PREVENTIVE
MEDICINE
8,
323-332 (1979)
The Prevalence of Carboxyhemoglobinemia in New Yorkers and Its Effects on the Coronary and Systemic Circulation1 STEPHEN
M. AYRES,~ ROBERTG.EVANS,ANDMETAE.BUEHLER
Department
of Internal
Medicine, St. Louis University St. Louis, Missouri 63104
School of Medicine,
Carboxyhemoglobin saturations ranging from 8.11 to 1.56% were found in a sample of more than 1,000 individuals engaged in various activities in New York City. The difference from lowest to highest carboxyhemoglobin in nonsmokers was 1.58%; in smokers it was as great as 5.0%. Experimental elevation of carboxyhemoglobin to levels similar to that seen in cigarette smokers produced a decrease in arterial and venous oxygen tensions and an increase in cardiac output and coronary blood flow. In contrast to the effect on the systemic vascular bed, carbon monoxide inhalation produced a decrease in myocardial oxygen extraction. These observations suggest that changes in coronary blood flow are a useful indicator of the effects of carbon monoxide when hemodynamically significant coronary artery disease prevents the expected increase in myocardial blood flow.
A large collection of epidemiologic observations has shown that mortality from coronary artery disease is several times more common in smoking men compared with nonsmoking men under the age of 60 (14). Similar data has been presented for women and it has been shown that the oral contraceptive acts as a powerful cofactor with cigarette smoking (12). Since it can be maintained that the genetic predisposition to smoke and to develop coronary disease are linked, studies showing the effect of smoking cessation become extremely important. Almost half of all British physicians stopped smoking during the past 20 years and the incidence of deaths from ischemic heart disease in exsmokers provides important evidence that smoking directly contributes to death from coronary artery disease (9). The death rate for physicians from ischemic heart disease under the age of 55 who continued to smoke was 3.5 times that of the lifelong nonsmokers. It fell to 1.9 in those who had stopped smoking for less than 5 years and to 1.3 in those who had stopped for between 5 and 9 years. Both nicotine and carbon monoxide could be responsible for the increased mortality associated with cigarette smoking. Nicotine produces sympathetic stimulation increasing cardiac work and oxygen requirements; a-adrenergic stimulation may produce constriction of the larger coronary arteries (7). Carbon monoxide decreases oxygen availability by binding with hemoglobin and interfering with the release of oxygen in the coronary microcirculation (5). ’ Presented at a Workshop on Carbon Monoxide and Cardiovascular Disease, Sponsored by the American Health Foundation and the Federal Health Office, Federal Republic of Germany, Berlin, October 10-12, 1978. * To whom requests for reprints should be addressed: Department of Internal Medicine, St. Louis University Hospital, 1325 S. Grand Blvd., St. Louis, MO. 63104.
323 0091-7435/79/030323-10$02.00/O Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
324
AYRES,
EVANS,
AND
BUEHLER
The present study presents data demonstrating that extremely high concentrations of carboxyhemoglobin may be observed in many cigarette smokers and that the level is related to both the intensity and frequency of cigarette smoking. Additional data show that acute administration of carbon monoxide decreases oxygen extraction by the myocardium and increases coronary blood flow preventing major decreases in coronary sinus oxygen tension. METHODS Several different groups of individuals were studied. The extent of carboxyhemoglobinemia was evaluated by obtaining alveolar air samples of over 1,000 individuals engaged in various activities in New York City. The bridge and tunnel workers (BTOs) worked primarily in the toll-collecting areas of the bridges and tunnels operated by the Triborough Bridge and Tunnel Authority; the two major tunnels studied, the Queens Midtown Tunnel and the Brooklyn Battery Tunnel, connect Manhattan with Queens and Brooklyn, respectively. The details of this study have been previously reported (4). The New York City patrolmen were studied after a tour of duty in a patrol car; the midtown Manhattan precincts were considered “high pollution” while precincts located in other parts of the city were considered “low pollution”. New Yorkers were studied at random at a sidewalk station located at Union Square. A detailed questionnaire was also obtained. A group of hospitalized patients, ail nonsmokers, were studied in a filtered-air environment located on the fifth floor of Saint Vincent’s Hospital and Medical Center. The studies on hemoglobin concentration were performed on 196 patients admitted to Saint Vincent’s Hospital for coronary arteriography. The blood samples were obtained at the time of arteriography. Blood carboxyhemoglobin was measured from alveolar samples for the epidemiology study. Almost all samples were analyzed by gas chromatography using a Beckman GC-5 chromatograph and a molecular sieve column. The samples from the policemen were analyzed by a CO detector that catalytically converts carbon monoxide to carbon dioxide and measures the hydrogen ion so generated (Ecolyzer). We and others (15) have shown the accuracy of this instrument relative to other techniques such as gas chromatography and infrared analysis. Blood carboxyhemoglobin was directly measured on venous or arterial samples for the hemodynamic studies and the studies made during coronary arteriography. Hemodynamic studies were performed on 41 patients during diagnostic catheterization and on 40 dogs. Myocardial metabolic studies were performed on 26 of the patients and in 25 of the canine studies. The precise details of these studies have been previously published (5). RESULTS Determinants of Carboxyhemoglobin Concentration Group means for carboxyhemoglobin saturations ranged from 8.11% in the smoking policemen working in congested traffic to 1.56% in the nonsmokers studied in a filtered-air facility on the fifth floor of a metropolitan hospital. Group means and standard deviations are shown in Table 1; complete data are plotted as cumulative frequency-distribution curves in Figs. 1 and 2.
WORKSHOP: CARBON MONOXIDE
325
AND CVD
TABLE 1 CARBOXYHEMOGLOBIN
CONCENTRATIONS
IN NEW YORKERS
Concentration (%) Group
Nonsmokers
Policemen (high)O Policemen (low) Tunnel workers Bridge workers Union Square’ Hospitalized
Smokers
3.14 f 0.74b
8.11 f 2.51
2.29 2 0.57 2.93 2 1.36
6.39
2.12 2 1.08 1.93 f 0.35 1.56 f 0.35
3.90 k 2.13 3.89 2 2.06
-+ 2.66
5.01 2 2.25
a High and low refer to highly and less highly congested precincts in New York City. b Mean ? SD. c Union Square studies are on New Yorkers picked at random.
The influence of automotive sources of carbon monoxide is demonstrated by the higher mean values for both smokers and nonsmokers working in highly congested areas (midtown Manhattan and East River tunnels) compared with those working in less highly congested areas. Lower concentrations were observed in the group studied in Union Square; the lowest values were found in patients resting in a filtered-air facility five floors above ground level. Significantly higher concentrations were observed in those studied in Union Square who had been riding in a bus or car immediately prior to testing (2.28 + 0.80%) compared with those who had been traveling in subway or train (I .74 ? 0.47%). The studies of the policemen were performed immediately after a tour of duty in a squad car. Two men were stationed in each car; the issue of passive smoking was not evaluated. Smoking, the data reveals, is the most important determinant of blood carboxyhemoglobin saturation. The difference in mean carboxyhemoglobin saturation in nonsmokers from the lowest to the highest automotive pollution exposure 1001
I
I
80 -
A
POLICEfvKN (HIGH)
A
PQLICENYN (LOW)
0
UNION SQUARE
0
BTO (BRIDGE)
W BTO (TUNNEL) 0
Carbxyhemoglobin
CLEAN AIR ROOM
Saturation.
%
FIG. 1. Cumulative frequency distribution of carboxyhemoglobin in nonsmokers.
326
AYRES,
EVANS,
AND
BUEHLER
a 10 12 6 Carboxyhemoglobin Saturation, %
14
16
FIG. 2. Cumulative frequency distribution of carboxyhemoglobin in smokers.
group is 1.58%; the difference due to smoking within each group may be as great as 5%. Considerable information relative to smoking habits and carboxyhemoglobin saturation emerges from the studies performed on individuals sampled at random in Union Square. Table 2 shows that higher carbon monoxide levels were observed in cigarette smokers compared with other smokers, long standing smokers compared with recent smokers, factory workers compared with clerical and professional individuals, and men compared with women. The brand of cigarette and the presence of a filter tip made no difference in the levels of carboxyhemoglobin. The data also show the importance of time of smoking to measurement of blood carbon monoxide concentrations. Figure 3 demonstrates that carboxyhemoglobin saturation was directly related to the number of cigarettes smoked prior to sampling and to the time of the last cigarette. The half-time for carbon monoxide excretion calculated from this data is 204 min or about 3.5 hr.
DIFFERENCES
IN CARBOXYHEMOGLOBIN
Group characteristics
2 TABLE SATURATION
AMONG GROUPS OF SMOKERS
COHb” (%)
P
Cigarettes only Pipe and/or cigars only
4.00 + 1.95 2.80 2 2.00
co.01
Cigarette smokers > 10 years Cigarette smokers < 10 years
4.31 ” 1.95 3.78 2 2.09
co.05
Male smokers Female smokers
4.01 2 2.16 3.41 + 1.71
MEDICINE
8,
323-332 (1979)
The Prevalence of Carboxyhemoglobinemia in New Yorkers and Its Effects on the Coronary and Systemic Circulation1 STEPHEN
M. AYRES,~ ROBERTG.EVANS,ANDMETAE.BUEHLER
Department
of Internal
Medicine, St. Louis University St. Louis, Missouri 63104
School of Medicine,
Carboxyhemoglobin saturations ranging from 8.11 to 1.56% were found in a sample of more than 1,000 individuals engaged in various activities in New York City. The difference from lowest to highest carboxyhemoglobin in nonsmokers was 1.58%; in smokers it was as great as 5.0%. Experimental elevation of carboxyhemoglobin to levels similar to that seen in cigarette smokers produced a decrease in arterial and venous oxygen tensions and an increase in cardiac output and coronary blood flow. In contrast to the effect on the systemic vascular bed, carbon monoxide inhalation produced a decrease in myocardial oxygen extraction. These observations suggest that changes in coronary blood flow are a useful indicator of the effects of carbon monoxide when hemodynamically significant coronary artery disease prevents the expected increase in myocardial blood flow.
A large collection of epidemiologic observations has shown that mortality from coronary artery disease is several times more common in smoking men compared with nonsmoking men under the age of 60 (14). Similar data has been presented for women and it has been shown that the oral contraceptive acts as a powerful cofactor with cigarette smoking (12). Since it can be maintained that the genetic predisposition to smoke and to develop coronary disease are linked, studies showing the effect of smoking cessation become extremely important. Almost half of all British physicians stopped smoking during the past 20 years and the incidence of deaths from ischemic heart disease in exsmokers provides important evidence that smoking directly contributes to death from coronary artery disease (9). The death rate for physicians from ischemic heart disease under the age of 55 who continued to smoke was 3.5 times that of the lifelong nonsmokers. It fell to 1.9 in those who had stopped smoking for less than 5 years and to 1.3 in those who had stopped for between 5 and 9 years. Both nicotine and carbon monoxide could be responsible for the increased mortality associated with cigarette smoking. Nicotine produces sympathetic stimulation increasing cardiac work and oxygen requirements; a-adrenergic stimulation may produce constriction of the larger coronary arteries (7). Carbon monoxide decreases oxygen availability by binding with hemoglobin and interfering with the release of oxygen in the coronary microcirculation (5). ’ Presented at a Workshop on Carbon Monoxide and Cardiovascular Disease, Sponsored by the American Health Foundation and the Federal Health Office, Federal Republic of Germany, Berlin, October 10-12, 1978. * To whom requests for reprints should be addressed: Department of Internal Medicine, St. Louis University Hospital, 1325 S. Grand Blvd., St. Louis, MO. 63104.
323 0091-7435/79/030323-10$02.00/O Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
324
AYRES,
EVANS,
AND
BUEHLER
The present study presents data demonstrating that extremely high concentrations of carboxyhemoglobin may be observed in many cigarette smokers and that the level is related to both the intensity and frequency of cigarette smoking. Additional data show that acute administration of carbon monoxide decreases oxygen extraction by the myocardium and increases coronary blood flow preventing major decreases in coronary sinus oxygen tension. METHODS Several different groups of individuals were studied. The extent of carboxyhemoglobinemia was evaluated by obtaining alveolar air samples of over 1,000 individuals engaged in various activities in New York City. The bridge and tunnel workers (BTOs) worked primarily in the toll-collecting areas of the bridges and tunnels operated by the Triborough Bridge and Tunnel Authority; the two major tunnels studied, the Queens Midtown Tunnel and the Brooklyn Battery Tunnel, connect Manhattan with Queens and Brooklyn, respectively. The details of this study have been previously reported (4). The New York City patrolmen were studied after a tour of duty in a patrol car; the midtown Manhattan precincts were considered “high pollution” while precincts located in other parts of the city were considered “low pollution”. New Yorkers were studied at random at a sidewalk station located at Union Square. A detailed questionnaire was also obtained. A group of hospitalized patients, ail nonsmokers, were studied in a filtered-air environment located on the fifth floor of Saint Vincent’s Hospital and Medical Center. The studies on hemoglobin concentration were performed on 196 patients admitted to Saint Vincent’s Hospital for coronary arteriography. The blood samples were obtained at the time of arteriography. Blood carboxyhemoglobin was measured from alveolar samples for the epidemiology study. Almost all samples were analyzed by gas chromatography using a Beckman GC-5 chromatograph and a molecular sieve column. The samples from the policemen were analyzed by a CO detector that catalytically converts carbon monoxide to carbon dioxide and measures the hydrogen ion so generated (Ecolyzer). We and others (15) have shown the accuracy of this instrument relative to other techniques such as gas chromatography and infrared analysis. Blood carboxyhemoglobin was directly measured on venous or arterial samples for the hemodynamic studies and the studies made during coronary arteriography. Hemodynamic studies were performed on 41 patients during diagnostic catheterization and on 40 dogs. Myocardial metabolic studies were performed on 26 of the patients and in 25 of the canine studies. The precise details of these studies have been previously published (5). RESULTS Determinants of Carboxyhemoglobin Concentration Group means for carboxyhemoglobin saturations ranged from 8.11% in the smoking policemen working in congested traffic to 1.56% in the nonsmokers studied in a filtered-air facility on the fifth floor of a metropolitan hospital. Group means and standard deviations are shown in Table 1; complete data are plotted as cumulative frequency-distribution curves in Figs. 1 and 2.
WORKSHOP: CARBON MONOXIDE
325
AND CVD
TABLE 1 CARBOXYHEMOGLOBIN
CONCENTRATIONS
IN NEW YORKERS
Concentration (%) Group
Nonsmokers
Policemen (high)O Policemen (low) Tunnel workers Bridge workers Union Square’ Hospitalized
Smokers
3.14 f 0.74b
8.11 f 2.51
2.29 2 0.57 2.93 2 1.36
6.39
2.12 2 1.08 1.93 f 0.35 1.56 f 0.35
3.90 k 2.13 3.89 2 2.06
-+ 2.66
5.01 2 2.25
a High and low refer to highly and less highly congested precincts in New York City. b Mean ? SD. c Union Square studies are on New Yorkers picked at random.
The influence of automotive sources of carbon monoxide is demonstrated by the higher mean values for both smokers and nonsmokers working in highly congested areas (midtown Manhattan and East River tunnels) compared with those working in less highly congested areas. Lower concentrations were observed in the group studied in Union Square; the lowest values were found in patients resting in a filtered-air facility five floors above ground level. Significantly higher concentrations were observed in those studied in Union Square who had been riding in a bus or car immediately prior to testing (2.28 + 0.80%) compared with those who had been traveling in subway or train (I .74 ? 0.47%). The studies of the policemen were performed immediately after a tour of duty in a squad car. Two men were stationed in each car; the issue of passive smoking was not evaluated. Smoking, the data reveals, is the most important determinant of blood carboxyhemoglobin saturation. The difference in mean carboxyhemoglobin saturation in nonsmokers from the lowest to the highest automotive pollution exposure 1001
I
I
80 -
A
POLICEfvKN (HIGH)
A
PQLICENYN (LOW)
0
UNION SQUARE
0
BTO (BRIDGE)
W BTO (TUNNEL) 0
Carbxyhemoglobin
CLEAN AIR ROOM
Saturation.
%
FIG. 1. Cumulative frequency distribution of carboxyhemoglobin in nonsmokers.
326
AYRES,
EVANS,
AND
BUEHLER
a 10 12 6 Carboxyhemoglobin Saturation, %
14
16
FIG. 2. Cumulative frequency distribution of carboxyhemoglobin in smokers.
group is 1.58%; the difference due to smoking within each group may be as great as 5%. Considerable information relative to smoking habits and carboxyhemoglobin saturation emerges from the studies performed on individuals sampled at random in Union Square. Table 2 shows that higher carbon monoxide levels were observed in cigarette smokers compared with other smokers, long standing smokers compared with recent smokers, factory workers compared with clerical and professional individuals, and men compared with women. The brand of cigarette and the presence of a filter tip made no difference in the levels of carboxyhemoglobin. The data also show the importance of time of smoking to measurement of blood carbon monoxide concentrations. Figure 3 demonstrates that carboxyhemoglobin saturation was directly related to the number of cigarettes smoked prior to sampling and to the time of the last cigarette. The half-time for carbon monoxide excretion calculated from this data is 204 min or about 3.5 hr.
DIFFERENCES
IN CARBOXYHEMOGLOBIN
Group characteristics
2 TABLE SATURATION
AMONG GROUPS OF SMOKERS
COHb” (%)
P
Cigarettes only Pipe and/or cigars only
4.00 + 1.95 2.80 2 2.00
co.01
Cigarette smokers > 10 years Cigarette smokers < 10 years
4.31 ” 1.95 3.78 2 2.09
co.05
Male smokers Female smokers
4.01 2 2.16 3.41 + 1.71
