Published online before print March 6, 2008, doi: 10.1161/STROKEAHA.107.505305
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(Stroke. 2008;39:1688.)
© 2008 American Heart Association, Inc.
Original Contributions |
Cigarette Smoking and Risk of Stroke in the Chinese Adult Population
From the Department of Epidemiology (T.N.K., J.C., C.-S.C., J.H.), Tulane University School of Public Health and Tropical Medicine, and the Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, La; and the Cardiovascular Institute and Fuwai Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College (D.G., J.-F.H., J.-C.C., X.D., X.W.), Beijing, China.
Correspondence to Jiang He, MD, PhD, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Avenue SL18, New Orleans, LA 70112. E-mail jhe{at}tulane.edu
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Abstract |
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Background and Purpose— We studied the relationship between cigarette smoking and stroke incidence and mortality in the Chinese adult population.
Methods— We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged 40 years and older. Data on cigarette smoking and other covariables were collected at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 to 2000, with a response rate of 93.4%.
Results— During an average of 8.3 years follow-up, a total of 6780 stroke events (3979 fatal strokes) were observed. The multivariate-adjusted relative risks (95% confidence interval) of stroke incidence and mortality associated with present cigarette smoking were 1.28 (1.19 to 1.37) and 1.13 (1.03 to 1.25) in men and 1.25 (1.13 to 1.37) and 1.19 (1.04 to 1.36) in women, respectively. The corresponding population attributable risks were 14.2% and 7.1% in men and 3.1% and 2.4% in women. Compared to never-smokers, the multivariate-adjusted relative risks of stroke incidence (95% confidence interval) were 1.21 (1.12 to 1.31), 1.21 (1.11 to 1.32), and 1.36 (1.25 to 1.47) for those who smoked 1 to 9, 10 to 19, and 
20 cigarettes per day; and 1.18 (1.09 to 1.28), 1.25 (1.15 to 1.35), and 1.34 (1.24 to 1.44) for those who smoked 1 to 11, 12 to 26, and >26 pack-years, respectively (both P<0.0001 for linear trends).
Conclusions— Our study identified a positive and dose-response relationship between cigarette smoking and risk of stroke. Smoking prevention and cessation programs should be an important strategy for reducing the burden of stroke in Chinese adults.
Key Words: smoking • stroke • relative risk • Chinese
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Introduction |
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Stroke is the second leading cause of deaths and the leading cause of long-term disability worldwide.1 In 2005, stroke caused an estimated 5.7 million deaths, and 87% of these deaths were in low-income and middle-income countries.2 Without intervention, the number of global stroke deaths is projected to rise to 6.5 million in 2015 and to 7.8 million in 2030, and the majority of these deaths will be borne by low-income and middle-income countries, especially by China.2
Cigarette smoking is an important risk factor for all-cause mortality as well as vascular disease mortality.1,3 Many prospective cohort studies conducted in Western populations have indicated a strong and independent relationship between cigarette smoking and risk of stroke.4,5 However, this relationship has not been well established in Asian populations.6,7 With a population of 1.3 billion, China is the world’s largest producer and consumer of tobacco.8 Establishing the association between cigarette smoking and risk of stroke in the Chinese population will enable the development of an effective prevention strategy aimed at reducing stroke-related mortality and disability burden in China.
The purpose of the present study was to examine the relationship between cigarette smoking and stroke incidence and mortality in a large population-based prospective cohort of Chinese adults. In addition, this study investigated the dose-response and gender-specific effects of cigarette smoking on the risk of stroke.
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Materials and Methods |
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Study Population
In 1991, the third China National Hypertension Survey was carried out in all 30 provinces of mainland China using a multi-stage random cluster sampling design to select a nationally representative sample of Chinese adults aged 15 years or older.9 In 1999 to 2000, investigators from each province were invited to participate in follow-up study. Of the 30 provinces, 13 were not included in the follow-up study because study participants’ contact information was not available. Overall, 83 533 men and 86 338 women aged 40 years or older at their baseline examination were eligible to participate in the follow-up study. From this population, a total of 158 666 (93.4%) study participants (or their proxies) were identified and interviewed as part of the follow-up study. In this report, study participants missing information on cigarette smoking status (n=14 578) were excluded from all analyses, and those with prevalent stroke (n=2291) were excluded from the analysis of stroke incidence. Participants included in the final analysis were not different from the overall study population in 1991 regarding their baseline characteristics.
Baseline Examination
Baseline data were collected at a single clinic visit by specially trained physicians and nurses using standardized methods with stringent levels of quality control.9 Data on demographic characteristics, medical history, and lifestyle risk factors were obtained using a standard questionnaire administered by trained staff. Cigarette smoking was defined as having smoked at least 1 cigarette per day for 1 year or more. For participants who reported past or present cigarette smoking, information on the number of cigarettes smoked per day along with the duration of cigarette smoking was also collected. Work-related physical activity was assessed, because leisure-time physical activity was uncommon. Alcohol consumption was defined as drinking alcohol at least 12 times during the last year. Body weight and height were measured in light indoor clothing without shoes according to a standardized protocol. Body mass index (BMI) was calculated as weight in kilograms divided by height in square meters. Three blood pressure (BP) measurements were taken after the study participant had been seated quietly for 5 minutes using a standard mercury sphygmomanometer according to a standard protocol.10 The mean of 3 systolic BP (SBP) measures was used in all analyses.
Follow-Up Data Collection
The follow-up examination, which was conducted between 1999 and 2000, included tracking study participants or their proxies to a present address, performing in-depth interviews to ascertain disease status and vital information, and obtaining hospital records and death certificates. If a study participant reported a hospitalization or emergency room overnight-stay attributable to stroke during the in-person interview, participant’s hospital records, including medical history, physical examination findings, laboratory test results, CT scan, MRI, discharge diagnosis, or autopsy reports were abstracted by trained staff using a standard form. All deaths reported during the in-person interview were verified by obtaining death certificates from the local public health department or police department. If death occurred during a hospitalization, the participant’s hospital records and autopsy results were also abstracted by trained staff using a standard form. If death occurred outside of the hospital, detailed information on medical history was obtained from a family member or healthcare provider. An end point assessment committee within each province reviewed all abstracted information to confirm or reject the occurrence of study outcomes using preestablished criteria.11
A study-wide end point assessment committee at the Chinese Academy of Medical Sciences in Beijing, China reviewed all hospital records and death certificates and determined the final diagnosis of event or the underlying cause of death. Two committee members independently verified the diagnosis, and discrepancies were adjudicated by discussion involving additional committee members. All members of the local and study-wide end point assessment committees were blinded to the study participant’s baseline risk factor information. Causes of death were coded according to the International Classification of Diseases, Ninth Revision (ICD-9). For this analysis, stroke incidence was defined as a confirmed diagnosis of stroke during the follow-up period or stroke listed as an underlying cause of death (ICD-9 430.0 to 438.9) among those without a history of stroke. Stroke mortality was defined as stroke listed as an underlying cause of death among all study participants. Of the 6780 stroke events, CT or MRI was available for 4430 (65.3%) stroke cases.
This study was approved by the Tulane University Health Sciences Center Institutional Review Board and the Cardiovascular Institute and Fu Wai Hospital Ethics Committee. Written informed consent was obtained from all study participants at their follow-up visit.
Statistical Analysis
Baseline characteristics were compared between present and former smokers and never-smokers using 
2 tests for categorical variables and ANOVA for continuous variables. Person-years of follow-up were calculated from the date of baseline examination until the date of stroke, death, or follow-up interview for each study participant. Age-standardized incidence and mortality were calculated using the 5-year age-specific incidence and mortality and the age distribution of the Chinese population from year 2000 census data.
Cox proportional hazards regression models were used to examine the association between smoking and stroke adjusted for baseline age, sex, education, alcohol consumption, physical activity, SBP, BMI, geographic region (north versus south), urbanization (rural versus urban), baseline cardiovascular disease (CVD), and the prevalence of diabetes at baseline as well as new onset diabetes during follow-up. Multivariate-adjusted relative risks were calculated using never-smokers as the reference category. The population attributable risks (PAR), measured as the percentage of stroke events or deaths that could be prevented if present cigarette smoking was eliminated in the population, were calculated. Dose-response relationships for present smokers were investigated using never-smokers as the reference group compared to 3 levels of daily cigarettes smoked (1 to 9, 10 to 19, and 20 cigarettes per day) and tertiles of pack-years (1 to 11, 12 to 26, and >26 pack-years). Subgroup analyses by gender and stroke subtype were also conducted. Methods to estimate variances that take into account sample clustering were used in Cox proportional hazards models.12 Statistical analyses were conducted using SAS statistical software (version 9.1; SAS Institute Inc).
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Results |
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Baseline characteristics of study participants are presented in Table 1. Overall, 62.1% of study participants were never-smokers, 2.3% were former smokers, and 35.6% were present smokers, with the prevalence of present cigarette smoking higher in men compared to women (59.1% versus 13.0%).
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During an average of 8.3 years follow-up we documented a total of 6780 stroke events, including 3979 stroke deaths. After adjustment for important covariables, present cigarette smoking remained a significant predictor of stroke incidence and mortality in the overall and gender-specific analyses (Table 2). The PAR attributable to present cigarette smoking was 8.2% (95% CI 5.8% to 10.8%) of incident strokes and 4.8% (95% CI 1.5% to 8.0%) of stroke deaths in the total population. PAR estimates were higher for men than women, with present smoking accounting for 14.2% (95% CI 9.2% to 18.6%) of stroke events and 7.1% (95% CI 1.0% to 13.5%) of stroke deaths in men compared to 3.1% (95% CI 1.4% to 4.9%) of stroke events and 2.4% (95% CI 0.3% to 4.9%) of stroke deaths in women.
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Tables 3 and 4
present relative risks of stroke incidence and mortality in present compared to never-smokers according to the number of cigarettes smoked per day and pack-years smoked, respectively. There was a significant and linear association between both the number of cigarettes smoked per day and pack-years smoked and stroke incidence in the overall and gender-specific analyses (all probability values for linear trends <0.01). Although present smoking was associated with an increased risk of stroke mortality, the association did not seem to be in a dose-response fashion.
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In addition, we conducted analyses by subtype of stroke. Of the 6780 confirmed stroke events, 3409 (50.3%) were classified as ischemic, including 1097 fatal ischemic strokes, 2353 (34.7%) were classified as hemorrhagic, including 2002 fatal hemorrhagic strokes, 950 (14.0%) were of unknown subtype (not classified as either ischemic or hemorrhagic), and 68 were classified as both ischemic and hemorrhagic subtypes. Those classified as both were removed from the subtype analysis. There was a strong and graded association between cigarette smoking and risk of ischemic stroke. Compared to never-smokers, the multivariate-adjusted relative risks of ischemic stroke (95% CI) were 1.25 (1.12 to 1.40), 1.31 (1.17 to 1.47), and 1.51 (1.36 to 1.67) for those who smoked 1 to 9, 10 to 19, and 20 cigarettes per day; and 1.19 (1.05 to 1.34), 1.36 (1.22 to 1.52), and 1.47 (1.32 to 1.62) for those who smoked 1 to 11, 12 to 26, and >26 pack-years, respectively (both P<0.0001 for linear trends). A positive association between cigarette smoking and hemorrhagic stroke was also observed, with corresponding relative risks of 1.19 (1.05 to 1.36), 1.14 (0.98 to 1.32), and 1.20 (1.04 to 1.37) for those who smoked 1 to 9, 10 to 19, and 20 cigarettes per day; and 1.20 (1.05 to 1.37), 1.17 (1.01 to 1.35), and 1.18 (1.03 to 1.35) for those who smoked 1 to 11, 12 to 26, and >26 pack-years, respectively (both probability values for linear trends=0.007).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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This study documents an independent and dose-response relationship between cigarette smoking and stroke incidence in a large, nationally representative sample of the Chinese adult population. A significantly elevated risk of stroke mortality was also observed among present compared to never-smokers, although evidence for a linear relationship between smoking and stroke mortality was less clear. These results were consistent among men and women and highlight cigarette smoking as an independent risk factor for stroke in Chinese adults. In addition, these findings indicate that prevention and cessation of cigarette smoking could reduce stroke morbidity and mortality by 8.2% and 4.7%, respectively, in the Chinese adult population.
Our study has several important strengths. It is the first large prospective cohort examining the association between cigarette smoking and risk of stroke in a population-based, nationally representative sample of Chinese adults. Information on baseline cigarette smoking, other covariables, and stroke outcomes were assessed using stringent quality control procedures, and a very high follow-up rate was attained. Our study also has certain limitations. Information on cigarette smoking was not collected in 2 provinces. Therefore, a relatively large number of study participants are missing information on cigarette smoking. However, it is unlikely that this type of missing information will bias the reported association in our study. In addition, data on cigarette smoking were collected only at the baseline examination, and therefore, changes in smoking status over the follow-up period could not be assessed. Moreover, data on serum lipids, diet, and leisure time physical activity were not obtained. Lack of adjustment for these variables may have resulted in a slight overestimate of the relative risk of stroke.
Whereas a positive association between cigarette smoking and stroke incidence and mortality have been established in Western populations, with relative risks of stroke ranging from 1.33 to 2.50 for present compared to never smokers,4,5,13,14 contradictory findings have been reported in Asian cohorts.6,15,16 Our study found a significantly increased risk of stroke incidence and mortality associated with present cigarette smoking, which has also been observed in other Japanese and Chinese populations.16–18 A recent study involving more than 500 000 participants from the Asia-Pacific region identified a 32% increased risk for stroke in present compared to never smokers, which was similar to our observation.7 In addition, our study identified a dose-response relationship between present cigarette smoking and stroke incidence. These results were consistent when considering both cigarettes smoked per day and pack-years smoked and in gender-subgroup and stroke subtype analyses. The dose-response relationship was also reported in prospective studies conducted in Western populations,4,5 in a Japanese cohort, and in Chinese patients with isolated systolic hypertension.7,17,18
Our study did not find strong evidence for a dose-response relationship between cigarette smoking and stroke mortality, despite a significantly increased risk of stroke death among present compared to never-smokers. Similar results were reported from 2 cohort studies conducted in Shanghai, China.6,15 In contrast, studies conducted in Western populations have identified significant positive linear relationships between smoking and stroke deaths.5,19,20 These differences could reflect true heterogeneity between populations. For example, hemorrhagic stroke accounts for less than 20% of all strokes in Western populations.21 However, approximately 30% to 40% of incident strokes and 50% of stroke deaths were hemorrhagic in the Chinese population.22 In the present study, hemorrhagic strokes accounted for only 34.7% of incident stroke cases but made up 50.3% of all stroke deaths, and a stronger dose-response relationship between cigarette smoking and ischemic compared to hemorrhagic stroke was observed.
Some studies have identified a stronger association between cigarette smoking and the risk of stroke in women compared to men.23,24 Conversely, gender subgroup analyses presented here indicate that the risk of stroke associated with cigarette smoking is consistent across genders, which are similar to results reported elsewhere.7,19 Despite the similar relative risks of cigarette smoking between genders, we found that cigarette smoking was responsible for approximately 14.2% of strokes in men compared to only 3.1% of strokes in women, which is consistent with past findings.25 This difference is attributed to the much higher prevalence of cigarette smoking in men than women (59.1% versus 13.0%, respectively).
In conclusion, these findings indicate an independent and graded association between cigarette smoking and the risk of stroke in Chinese men and women. These results, combined with the large stroke burden and high prevalence of cigarette smoking in China, highlight the importance of smoking prevention and cessation programs. Implementation of such public health initiatives might be a vital component for reducing stroke morbidity and mortality in Chinese adults.
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Acknowledgments |
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Sources of Funding
This study was supported by a national Grant-in-Aid (9750612N) from the American Heart Association, Dallas, Tex, and partially supported by a grant (R01 HL68057) from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Md, and by a grant (1999-272) from the Chinese Ministry of Health, Beijing, China, and by the Chinese Academy of Medical Sciences, Beijing, China.
Disclosures
None.
Received September 26, 2007; revision received November 11, 2007; accepted November 21, 2007.
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