- Email: [email protected]
The association of cigarette smoking with self-reported disease before middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) study
Preventive Medicine 42 (2006) 193 – 199 www.elsevier.com/locate/ypmed
The association of cigarette smoking with self-reported disease before middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) study Atsushi Hozawa a,b , Thomas Houston c , Michael W. Steffes d , Rachel Widome a , O. Dale Williams c , Carlos Iribarren e , Mark J. Pletcher f , Martha L. Daviglus g , J. Jeffrey Carr h , David R. Jacobs Jr. a,i,⁎ a
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA b Division of Epidemiology and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan c Division of General Internal Medicine, University of Alabama at Birmingham, AL 35294, USA d Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55454, USA e Division of Research, Kaiser Permanente, Oakland, CA 94612, USA f Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA g Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA h Wake Forest University Health Sciences, Departments of Radiology and Public Health Sciences, Winston-Salem, NC 27157, USA i Department of Nutrition, University of Oslo, Oslo, Norway Available online 15 February 2006
Abstract Background. Evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited. Therefore, we assessed associations between cigarette smoking and several self-reported illnesses in a prospective cohort study in healthy young adults. Methods. Data were derived from 4472 adults aged 18 to 30 years at baseline participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study and reexamined at least once after 7, 10, or 15 years. Results. Cigarette smoking in 1985–86 was related to self-reported smoking-related cancers, circulatory disease, and peptic ulcer. Incidence of these diseases was 9.3/1000 person years among current smokers vs. 4.5/1000 person years among never smokers with no exposure to passive smoke, relative risk (adjusted for race, sex, education, and center) 1.96 (1.42–2.70). Assuming causal relationships, 32% of these premature incidents were attributable to smoking. The relative risks of liver disease, migraine headache, depression, being ill the day before the examination, and chronic cough and phlegm production were also higher in smokers. Conclusions. Smokers aged 18–30 followed for 7 to 15 years reported an excess of both major and minor ailments related to earlier and current smoking. Thus, prevention, cessation, and avoiding passive smoking should remain strong goals among young people. © 2005 Elsevier Inc. All rights reserved. Keywords: Smoking; Cancer; Cardiovascular diseases; Peptic ulcer; Passive smoking and prospective studies
Introduction
⁎ Corresponding author. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Division of Epidemiology, 1300 South Second St., Suite 300, Minneapolis, MN 55454, USA. Fax: +1 612 624 0315. E-mail address: [email protected] (D.R. Jacobs). 0091-7435/$ - see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2005.12.008
The harmful health effects of cigarette smoking are well accepted. The Surgeon General's Report, for example, identified smoking as a cause of cancer, cardiovascular diseases, peptic ulcer, or respiratory diseases (U.S. Department of Health and Human Services, 2004). In the United States, a national health objective for 2010 is to reduce adult cigarette smoking prevalence to ≤12% (U.S. Department of Health and Human
194
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
Services, 2000). To assess progress toward this objective, the Centers for Disease Control (CDC) analyzed self-reported data from the 2002 National Health Interview Survey (NHIS) sample adult core questionnaire, which indicated that approximately 22.5% of adults were current smokers, ranging from 28.5% for those aged 18–24 years to 9.3% for those aged ≥65 years (CDC, 2004). Although this prevalence is slightly lower than the 22.8% prevalence among U.S. adults in 2001 and the 24.1% prevalence in 1998, the rate of decline has been insufficient to achieve the 2010 national health objective. Furthermore, the proportion of 18- to 24-year-old cigarette smokers increased to 28.5% in 2002 27.9% in 1998 (CDC, 2000). It has been suggested that more information available to young adults about the immediate dangers of smoking would reduce smoking and result in a long-term public health gain. However, evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited (U.S. Department of Health and Human Services, 1994; McCarron et al., 2001; Raitakari et al., 2003; Berenson et al., 1998; Paffenbarger et al., 1995; Navas-Nacher et al., 2001; Castle et al., 2002; Boffetta et al., 2001; Beckett et al., 2001; Strachan et al., 1996); few of the studies are comprehensive (U.S. Department of Health and Human Services, 1994; McCarron et al., 2001); none extensively assessed risk after only 7–15 years; and none separated passive smokers from unexposed never smokers. Therefore, we assessed the effect of active and passive cigarette smoking on self-reported clinical diseases during 15 years of follow-up of black and white men and women initially aged 18–30 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. We hypothesized that smoking status is strongly related to an early excess of cancer, cardiovascular diseases, peptic ulcer, and respiratory diseases. Methods Participants The CARDIA study, a biethnic, prospective, multicenter epidemiologic study of the evolution of risk factors in young adults, has been described (Friedman et al., 1988). Briefly, from 1985 to 1986, 5115 African American and White individuals aged 18 to 30 years were examined in Birmingham, Chicago, Minneapolis, and Oakland. Recruitment was stratified to achieve balance at each site in race, sex, education, and age. Fifty percent of invited individuals contacted were examined (47% African Americans and 60% of Whites) and became the CARDIA cohort. Participants were recontacted annually and reexamined in year 2, year 5, year 7, year 10, and year 15 (2000–2001). Of the 5115 initial participants, we included 4485 (87.7%) who were reexamined at least once at the 7, 10, or 15 year follow-up examinations. We excluded 13 more participants with incomplete information on year 0 smoking status including lack of information on passive smoking; 4472 participants entered this analysis for study of the summary smoking-related disease outcome, less prevalent cases at baseline.
Therefore, in this analysis, our study participants consisted of 2479 never smokers, 524 past smokers, and 1469 current smokers. Never smokers were further divided as those not exposed to passive smoking and passive smokers (serum cotinine concentration 2–13 ng/mL or sum of hours exposed to environmental smoking at home, small place other than their home, and a large indoor area at least 7 h per week). We excluded the 3 never smokers who had cotinine 0 ng/mL, but neither year 0 nor year 2 passive smoking information was available. This formula classified the 2479 never smokers into 871 never smokers not exposed to passive smoking and 1608 passive smokers.
Definition of self-report diseases Dependent variables were queried at various examinations, most in the form “Has a doctor or nurse ever told you that you have (certain condition)” (Table 1). Depression was defined by The Center for Epidemiological Studies Depression Scale (CES-D) score ≥16 (years 10 and 15 only) instead of using self-reported mental illness (Radloff, 1977). Based on the Surgeon General's 2004 report (U.S. Department of Health and Human Services, 2004), we classified hematologic, cervical, and stomach cancers as smoking-related cancers (no lung cancers occurred); the remaining cancers being classified as “other”. We also grouped participants who had ever been told that they had heart attack, angina, peripheral vascular disease (PVD), stroke, or transient ischemic attack (TIA) as experiencing cardiovascular diseases, and those who had asthma, emphysema, or chronic bronchitis as having respiratory diseases. We have limited information about validity of diagnoses because CARDIA does not collect information beyond self-report except for hospitalized cardiovascular and respiratory events. Of 44 self-reported cases of heart attack or angina, 36% reported an associated hospitalization; 56% of these were confirmed by hospital records. Of 92 participants who first self-reported a circulatory disease at years 2, 5, 7, or 10, 47% later mentioned the condition again; the corresponding cancer numbers were 141 participants, 55% of whom later mentioned that diagnosis. Thus, about half of the self-reported circulatory and cancer cases met some standard for validity or reliability; the other cases may have been less severe outpatients, the participant forgetting or not wanting to talk about an unpleasant event or misunderstandings by the participant.
Statistical analyses We considered an event to have occurred at the first examination in which a diagnosis was mentioned (so that time to event was always 2, 5, 7, 10, or 15 years, depending on when the questions about disease were asked). For each disease, we excluded prevalent cases at year 0. We reported the number of participants at risk and the number of events in each year, based on each participant's year 0 smoking category. In additional analyses to reduce false positive classification, we also used a more restrictive definition of cases as follows: (1) cases reported twice or (2) cases reported once, only at their final examination. We used Cox proportional hazards regression analysis to estimate the risk of disease according to smoking categories, while adjusting for age, education, clinical center, sex, and race as potential confounders. The reference category was never smokers not exposed to passive smoke. For circulatory disease, we also computed risk of disease by smoking category after adjustment for systolic blood pressure (SBP), antihypertensive medication, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, logtransformed triglyceride (TG), and ethanol intake, with negligible effect on the relative risk (data are not shown). We adjusted liver disease for ethanol intake. We computed attributable risks for diseases strongly believed to be causally related to smoking (U.S. Department of Health and Human Services, 2004). Population attributable fraction (PAF) was calculated as p * {RR −1}/RR where p = proportion of cases exposed to the risk factor (Rockhill et al., 1998).
Smoking status
Results
Year 0 smoking status (current, former, and never) was interviewerascertained supplemented by serum cotinine measurements. We further classified 88 of 2567 self-reported never smokers and 66 of 590 self-reported past smokers as current smokers because serum cotinine concentration was ≥14 ng/mL at CARDIA year 0.
Risk of smoking-related diseases The 4472 participants included 55.2% women, 49.9% black, and 61.8% with education beyond high school. Mean age
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
195
Table 1 Criteria for disease identification Disease
Criteria
Examinations included
Cancer
Subjects who had ever been told by a doctor or nurse that they had cancer Hematologic, cervical, and stomach cancers
Years 0, 2, 5, 7, 10, and 15
Smoking-related a Other a
Cardiovascular diseases
Asthma
Respiratory disease
Depression
Peptic ulcer b, kidney disease, thyroid disease, gallbladder disease, migraine, and liver disease Recent minor illness
Cough and phlegm
Breast, testes, bone, melanoma, other skin, brain, colon, and other cancers Subjects who had ever been told by a doctor or nurse that they had heart attack, angina, peripheral vascular disease, stroke, or transient ischemic attack Subjects who had ever been told by a doctor or nurse that they had asthma plus subjects who were taking a medication typically used to treat asthma Subjects who had ever been told by a doctor or nurse that they had chronic bronchitis or emphysema plus the subjects who had asthma Subjects whose Center for Epidemiological Studies Depression Scale (CES-D) score at either year 10 or 15 was 16 or more Subjects who had ever been told by a doctor or nurse that they had these diseases
Subjects who answered that they had been ill in the past 24 h at the follow-up survey (e.g., cold, flu, fever, and vomiting) Subjects who answered that they usually had cough or that they usually brought up phlegm from their chest
Hematologic and stomach: Years 2, 5, 7, 10, and 15; cervical: years 2, 7, 10, and 15 Breast, testes, bone, melanoma, other skin, brain, and other cancers: years 2, 5, 7, 10, and 15; colon: years 2, 7, 10, and 15 Heart attack and angina: years 0, 2, 5, 7, 10, and 15; peripheral vascular disease, stroke, or transient ischemic attack: years 7, 10, and 15 Information from self report: years 0, 2, 7, 10, and 15; Drug information: years 0, 2, 5, 7, 10, and 15 Years 0, 7, 10, and 15
Years 10 and 15
Kidney, thyroid, peptic ulcer, liver, and gallbladder: years 0, 2, 5, 7, 10, and 15; migraine: years 7, 10, and 15 Years 7, 10, and 15
Years 0 and 10
The condition is considered to be present if the criterion is satisfied at any examination. a These criteria were based on the Surgeon General's report 2004 (1). b “Ulcer, stomach, or duodenum” in years 0 and 2; “ulcer in the digestive tract other than Crohn's disease or ulcerative colitis” in years 7, 10, and 15.
(standard deviation) was 24.9 (3.6) years for men and 25.0 (3.7) years for women at year 0. Smoking initiation mean age was 16.9 (3.2) years. Cessation among former smokers occurred at mean age 23.0 (3.7) years. The 4472 participants had mean age 38.9 (4.5) years at their final examination, 3.7% were under 30 years of age; 14.8% were 30–34 years; 32.7% were 35–39 years; and 48.8% were at least 40 years. Among the 630 CARDIA participants who provided their smoking status at year 0 and were not included in these analyses, 45.4% were smokers at year 0 compared to 32.9% of the 4472 included. Table 2 shows the incidences of cancers, cardiovascular diseases, peptic ulcer, or respiratory diseases according to year 0 smoking status. Smoking-related cancers, cardiovascular diseases, and peptic ulcer were each associated with smoking, but other cancers and respiratory diseases were not associated. Although not statistically significant, these diseases were also more frequent with passive smoking. As hypothesized, 54.0% of smoking-related cancer diagnoses, 39.8% of circulatory disease diagnoses, and 26.6% of peptic ulcer cases were attributable to current, former, or passive smoking at year 0. We also addressed the total burden of these diseases in nonsmokers and smokers. When we pooled smoking-related cancers, cardiovascular diseases, and peptic ulcer, we found the concomitant risk was significantly higher in current smokers (relative hazard (RH): 1.96; 95% confidence interval (CI): 1.42–2.70) than never smokers not exposed
to passive smoking. Twenty-one percent of the premature incidence for these diseases was attributable to current smoking and 32% to any passive, former, or current smoking. Although the relative risk of 1.32 for passive smoking was not statistically significantly greater than that for never smokers not exposed to passive smoking, their isolation increased the risk estimate for former and current smokers. Thus, compared to never smokers including passive smokers, the RH for smoking-related disease of current smoking was only 1.63 and the total attributable to any active or former smoking was 18.2%. Incidence rates for smoking-related diseases were 4.8/1000 person years higher in current smokers compared with never smoked not exposed to passive smoking. When we restricted cases to 2 or more self-reports or report only at their last examination, we found 282 cases of the composite smoking-related diseases. The risk was similar in magnitude (RH for current smoker: 1.71; 95% CI: 1.18–2.46, RH for former smoker: 1.43; 95% CI: 0.91–2.24, RH for passive smoker: 1.18; 95% CI: 0.82–1.71) compared with never smokers) to the results obtained when the single-mentioned cases were included. Risk of other ailments Several other conditions developed at a higher rate among those who were cigarette smokers at year 0. Prevalence of
196
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
Table 2 Relative hazards (RH) for incidence of several self-report diseases compared with never smokers who were also not passive smokers
All cancers
Smoking-related cancer c
Other cancers e
Circulatory diseases f
Peptic ulcer
Respiratory disease g
Smoke-related disease h
N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
864 30 2.47 1 864 6 0.49 1
1600 68 3.05 1.38 (0.90–2.13) 1600 19 0.84 1.65 (0.66–4.16) 11.4% 1600 52 2.32 1.23 (0.77–1.96) 1607 49 2.13 1.50 (0.87–2.59) 10.5% 1551 73 3.37 1.21 (0.80–1.83) 5.6% 1442 202 10.46 1.09 (0.86–1.38) 1542 126 6.01 1.32 (0.95–1.82) 7.7%
519 25 3.49 1.27 (0.75–2.18) 519 11 1.51 3.31 (1.21–9.07) 11.6% 519 20 2.78 1.11 (0.62–1.99) 524 24 3.27 1.99 (1.07–3.68) 7.6% 489 19 2.72 0.98 (0.56–1.74) 0.0% 465 68 11.03 1.15 (0.84–1.56) 484 45 6.79 1.42 (0.95–2.12) 3.4%
1447 66 3.40 1.53 (0.98–2.40) 1447 30 1.53 3.16 (1.29–7.71) 31.1% 1447 46 2.35 1.27 (0.77–2.08) 1465 65 3.17 2.08 (1.21–3.55) 21.6% 1405 103 5.47 1.87 (1.24–2.80) 21.0% 1290 205 12.34 1.23 (0.96–1.57) 1382 166 9.29 1.96 (1.42–2.70) 20.8%
864 27 2.22 1 871 18 1.37 1.00 855 33 2.75 1 793 102 9.50 1 849 53 4.49 1
Results from Cox proportional hazard models. CARDIA 1985–2001. PAF is computed only for those disease categories where a causal relation to smoking is plausible. a Never smoked, serum cotinine b2 ng/mL and exposed to environmental smoking less than 7 h/week. b Never smoked, serum cotinine 2–13 ng/mL or exposed to environmental smoking 7 or more hours/week. c Cervical cancer (51), hematologic cancer (11), and stomach cancer (5). One case overlapped. d PAF: population attributable fraction; calculated separately for each disease category as p * (RH − 1) / RH where p = proportion of cases exposed to the risk factor. e Breast cancer (25 cases), testes cancer (2), bone cancer (4), melanoma (20), skin cancer (34), brain cancer (7), colon cancer (5), and other cancers cases (48). f Heart attack (21 cases), angina (26), stroke or transient ischemic attack (TIA) (35), peripheral vascular disease (PVD) (85). Eleven cases overlapped. g Asthma (454 cases), chronic bronchitis (153), and emphysema (3). 33 cases overlapped. h Smoking-related cancer, cardiovascular diseases, and peptic ulcer.
chronic cough or phlegm production at year 0 was higher in smokers (Table 3): 11% in never smokers not exposed to passive smoking vs. 40% in current smokers, adjusted odds ratio (OR): 5.20; 95% CI: 4.08–6.64. Ten-year incident cough and phlegm was 5% in never smokers not exposed to passive smoking vs. 16% in current smokers (adjusted OR 3.01; 95% CI: 1.98–4.58). The risk of new onset of cough and phlegm was also statistically significant for passive smoking (adjusted OR = 1.87; 95% CI: 1.24–2.82). There was also elevated risk for liver diseases (attenuated to RH 1.83 (1.07–3.13) after further adjustment for ethanol intake), migraine headache, and depression (Table 4). The risk of “being sick with cold, flu, or vomiting in the past 24 h” was marginally significantly increased. Also examined and not related to smoking were kidney, thyroid, and gallbladder diseases.
Discussion In this prospective study, we demonstrated that cigarette smoking was related to the incidence of smoking-related cancer, cardiovascular diseases, and peptic ulcer as hypothesized. If all relations reported here were causal, as might be suspected, and if excess risks among current smokers were eliminated, 21% or 81 of the 390 smoking-related disease events (smoking-related cancer, cardiovascular diseases, and peptic ulcer) would be avoided. Furthermore, if passive and former smoking were also eliminated, an additional 11% of smoking-related diseases could be preventable. Although the extent of disease suffered during 7 to 15 years of follow-up (at the end of which participants ranged in age from 25 to 46) was less than that reported in older adults (McCarron et al., 2001), we did find a 1.96-fold excess incidence rate among
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
197
Table 3 Relationship of smoking status with cough and phlegm using cross sectional and longitudinal analysis
Cross sectional Year 0
Longitudinal according to year 0 smoking (excluding cough and phlegm at year 0 and those not attending year 10) year 0–year 10
N Events Percent events OR (95% CI) N Events Percent events OR (95% CI)
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
870 95 10.9% 1.00 693 32 4.6% 1.00
1605 290 18.1% 1.78 (1.38–2.28) 1165 104 8.9% 1.87 (1.24–2.82)
524 91 17.4% 1.70 (1.24–2.32) 375 39 10.4% 2.50 (1.53–4.10)
1466 591 40.3% 5.20 (4.08–6.64) 745 116 15.6% 3.01 (1.98–4.58)
N: numbers of subjects, OR: odds ratio, CI: confidence interval. a Never smoked, serum cotinine b2 ng/mL and exposed to environmental smoking less than 7 h/week. b Never smoked, serum cotinine 2–13 ng/mL or exposed to environmental smoking 7 or more hours/week.
current smokers compared to never smokers not exposed to passive smoking. In this study, we demonstrated that participants who smoked at an early age (18–30 years) have substantial risks of smokingrelated cancers, cardiovascular diseases, and peptic ulcer within 7 to 15 years. Although other investigators have observed
similar findings (McCarron et al., 2001; Raitakari et al., 2003; Berenson et al., 1998; Paffenbarger et al., 1995; Navas-Nacher et al., 2001; Castle et al., 2002; Boffetta et al., 2001; Beckett et al., 2001; Strachan et al., 1996), the current data more comprehensively demonstrate the risks of several diseases after a relatively short smoking exposure and at a very young
Table 4 Relative hazards (RH) for incidence of several self-report conditions or diseases according to year 0 smoking status
Kidney disease
Migraine
Thyroid disease
Gallbladder disease
Liver disease
Depression c
Being ill in the past 24 h
N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI)
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
844 73 6.34 1.00 871 120 10.15 1.00 848 41 3.44 1.00 864 21 1.72 1.00 862 19 1.57 1.00 772 161 14.91 1.00 871 158 13.86 1.00
1544 120 5.71 0.93 (0.70–1.25) 1608 257 11.99 1.20 (0.97–1.50) 1588 66 2.97 0.92 (0.62–1.36) 1598 47 2.10 1.14 (0.68–1.92) 1593 42 1.89 1.25 (0.73–2.15) 1431 347 17.65 1.11 (0.92–1.34) 1608 336 16.11 1.21 (1.00–1.46)
506 44 6.40 0.96 (0.66–1.40) 524 91 13.17 1.23 (0.93–1.62) 512 33 4.66 1.24 (0.78–1.97) 520 15 2.06 1.08 (0.55–2.11) 516 16 2.22 1.19 (0.61–2.33) 440 87 14.24 0.96 (0.74–1.25) 524 107 15.60 1.12 (0.87–1.43)
1389 124 6.81 1.11 (0.82–1.50) 1469 261 13.77 1.35 (1.08–1.68) 1434 51 2.62 0.85 (0.56–1.30) 1452 51 2.59 1.30 (0.77–2.19) 1454 75 3.85 2.08 (1.23–3.52) 1226 394 24.20 1.36 (1.13–1.65) 1469 295 16.12 1.22 (1.00–1.49)
Results from Cox proportional hazard models. CARDIA 1985–2001. Adjusted for age at baseline, sex, race, center, and education. N: number of subjects; RH: relative hazards; CI: confidence interval. a Never smoked, serum cotinine b2 ng/mL and sum of hours/week exposed to environmental smoking less than 7. b Never smoked, serum cotinine 2–13 ng/mL or sum of hours/week exposed to environmental smoking was 7 and more. c Assessed by CES-D, subjects who attended year 10 or year 15 at least one time.
198
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
age of follow-up. One comprehensive study reported eventual risk of dying in young smokers, but they followed for 41.3 years and did not assess when in that follow-up period the harmful effect was first seen (McCarron et al., 2001). The CARDIA study showed a significant difference in total and AIDS mortality between smokers and nonsmokers aged 18–30 during a median 13 years follow-up (Iribarren et al., 2005). Consistent with both the current and the previous (Iribarren et al., 2005) CARDIA report, Doll et al. (2004) reported that the mortality ratio (cigarette smoker vs. nonsmoker) was lowest in their youngest age group (relative risk: 1.6, 2.3, 2.5, 2.7, and 2.2 for age groups 35–44, 45–54, 55–64, 65–74, and 75–84, respectively). They (Doll et al., 2004) also reported smokers who quit before 44 years of age had a survival rate not different from nonsmokers and from early quitters, consistent with our finding of limited excess risk among former smokers. Since recent studies reported that passive smoking causes several smoking-related diseases (Whincup et al., 2004; Vineis et al., 2005), traditional analyses, which pool passive smokers and those never smokers not exposed to passive smoking as the reference group, likely underestimate the risk of smoking. Using never smokers not exposed to passive smoke as the reference, we showed that 32% of smoking-related diseases were preventable, 14% higher than parallel traditional analyses. Thus, smoking prevention and cessation should yield better health for both passive and active smokers, in line with apparent reductions in disease rates after smoking was banned from bars and restaurants in Ireland (Anonymous, 2005). Our study has some limitations. First, CARDIA collects medical records for event validation only for deaths and hospitalized circulatory and respiratory diseases; we used the much more extensive CARDIA data subset of self-reported clinical diagnoses. These self-reports likely include some false positives and miss some true positives. When we used stricter criteria for disease, the magnitude of the excess risk of smoking did not change. We were able to validate a few of the circulatory cases and showed that about half of the circulatory and cancer self-reports occurring by year 10 were confirmed in a later examination. If, as is likely, the probability of reporting false positively is unrelated to smoking, our estimates are smaller than the true risk. Use of the full database of self-report of various diseases and conditions did allow a broad examination of smoking risks. Second, we excluded the participants who did not attend any of the year 7, year 10, or year 15 visits. Because 45% of these non-responders were smokers, compared to 33% of included participants, they were likely to have a worse health status than were participants who attended these visits, and our estimate of the risks of cigarette smoking on health conditions may again be underestimated. Third, we cannot completely rule out residual confounding, although adjustment for age, race, sex, education, blood pressure, plasma lipids, and alcohol intake did not alter our findings. Fourth, since we did not specifically query other smoking-related cancers, including bladder, oral, esophagus, kidney, laryngeal, and pancreas cancer, we did not include these cancers as smoking-related cancers; however, there would be extremely few of these cancers in this young cohort, just as there were no reported lung cancers.
In conclusion, we find that major and minor smoking-related ailments are not limited to older adults but also occur in excess among young adult smokers. About a third of these serious disease outcomes (and many less serious ailments) among the young adults in our cohort could have been prevented by not smoking and avoiding passive smoke. Thus, even young adults need to worry about smoking, that is, serious adverse health effects from cigarette smoking do occur after only a few years of exposure. Younger smokers must be advised to quit and nonsmokers never to begin smoking and to avoid passive smoke to maintain better health. Acknowledgments Supported in part by National Heart, Lung, and Blood Institute contracts N01-HC-48047, N01-HC-48048, N01-HC48049, N01-HC-48050, and N01-HC-95095 (CARDIA). Dr. Hozawa was also supported by a grant to the Japan Society for the Promotion of Science (JSPS) Research (14010301) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the BANYU FELLOWSHIP PROGRAM sponsored by Banyu Life Science Foundation International. References Anonymous, 2005. Ireland's smoking ban is an admirable achievement. Lancet 365, 1282. Beckett, W.S., Jacobs Jr., D.R., Yu, X., Iribarren, C., Williams, O.D., 2001. Asthma is associated with weight gain in females but not males, independent of physical activity. Am. J. Respir. Crit. Care Med. 164, 2045–2050. Berenson, G.S., Srinivasan, S.R., Bao, W., Newman III, W.P., Tracy, R.E., Wattigney, W.A., 1998. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N. Engl. J. Med. 338, 1650–1656. Boffetta, P., Kreuzer, M., Benhamou, S., et al., 2001. Risk of lung cancer from tobacco smoking among young women from Europe. Int. J. Cancer 91, 745–746. Castle, P.E., Wacholder, S., Lorincz, A.T., et al., 2002. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J. Natl. Cancer Inst. 94, 1406–1414. CDC, 2000. Cigarette smoking among adults—United States, 1998. MMWR Recomm. Rep. 49, 881–884. CDC, 2004. Cigarette smoking among adults—United States, 2002. MMWR Recomm. Rep. 53, 427–431. Doll, R., Peto, R., Boreham, J., Sutherland, I., 2004. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ 328, 1519. Friedman, G.D., Cutter, G.R., Donahue, R.P., et al., 1988. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J. Clin. Epidemiol. 41, 1105–1116. Iribarren, C., Jacobs, D.R., Kiefe, C., 2005. Causes and demographic, medical, lifestyle and psychological predictors of premature mortality: the CARDIA study. Soc. Sci. Med. 60, 471–482. McCarron, P., Smith, G.D., Okasha, M., McEwen, J., 2001. Smoking in adolescence and young adulthood and mortality in later life: prospective observational study. J. Epidemiol. Community Health 55, 334–335. Navas-Nacher, E.L., Colangelo, L., Beam, C., Greenland, P., 2001. Risk factors for coronary heart disease in men 18 to 39 years of age. Ann. Intern. Med.134, 433–439. Paffenbarger Jr., R.S., Wing, A.L., Hyde, R.T., 1995. Physical activity as an index of heart attack risk in college alumni 1978. Am. J. Epidemiol. 108, 161–175.
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199 Radloff, L.S., 1977. The CES-D scale: a self-report depression scale for research in the general population. Appl. Psychol. Meas. 1, 385–401. Raitakari, O.T., Juonala, M., Kahonen, M., et al., 2003. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 290, 2277–2283. Rockhill, B., Newman, B., Weinberg, C., 1998. Use and misuse of population attributable fractions. Am. J. Public Health 88, 15–19. Strachan, D.P., Butland, B.K., Anderson, H.R., 1996. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ 312, 1195–1199. U.S. Department of Health and Human Services, 1994. Preventing Tobacco Use Among Young People: a report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.
199
U.S. Department of Health and Human Services, 2000. Healthy People 2010, 2nd ed. With understanding and improving health and objectives for improving health (2 vols.). Washington, DC: U.S. Department of Health and Human Services, (objective 27.1a). U.S. Department of Health and Human Services, 2004. The health consequences of smoking: a report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Vineis, P., Airoldi, L., Veglia, P., Olgiati, L., Pastorelli, R., Autrup, H., et al., 2005. Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ 330, 277. Whincup, P.H., Gilg, J.A., Emberson, J.R., et al., 2004. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ 329, 200–205.
The association of cigarette smoking with self-reported disease before middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) study Atsushi Hozawa a,b , Thomas Houston c , Michael W. Steffes d , Rachel Widome a , O. Dale Williams c , Carlos Iribarren e , Mark J. Pletcher f , Martha L. Daviglus g , J. Jeffrey Carr h , David R. Jacobs Jr. a,i,⁎ a
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA b Division of Epidemiology and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan c Division of General Internal Medicine, University of Alabama at Birmingham, AL 35294, USA d Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55454, USA e Division of Research, Kaiser Permanente, Oakland, CA 94612, USA f Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA g Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA h Wake Forest University Health Sciences, Departments of Radiology and Public Health Sciences, Winston-Salem, NC 27157, USA i Department of Nutrition, University of Oslo, Oslo, Norway Available online 15 February 2006
Abstract Background. Evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited. Therefore, we assessed associations between cigarette smoking and several self-reported illnesses in a prospective cohort study in healthy young adults. Methods. Data were derived from 4472 adults aged 18 to 30 years at baseline participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study and reexamined at least once after 7, 10, or 15 years. Results. Cigarette smoking in 1985–86 was related to self-reported smoking-related cancers, circulatory disease, and peptic ulcer. Incidence of these diseases was 9.3/1000 person years among current smokers vs. 4.5/1000 person years among never smokers with no exposure to passive smoke, relative risk (adjusted for race, sex, education, and center) 1.96 (1.42–2.70). Assuming causal relationships, 32% of these premature incidents were attributable to smoking. The relative risks of liver disease, migraine headache, depression, being ill the day before the examination, and chronic cough and phlegm production were also higher in smokers. Conclusions. Smokers aged 18–30 followed for 7 to 15 years reported an excess of both major and minor ailments related to earlier and current smoking. Thus, prevention, cessation, and avoiding passive smoking should remain strong goals among young people. © 2005 Elsevier Inc. All rights reserved. Keywords: Smoking; Cancer; Cardiovascular diseases; Peptic ulcer; Passive smoking and prospective studies
Introduction
⁎ Corresponding author. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Division of Epidemiology, 1300 South Second St., Suite 300, Minneapolis, MN 55454, USA. Fax: +1 612 624 0315. E-mail address: [email protected] (D.R. Jacobs). 0091-7435/$ - see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2005.12.008
The harmful health effects of cigarette smoking are well accepted. The Surgeon General's Report, for example, identified smoking as a cause of cancer, cardiovascular diseases, peptic ulcer, or respiratory diseases (U.S. Department of Health and Human Services, 2004). In the United States, a national health objective for 2010 is to reduce adult cigarette smoking prevalence to ≤12% (U.S. Department of Health and Human
194
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
Services, 2000). To assess progress toward this objective, the Centers for Disease Control (CDC) analyzed self-reported data from the 2002 National Health Interview Survey (NHIS) sample adult core questionnaire, which indicated that approximately 22.5% of adults were current smokers, ranging from 28.5% for those aged 18–24 years to 9.3% for those aged ≥65 years (CDC, 2004). Although this prevalence is slightly lower than the 22.8% prevalence among U.S. adults in 2001 and the 24.1% prevalence in 1998, the rate of decline has been insufficient to achieve the 2010 national health objective. Furthermore, the proportion of 18- to 24-year-old cigarette smokers increased to 28.5% in 2002 27.9% in 1998 (CDC, 2000). It has been suggested that more information available to young adults about the immediate dangers of smoking would reduce smoking and result in a long-term public health gain. However, evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited (U.S. Department of Health and Human Services, 1994; McCarron et al., 2001; Raitakari et al., 2003; Berenson et al., 1998; Paffenbarger et al., 1995; Navas-Nacher et al., 2001; Castle et al., 2002; Boffetta et al., 2001; Beckett et al., 2001; Strachan et al., 1996); few of the studies are comprehensive (U.S. Department of Health and Human Services, 1994; McCarron et al., 2001); none extensively assessed risk after only 7–15 years; and none separated passive smokers from unexposed never smokers. Therefore, we assessed the effect of active and passive cigarette smoking on self-reported clinical diseases during 15 years of follow-up of black and white men and women initially aged 18–30 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. We hypothesized that smoking status is strongly related to an early excess of cancer, cardiovascular diseases, peptic ulcer, and respiratory diseases. Methods Participants The CARDIA study, a biethnic, prospective, multicenter epidemiologic study of the evolution of risk factors in young adults, has been described (Friedman et al., 1988). Briefly, from 1985 to 1986, 5115 African American and White individuals aged 18 to 30 years were examined in Birmingham, Chicago, Minneapolis, and Oakland. Recruitment was stratified to achieve balance at each site in race, sex, education, and age. Fifty percent of invited individuals contacted were examined (47% African Americans and 60% of Whites) and became the CARDIA cohort. Participants were recontacted annually and reexamined in year 2, year 5, year 7, year 10, and year 15 (2000–2001). Of the 5115 initial participants, we included 4485 (87.7%) who were reexamined at least once at the 7, 10, or 15 year follow-up examinations. We excluded 13 more participants with incomplete information on year 0 smoking status including lack of information on passive smoking; 4472 participants entered this analysis for study of the summary smoking-related disease outcome, less prevalent cases at baseline.
Therefore, in this analysis, our study participants consisted of 2479 never smokers, 524 past smokers, and 1469 current smokers. Never smokers were further divided as those not exposed to passive smoking and passive smokers (serum cotinine concentration 2–13 ng/mL or sum of hours exposed to environmental smoking at home, small place other than their home, and a large indoor area at least 7 h per week). We excluded the 3 never smokers who had cotinine 0 ng/mL, but neither year 0 nor year 2 passive smoking information was available. This formula classified the 2479 never smokers into 871 never smokers not exposed to passive smoking and 1608 passive smokers.
Definition of self-report diseases Dependent variables were queried at various examinations, most in the form “Has a doctor or nurse ever told you that you have (certain condition)” (Table 1). Depression was defined by The Center for Epidemiological Studies Depression Scale (CES-D) score ≥16 (years 10 and 15 only) instead of using self-reported mental illness (Radloff, 1977). Based on the Surgeon General's 2004 report (U.S. Department of Health and Human Services, 2004), we classified hematologic, cervical, and stomach cancers as smoking-related cancers (no lung cancers occurred); the remaining cancers being classified as “other”. We also grouped participants who had ever been told that they had heart attack, angina, peripheral vascular disease (PVD), stroke, or transient ischemic attack (TIA) as experiencing cardiovascular diseases, and those who had asthma, emphysema, or chronic bronchitis as having respiratory diseases. We have limited information about validity of diagnoses because CARDIA does not collect information beyond self-report except for hospitalized cardiovascular and respiratory events. Of 44 self-reported cases of heart attack or angina, 36% reported an associated hospitalization; 56% of these were confirmed by hospital records. Of 92 participants who first self-reported a circulatory disease at years 2, 5, 7, or 10, 47% later mentioned the condition again; the corresponding cancer numbers were 141 participants, 55% of whom later mentioned that diagnosis. Thus, about half of the self-reported circulatory and cancer cases met some standard for validity or reliability; the other cases may have been less severe outpatients, the participant forgetting or not wanting to talk about an unpleasant event or misunderstandings by the participant.
Statistical analyses We considered an event to have occurred at the first examination in which a diagnosis was mentioned (so that time to event was always 2, 5, 7, 10, or 15 years, depending on when the questions about disease were asked). For each disease, we excluded prevalent cases at year 0. We reported the number of participants at risk and the number of events in each year, based on each participant's year 0 smoking category. In additional analyses to reduce false positive classification, we also used a more restrictive definition of cases as follows: (1) cases reported twice or (2) cases reported once, only at their final examination. We used Cox proportional hazards regression analysis to estimate the risk of disease according to smoking categories, while adjusting for age, education, clinical center, sex, and race as potential confounders. The reference category was never smokers not exposed to passive smoke. For circulatory disease, we also computed risk of disease by smoking category after adjustment for systolic blood pressure (SBP), antihypertensive medication, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, logtransformed triglyceride (TG), and ethanol intake, with negligible effect on the relative risk (data are not shown). We adjusted liver disease for ethanol intake. We computed attributable risks for diseases strongly believed to be causally related to smoking (U.S. Department of Health and Human Services, 2004). Population attributable fraction (PAF) was calculated as p * {RR −1}/RR where p = proportion of cases exposed to the risk factor (Rockhill et al., 1998).
Smoking status
Results
Year 0 smoking status (current, former, and never) was interviewerascertained supplemented by serum cotinine measurements. We further classified 88 of 2567 self-reported never smokers and 66 of 590 self-reported past smokers as current smokers because serum cotinine concentration was ≥14 ng/mL at CARDIA year 0.
Risk of smoking-related diseases The 4472 participants included 55.2% women, 49.9% black, and 61.8% with education beyond high school. Mean age
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
195
Table 1 Criteria for disease identification Disease
Criteria
Examinations included
Cancer
Subjects who had ever been told by a doctor or nurse that they had cancer Hematologic, cervical, and stomach cancers
Years 0, 2, 5, 7, 10, and 15
Smoking-related a Other a
Cardiovascular diseases
Asthma
Respiratory disease
Depression
Peptic ulcer b, kidney disease, thyroid disease, gallbladder disease, migraine, and liver disease Recent minor illness
Cough and phlegm
Breast, testes, bone, melanoma, other skin, brain, colon, and other cancers Subjects who had ever been told by a doctor or nurse that they had heart attack, angina, peripheral vascular disease, stroke, or transient ischemic attack Subjects who had ever been told by a doctor or nurse that they had asthma plus subjects who were taking a medication typically used to treat asthma Subjects who had ever been told by a doctor or nurse that they had chronic bronchitis or emphysema plus the subjects who had asthma Subjects whose Center for Epidemiological Studies Depression Scale (CES-D) score at either year 10 or 15 was 16 or more Subjects who had ever been told by a doctor or nurse that they had these diseases
Subjects who answered that they had been ill in the past 24 h at the follow-up survey (e.g., cold, flu, fever, and vomiting) Subjects who answered that they usually had cough or that they usually brought up phlegm from their chest
Hematologic and stomach: Years 2, 5, 7, 10, and 15; cervical: years 2, 7, 10, and 15 Breast, testes, bone, melanoma, other skin, brain, and other cancers: years 2, 5, 7, 10, and 15; colon: years 2, 7, 10, and 15 Heart attack and angina: years 0, 2, 5, 7, 10, and 15; peripheral vascular disease, stroke, or transient ischemic attack: years 7, 10, and 15 Information from self report: years 0, 2, 7, 10, and 15; Drug information: years 0, 2, 5, 7, 10, and 15 Years 0, 7, 10, and 15
Years 10 and 15
Kidney, thyroid, peptic ulcer, liver, and gallbladder: years 0, 2, 5, 7, 10, and 15; migraine: years 7, 10, and 15 Years 7, 10, and 15
Years 0 and 10
The condition is considered to be present if the criterion is satisfied at any examination. a These criteria were based on the Surgeon General's report 2004 (1). b “Ulcer, stomach, or duodenum” in years 0 and 2; “ulcer in the digestive tract other than Crohn's disease or ulcerative colitis” in years 7, 10, and 15.
(standard deviation) was 24.9 (3.6) years for men and 25.0 (3.7) years for women at year 0. Smoking initiation mean age was 16.9 (3.2) years. Cessation among former smokers occurred at mean age 23.0 (3.7) years. The 4472 participants had mean age 38.9 (4.5) years at their final examination, 3.7% were under 30 years of age; 14.8% were 30–34 years; 32.7% were 35–39 years; and 48.8% were at least 40 years. Among the 630 CARDIA participants who provided their smoking status at year 0 and were not included in these analyses, 45.4% were smokers at year 0 compared to 32.9% of the 4472 included. Table 2 shows the incidences of cancers, cardiovascular diseases, peptic ulcer, or respiratory diseases according to year 0 smoking status. Smoking-related cancers, cardiovascular diseases, and peptic ulcer were each associated with smoking, but other cancers and respiratory diseases were not associated. Although not statistically significant, these diseases were also more frequent with passive smoking. As hypothesized, 54.0% of smoking-related cancer diagnoses, 39.8% of circulatory disease diagnoses, and 26.6% of peptic ulcer cases were attributable to current, former, or passive smoking at year 0. We also addressed the total burden of these diseases in nonsmokers and smokers. When we pooled smoking-related cancers, cardiovascular diseases, and peptic ulcer, we found the concomitant risk was significantly higher in current smokers (relative hazard (RH): 1.96; 95% confidence interval (CI): 1.42–2.70) than never smokers not exposed
to passive smoking. Twenty-one percent of the premature incidence for these diseases was attributable to current smoking and 32% to any passive, former, or current smoking. Although the relative risk of 1.32 for passive smoking was not statistically significantly greater than that for never smokers not exposed to passive smoking, their isolation increased the risk estimate for former and current smokers. Thus, compared to never smokers including passive smokers, the RH for smoking-related disease of current smoking was only 1.63 and the total attributable to any active or former smoking was 18.2%. Incidence rates for smoking-related diseases were 4.8/1000 person years higher in current smokers compared with never smoked not exposed to passive smoking. When we restricted cases to 2 or more self-reports or report only at their last examination, we found 282 cases of the composite smoking-related diseases. The risk was similar in magnitude (RH for current smoker: 1.71; 95% CI: 1.18–2.46, RH for former smoker: 1.43; 95% CI: 0.91–2.24, RH for passive smoker: 1.18; 95% CI: 0.82–1.71) compared with never smokers) to the results obtained when the single-mentioned cases were included. Risk of other ailments Several other conditions developed at a higher rate among those who were cigarette smokers at year 0. Prevalence of
196
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
Table 2 Relative hazards (RH) for incidence of several self-report diseases compared with never smokers who were also not passive smokers
All cancers
Smoking-related cancer c
Other cancers e
Circulatory diseases f
Peptic ulcer
Respiratory disease g
Smoke-related disease h
N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) PAF d N Event Event/1000 person years RH (95% CI) N Event Event/1000 person years RH (95% CI) PAF d
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
864 30 2.47 1 864 6 0.49 1
1600 68 3.05 1.38 (0.90–2.13) 1600 19 0.84 1.65 (0.66–4.16) 11.4% 1600 52 2.32 1.23 (0.77–1.96) 1607 49 2.13 1.50 (0.87–2.59) 10.5% 1551 73 3.37 1.21 (0.80–1.83) 5.6% 1442 202 10.46 1.09 (0.86–1.38) 1542 126 6.01 1.32 (0.95–1.82) 7.7%
519 25 3.49 1.27 (0.75–2.18) 519 11 1.51 3.31 (1.21–9.07) 11.6% 519 20 2.78 1.11 (0.62–1.99) 524 24 3.27 1.99 (1.07–3.68) 7.6% 489 19 2.72 0.98 (0.56–1.74) 0.0% 465 68 11.03 1.15 (0.84–1.56) 484 45 6.79 1.42 (0.95–2.12) 3.4%
1447 66 3.40 1.53 (0.98–2.40) 1447 30 1.53 3.16 (1.29–7.71) 31.1% 1447 46 2.35 1.27 (0.77–2.08) 1465 65 3.17 2.08 (1.21–3.55) 21.6% 1405 103 5.47 1.87 (1.24–2.80) 21.0% 1290 205 12.34 1.23 (0.96–1.57) 1382 166 9.29 1.96 (1.42–2.70) 20.8%
864 27 2.22 1 871 18 1.37 1.00 855 33 2.75 1 793 102 9.50 1 849 53 4.49 1
Results from Cox proportional hazard models. CARDIA 1985–2001. PAF is computed only for those disease categories where a causal relation to smoking is plausible. a Never smoked, serum cotinine b2 ng/mL and exposed to environmental smoking less than 7 h/week. b Never smoked, serum cotinine 2–13 ng/mL or exposed to environmental smoking 7 or more hours/week. c Cervical cancer (51), hematologic cancer (11), and stomach cancer (5). One case overlapped. d PAF: population attributable fraction; calculated separately for each disease category as p * (RH − 1) / RH where p = proportion of cases exposed to the risk factor. e Breast cancer (25 cases), testes cancer (2), bone cancer (4), melanoma (20), skin cancer (34), brain cancer (7), colon cancer (5), and other cancers cases (48). f Heart attack (21 cases), angina (26), stroke or transient ischemic attack (TIA) (35), peripheral vascular disease (PVD) (85). Eleven cases overlapped. g Asthma (454 cases), chronic bronchitis (153), and emphysema (3). 33 cases overlapped. h Smoking-related cancer, cardiovascular diseases, and peptic ulcer.
chronic cough or phlegm production at year 0 was higher in smokers (Table 3): 11% in never smokers not exposed to passive smoking vs. 40% in current smokers, adjusted odds ratio (OR): 5.20; 95% CI: 4.08–6.64. Ten-year incident cough and phlegm was 5% in never smokers not exposed to passive smoking vs. 16% in current smokers (adjusted OR 3.01; 95% CI: 1.98–4.58). The risk of new onset of cough and phlegm was also statistically significant for passive smoking (adjusted OR = 1.87; 95% CI: 1.24–2.82). There was also elevated risk for liver diseases (attenuated to RH 1.83 (1.07–3.13) after further adjustment for ethanol intake), migraine headache, and depression (Table 4). The risk of “being sick with cold, flu, or vomiting in the past 24 h” was marginally significantly increased. Also examined and not related to smoking were kidney, thyroid, and gallbladder diseases.
Discussion In this prospective study, we demonstrated that cigarette smoking was related to the incidence of smoking-related cancer, cardiovascular diseases, and peptic ulcer as hypothesized. If all relations reported here were causal, as might be suspected, and if excess risks among current smokers were eliminated, 21% or 81 of the 390 smoking-related disease events (smoking-related cancer, cardiovascular diseases, and peptic ulcer) would be avoided. Furthermore, if passive and former smoking were also eliminated, an additional 11% of smoking-related diseases could be preventable. Although the extent of disease suffered during 7 to 15 years of follow-up (at the end of which participants ranged in age from 25 to 46) was less than that reported in older adults (McCarron et al., 2001), we did find a 1.96-fold excess incidence rate among
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
197
Table 3 Relationship of smoking status with cough and phlegm using cross sectional and longitudinal analysis
Cross sectional Year 0
Longitudinal according to year 0 smoking (excluding cough and phlegm at year 0 and those not attending year 10) year 0–year 10
N Events Percent events OR (95% CI) N Events Percent events OR (95% CI)
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
870 95 10.9% 1.00 693 32 4.6% 1.00
1605 290 18.1% 1.78 (1.38–2.28) 1165 104 8.9% 1.87 (1.24–2.82)
524 91 17.4% 1.70 (1.24–2.32) 375 39 10.4% 2.50 (1.53–4.10)
1466 591 40.3% 5.20 (4.08–6.64) 745 116 15.6% 3.01 (1.98–4.58)
N: numbers of subjects, OR: odds ratio, CI: confidence interval. a Never smoked, serum cotinine b2 ng/mL and exposed to environmental smoking less than 7 h/week. b Never smoked, serum cotinine 2–13 ng/mL or exposed to environmental smoking 7 or more hours/week.
current smokers compared to never smokers not exposed to passive smoking. In this study, we demonstrated that participants who smoked at an early age (18–30 years) have substantial risks of smokingrelated cancers, cardiovascular diseases, and peptic ulcer within 7 to 15 years. Although other investigators have observed
similar findings (McCarron et al., 2001; Raitakari et al., 2003; Berenson et al., 1998; Paffenbarger et al., 1995; Navas-Nacher et al., 2001; Castle et al., 2002; Boffetta et al., 2001; Beckett et al., 2001; Strachan et al., 1996), the current data more comprehensively demonstrate the risks of several diseases after a relatively short smoking exposure and at a very young
Table 4 Relative hazards (RH) for incidence of several self-report conditions or diseases according to year 0 smoking status
Kidney disease
Migraine
Thyroid disease
Gallbladder disease
Liver disease
Depression c
Being ill in the past 24 h
N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI) N Events Event/1000 person years RH (95% CI)
Never smoker (no passive smoking) a
Passive smoker b
Former smoker
Current smoker
844 73 6.34 1.00 871 120 10.15 1.00 848 41 3.44 1.00 864 21 1.72 1.00 862 19 1.57 1.00 772 161 14.91 1.00 871 158 13.86 1.00
1544 120 5.71 0.93 (0.70–1.25) 1608 257 11.99 1.20 (0.97–1.50) 1588 66 2.97 0.92 (0.62–1.36) 1598 47 2.10 1.14 (0.68–1.92) 1593 42 1.89 1.25 (0.73–2.15) 1431 347 17.65 1.11 (0.92–1.34) 1608 336 16.11 1.21 (1.00–1.46)
506 44 6.40 0.96 (0.66–1.40) 524 91 13.17 1.23 (0.93–1.62) 512 33 4.66 1.24 (0.78–1.97) 520 15 2.06 1.08 (0.55–2.11) 516 16 2.22 1.19 (0.61–2.33) 440 87 14.24 0.96 (0.74–1.25) 524 107 15.60 1.12 (0.87–1.43)
1389 124 6.81 1.11 (0.82–1.50) 1469 261 13.77 1.35 (1.08–1.68) 1434 51 2.62 0.85 (0.56–1.30) 1452 51 2.59 1.30 (0.77–2.19) 1454 75 3.85 2.08 (1.23–3.52) 1226 394 24.20 1.36 (1.13–1.65) 1469 295 16.12 1.22 (1.00–1.49)
Results from Cox proportional hazard models. CARDIA 1985–2001. Adjusted for age at baseline, sex, race, center, and education. N: number of subjects; RH: relative hazards; CI: confidence interval. a Never smoked, serum cotinine b2 ng/mL and sum of hours/week exposed to environmental smoking less than 7. b Never smoked, serum cotinine 2–13 ng/mL or sum of hours/week exposed to environmental smoking was 7 and more. c Assessed by CES-D, subjects who attended year 10 or year 15 at least one time.
198
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199
age of follow-up. One comprehensive study reported eventual risk of dying in young smokers, but they followed for 41.3 years and did not assess when in that follow-up period the harmful effect was first seen (McCarron et al., 2001). The CARDIA study showed a significant difference in total and AIDS mortality between smokers and nonsmokers aged 18–30 during a median 13 years follow-up (Iribarren et al., 2005). Consistent with both the current and the previous (Iribarren et al., 2005) CARDIA report, Doll et al. (2004) reported that the mortality ratio (cigarette smoker vs. nonsmoker) was lowest in their youngest age group (relative risk: 1.6, 2.3, 2.5, 2.7, and 2.2 for age groups 35–44, 45–54, 55–64, 65–74, and 75–84, respectively). They (Doll et al., 2004) also reported smokers who quit before 44 years of age had a survival rate not different from nonsmokers and from early quitters, consistent with our finding of limited excess risk among former smokers. Since recent studies reported that passive smoking causes several smoking-related diseases (Whincup et al., 2004; Vineis et al., 2005), traditional analyses, which pool passive smokers and those never smokers not exposed to passive smoking as the reference group, likely underestimate the risk of smoking. Using never smokers not exposed to passive smoke as the reference, we showed that 32% of smoking-related diseases were preventable, 14% higher than parallel traditional analyses. Thus, smoking prevention and cessation should yield better health for both passive and active smokers, in line with apparent reductions in disease rates after smoking was banned from bars and restaurants in Ireland (Anonymous, 2005). Our study has some limitations. First, CARDIA collects medical records for event validation only for deaths and hospitalized circulatory and respiratory diseases; we used the much more extensive CARDIA data subset of self-reported clinical diagnoses. These self-reports likely include some false positives and miss some true positives. When we used stricter criteria for disease, the magnitude of the excess risk of smoking did not change. We were able to validate a few of the circulatory cases and showed that about half of the circulatory and cancer self-reports occurring by year 10 were confirmed in a later examination. If, as is likely, the probability of reporting false positively is unrelated to smoking, our estimates are smaller than the true risk. Use of the full database of self-report of various diseases and conditions did allow a broad examination of smoking risks. Second, we excluded the participants who did not attend any of the year 7, year 10, or year 15 visits. Because 45% of these non-responders were smokers, compared to 33% of included participants, they were likely to have a worse health status than were participants who attended these visits, and our estimate of the risks of cigarette smoking on health conditions may again be underestimated. Third, we cannot completely rule out residual confounding, although adjustment for age, race, sex, education, blood pressure, plasma lipids, and alcohol intake did not alter our findings. Fourth, since we did not specifically query other smoking-related cancers, including bladder, oral, esophagus, kidney, laryngeal, and pancreas cancer, we did not include these cancers as smoking-related cancers; however, there would be extremely few of these cancers in this young cohort, just as there were no reported lung cancers.
In conclusion, we find that major and minor smoking-related ailments are not limited to older adults but also occur in excess among young adult smokers. About a third of these serious disease outcomes (and many less serious ailments) among the young adults in our cohort could have been prevented by not smoking and avoiding passive smoke. Thus, even young adults need to worry about smoking, that is, serious adverse health effects from cigarette smoking do occur after only a few years of exposure. Younger smokers must be advised to quit and nonsmokers never to begin smoking and to avoid passive smoke to maintain better health. Acknowledgments Supported in part by National Heart, Lung, and Blood Institute contracts N01-HC-48047, N01-HC-48048, N01-HC48049, N01-HC-48050, and N01-HC-95095 (CARDIA). Dr. Hozawa was also supported by a grant to the Japan Society for the Promotion of Science (JSPS) Research (14010301) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the BANYU FELLOWSHIP PROGRAM sponsored by Banyu Life Science Foundation International. References Anonymous, 2005. Ireland's smoking ban is an admirable achievement. Lancet 365, 1282. Beckett, W.S., Jacobs Jr., D.R., Yu, X., Iribarren, C., Williams, O.D., 2001. Asthma is associated with weight gain in females but not males, independent of physical activity. Am. J. Respir. Crit. Care Med. 164, 2045–2050. Berenson, G.S., Srinivasan, S.R., Bao, W., Newman III, W.P., Tracy, R.E., Wattigney, W.A., 1998. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N. Engl. J. Med. 338, 1650–1656. Boffetta, P., Kreuzer, M., Benhamou, S., et al., 2001. Risk of lung cancer from tobacco smoking among young women from Europe. Int. J. Cancer 91, 745–746. Castle, P.E., Wacholder, S., Lorincz, A.T., et al., 2002. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J. Natl. Cancer Inst. 94, 1406–1414. CDC, 2000. Cigarette smoking among adults—United States, 1998. MMWR Recomm. Rep. 49, 881–884. CDC, 2004. Cigarette smoking among adults—United States, 2002. MMWR Recomm. Rep. 53, 427–431. Doll, R., Peto, R., Boreham, J., Sutherland, I., 2004. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ 328, 1519. Friedman, G.D., Cutter, G.R., Donahue, R.P., et al., 1988. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J. Clin. Epidemiol. 41, 1105–1116. Iribarren, C., Jacobs, D.R., Kiefe, C., 2005. Causes and demographic, medical, lifestyle and psychological predictors of premature mortality: the CARDIA study. Soc. Sci. Med. 60, 471–482. McCarron, P., Smith, G.D., Okasha, M., McEwen, J., 2001. Smoking in adolescence and young adulthood and mortality in later life: prospective observational study. J. Epidemiol. Community Health 55, 334–335. Navas-Nacher, E.L., Colangelo, L., Beam, C., Greenland, P., 2001. Risk factors for coronary heart disease in men 18 to 39 years of age. Ann. Intern. Med.134, 433–439. Paffenbarger Jr., R.S., Wing, A.L., Hyde, R.T., 1995. Physical activity as an index of heart attack risk in college alumni 1978. Am. J. Epidemiol. 108, 161–175.
A. Hozawa et al. / Preventive Medicine 42 (2006) 193–199 Radloff, L.S., 1977. The CES-D scale: a self-report depression scale for research in the general population. Appl. Psychol. Meas. 1, 385–401. Raitakari, O.T., Juonala, M., Kahonen, M., et al., 2003. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 290, 2277–2283. Rockhill, B., Newman, B., Weinberg, C., 1998. Use and misuse of population attributable fractions. Am. J. Public Health 88, 15–19. Strachan, D.P., Butland, B.K., Anderson, H.R., 1996. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ 312, 1195–1199. U.S. Department of Health and Human Services, 1994. Preventing Tobacco Use Among Young People: a report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.
199
U.S. Department of Health and Human Services, 2000. Healthy People 2010, 2nd ed. With understanding and improving health and objectives for improving health (2 vols.). Washington, DC: U.S. Department of Health and Human Services, (objective 27.1a). U.S. Department of Health and Human Services, 2004. The health consequences of smoking: a report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Vineis, P., Airoldi, L., Veglia, P., Olgiati, L., Pastorelli, R., Autrup, H., et al., 2005. Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ 330, 277. Whincup, P.H., Gilg, J.A., Emberson, J.R., et al., 2004. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ 329, 200–205.