Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement
http://www.100md.com
《英国医生杂志》
1 Department of Community Health Sciences, St George's Hospital Medical School, London SW17 0RE, 2 Department of Primary Care and Population Sciences, Royal Free Campus, Royal Free and University College Medical School, London NW3 2PF, 3 Cancer Research UK Health Behaviour Research Unit, Department of Epidemiology and Public Health, Royal Free and University College Medical School, London WC1E 6BT, 4 Medical Toxicology Unit, New Cross Hospital, London SE14 5ER
Correspondence to: P H Whincup p.whincup@sghms.ac.uk
Abstract
Active cigarette smoking is a well established major preventable risk factor for coronary heart disease (CHD).1 Many studies have reported that passive smoking is also associated with increased risk of CHD.2 3 Generally such studies have compared the risks of non-smokers who do or do not live with cigarette smokers,4-9 though a few have also considered occupational exposure.10-12 Meta-analyses of case-control and cohort studies examining the effect of living with a cigarette smoker on risk among non-smokers have generally shown an overall increase in risk of about one quarter, after adjustment for potential confounding factors2 3 and with little evidence of publication bias. Passive smoking may also be related to risk of stroke.13
Although living with someone who smokes is an important component of exposure to passive smoking, it accounts for less than half of the variation in cotinine concentration among non-smokers14 and does not take account of additional exposure in workplaces and in public places (particularly pubs and restaurants).15 Biomarkers of passive exposure to smoking, particularly cotinine (a nicotine metabolite), can provide a summary measure of exposure from all these sources.16 Although cotinine concentration in non-smokers has been related to prevalent CHD,17 there are no published reports of the prospective associations between serum cotinine concentration and risk of CHD and stroke in non-smokers. We have examined these associations in the British regional heart study, a prospective study of cardiovascular disease in middle aged men, using retained baseline samples for retrospective measurement of cotinine.
Methods
In the last 18 towns of the study, 5661 men took part (78% response rate). For 4729 of these we had detailed histories on smoking and blood samples for cotinine analysis. These men resembled the whole study population in reported smoking habits and risks of CHD and stroke. A total of 2158 men reported that they were current non-smokers, of whom 2105 (97.5%) had serum cotinine concentrations < 14.1 ng/ml. Of these, 945 men were classified as lifelong non-smokers, the remaining 1160 as former smokers. The cotinine distributions of these two groups (fig 1) were skewed, with a slightly higher geometric mean cotinine among former smokers than among lifelong non-smokers (1.49 1.18 ng/ml). Few men in either group had cotinine concentrations close to the 14.1 ng/ml cut off.
Fig 1 Distribution of serum cotinine concentrations among current non-smokers; lifelong non-smokers and former smokers are shown separately
Serum cotinine and cardiovascular risk factors—Among current non-smokers, cotinine concentrations were not consistently related to age, total cholesterol concentration, physical activity score, or prevalent CHD but showed graded positive associations with mean body mass index, systolic and diastolic blood pressure, high density lipoprotein cholesterol, white cell count, and triglycerides (weakly) and positive associations with the prevalence of former smoking, heavy drinking, and manual occupation (table 1). Cotinine concentrations were inversely associated with FEV1, prevalence of low alcohol intake, and residence in southern England. These associations were generally little affected when we excluded former smokers. Light active smokers had lower mean body mass index, diastolic blood pressure, and FEV1 and a higher mean white cell count than men who did not smoke.
Table 1 Means (SDs) and numbers (percentages) of cardiovascular risk factors by cotinine concentration: non-smokers and light active cigarette smokers
Serum cotinine concentration and CHD risk—We examined the association between quarters of the cotinine distribution and CHD hazard ratios among all 2105 current non-smokers using the complete follow up period (table 2). The risks in the upper three cotinine groups were markedly higher than the risk in the lowest group, with a relative hazard of 1.61 in the highest group in the simplest model (adjusted for town and age), a hazard estimate similar to that of light active smokers. The association between cotinine concentration and CHD seemed graded and was not markedly affected by adjustment for other cardiovascular risk factors. The results of analyses restricted to lifelong non-smokers were similar, though the confidence intervals were wider. Exclusion of men with pre-existing CHD had no effect on these findings (data not presented). When we examined the overall association between cotinine concentration and CHD, we found that a doubling of cotinine concentration was associated with a hazard increase of 16% (95% confidence interval 6% to 27%).
Table 2 Hazard ratios for cotinine group and risk of coronary heart disease (CHD) over 20 years of follow up
Influence of follow up period—In a Kaplan-Meier plot showing the cumulative proportions of men with major CHD over time among three groups (light passive (lowest cotinine quarter), heavy passive (upper three cotinine quarters), and light active (1-9 cigarettes/day)) we found that the heavy passive and light active groups diverged rapidly from the light passive group during the first years of follow up but remained almost parallel during later years (fig 2). The corresponding hazard ratios for cotinine and risk of CHD in separate five year follow up periods were highest in the early years of follow up and declined with increasing duration of follow up (table 3). These patterns were little affected by adjustment for cardiovascular risk factors, and again the hazard ratios for the heavier passive smoking groups were comparable with those of light active smokers. Restriction of these analyses to lifelong non-smokers or to men with no evidence of pre-existing CHD had no material effect on the results.
Fig 2 Proportion of men with major CHD by years of follow up in each smoking group. "Light passive" refers to lowest quarter of cotinine concentration among non-smokers (0-0.7 ng/ml), "heavy passive" to upper three quarters of cotinine concentration combined (0.8 to 14.0 ng/ml), "light active" to men smoking 1-9 cigarettes a day
Table 3 Cotinine group and risk of coronary heart disease (CHD): hazard ratios (95% confidence intervals) for specific 5 year follow up periods
Serum cotinine exposure and stroke—There was no strong association between cotinine concentration and stroke among non-smokers, either before or after adjustment for major cardiovascular risk factors (table 4). Analyses based on lifelong non-smokers showed similar results. For stroke, there was no strong evidence that hazard ratios changed over time (data not presented).
Table 4 Hazard ratios for cotinine group and risk of stroke over 20 years of follow up
Discussion
Parish S, Collins R, Peto R, Youngman L, Barton J, Jayne K, et al. Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14 000 cases and 32 000 controls in the United Kingdom. The international studies of infarct survival (ISIS) collaborators. BMJ 1995;311: 471-7.
Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. BMJ 1997;315: 973-80.
He J, Vupputuri S, Allen K, Prerost MR, Hughes J, Whelton PK. Passive smoking and the risk of coronary heart disease—a meta-analysis of epidemiologic studies. N Engl J Med 1999;340: 920-6.
Hirayama T. Passive smoking. N Z Med J 1990;103: 54.
Garland C, Barrett-Connor E, Suarez L, Criqui MH, Wingard DL. Effects of passive smoking on ischemic heart disease mortality of nonsmokers. A prospective study. Am J Epidemiol 1985;121: 645-50.
Butler TL. The relation of passive smoking to various health outcomes among Seventh Day Adventists in California. Los Angeles: University of California, 1988. (PhD thesis.)
Sandler DP, Comstock GW, Helsing KJ, Shore DL. Deaths from all causes in non-smokers who lived with smokers. Am J Public Health 1989;79: 163-7.
Hole DJ, Gillis CR, Chopra C, Hawthorne VM. Passive smoking and cardiorespiratory health in a general population in the west of Scotland. BMJ 1989;299: 423-7.
Humble C, Croft J, Gerber A, Casper M, Hames CG, Tyroler HA. Passive smoking and 20-year cardiovascular disease mortality among nonsmoking wives, Evans County, Georgia. Am J Public Health 1990;80: 599-601.
Svendsen KH, Kuller LH, Martin MJ, Ockene JK. Effects of passive smoking in the Multiple Risk Factor Intervention Trial. Am J Epidemiol 1987;126: 783-95.
Steenland K, Thun M, Lally C, Heath C, Jr. Environmental tobacco smoke and coronary heart disease in the American Cancer Society CPS-II cohort. Circulation 1996;94: 622-8.
Kawachi I, Colditz GA, Speizer FE, Manson JE, Stampfer MJ, Willett WC, et al. A prospective study of passive smoking and coronary heart disease. Circulation 1997;95: 2374-9.
Bonita R, Duncan J, Truelsen T, Jackson RT, Beaglehole R. Passive smoking as well as active smoking increases the risk of acute stroke. Tob Control 1999;8: 156-60.
Jarvis MJ, Feyerabend C, Bryant A, Hedges B, Primatesta P. Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners. Tob Control 2001;10: 368-74.
Jarvis MJ, Foulds J, Feyerabend C. Exposure to passive smoking among bar staff. Br J Addict 1992;87: 111-3.
Jarvis M, Tunstall-Pedoe H, Feyerabend C, Vesey C, Salloojee Y. Biochemical markers of smoke absorption and self reported exposure to passive smoking. J Epidemiol Community Health 1984;38: 335-9.
Tunstall-Pedoe H, Brown CA, Woodward M, Tavendale R. Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study. J Epidemiol Community Health 1995;49: 139-43.
Walker M, Shaper AG, Lennon L, Whincup PH. Twenty year follow-up of a cohort based in general practices in 24 British towns. J Public Health Med 2000;22: 479-85.
Feyerabend C, Russell MA. A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids. J Pharm Pharmacol 1990;42: 450-2.
Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987;77: 1435-8.
Shaper AG, Wannamethee G, Whincup P. Alcohol and blood pressure in middle-aged British men. J Hum Hypertens 1988;2: 71-8.
Shaper AG, Wannamethee G, Weatherall R. Physical activity and ischaemic heart disease in middle-aged British men. Br Heart J 1991;66: 384-94.
Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996;18: 188-204.
Jarvis MJ, Goddard E, Higgins V, Feyerabend C, Bryant A, Cook DG. Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys. BMJ 2000;321: 343-5.
Walker A, O'Brien M, Traynor J, Fox K, Goddard E, Foster K. Living in Britain: results from the 2001 general household survey. London: Stationery Office, 2002.
Enstrom JE, Kabat GC. Environmental tobacco smoke and tobacco related mortality in a prospective study of Californians, 1960-98. BMJ 2003;326: 1057-67.(Peter H Whincup, professo)
Correspondence to: P H Whincup p.whincup@sghms.ac.uk
Abstract
Active cigarette smoking is a well established major preventable risk factor for coronary heart disease (CHD).1 Many studies have reported that passive smoking is also associated with increased risk of CHD.2 3 Generally such studies have compared the risks of non-smokers who do or do not live with cigarette smokers,4-9 though a few have also considered occupational exposure.10-12 Meta-analyses of case-control and cohort studies examining the effect of living with a cigarette smoker on risk among non-smokers have generally shown an overall increase in risk of about one quarter, after adjustment for potential confounding factors2 3 and with little evidence of publication bias. Passive smoking may also be related to risk of stroke.13
Although living with someone who smokes is an important component of exposure to passive smoking, it accounts for less than half of the variation in cotinine concentration among non-smokers14 and does not take account of additional exposure in workplaces and in public places (particularly pubs and restaurants).15 Biomarkers of passive exposure to smoking, particularly cotinine (a nicotine metabolite), can provide a summary measure of exposure from all these sources.16 Although cotinine concentration in non-smokers has been related to prevalent CHD,17 there are no published reports of the prospective associations between serum cotinine concentration and risk of CHD and stroke in non-smokers. We have examined these associations in the British regional heart study, a prospective study of cardiovascular disease in middle aged men, using retained baseline samples for retrospective measurement of cotinine.
Methods
In the last 18 towns of the study, 5661 men took part (78% response rate). For 4729 of these we had detailed histories on smoking and blood samples for cotinine analysis. These men resembled the whole study population in reported smoking habits and risks of CHD and stroke. A total of 2158 men reported that they were current non-smokers, of whom 2105 (97.5%) had serum cotinine concentrations < 14.1 ng/ml. Of these, 945 men were classified as lifelong non-smokers, the remaining 1160 as former smokers. The cotinine distributions of these two groups (fig 1) were skewed, with a slightly higher geometric mean cotinine among former smokers than among lifelong non-smokers (1.49 1.18 ng/ml). Few men in either group had cotinine concentrations close to the 14.1 ng/ml cut off.
Fig 1 Distribution of serum cotinine concentrations among current non-smokers; lifelong non-smokers and former smokers are shown separately
Serum cotinine and cardiovascular risk factors—Among current non-smokers, cotinine concentrations were not consistently related to age, total cholesterol concentration, physical activity score, or prevalent CHD but showed graded positive associations with mean body mass index, systolic and diastolic blood pressure, high density lipoprotein cholesterol, white cell count, and triglycerides (weakly) and positive associations with the prevalence of former smoking, heavy drinking, and manual occupation (table 1). Cotinine concentrations were inversely associated with FEV1, prevalence of low alcohol intake, and residence in southern England. These associations were generally little affected when we excluded former smokers. Light active smokers had lower mean body mass index, diastolic blood pressure, and FEV1 and a higher mean white cell count than men who did not smoke.
Table 1 Means (SDs) and numbers (percentages) of cardiovascular risk factors by cotinine concentration: non-smokers and light active cigarette smokers
Serum cotinine concentration and CHD risk—We examined the association between quarters of the cotinine distribution and CHD hazard ratios among all 2105 current non-smokers using the complete follow up period (table 2). The risks in the upper three cotinine groups were markedly higher than the risk in the lowest group, with a relative hazard of 1.61 in the highest group in the simplest model (adjusted for town and age), a hazard estimate similar to that of light active smokers. The association between cotinine concentration and CHD seemed graded and was not markedly affected by adjustment for other cardiovascular risk factors. The results of analyses restricted to lifelong non-smokers were similar, though the confidence intervals were wider. Exclusion of men with pre-existing CHD had no effect on these findings (data not presented). When we examined the overall association between cotinine concentration and CHD, we found that a doubling of cotinine concentration was associated with a hazard increase of 16% (95% confidence interval 6% to 27%).
Table 2 Hazard ratios for cotinine group and risk of coronary heart disease (CHD) over 20 years of follow up
Influence of follow up period—In a Kaplan-Meier plot showing the cumulative proportions of men with major CHD over time among three groups (light passive (lowest cotinine quarter), heavy passive (upper three cotinine quarters), and light active (1-9 cigarettes/day)) we found that the heavy passive and light active groups diverged rapidly from the light passive group during the first years of follow up but remained almost parallel during later years (fig 2). The corresponding hazard ratios for cotinine and risk of CHD in separate five year follow up periods were highest in the early years of follow up and declined with increasing duration of follow up (table 3). These patterns were little affected by adjustment for cardiovascular risk factors, and again the hazard ratios for the heavier passive smoking groups were comparable with those of light active smokers. Restriction of these analyses to lifelong non-smokers or to men with no evidence of pre-existing CHD had no material effect on the results.
Fig 2 Proportion of men with major CHD by years of follow up in each smoking group. "Light passive" refers to lowest quarter of cotinine concentration among non-smokers (0-0.7 ng/ml), "heavy passive" to upper three quarters of cotinine concentration combined (0.8 to 14.0 ng/ml), "light active" to men smoking 1-9 cigarettes a day
Table 3 Cotinine group and risk of coronary heart disease (CHD): hazard ratios (95% confidence intervals) for specific 5 year follow up periods
Serum cotinine exposure and stroke—There was no strong association between cotinine concentration and stroke among non-smokers, either before or after adjustment for major cardiovascular risk factors (table 4). Analyses based on lifelong non-smokers showed similar results. For stroke, there was no strong evidence that hazard ratios changed over time (data not presented).
Table 4 Hazard ratios for cotinine group and risk of stroke over 20 years of follow up
Discussion
Parish S, Collins R, Peto R, Youngman L, Barton J, Jayne K, et al. Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14 000 cases and 32 000 controls in the United Kingdom. The international studies of infarct survival (ISIS) collaborators. BMJ 1995;311: 471-7.
Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. BMJ 1997;315: 973-80.
He J, Vupputuri S, Allen K, Prerost MR, Hughes J, Whelton PK. Passive smoking and the risk of coronary heart disease—a meta-analysis of epidemiologic studies. N Engl J Med 1999;340: 920-6.
Hirayama T. Passive smoking. N Z Med J 1990;103: 54.
Garland C, Barrett-Connor E, Suarez L, Criqui MH, Wingard DL. Effects of passive smoking on ischemic heart disease mortality of nonsmokers. A prospective study. Am J Epidemiol 1985;121: 645-50.
Butler TL. The relation of passive smoking to various health outcomes among Seventh Day Adventists in California. Los Angeles: University of California, 1988. (PhD thesis.)
Sandler DP, Comstock GW, Helsing KJ, Shore DL. Deaths from all causes in non-smokers who lived with smokers. Am J Public Health 1989;79: 163-7.
Hole DJ, Gillis CR, Chopra C, Hawthorne VM. Passive smoking and cardiorespiratory health in a general population in the west of Scotland. BMJ 1989;299: 423-7.
Humble C, Croft J, Gerber A, Casper M, Hames CG, Tyroler HA. Passive smoking and 20-year cardiovascular disease mortality among nonsmoking wives, Evans County, Georgia. Am J Public Health 1990;80: 599-601.
Svendsen KH, Kuller LH, Martin MJ, Ockene JK. Effects of passive smoking in the Multiple Risk Factor Intervention Trial. Am J Epidemiol 1987;126: 783-95.
Steenland K, Thun M, Lally C, Heath C, Jr. Environmental tobacco smoke and coronary heart disease in the American Cancer Society CPS-II cohort. Circulation 1996;94: 622-8.
Kawachi I, Colditz GA, Speizer FE, Manson JE, Stampfer MJ, Willett WC, et al. A prospective study of passive smoking and coronary heart disease. Circulation 1997;95: 2374-9.
Bonita R, Duncan J, Truelsen T, Jackson RT, Beaglehole R. Passive smoking as well as active smoking increases the risk of acute stroke. Tob Control 1999;8: 156-60.
Jarvis MJ, Feyerabend C, Bryant A, Hedges B, Primatesta P. Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners. Tob Control 2001;10: 368-74.
Jarvis MJ, Foulds J, Feyerabend C. Exposure to passive smoking among bar staff. Br J Addict 1992;87: 111-3.
Jarvis M, Tunstall-Pedoe H, Feyerabend C, Vesey C, Salloojee Y. Biochemical markers of smoke absorption and self reported exposure to passive smoking. J Epidemiol Community Health 1984;38: 335-9.
Tunstall-Pedoe H, Brown CA, Woodward M, Tavendale R. Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study. J Epidemiol Community Health 1995;49: 139-43.
Walker M, Shaper AG, Lennon L, Whincup PH. Twenty year follow-up of a cohort based in general practices in 24 British towns. J Public Health Med 2000;22: 479-85.
Feyerabend C, Russell MA. A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids. J Pharm Pharmacol 1990;42: 450-2.
Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987;77: 1435-8.
Shaper AG, Wannamethee G, Whincup P. Alcohol and blood pressure in middle-aged British men. J Hum Hypertens 1988;2: 71-8.
Shaper AG, Wannamethee G, Weatherall R. Physical activity and ischaemic heart disease in middle-aged British men. Br Heart J 1991;66: 384-94.
Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996;18: 188-204.
Jarvis MJ, Goddard E, Higgins V, Feyerabend C, Bryant A, Cook DG. Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys. BMJ 2000;321: 343-5.
Walker A, O'Brien M, Traynor J, Fox K, Goddard E, Foster K. Living in Britain: results from the 2001 general household survey. London: Stationery Office, 2002.
Enstrom JE, Kabat GC. Environmental tobacco smoke and tobacco related mortality in a prospective study of Californians, 1960-98. BMJ 2003;326: 1057-67.(Peter H Whincup, professo)