Smoking, Carbon Monoxide, and Coronary Heart Disease
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Wald et al.13 have shown that carboxyhemoglobin levels in tobacco smokers correlate better
with the presence of coronary heart disease than the
smoking history. Cohen, Deane, and Goldsmith'4
demonstrated an association between atmospheric
carbon monoxide pollution in Los Angeles and case
fatality rates for patients with acute myocardial
infarction. Carbon monoxide exposure has also been
suspected of playing a role in the pathogenesis of
coronary atherosclerosis.15' 16 However, adequate
prospective epidemiologic studies need to be done
to determine the effect of atmospheric carbon
monoxide pollution on the pathogenesis of coronary
heart disease and on mortality from coronary heart
disease.
Smokers who inhale develop high levels of
carboxyhemoglobin. We observed that smokers who
inhaled smoke from eight nonnicotine cigarettes,
which they smoked at the rate of one cigarette
every 30 minutes at their normal pace of activities,
developed a mean increase in venous carboxyhemoglobin level from 1.58 to 7.79%.9 This increased
carboxyhemoglobin level was associated with a
decrease in exercise time until the onset of angina
and with a reduction in the product of systolic
blood pressure times heart rate at the onset of
angina, with angina pectoris developing sooner,
after less cardiac work.
Ayres et al.'7 have shown that acute elevation of
the venous carboxyhemoglobin level from a control
level of 0.98% to 8.96% in patients with coronary
heart disease and noncoronary heart disease caused
a 20% average decrease in mixed venous oxygen
tension. This greater reduction in mixed venous
oxygen tension relative to the increase in venous
carboxyhemoglobin level resulted from a leftward
shift of the oxyhemoglobin dissociation curve, with
tighter binding of oxygen to hemoglobin in the
presence of carboxyhemoglobin. The increased
carboxyhemoglobin level caused an increase in
coronary blood flow in their patients with noncoronary heart disease but not in their patients with
coronary heart disease. Myocardial oxygen extraction and extraction ratios also significantly decreased in their patients with coronary and with
noncoronary heart disease, but the myocardial
lactate extraction ratio significantly changed to
lactate production only in their patients with
coronary heart disease.
M ANY STUDIES have documented a significant association between cigarette smoking
and the incidence of myocardial infarction and
death from coronary heart disease, independent of
other risk factors, especially in young and middleaged men.1-5 Moreover, heavy cigarette smokers
have a significantly higher incidence of myocardial
infarction and mortality from coronary heart
disease than light cigarette smokers. In addition,
cigarette smokers who stop smoking have a
significantly lower incidence of myocardial infarction and mortality from coronary heart disease than
those who continue to smoke. Cigarette smoking
has also been correlated with a shorter survival
time in patients dying eight hours after the onset
of a heart attack.6
Smoking cigarettes also causes patients with
angina pectoris due to coronary artery disease to
have a significant decrease in exercise performance
before the onset of angina.7-9 Smoking highnicotine cigarettes7 aggravates exercise-induced
angina more than smoking low-nicotine8 or nonnicotine cigarettes.'0 Smoking low-nicotine cigarettes8 aggravates exercise-induced angina more
than smoking nonnicotine cigarettes.'0
Smoking high-nicotine7 " or low-nicotine cigarettes8s 11 causes an increase in systolic blood
pressure and in heart rate, consequently increasing
the myocardial oxygen demand. This increase in
systolic blood pressure and in heart rate does not
occur after smoking nonnicotine cigarettes.9-1"
However, smoking high-nicotine, low-nicotine, or
nonnicotine cigarettes causes an elevated carboxyhemoglobin level,9 11, 12 which decreases the
amount of oxygen available to the myocardium.
Therefore, anginal patients develop angina pectoris
sooner after exercise following cigarette smoking for
at least two reasons: increased myocardial oxygen
demand in the presence of nicotine, and decreased
oxygen delivery to the myocardium, whether or not
nicotine is present.
From the Cardiology Section, Medical Service, Long
Beach Veterans Administration Hospital, and the University
of California College of Medicine, Irvine.
Address for reprints: Wilbert S. Aronow, M.D., Cardiology Section, Veterans Administration Hospital, Long
Beach, California 90801.
Circulation, Volume XLVIII, December 1973
1169
1170
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Heavy atmospheric carbon monoxide pollution
may also lead to increased carboxyhemoglobin
levels. Carbon monoxide emission in motor vehicle
exhaust is highest during idling and deceleration.
Peak atmospheric carbon monoxide exposures have
been reported to reach as high as 147 ppm in Los
Angeles freeway traffic and 141 ppm in New York
expressway traffic."8 The atmospheric carbon monoxide level also reached a peak level of 135 ppm at
traffic intersections in Dayton, Ohio.19 We found
that anginal patients who were driven for 90
minutes in Los Angeles County peak early-morning
freeway traffic during the winter developed an
increase in mean arterial carboxyhemoglobin level
from 1.12% to 5.08%.20 Two hours after exposure to
this heavy freeway traffic, their mean arterial
carboxyhemoglobin level was still 2.91%.
The increased arterial carboxyhemoglobin level
caused by exposure to heavy freeway traffic caused
a significant reduction in exercise time until the
onset of angina pectoris, associated with a significant decrease in product of systolic blood
pressure times heart rate at the onset of angina,
immediately after breathing freeway air for 90 min
and two hours after return from the freeway trip.20
Since our anginal patients could not adequately
increase their coronary blood flow while exercising,
and since their elevated carboxyhemoglobin level
made less oxygen deliverable to the myocardium,
their myocardial oxygen demand exceeded their
myocardial oxygen supply, inducing angina pectoris
sooner, after less myocardial work. That this
significant decrease in exercise performance until
the onset of angina pectoris, associated with a
significant decrease in product of systolic blood
pressure times heart rate at the onset of angina, was
related to carbon monoxide exposure rather than to
the stress of freeway travel was supported by the
absence of these findings when compressed, purified
air was supplied by mask to the same patients
during an equivalent freeway trip.
We also observed that three of our ten anginal
patients developed ischemic ST segment depression
of at least 1 mm greater amplitude than in the
control Holter electrocardiographic recordings
while breathing freeway air during peak freeway
traffic, whereas none of our ten anginal patients
developed ischemic ST segment depression while
breathing compressed, purified air during peak
freeway traffic.20 The increased carboxyhemoglobin
levels, plus exposure to other pollutants, and the
stress of being driven during heavy freeway traffic
EDITORIALS
may have precipitated the electrocardiographic
abnormalities.
We found no significant difference in ischemic ST
segment depression at the onset of exercise-induced
angina after breathing freeway air in comparison
with the control period or with the period after
breathing compressed, purified air.20 However,
ischemic ST segment depression at the onset of
exercise-induced angina pectoris occurred earlier,
after less exertion, and at a lower product of systolic
blood pressure times heart rate in our anginal
patients immediately and two hours after breathing
freeway air when compared with the pretravel
control periods or with the control period after
breathing compressed, purified air.
Two very recent double-blind studies have also
confirmed that carbon monoxide exposure in
concentrations found during heavy atmospheric
pollution aggravates exercise-induced angina pectoris. Anderson et al.21 demonstrated in a doubleblind study that mean venous carboxyhemoglobin
level in ten anginal patients who breathed 50 ppm
of carbon monoxide for four hours increased from
1.3% to 2.9%. Their anginal patients had a significant
decrease in exercise performance until the onset of
angina pectoris after exposure to carbon monoxide
compared to breathing compressed, purified air.
Ischemic ST segment depression after exerciseinduced angina pectoris in general appeared earlier
and was deeper after breathing carbon monoxide
compared to breathing compressed, purified air.
However, these investigators did not quantitate the
amount of ischemic ST depression.
We observed in a double-blind study that ten
anginal patients who breathed 50 ppm of carbon
monoxide for two hoiurs increased their mean
venous carboxyhemoglobin level from 1.03% to
2.68%.22 After exposure to carbon monoxide, our
anginal patients had a significant decrease from the
control value in exercise time until the onset of
angina pectoris, associated with a significant
decrease in the product of systolic blood pressure
times heart rate at the onset of angina, but the same
phenomena were not observed after the patients
breathed compressed, purified air. Ischemic ST
segment depression was not observed in the Holter
electrocardiographic recordings while the patients
were breathing either carbon monoxide or compressed, purified air. We observed an increase in mean
maximal ischemic ST segment depression from 1.30
mm to 1.45 mm after exercise-induced angina after
breathing carbon monoxide compared to the control
Circulation, Volume XLVIII, December 1973
EDITORIALS
1171
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
period. This increased ischemic ST segment depression after exercise-induced angina was not statistically significant. However, ischemic ST segment
depression after exercise-induced angina occurred
earlier, after less exertion, and at a lower product of
systolic blood pressure times heart rate in our
anginal patients after breathing carbon monoxide
compared with the control periods or with the
period after breathing compressed, purified air.
In summary, compelling evidence exists to
indicate that cigarette smoking predisposes to
coronary heart disease, causes an increased mortality from coronary heart disease, and aggravates
angina pectoris. The medical profession should
accept the responsibility to better educate the
public against the hazards of smoking and to
promote programs which will help people to stop
smoking.
Heavy atmospheric carbon monoxide pollution
also clearly aggravates angina pectoris due to
coronary heart disease. Transient peaks of up to 90
ppm of carbon monoxide were measured passing
across the face of a person who sat next to a subject
who was smoking a cigarette for 10 minutes in an
exposure chamber.23 Therefore, restrictions on
smoking in public places may be necessary to
protect patients with coronary heart disease. The
medical profession should also assume leadership in
educating the public on the need for measures such
as mass transit systems (especially in congested
urban areas with heavy atmospheric pollution),
smaller and less polluting cars, and restricted use of
the automobile in urban areas to protect the welfare
of the significant segment of our urban population
who have coronary heart disease.
Finally, the medical profession should assume
responsibility for collaborative efforts with other
members of the scientific community to obtain more
comprehensive data to determine the safe levels of
carbon monoxide and other pollutants in our
environment for healthy people and for those with
various coronary, pulmonary, and other disease
states. Nonetheless, sufficient evidence already
exists to indicate that we should act now.
WILBERT S. ARONOW
References
1. HAMMOND EC: Smoking in relation to death rates of 1
million men and women. In National Cancer Institute
Monograph No. 19, U. S. Government Printing
Office, Washington, D.C. 1966, p 127
Circulation, Volume XLVIII, December 1973
2. KAHN HA: The Dorn study of smoking and mortality
among U. S. veterans: Report on eight and one-half
years of observation. In National Cancer Institute
Monograph No. 19, U. S. Government Printing
Office, Washington, D.C. 1966, p 127
3. DOLL R, HILL AB: Mortality in relation to smoking:
Ten years' observations of British doctors. Br Med J
1: 1399, 1460, 1964
4. DOYLE JT, DAWBER TR, KANNEL WB, KINCH SH,
KAHN HA: The relationship of cigarette smoking to
coronary heart disease. JAMA 190: 886, 1964
5. FRANK CW, WEINBLATT E, SHAPMIO S, SAGER RV:
6.
7.
8.
9.
10.
1 1.
Myocardial infarction in men: Role of physical
activity and smoking in incidence and mortality.
JAMA 198: 1241, 1966
SPAIN DM, BRADESS VA: Sudden death from coronary
heart disease: Survival time, frequency of thrombi,
and cigarette smoking. Chest 58: 107, 1970
ARONOW WS, KAPLAN MA, JACOB D: Tobacco: A
precipitating factor in angina pectoris. Ann Intern
Med 69: 529, 1968
ARONOW WS, SWANSON AJ: The effect of low-nicotine
cigarettes on angina pectoris. Ann Intern Med 69:
599, 1968
ARONOW WS, ROKAW SN: Carboxyhemoglobin caused
by smoking nonnicotine cigarettes: Effects in angina
pectoris. Circulation 44: 782, 1971
ARONOW WS, SWANSON AJ: Non-nicotinized cigarettes
and angina pectoris. Ann Intern Med 70: 1227,
1969
ARONOW WS, DENDINGE1R J, ROKAW SN: Heart rate
and carbon monoxide level after smoking high-, low-,
and non-nicotine cigarettes. A study in male patients
with angina pectoris. Ann Intern Med 74: 697,
1971
12. COHEN SI, PERKINS NM, URY HK, GOLDSMIrH JR:
Carbon monoxide uptake in cigarette smoking. Arch
Environ Health 22: 55, 1971
13. WALD N, HOWARD S, SMITH PG, KJELDSEN K:
Association between atherosclerotic diseases and
carboxyhaemoglobin levels in tobacco smokers. Br
Med J 1: 761, 1973
14. COHEN SI, DEANE M, GOLDSMITH JR: Carbon monoxide
and survival from myocardial infarction. Arch Environ
Health 19: 510, 1969
15. AsTRuP P: Effects of hypoxia and of carbon monoxide
exposures on experimental atherosclerosis. Ann Intern
Med 71: 426, 1969
16. WHEREAT AF: Is atherosclerosis a disorder of
intramitochondrial respiration? Ann Intern Med 73:
125, 1970
17. AYRES SM, MUELLER HS, GREGORY JJ, GIANNELLI S
JR, PENNY JL: Systemic and myocardial hemodynamic responses to relatively small concentrations
of carboxyhemoglobin (COHB). Arch Environ
Health 18: 699, 1969
18. LYNN DA, TABOR E, OTrr W, SMITH R: Present and
future commuter exposures to carbon monoxide.
Presented at the 60th Annual Meeting, Air Pollution
Control Association, Cleveland, Ohio, 1967. Quoted
by JAFFE LS: Sources, characteristics, and fate of
atmospheric carbon monoxide. Ann NY Acad Sci
174: 76, 1970
1172
19. RAMSEY JM: Concentrations of carbon monoxide at
traffic intersections in Dayton, Ohio. Arch Environ
Health 13: 44, 1966
20. ARONOW WS, HARRIS CN, ISBELL MW, RoKAw SN,
IMPARATO B: Effect of freeway travel on angina
pectoris. Ann Intern Med 77: 669, 1972
21. ANDERSON EW, ANDELMAN RJ, STRAUCH JM, FORTUIN
NJ, KNELSON JH: Effects of low-level carbon monoxide exposure on onset and duration of angina pectoris.
EDITORIALS
A study in ten patients with ischemic heart disease.
Ann Intern Med 79: 46, 1973
22. ARONOW WS, ISBELL MW: Carbon monoxide effect on
exercise-induced angina. Ann Intern Med 79: 392,
1973
23. LAwTHER PJ, COMMINS BT: Cigarette smoking and
exposure to carbon monoxide. Ann NY Acad Sci 174:
135, 1970
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Circulation, Volume XLVII, December 1973
Smoking, Carbon Monoxide, and Coronary Heart Disease
WILBERT S. ARONOW
Circulation. 1973;48:1169-1172
doi: 10.1161/01.CIR.48.6.1169
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1973 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World
Wide Web at:
http://circ.ahajournals.org/content/48/6/1169.citation
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click Request
Permissions in the middle column of the Web page under Services. Further information about this process is available
in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation is online at:
http://circ.ahajournals.org//subscriptions/