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Background With China's rapid economic development, the disease burden may have changed in the country. We studied the major causes of death and modifiable risk factors in a nationally representative cohort of 169,871 men and women 40 years of age and older in China.
Methods Baseline data on the participants' demographic characteristics, medical history, lifestyle-related risk factors, blood pressure, and body weight were obtained in 1991 with the use of a standard protocol. The follow-up evaluation was conducted in 1999 and 2000, with a follow-up rate of 93.4 percent.
Results We documented 20,033 deaths in 1,239,191 person-years of follow-up. The mortality from all causes was 1480.1 per 100,000 person-years among men and 1190.2 per 100,000 person-years among women. The five leading causes of death were malignant neoplasms (mortality, 374.1 per 100,000 person-years), diseases of the heart (319.1), cerebrovascular disease (310.5), accidents (54.0), and infectious diseases (50.5) among men and diseases of the heart (268.5), cerebrovascular disease (242.3), malignant neoplasms (214.1), pneumonia and influenza (45.9), and infectious diseases (35.3) among women. The multivariate-adjusted relative risk of death and the population attributable risk for preventable risk factors were as follows: hypertension, 1.48 (95 percent confidence interval, 1.44 to 1.53) and 11.7 percent, respectively; cigarette smoking, 1.23 (95 percent confidence interval, 1.18 to 1.27) and 7.9 percent; physical inactivity, 1.20 (95 percent confidence interval, 1.16 to 1.24) and 6.8 percent; and underweight (body-mass index [the weight in kilograms divided by the square of the height in meters] below 18.5), 1.47 (95 percent confidence interval, 1.42 to 1.53) and 5.2 percent.
Conclusions Vascular disease and cancer have become the leading causes of death among Chinese adults. Our findings suggest that control of hypertension, smoking cessation, increased physical activity, and improved nutrition should be important strategies for reducing the burden of premature death among adults in China.
Cross-sectional studies, which provide a point estimate of disease burden, have indicated that the prevalence of chronic diseases and their risk factors has increased in developing countries.6,7,8 However, large, prospective cohort studies involving representative samples of the general population are needed to provide valid information on cause-specific mortality in the populations of these countries and to provide a scientific basis for rational allocation of health care resources. We conducted a large, prospective cohort study involving a representative sample of the general adult population 40 years of age and older in China to determine cause-specific mortality and to examine major preventable risk factors for total mortality.
Methods
Study Population
In 1991, a multistage, random cluster-sampling design was used to identify a representative sample of the general Chinese population 15 years of age and older from all 30 provinces for the China National Hypertension Survey.9 In 1999, investigators from each province were invited to participate in the China National Hypertension Survey Epidemiology Follow-up Study. Of the 30 provinces included in the initial study, 13 were not included in the follow-up study because contact information for the study participants in those provinces was not available. However, sampling was conducted independently within each province for the 1991 China National Hypertension Survey, and study participants in the 17 provinces that were included in the follow-up study were evenly distributed among the different geographic regions of the entire country representing various stages of economic development. Therefore, our study participants probably represent the general adult population in China. Overall, 83,533 men and 86,338 women who were 40 years of age or older at the time of their baseline examinations were eligible for participation in the follow-up study. Of these, a total of 158,666 participants or their proxies (93.4 percent) were identified and interviewed as part of the follow-up study.
Baseline Examination
Baseline data were collected during a single clinic visit by physicians and nurses trained in the use of standard methods and with stringent quality control.9 Data on demographic characteristics, medical history, and lifestyle-related risk factors were obtained. The assessment of physical activity involved only work-related physical activity. Cigarette smoking was defined as smoking at least one cigarette per day for one or more years. Data were collected on the amount and type of alcohol consumed during the previous year.
Three blood-pressure readings, measured with the use of a mercury sphygmomanometer according to a standard protocol, were obtained after the participant had been sitting quietly for five minutes.10 The first and fifth Korotkoff sounds were recorded as systolic and diastolic blood pressure, respectively. Hypertension was defined as one or more of the following: a mean systolic blood pressure greater than or equal to 140 mm Hg, a mean diastolic blood pressure greater than or equal to 90 mm Hg, or the use of antihypertensive medication.11 Body weight and height were measured when the participant was wearing light indoor clothing but not shoes, with the use of a standard protocol. Underweight was defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of less than 18.5 and overweight or obesity as a body-mass index of 25.0 or greater.12
Follow-up Data
Follow-up examinations, which were conducted in 1999 and 2000, included tracking participants or their proxies to a current address; conducting in-depth interviews to obtain information on the history of disease, hospitalizations, and death; and obtaining hospital records and death certificates. All deaths identified in interviews with participants' proxies were verified by death certificates obtained from the local departments of public health or police. If death occurred while a participant was hospitalized, the participant's hospital records, including medical history, findings on physical examination, laboratory findings, autopsy findings, and discharge diagnosis, were abstracted by trained staff using a standard form. In addition, photocopies of selected sections of the participant's inpatient record, discharge summary, electrocardiogram, and pathology reports were obtained.
An end-point assessment committee in each province reviewed and confirmed (or rejected) the hospital's discharge diagnosis and the cause of death on the basis of the abstracted information, using prespecified criteria. A study-wide end-point assessment committee at the Chinese Academy of Medical Sciences in Beijing reviewed all death records and determined the final underlying cause of death. Two committee members independently of each other verified the cause of death, and discrepancies were adjudicated by discussion involving other members of the committee. All members of the local and study-wide end-point assessment committees were unaware of information about the baseline risk factors of the study participants. The causes of death were coded according to the International Classification of Diseases, Ninth Revision (ICD-9).
The current study was approved by the Tulane University Health Sciences Center's institutional review board. Written informed consent was obtained from all study participants at their follow-up visit.
Statistical Analysis
Person-years of follow-up were calculated for each study participant and grouped according to sex and to age in five-year categories. Age-standardized mortality was calculated with the use of the five-year age-specific mortality and the age distribution of the Chinese population, obtained from the 2000 census data. Age-standardized cause-specific mortality was calculated separately for men and women, for residents of urban and rural areas, and for those living in northern and southern China, where diet and other lifestyle-related risk factors were different.13 For example, the dietary intake of sodium was higher among residents of northern China, as compared with those of southern China, whereas physical activity was lower.
Cox proportional-hazards models were used to estimate the relative risk of death for preventable risk factors. Heavy alcohol consumption (i.e., three or more drinks per day) was not related to an increase in total mortality, but we included alcohol consumption as a covariate because it was strongly related to other risk factors included in the study. A self-reported history of diabetes was also included as a covariate, because it was significantly associated with total mortality. Because the total mortality for current and former cigarette smokers was similar, the relative risk of ever having smoked as compared with never having smoked was calculated. As compared with normal weight (a body-mass index of 18.5 to 24.9), overweight or obesity was not associated with increased mortality. In contrast, because underweight was associated with increased total mortality, the relative risk of underweight was estimated.
In the final multivariate models, all preventable risk factors, such as hypertension, cigarette smoking, physical inactivity, and underweight, as well as the covariates, including baseline age, sex, the presence or absence of a high-school education, alcohol consumption, self-reported history of diabetes, geographic region (north vs. south), and urbanization (urban vs. rural residence), were included simultaneously. The population attributable risk, measured as the percentage of deaths that could be prevented in the total population if the risk factor of interest were eliminated, was calculated.14 Statistical analyses were conducted with the use of SAS software, version 8 (SAS Institute).
Results
The baseline characteristics of the study participants according to sex are presented in Table 1. Overall, 49.2 percent of the study participants were men and 50.8 percent were women. The mean age was 55.8 years, with a range from 40 to 105 years.
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Our study indicates that diseases of the heart, malignant neoplasms, and cerebrovascular disease are the leading causes of death in the Chinese population of adults 40 years of age and older. Together, these causes accounted for approximately two thirds of the total mortality in the study population.
These findings have important public health implications. Historically, infant mortality and death from infectious diseases have been the major causes of death in developing countries.15 Even in recent years, the public health priorities, which are set by government policymakers in these countries and by international agencies, have been to reduce infant and maternal mortality and to control infectious diseases.16,17 The results of the present study call for serious attention to be given to the consequences of chronic diseases in developing countries.
Few previous studies have reported cause-specific mortality in China.18,19,20 According to vital statistics available for 13 cities in China, diseases of the respiratory system, acute infectious diseases, and tuberculosis were the leading causes of death in 1957, accounting for 16.9 percent, 7.9 percent, and 7.5 percent of the total deaths, respectively. In the same period, diseases of the heart, cerebrovascular disease, and malignant neoplasms were the fifth, sixth, and seventh leading causes of death, accounting for 6.6 percent, 5.5 percent, and 5.2 percent of total deaths, respectively.18 Although there are differences in the reporting and classification of deaths between these studies and ours, our data support the notion that a transition in disease burden has occurred in China.
Typically, chronic diseases have been considered a public health problem only in developed countries and among the elderly.3 Our study suggests that chronic diseases affect a much higher proportion of people during their prime working years in China, as compared with developed countries.21 For example, the mortality was 265.9 per 100,000 person-years for malignant neoplasm, 171.5 per 100,000 person-years for cerebrovascular disease, and 159.1 per 100,000 person-years for diseases of the heart in the Chinese population 40 to 64 years of age in our study. In the U.S. population 45 to 64 years of age, the corresponding mortality rates in 2002 were 215.1, 23.8, and 150.5 per 100,000 person-years.21 The economic impact of chronic disease on society, including the direct costs of health care and the indirect costs resulting from lost productivity due to illness and death, is substantial. The higher number of deaths due to chronic disease among rural residents, as compared with urban residents, in China is a particular concern because of the scarce health care resources available in rural China and the fact that infant mortality and infectious diseases remain serious public health challenges in this setting.
Hypertension is the most common risk factor for cardiovascular and cerebrovascular diseases worldwide.6 The prevalence of hypertension has been increasing in China in recent decades, whereas rates of awareness, treatment, and control remain unacceptably low.22 Our results indicate that hypertension is the leading preventable risk factor for death among Chinese adults 40 years of age and older; total mortality was 48 percent higher among study participants who had hypertension than among those who did not have hypertension. Furthermore, our findings suggest that the prevention and control of hypertension could reduce the total mortality by 11.7 percent in the total study population. These results are consistent with other analyses that have suggested that hypertension is the leading risk factor for the global burden of disease.3,4
Our study also indicates that cigarette smoking is a major preventable risk factor for death in China. If cigarette smoking were eliminated, we estimate that the total mortality could be reduced by 10.0 percent among men and by 3.5 percent among women in China. This estimate does not take into account the possible effects of passive smoking.23 Our data are in agreement with those from several prospective cohort studies and case – control studies conducted in China, which have documented that cigarette smoking increases the mortality from cancer, respiratory disease, and cardiovascular disease.24,25,26,27,28 Although our study did not detect a significant difference in total mortality between current and former smokers, epidemiologic investigations indicate that a reduction in mortality occurs gradually after smoking is stopped.29 In our study, the average interval since a participant had stopped smoking was only seven years. In addition, we found that physical inactivity was related to an increase in total mortality in China. These findings suggest that increasing physical activity could play an important role in the reduction of total mortality in China.
Finally, our study identified underweight as a preventable risk factor for total mortality. The population attributable risk for underweight was slightly higher among rural residents than among urban residents. Underweight, which may reflect malnutrition, was reported as the leading cause of the disease burden in developing countries with high mortality and an important contributor to the burden of disease in developing countries with low mortality, in a recent report from the World Health Organization.30
Some limitations of our study should be noted. We did not collect data on dietary patterns, leisure-time physical activity, serum lipid levels or results of other laboratory tests, or changes in body weight (or changes in other risk factors) over time. Therefore, the contribution of these factors to total mortality could not be estimated. A diagnosis of diabetes was based only on self-reports; it is likely that this resulted in an underestimation of the population attributable risk of death due to diabetes. The lack of autopsy data to confirm causes of death may have introduced some misclassification bias. However, we maintained a very high follow-up rate and used a stringent approach to classifying outcomes on the basis of medical records.
In summary, our study indicates that diseases of the heart, malignant neoplasms, and cerebrovascular disease account for approximately two thirds of the total deaths in the Chinese population 40 years of age and older. Furthermore, hypertension, cigarette smoking, physical inactivity, and underweight are leading preventable risk factors for death. Control of hypertension, smoking cessation, increased physical activity, and improved nutrition are likely to be important strategies for reducing the burden of mortality in China.
Supported by grants from the American Heart Association (9750612N), the National Heart, Lung, and Blood Institute (U01 HL072507), and the Chinese Academy of Medical Sciences (Beijing).
All investigators participating in this study are listed in the Appendix.
Source Information
From the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine (J.H., K.R., C.-S.C., J.C., R.P.W., P.K.W.), and the Department of Medicine, Tulane University School of Medicine (J.H., J.C., P.K.W.) — both in New Orleans; the Cardiovascular Institute, Fuwai Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, and the National Center for Cardiovascular Disease Control and Research, Beijing (D.G., X.W., X.D.); Anzhen Hospital, Capital University of Medical Sciences, Beijing (C.Y.); West China College of Medicine, Sichuan University, Chendu, China (J.W.); and the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (M.J.K.).
Address reprint requests to Dr. He at the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Ave., Mail Stop SL18, New Orleans, LA 70112, or at jhe{at}tulane.edu.
References
The following investigators participated in this study: Steering Committee: J. He (coprincipal investigator), D. Gu (coprincipal investigator), J. Chen, R. Hui, M.J. Klag, L. Kong, S. Tao, J. Wang, P.K. Whelton, X. Wu, and C. Yao; Participating Institutions and Principal Staff: Tulane University Health Sciences Center, New Orleans: C.-S. Chen, J. Chen, J. He, K. Reynolds, P.K. Whelton, R.P. Wildman; Johns Hopkins Bloomberg School of Public Health, Baltimore: M.J. Klag; Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing: X. Duan, W. Gan, D. Gu, G. Huang, S. Tao, X. Wu, W. Yang, J. Zhao; Chinese Ministry of Health, Beijing: L. Kong; Tianjin City Bureau of Public Health, Tianjin, China: G. Zheng; Tianjin City Center of Disease Control and Prevention, Tianjin, China: G. Song; Guangdong Provincial People's Hospital and Cardiovascular Institute, Guangdong, China: X. Liu, J. Mai; Anzhen Hospital, Capital University of Medical Sciences, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing: C. Yao; Capital Iron and Steel Company's Hospital, Beijing: X. Yu; Fangshan District Hospital, Beijing: X. Xu; Zhejiang Provincial Center for Cardiovascular Disease Prevention and Research, Zhejiang, China: H. Jin, X. Tang; Fujian Provincial People's Hospital, Fujian, China: X. Pu, L. Yu; Shandong Provincial Academy of Medical Sciences, Shandong, China: S. Zhang; Guangxi Medical University, Guangxi, China: L. Zhu; Xi'an Jiaotong University Medical School, Shanxi, China: J. Mo; Henan Provincial Academy of Medical Sciences, Henan, China: J. Guo; Tongji Medical College and School of Public Health, Huazhong University of Science and Technology, Hubei, China: Y. Hu, Y. Yu; Sichuan Provincial Center of Disease Control and Prevention, Sichuan, China: X. Wu; West China College of Medicine, Sichuan University, Sichuan, China: J. Wang; Nanjing Medical University, Jiangsu, China: H. Shen, C. Yao; Beihua University Medical School, Jilin, China: L. Xu, G. Zhao; Inner Mongolia Hospital, Inner Mongolia, China: X. Gao, J. Zhou; First Clinical College of Harbin Medical University, Heilongjiang, China: Y. Li; Daqing City Center of Disease Control and Prevention, Heilongjiang, China: Z. Li; Hebei Provincial Academy of Medical Sciences, Hebei, China: H. Zhang; Zhongshan Hospital and Institute of Cardiovascular Diseases, Fudan University, Shanghai, China: X. Pan.
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Related Letters:
Major Causes of Death in China
Wagner P. D., Viegi G., Luna C. M., Fukuchi Y., Kvale P. A., Sony A. E., Wei M., Wang K., Wang B., Barnett V. T., He J., Gu D., Whelton P. K.
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N Engl J Med 2006;
354:874-876, Feb 23, 2006.
Correspondence
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