under real life and artifically exaggerated conditions. They were generally in the range 1- 1.5%o under realistic exposure conditions. 6. Effect of ETS exposure on heart rate of healthy subjects Normal healthy subjects exposed' to ETS for period's up to two hours under resting or exercise conditions have been studied. There were no significant changes in heart rate or blood pressure in adult men and women, indicative of the absorption of negligible amounts of nicotine (National Research Council, 1986). 7. Effect of ETS exposure on heart rate of angina patients Various studies, conducte& mainly by Aronow and colleagues, have demonstrated that exercise-induced angina develops more rapidly in patients diagnosed with classic stable angina pectoris exposed to 50 parts per million carbon monoxide for periods from 1-4 hours. These concentrations are on the high side compared with those measured by Kirk et al: (I988) and measured levels of COHb were in fact in the range 2-4%. Only one 112

CORONARY HEART DISEASE f experiment on the effects of ETS exposure has been reported (Aronow, r 1978) in which 10 patients were exposed to other people's smoke (15 o cigarettes) in a small room during two hours. Even under good conditions of ventilation, when the mean carboxyhaemoglobin level was only 1.77%, at there was an apparent substantial reduction in the duration of exercise until ~o the onset of pain. The results of this experiment are questionable because ., a b Adverse Allrisli effect on CHD factors ad'equately covered' Yes, but sample No sizewassmall Yes, relative No risk 1.3 for husbands smoking more than 19 dgarettes/day' Yes,bur No questionable statistinlly NS ? not much information given No Yes NS = nousignifimt 113 the study was not conducted on a strict double blind basis,,the measured end point was a subjective one, and furthermore, the validity of Aronow's work has beenicritjcally questioned'(Budiansky, 1983). need to use elaborate, and appropriate, statistical techniques if they are to provide unequivocal results. This is particularly true of studies concerned with effects of ETS on non-smokers, where, based on dosimetry considerations which have already been discussed, any effects might be expected to be small. Last, but not least, the question of misclassification of smoking status, to which detailed reference has been made in the lung Because of' the many factors that play a role in the development of fatal CHD, epidemiology studies need to be carefully designed4nd', in addition, Tabtel. ETS and CHD-EpidemioloYy Studies Author Subjects Major Disease Interest Gilliserel: Non-smoking Lung 1984) women cancea Hirayama Non-smoking Lung (d984,1985) , women clncer Gtrltndaal. Non-smoking CHD (Q985) women Svendsen Non-smoking CHD (1985) mea Leeaal. Non-smoking Various (1986)' women

OTHER PEOPLE'S TOBACCO SMOKE cancer chapter, has not been considered in any CHD/ETS study apart from the case control study of Lee er al. (1986). This factor is as relevant to CHD as it is to lung cancer. Rather than record the detailed numerical findings of the various studies that have been conducted, I will'summarise the authors' conclitsions(Tabie 1). It is clear that the evidence for a harmful'effect of ETS in enhancing CHD risk in non-smokers is not very convincing, as the US National Research Council also concluded in the following statement: 'With respect to chronic cardiovascular morbidity and mortality, although biologically plausible, there is no evidence of statistically significant effects due to ETS exposure, apart from the study of Hirayama in Japan.' There are now, however, two reasons to cast doubt on the Hirayama data. Misclassificatioz of smoking status almost certainly accentuates the apparent risk, even if it does not altogether explain it. Secondly, when1e reported on the first 14 years of his prospective study in 1981, there was no mention of a higher mortality rate from CHD of non-smoking women married'to smokers. It is difficult to believe that a previously unsuspected risk could become apparent merely as a consequence of 3 more years of follow-up. Any author is entitled~ to his opinions, bur in the public health area there is a danger that' if such opinions are reiterated sufficiently often, they may ultimately become accepted as facts. Lee er al. (1986), having considered alll the available evidence, concluded that any effect of ETS exposure on risk of any of the major diseases that have been associated with active smoking is at most small, and may not exist. The case for exposure to ETS carrying any increased risk of death from CHD is the weakest of all. It has already been poiated'out that in many studies the association between active cigarette smoking and CH'D is much weaker in female smokers than in male smokers, or even non-existent. If an effect of smoking on the development of CHD cannot be convincingly demonstrated in female active smokers, it is difficult to assume that such an effect is possible in females exposed to ETS (Schievelbein and Richter, 1984) unless there issomethings particularly noxious in ETS, about which we are currently unaware. This seems unlikely. At a recent meeting in Montreal, Wexler (1990) and a discussion panel also conduded that currently there is no clear demonstration of any increased risk of cardiovascular disease from exposure to ETS. There is another and independent piece of evidence that casts doubt on any significant role of ETS in the development of CHD. Pipe smokers inhale tobacco smoke both actively, to a limited extent, and passively. They commonly surround themselves in a cloud of tobacco smoke, so that they are probably exposed to the highest concentrations of ETS of any group. Yet they enjoy relative immunity from the three major diseases whichtave tN ` I

CORONARY HEART DISEASE D' I been associated with active smoking. In conclusion, therefore, non- smokers would be h b muc tt d' d h h e e er a vts to wata t etrwetght, dtet and blood pressure than to worry about arty long-term harmful cardiovascular effects r I of exposure to ETS! ~ D n 0 F Referenees Aronow, W.S. (1978):,Effects of'~passive smoking on angina pectoris. New England7ournal of' Medicane, 294, 21-24. Budianskv, S. (1983): Food and drug data fudged. Nature, 302, 560. Cohen„A.J: and Roe„F.J.C. (1981)i Monograph on thrpharmacology and toxicology of nicotine.Occssional Paper4'. London: Tobacco Advisory Couneill Garland, C., Barrett.Corutor, E., Suarez, L., Criqui; M.H. and' Wingard, D.L. (d985): Effects of passive smoking on ischaesnic heart disease: mortality of non-smokers. A merican Yomnal ujEpidemiology, 121, 645-650; Gillis, C.R., Hole, D.J., Hawthorne, V.M. and Boyle, P. (1,984): T}ie effecrof environmental tobacco smoke in two urban communities in the West of Scotland. Europran Journal of Respvatory Uiseasss,,65, 121-126. Hinyama, T. (1984). Lung cancen in Japanr effects of nutrition and passive smoking. In: M. Miull and P. Correa (Eds.)~ Lung Cancer : Causes and Prevention. Deerfield Beaeh{ Florida: VCH, pp.175-195. Huayama,,T. (1985): Passive smoking - a new target of epidemiology. Tokai 3ovrnal'oJ Cli>rical and Ezperimental Medicine.,,10; 287-293: Independent Scientific Committer on Smoking and Health (1988). Fourth Report. London:: Her Majesty's Stationery Office.. Jarvis, M.J., TunstalJ-Pedoe, H., Feyerabend, C.,, Vesey, C. and Saloojee, Y. (1984). Biochemical tnarkers of smoke absorption and self-reported exposurt to passive smoking. Journal ofEpidemiology and Conmunity Health, 38, 335-339. Kannel, W.B. (1981), Update on the role of'cigarette smoking in coronary artery disease. American HeartJourna1;,101, 319=328: Kirk, P.W.W., Htmter, M., Back, S.O.,,Lester„J.N. and Perry„R. (1988). Enviionmental tobacco smoke in indoorair. In: ,R. Perry and P. W. W: Kirk (Eds.), Indoor and Ambwu Air Qualiry. London: Selper Ltd., pp.99-11Z. Lee, P.N., Chamberlairt, J'. nnd Altlersonj M.R. (1986); Relationship of passive smoking to risk oflung nnctr and other smoking-associated diseases. Bruishjotanal oJCancer, 54, 97- 105. National~Resnrcb Council (1986). Esraimmneeral Tobacco Smoke. Meassoiity Ezposava a.d' Assessing Health Effects. Washington, DC: National Academy Press. Pentecost, B. and' Shillingford, J. (1964). The acute effects of smoking on myacardial performance in patienu with coronary arterial disease. Brstislt Hearr]ournal;,26, 422-429. Royal College of Physicians (!%2, 1971, 1977, 1983). Four Reports on Sntokneg and Health. London: Pitman Medical. Schievelbein, H. and Richter, F. (1984). The influence of passive smoking on the cardiovaseulir system. Prevrntive Medicine, 13, 626-644. Seltzer, C.C. (1980). Smoking and coronary heart disease: What are we to believe? Editorial,, Amencan Hearr Joimral, 100, 275-280.

OTHER PEOPLE'S TOBACCO SMOKE Sdtaer, C.C. (1,981)j Cigarette smoking and coronary artery diseax:, a questiotnble connection. in: W.R. Finger (Ed.), The Tobucco Irsdustry in Tranririmt. Lezington,. Massachusetts, Lexington Books, pp.267-277. Surgeon General's Report (1983), The Health'Conttqrenca ofSmoking: CardioiascvlarDusau. Rockville, Maryland: US Department of Health and Human Services. Susgcon General's Report (1986). The Health Consequences ojlncoluntary Smoking. Rockvilk, Maryland: US Department of Health and Human Services. Svendsea, K.H., Kuilcr, L.H. and Neaton, J.D. (1985). Effects of passive smoking io the Multiple Risk Factor Intervention Trial (MRFIT). Cucularion, 72f{, Part II. Wezler, L.M. (1990). Environmental !tobacco smoke and'cardiovascvlar disease : A critique of the epidemiological literature and recommendations for futtue research. In: D.J. Ecobichon and J.M. Wu (Eds.), Ersanoronental Tobacco Smoke. Proceedings of the Intetnational~ Symposium at McGill' University; 1989. Lexington, Massachusetts andi Toronto: Lexington Books, pp.139-152., Wynder, E.L., Hoffman, D. and Gori, G.B: (1976). Smoking and Health. Proceedings of3rd World Conference, New York City, June 1975. Volume 1. Modi'/ving the Risk for the Smoker. DHEW Publication No (NIH) 76-1221. 116