STRICTLY PRMTE AND a)NFIDENTIAL
AIDE-NEMOIRE
Prepared by Smoking and Health Group, GR&DC,
Southampton.
The Effects of Carbon Monoxide in the Context of
Whole Tobacco Smoke
Carbon monoxide binds with haemoglobin, the oxygen
carrying protein in
the blood, forming carboxyhaemDglobin. Several
reports have suggested an
association between atherosclerotic diseases and
carboxyhaemoglobin levels
in tobacco smokers (Wald et al, 1973; Aronow et
al, 1974). However, more
recent epidemiological evidence has failed to
demonstrate any relationship
between a smoker's carbon monoxide exposure and
incidence of coronary heart
disease or myocardial infarction (Lee and
Garfinkel, 1981; Borland et al,
1983). In addition Aronow's work on carbon
monoxide is being re-examined,
since it has been shown that he submitted false
data to the FDA when
examining a number of drugs (Budiansky, 1983).
Kaufman (1983) concluded
that there was no significant association between
the nicotine or carbon
monoxide yields of cigarettes and the risk of
myocardial infarction,
although Wald (1983) suggests that this might
simply be due to the levels
of carbon monoxide being approximately constant
due to compensation.
2. In the broader context of possible effects of
cigarette smoking (rather
than carbon monoxide in particular) the incidence
of myocardial infarction
and deaths from coronary heart disease is said to
fall after quitting smoking
although the data are controversial (Doll and
Hill, 1964; Friedman et al,
1979). However, the results of three Multiple Risk
Factor Intervention
Trials do not provide any convincing evidence that
the intervention
strategies, which include encouraging people to
stop smoking, had any
beneficial effect on Coronary heart disease or
total mortality (Multiple
Risk Factor Interventional Trial Research Group
1982, Oslo Study 1982, Rose
et al, 1983). Only in one study (Belgian Heart
Disease Prevention Project,
Konnitzer et al, 1983) is there a small decrease
in coronary mortality
(20.8%, n.s.) or Coronary Heart Disease Incidence
(24.5%, p = 0.031).
3. A recent study in America (Phillips et al,
1983) is also understood
to have found no evidence that such commonly
suspected risk factors as
cholesterol, high density lipoproteins, high blood
pressure and cigarette
smoking differed among those who did and did not
have heart attacks. The
findings suggest that heart disease could be
primarily a hormonal disorder,
linked to levels of estradiol, a sex hormone
occurring in both men and
women.
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4. Studies in animals suggested that a high
cholesterol diet in conjunction
with exposure to carbon monoxide increased the
risk of atherosclerosis
(Astrup, 1972). Subsequent studies failed to
confirm this theory, which
has since been withdrawn (Hugod and Astrup, 1981).
In any case, it is not
known whether it is possible to extrapolate from
such animal models to
humans.
5. It should also be borne in mind that in
addition to binding of haeMD-
globin in blood, carbon monoxide also binds to
proteins of the heart muscle
reducing the heart's utilisation of oxygen.
Nicotine in tobacco smoke
increases the heart's demand for oxygen while
carbon monoxide reduces
oxygen availability. However, this area has
received relatively little
attention
6. In general,smoking causes an arousal of the
Central Nervous System
(e.g.as demonstrated by Warburton, 1982). This
implies that the obser-
vation that pure carbon monoxide (up to 11% COHb)
has no adverse effect on
driving performance (Guillerm, 1978) can be
extrapolated to whole smoke.
7. A draft conclusion drawn by some workers in
this field might be a
suitable epilogue to this aide--memoire, although
of course it may be modified
before publication.
"In conclusion, therefore, we have failed to
demonstrate an association
between swkers' CO exposure and incidence of
subsequent CHD. In addition,
we have been unable to show an association between
CO exposure and prevalence
of chronic airflow obstruction. On the present
evidence we think it prema-
ture to recommend manufacturers to reduce
cigarette CO yields. We are con- C--D
oerned that publishing CO yields on the packet
would delude the prospective
purchaser into believing that he was reducing his
risk of developing CHD (Z~
(-M
or chronic air flow obstruction by smoking a 'low
CO cigarette'." (anon,
1983).
'J ~Je C-Q V Fo 6 1 a-\/ 0
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-3-
REFERENCES
ARONOW, W.S. Stenmr, E,,A, & Istrell, M.W. (1974)
Circulation, 49, 415-417.
ASTRUP, P. (1972) British Med. J. IV, 447-452
BORLAND, C.D.R., Chamberlain, A. T., Shipley, M,
Higenbottam, T.W. and
Rose, G. Paper presented at the International
Conference on the Environment
and Lung Disease, March 1983, Taormina, Italy.
BUDIANSKY, S. (1983), Nature, 302, 560.
DOLL, R. and Hill, A.B. (1964) Br. Med. J. i,
1399-1410 and 1460-1462.
FRIEDMAN, G.D., Sigelaub, A.B., Dales, L.G. and
Seltzer, C.C. (1979) J.
Chron.DiS. 32, 175-190.
HU", C. and Astrup, P. (1981) In Smoking and
Arterial Disease, Chapter
12, pp 89-94, Ed. Greenhalgh, R.M., Pitman Press,
Bath.
KONNI,i7t,ER, M. et al, (1983). The Lancet, 1983,
1, 1066-1070.
LEE, P.N. and Garfinkel, L. (1981) J. Epidemiol.
Comm. Hlth., 35, 16-22.
MULTIPLE Risk Factor Intervention Trial Research
Group (1982) J.A.M.A.,
248, 1465-1477.
OSLO STLMY 1982 Reference to follow.
PHILLIPS, G.B. Reported in International Herald
Tribune, 4 May, 1983, p6.
R.WE, G., Tunstall Pedoe H.D. and Heller, R.F.
(1983) The Lancet, 1, 1062-
1065.
ROYkL COT.r.PrE of Physicians (1971) Smoking and
Health Now, Pitman, Tunbridge
Wells.
WALD, N.J., Howard, S., Smith, P.G. and Kjeldsen,
K. (1973) Br. Med. J., 1,
761-765.
MUD, N.J., Boreham, J. and Bailey, A. Letter
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Med., 1983 (Circulated as TE 850).
MPBURTON, (1982) Nicotine and the Smoking Habit,
Limited Circulation.
BATCO document for Province of BritiSh Colurnbia
29 October 1999