Cotinine Levels in Professional. Baseball Players. I. E.hI. P. David Siegel, MD, MPH, Neal Benowitz, MD, I1irginia L. Emster, PhD,. Deborah G. Grady, MD, MPH, ...
Smokeless Tobacco, Cardiovascular Risk Factors, and Nicotine and Cotinine Levels in Professional Baseball Players
I.
E.hI
P.
David Siegel, MD, MPH, Neal Benowitz, MD, I1irginia L. Emster, PhD, Deborah G. Grady, MD, MPH, and Walter W. Hauck PhD
Introduction The use of smokeless tobacco (ST)oral snuff or chewing tobacco-increased in popularity in the 1970s and 1980s. Approximately 10 million Americans used ST in the past year; 3 million were less than 21 years of age. ' Among young men, the use of moist snuff has become particularly widespread.2 Smokeless tobacco use results in considerable systemic exposure to nicotine.34 The results of studies of cigarette smokers have led to concern that nicotine may increase the risk of atherosclerotic vascular disease.5 Nicotine may contribute to atherosclerosis by affecting lipid metabolism, coagulation, hemodynamic status, or all three. Smokers have higher levels of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol and lower levels of high-density lipoprotein (HDL) cholesterol than do nonsmokers." Cigarette smoking or the administration of nicotine acutely increases heart rate and blood pressure, although in habitual cigarette smokers blood pressure tends to be lower than in nonsmokers.9 Circulating leukocytes, primarily neutrophils, are higher in smokers than in nonsmokers, and leukocyte counts return toward nonsmoking levels after smoking cessation."' 11 Neutrophils may generate oxygen-free radicals and other substances that promote thrombosis, and they may accelerate endothelial cell growth, both of which could contribute to the acceleration of atherosclerotic vascular disease.5' 1Whether nicotine exposure from ST use has similar effects on lipid metabolism, neutrophils, blood pressure, and heart rate, and thus predisposes to atherosclerotic vascular disease, has not been established.
In studies performed on a research ward, ST use resulted in systemic absorption of nicotine and cardiovascular effects similar to those observed with cigarette smoking.'-3 In reports of small numbers of individuals, ST use has been associated with hypertension, perhaps related to ST's salt content or to nicotine-related catecholamine release."'-'5 One recent study reported an association between ST use and elevated levels of total serum cholesterol.8 We recently completed a comprehensive study of the health effects of ST use in professional baseball players.'6 A part of the study's purpose was to determine whether ST use was associated with changes in cardiovascular risk profiles. Specifically, we measured blood pressure, heart rate, total serum cholesterol, HDL cholesterol, and white blood cell counts. We also quantitated nicotine intake from ST by measuring plasma nicotine and its metabolite cotinine in plasma.
Methods Study Population A detailed discussion of the study methods and highlights of findings from David Siegel and Deborah G. Grady are with the Department of Epidemiology and Biostatistics and the Department of Medicine; Neal Benowitz is with the Department of Medicine; and Virginia L. Ernster and Walter W. Hauck are with the Department of Epidemiology and Biostatistics-all at the University of California, San Francisco. Requests for reprints should be sent to David Siegel, MD, Prevention Sciences Group, 74 New Montgomery, San Francisco, CA
9410)5.
This paper was submitted to the journal April 10, 1991, and accepted with revisions September 20, 1991.
Editor's Note: See related Commentary by Connolly on page 351. American Journal of Public Health 417
Siegl et al. the first year of the project have been presented elsewhere.16 We report here detailed findings from the first 2 years of the study on cardiovascular risk factors and nicotine and cotinine levels in the participants. During February and March of 1988 and 1989, we studied 1061 members of the seven major league professional baseball teams and their associated minor league teams that conduct spring training in the greater Phoenix and Tucson, Ariz, area. All players and coaches on the teams were invited to participate in the study. After giving informed consent, all participants completed a questionnaire that provided demographic data and information about cigarette smoking and coffee and alcohol consumption. There were only 41 current cigarette smokers and they were excluded from analyses. Detailed information concerning patterns of ST use, including type and brand used most often, was collected. Analyses of type (snuff or chewing tobacco) and brand were based on the type and brand usually used. The amount of ST used was based on the number of cans of snuff or pouches of chewing tobacco reportedly used per week. Because many participants who usually used one type of ST occasionally used the other type, the combined number of hours that tobacco of either type was held in the mouth per day was also calculated. Recency of use was determined as hours since ST was last used. The participants were classified on the basis of their self-reported ST use as nonusers (those who had never used ST or who had used ST in the past but never more frequently than once a month) and users (those who had used ST within the past week). Former users (those who had used ST more than once a month in the past but had not used ST within the previous month) and infrequent current users (those who had used ST within the past month but not within the past week) were excluded from analyses. For any player for whom we had data from both 1988 and 1989, we used only the data from the year for which the data were most complete. If data from both years were equally complete, 1989 data were used for that player. Data from a total of 477 ST users and 584 nonusers are included in this report.
Blood Pressure and Pulse After the participants completed the questionnaire, their heart rate and blood pressure were measured twice, several minutes apart, in a sitting position. Systolic blood pressure was recorded at the 418 American Journal of Public Health
levelwhen phase 1 Korotkoffsoundswere first heard and diastolic blood pressure was recorded at the beginning of phase 5 with the disappearance of sounds. To avoid the effects of physical activity, we included in our analysis of blood pressure and pulse rates only measurements from individuals who had not come to the examination directly from the playing field.
Biochemical Measurements Blood was drawn to measure total serum cholesterol; HDL cholesterol; nicotine, cotinine, and caffeine levels; and white blood cell count. Biochemical validation of self-reported ST use included measurement of cotinine (the primary metabolite of nicotine) and thiocyanate (a marker of tobacco smoke exposure) by gas chromatography.17 Low serum cotinine level (< 12 ng/mL) together with normal serum thiocyanate levels (250 ng/mL (data not shown). Participants who reported using ST more hours per day, as well as those who reported more recent use, also had higher adjusted mean serum cotinine levels (P < .001). Similar statistically significant results were found for adjusted mean serum nicotine levels (data not shown). Participants who had used ST for more years had higher adjusted mean serum caffeine levels than those who had used ST for a shorter period (P = .03, data not shown).
Cotinine and Nicotine Levels and Cardiovascular Risk Factors There was no difference in adjusted systolic and diastolic blood pressure, pulse rate, white blood cell count, and total or HDL cholesterol levels between participants who used snuff exclusively and those who used chewing tobacco exclusively (Table 4). We examined the association between the above measures and serum cotinine and serum nicotine levels, adjusting for age, race, alcohol use, and serum caffeine (data not shown). There was no association between serum cotinine levels and any of these measures. Interestingly, we failed to confirm our previous finding of a weak inverse association between serum cotinine levels and serum HDL cholesterol levels.'6 However, higher mean serum nicotine levels were associated with higher diastolic blood pressure levels (P = .02), and there was a trend toward higher pulse rates (P = .09), total cholesterol levels (P= .10), and white blood cell counts (P= .15) with higher mean serum nicotine levels.
Discussion This group of professional baseball players is the largest population of ST users in which nicotine and associated cardiovascular risk factors have been examined. The large sample size and the high prevalence of ST use provided ample power to detect relatively minor effects of ST use on the cardiovascular risk factors studied. Despite this, we did not find differences in systolic and diastolic blood pressure, total and HDL cholesterol, and white blood cell count between ST users and nonusers. These findings are similar to those that we reported after the first year of the studyl6 and contrast with the results of experimental studies of ST users in which ST use throughout the day proMarch 1992, Vol. 82, No. 3
duced the same cardiovascular effects as cigarette smoking.13 Additionally, we analyzed the effect of ST use on serum nicotine and cotinine levels and their association with cardiovascular risk factors. Cotinine is the major metabolite of nicotine and has a much longer half-life than nicotine.'2 For these reasons cotinine is widely used as a biochemical marker of average daily intake of nicotine. Determination of serum cotinine, however, is a relatively insensitive way to detect exactly when tobacco was last used. The mean serum cotinine level was 144 ng/mL for
snuff users and 82 ng/mL for chewers. The average cotinine levels for snuff users were similar to those previously reported in a group of college athletes, but were considerably lower than those measured in a research ward study of ST use and cigarette smoking.313 These cotinine levels are also lower than the average level of 300 ng/mL found in cigarette smokers.'2 Since a cotinine level of 100 ng/mL corresponds to a nicotine intake of about 12 mg,'2we estimated that daily intake ofnicotine was 17.0 mg for snuff users and 9.9 mg for chewing tobacco users. The low American Journal of Public Health 419
Siege
et al.
cotinine levels in our subjects were consistent with relatively light use of ST, as reflected by an average of 1.1 hours of snuff use per day and 0.7 hours of chewing tobacco use per day. As expected, serum cotinine levels tended to be higher with greater duration of ST use and greater number of hours of ST use per day, and was lower with greater number of hours since the last dose of ST. Overall, the serum cotinine data indicate that baseball players are relatively light users of ST compared with other populations. Our data also indicate that ST use in baseball 420 American Journal of Public Health
players is seasonal; about 50% of the baseball players in our study who reported current-week ST use indicated that they use ST primarily during the baseball season and rarely use it during the off season. The pattem of ST use and low levels of nicotine intake suggests that baseball players may be less dependent on nicotine than are other tobacco users. Our finding that cotinine levels were lower with chewing tobacco use than with snuff use was surprising in light of the observation that nicotine intake for a single chew is substantially greater than that
from a single use of snuff, and daily nicotine levels with ad lib use of both in an experimental study have been found to be similar.4,13 Our results suggest that chewers use ST in a manner that does not extract as much nicotine from ST as snuff users. The relationship between hours of use per day and serum cotinine was not highly correlated, suggesting that nicotine intake may be more efficient with shorter periods of daily use than with longer periods of use. This type of dose response could be observed if ST is held in the mouth for long periods of time, since the most rapid absorption of nicotine through ST occurs ip the first 15 to 20 minutes.4 We found an association between higher serum nicotine levels and increased diastolic blood pressure and trends between higher plasma nicotine levels and increased heart rate and white blood cell count. Serum nicotine reflects the recency of tobacco use, and changes in blood pressure, pulse rate, and white blood cell count might reflect a direct pharmacologic response.12 Our diastolic blood pressure finding is consistent with findings from other studies showing that ST use acutely increases blood pressure.20,21 The smokeless tobacco users in this study drank more alcohol than did nonusers. This finding is similar to those ofother studies of ST use, in both adolescents and adults.2 We also found that plasma caffeine levels were higher in ST users than nonusers, perhaps reflecting a tendency toward more psychoactive drug use in ST users. Other studies have found that cigarette smokers drink more caffeine-contamiing beverages than do nonsmokers.23 Thus, future studies of the cardiovascular effects of ST should control for the potentially confounding effects of caffeine and alcohol. Although our findings did not show major adverse effects of ST use on cardiovascular risk factors, we cannot exclude the possibility that daily ST use for manyyears may have an adverse effect on the cardiovascular system. Previous reports have descnbed long-term harmful effects of ST use, including a strong association with oral cancer.2-26 Our participants differed from those in other studies of ST use in that their ST use was generally seasonal and of short duration (less than 10 years). Our participants were also professional athletes who exercised regularly and who were generally physically fit, factors that might minimize the harmful effects of STon the cardiovascular system. Similar large studies should be done in older populations of more sedentary inMarch 1992, Vol. 82, No. 3
Smokeless Tobacco and Cardiovascular Risk
dividuals to detect the impact of ST use in individuals more prone to cardiac disease. O
Acknowledgment This research was supported by grants 5 P01 DE08547-02 from the National Institute of Dental Research and DA 02277 from the National Institute on Drug Abuse, Bethesda, Md.
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