CORRESPONDENCE: RESEARCH CORRESPONDENCE
The Underestimated Impact of Smoking and Smoking Cessation on the Risk of Secondary Cardiovascular Disease Events in Patients With Stable Coronary Heart Disease: Prospective Cohort Study
Dorothee Twardella, DrPH, MPH,
Dietrich Rothenbacher, MD, MPH,
Harry Hahmann, MD,
Bernd Wüsten, MD and
Hermann Brenner, MD, MPH*
* German Center for Research on Ageing, Bergheimerstr. 20, 69115 Heidelberg, Germany (Email: brenner{at}dzfa.uni-heidelberg.de).
To the Editor: Numerous studies have reported beneficial effects of smoking cessation in terms of decreased cardiovascular morbidity and mortality in patients with coronary heart disease (1). However, all of these studies primarily relied on self-reported smoking status. Additionally, changes in smoking status during follow-up were often not considered in the analysis. Both limitations bear the potential for misclassification of smoking behavior and thus for dilution of differences between continuous smokers and quitters and for underestimation of the beneficial effect of smoking cessation. The aim of our analysis was to assess the impact of smoking and smoking cessation on the risk of secondary cardiovascular disease (CVD) events by combining self-reported smoking data with measurements of a biomarker for active smoking (serum cotinine), and by accounting for changes in smoking status during the follow-up period.
We conducted a prospective cohort study among 1,206 patients (58% of eligible) age 30 to 70 years participating in a 3-week in-patient rehabilitation (rehab) in two rehab clinics in Germany several weeks after acute manifestation of coronary heart disease (CHD) (2). Baseline data were collected at rehab admission and discharge, and active follow-up was conducted one and three years after rehab discharge. Four methods were used to categorize participants according to their smoking status:
- A Self-reported smoking status at the beginning of rehab only: never smokers, former smokers (ex-smokers who had quit before the acute manifestation of CHD), recent quitters (ex-smokers who quit after the acute manifestation of CHD), or continued smokers (smokers who did not quit until the beginning of rehab).
- B Serum cotinine levels at rehab discharge:
 15 ng/ml = smoker; <15 ng/ml = nonsmoker (3).
- C Baseline smoking status based on both self-report and serum cotinine measurements: Analogous to (A), but patients were reclassified as continued smokers if they were cotinine positive at rehab discharge, and self-reported continued smokers were reclassified as recent quitters, if they were cotinine negative at the end of rehab.
- D Analogous to (C), but patients who changed smoking status during follow-up (according to serum cotinine at one-year follow-up) were excluded.
Secondary CVD events during follow-up were defined as death from CVD (International Classification of Diseases, 9th revision, positions 390 to 459) or a nonfatal myocardial infarction or ischemic cerebrovascular event (stroke or transient ischemic attack), both as reported by the primary care physician.
To study associations between smoking status and the occurrence of secondary CVD events during the first three years after rehab discharge, we employed the Cox proportional hazards model using the SAS procedure PHREG (SAS Institute, Cary, North Carolina). Associations were derived in bivariate and multivariable models, with adjustment for those variables that were shown to be important in a forward selection procedure (two-sided p value of the log-likelihood statistic <0.2).
A total of 1,029 patients with complete data on self-reported smoking and cotinine levels and follow-up data on CVD events (85% of the 1,206 recruited participants) were included in analysis. Median follow-up time was 1,137 days. Mean age was 59 years, 85% were male, and 58% had suffered a myocardial infarction. According to self-report at rehab admission, about one-third of patients had never smoked regularly (Table 1). Among self-reported current smokers, 44% were cotinine negative at rehab discharge, suggesting smoking cessation during rehab, and 26%, 10%, and 6% of self-reported recent quitters, former smokers, and never smokers, respectively, were cotinine positive, indicating relapse during rehab or misreporting of smoking status. After reclassification of all cotinine-positive patients to continued smokers and cotinine-negative self-reported smokers to recent quitters, 30% of participants were categorized as never smokers, 40% as former smokers, about 15% as recent quitters, and 15% as continued smokers.
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Table 1. Self-Reported Smoking Status at the Beginning of Rehabilitation and Smoking Status According to Cotinine Level at the End of Rehabilitation
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Among the participants categorized as continued smokers at rehab, 37% stopped smoking during the first year after rehab, and 39% of recent quitters, 13% of former smokers, and 9% of never smokers were found to be cotinine positive at one-year follow-up.
During the three-year follow-up period, 68 patients were affected by secondary CVD events, of which 17 were fatal. Independent of the definition, smoking status was associated with the occurrence of a secondary CVD event, but the strength of association increased with increasing strictness of definition (Table 2). In the final adjusted analysis, the hazard ratios were 0.42 for recent quitters, 0.51 for former smokers, and 0.26 for never smokers compared to continued smokers (p value for trend 0.005).
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Table 2. Association Between Smoking and Fatal or Nonfatal Secondary CVD Events in Patients with CHD According to Definition of Smoking Status
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Our results are in line with findings reported in a recently published meta-analysis (1) and corroborate and strongly extend earlier findings from the same cohort regarding the short-term effects of smoking (2). In this previous analysis, which had been restricted to secondary CVD events during the first year after discharge from rehab and which had included coronary artery revascularization procedures besides myocardial infarction, stroke, and CVD death as end points, we also had observed a decreased risk in patients who never smoked (odds ratio [OR] = 0.44), who reported former smoking (OR = 0.64), and who were categorized as recent quitters (OR = 0.71) in comparison with continued smokers. The current study, which is based on a much longer follow-up, an exclusive focus on "hard" disease endpoints, and the use of repeated measurements of smoking status, suggests that pertinent risk reductions may be even stronger in the long run.
The proportions of cotinine-positive subjects in the group of self-reported never smokers at rehab (6%) and at one-year follow-up (9%) may serve as estimates for the proportion of deceivers (persons misreporting their smoking status). Although false-positive test results cannot be ruled out, exposure to environmental tobacco smoke, which may have a major impact on prognosis, is unlikely to cause a serum cotinine level as high as our cutpoint (4). The finding that 20% of patients changed smoking status in the first year of follow-up further underlines the relatively high dynamics of smoking status shortly after the occurrence of CHD.
We conclude that the impact of smoking abstinence on long-term prognosis of patients with CHD may be considerably larger than suggested by previous studies which relied on self-reports of smoking status. Our results underline the importance of efforts to support smoking cessation and to prevent relapse in patients with coronary heart disease.
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Footnotes
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Please note: Funded by German Federal Ministry of Education and Research, grant number 01 GD 0820/0, and Association of German Pension Fund Agencies, grant number 02 7 08.
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References
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1. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease Cochrane Database Syst Rev 2004;1CD003041.2. Twardella D, Küpper-Nybelen J, Rothenbacher D, Hahmann H, Wüsten B, Brenner H. Short-term benefit of smoking cessation in patients with coronary heart diseaseestimates based on self-reported smoking data and serum cotinine measurements. Eur Heart J 2004;25:2101-2108.[Abstract/Free Full Text] 3. Seccareccia F, Zuccaro P, Pacifici R, et al. Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studiesthe experience of the MATISS project. Eur J Epidemiol 2003;18:487-492.[CrossRef][Web of Science][Medline] 4. Whincup PH, Gilg JA, Emberson JR, et al. Passive smoking and risk of coronary heart disease and strokeprospective study with cotinine measurement. BMJ 2004;329:200-205.[Abstract/Free Full Text]
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