A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

Chronic Effects of High Fine Particulate Matter Exposure on Lung Cancer in China.

Rationale: Limited cohort studies have evaluated chronic effects of high fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5]) exposure on lung cancer.Objectives: To investigate the response pattern of lung cancer associated with high PM2.5 exposure.Methods: A Chinese cohort of 118,551 participants was followed up from 1992 to 2015. By incorporating PM2.5 exposure at 1 km spatial resolution generated using the satellite-based model during 2000-2015, we estimated the association between lung cancer and time-weighted average PM2.5 concentration using Cox proportional hazard models.Measurements and Main Results: A total of 844 incident lung cancer cases were identified during 915,053 person-years of follow-up. Among them, 701 lung cancer deaths occurred later. The exposure-response curves for lung cancer associated with PM2.5 exposure were nonlinear, with steeper slopes at the higher concentrations. Adjusted for age, sex, geographical region, urbanization, education level, smoking status, alcohol consumption, work-related physical activity, and body mass index, participants exposed to the second-fifth quintiles of PM2.5 had higher risk for lung cancer incidence than those exposed to the first quintile, with hazard ratios of 1.44 (95% confidence interval [CI], 1.10-1.88), 1.49 (95% CI, 1.12-1.99), 2.08 (95% CI, 1.42-3.04), and 2.45 (95% CI, 1.83-3.29), respectively. The corresponding hazard ratios for lung cancer mortality were 1.83 (95% CI, 1.33-2.50), 1.80 (95% CI, 1.29-2.53), 2.50 (95% CI, 1.62-3.86), and 2.95 (95% CI, 2.09-4.17), respectively.Conclusions: We provide strong evidence that high PM2.5 exposure leads to an elevated risk of lung cancer incidence and mortality, highlighting that remarkable public health benefits could be obtained from the improvement of air quality in highly polluted regions.

Benefits of active commuting on cardiovascular health modified by ambient fine particulate matter in China: A prospective cohort study.

BACKGROUND: Active commuting as a contributor to daily physical activity is beneficial for cardiovascular health, but leads to more chances of exposure to ambient air pollution. This study aimed to investigate associations between active commuting to work with cardiovascular disease (CVD), mortality and life expectancy among general Chinese adults, and to further evaluate the modification effect of fine particulate matter (PM2.5) exposure on these associations. METHODS: We included 76,176 Chinese adults without CVD from three large cohorts of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project. Information about commuting mode and physical activity were collected by unified questionnaire. Satellite-based PM2.5 concentrations at 1-km spatial resolution was used for estimating PM2.5 exposure of participants. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD incidence, mortality and all-cause mortality were estimated using Cox proportional hazards regression models. Multiplicative interaction term of commuting mode and PM2.5 level was tested to investigate potential effect modification. RESULTS: During 448,499 person-years of follow-up, 2230 CVD events and 2777 all-cause deaths were recorded. Compared with the non-active commuters, the multivariable-adjusted HRs (95% CIs) of CVD incidence and all-cause mortality were 0.95(0.85-1.05) and 0.79(0.72-0.87) for walking commuters, respectively. Corresponding HRs (95% CIs) for cycling commuters were 0.71(0.62-0.82) and 0.67(0.59-0.76). Active commuters over 45 years old were estimated to have more CVD-free years and life expectancy than non-active commuters under lower PM2.5 concentration. However, these beneficial effects of active commuting were alleviated or counteracted by long-term exposure to high PM2.5 concentration. Significant multiplicative interaction of commuting mode and PM2.5 level was showed in all-cause mortality, with the lowest risk observed in cycling participants exposed to lower level of PM2.5. CONCLUSIONS: Active commuting was associated with lower risk of CVD, all-cause mortality, and longer life expectancy among Chinese adults under ambient settings with lower PM2.5 level. It will be valuable to encourage active commuting among adults and develop stringent strategies on ambient PM2.5 pollution control for prevention of CVD and prolongation of life expectancy.

Long-Term Effects of High Exposure to Ambient Fine Particulate Matter on Coronary Heart Disease Incidence: A Population-Based Chinese Cohort Study.

Evidence of long-term effects of high exposure to ambient fine particulate matter (PM2.5) on coronary heart disease (CHD) remains limited. We incorporated the high-resolution satellite-based PM2.5 estimates with a large-scale, population-based Chinese cohort comprising 118 229 individuals, to assess the CHD risk of long-term exposure to high PM2.5. During the follow-up of 908 376 person-years, 1586 incident CHD cases were identified. The long-term average PM2.5 concentration for study population was 64.96 µg/m3, ranging from 31.17 to 96.96 µg/m3. For an increment of 10 µg/m3 in PM2.5, the multivariate-adjusted hazard ratios (HRs) were 1.43 (95% confidence interval [CI]: 1.35-1.51) for total CHD, 1.45 (95% CI: 1.36-1.56) for nonfatal CHD, and 1.38 (95% CI: 1.25-1.53) for fatal CHD, respectively. The effects were different across specific CHD outcomes, with greater effects for unstable angina (HR, 1.71 [95% CI, 1.56-1.88]), and weaker effects for acute myocardial infarction (HR, 1.28 [95% CI, 1.19-1.39]) and other CHD (HR, 1.27 [95% CI, 1.10-1.48]). The exposure-response curve suggested that HRs increased with elevated PM2.5 concentration over the entire exposure range. Elderly and hypertensive individuals were more susceptible to PM2.5-induced CHD. Our findings demonstrate the adverse health effects of severe air pollution and highlight the potential health benefits of air quality improvement.

Impact of healthy lifestyles on cancer risk in the Chinese population.

BACKGROUND: Although cancer has become one of the leading health burdens, to the authors' knowledge, evidence regarding its relationship with a healthy lifestyle in the Chinese population remains limited. METHODS: The authors evaluated the association between clustering of healthy lifestyle factors and cancer risk using 3 prospective cohort studies with 101,208 Chinese adults from the general population. Hazard ratios (HRs) and corresponding 95% confidential intervals (95% CIs) related to healthy lifestyle factors were calculated using Cox proportional hazard models, and population-attributable risk percentages were estimated further. RESULTS: The results demonstrated that each additional healthy lifestyle factor was associated with a 6% (range, 3%-9%) lower risk of overall cancer. Compared with having none to 3 healthy lifestyle factors, HRs related to adherence to all 6 healthy lifestyle factors were 0.78 (95% CI, 0.60-1.02) and 0.82 (95% CI, 0.67-1.00), respectively, for men and women. It was estimated that approximately 18.4% and 2.3%, respectively, of overall cancer cases for men and women were attributable to nonadherence to all 6 healthy lifestyle factors. CONCLUSIONS: The results of the current study indicate that adherence to clustering of healthy lifestyle factors was associated with a reduced risk of cancer incidence among Chinese adults. Greater efforts urgently are needed to promote the adoption of multiple healthy lifestyle behaviors to reduce the increasing burden of cancer.

Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China).

BACKGROUND: The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were formulated primarily in white populations. The China-PAR project (Prediction for ASCVD Risk in China) is aimed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts. METHODS: Two prospective studies followed up together with a unified protocol were used as the derivation cohort to develop 10-year ASCVD risk equations in 21 320 Chinese participants. The external validation was evaluated in 2 independent Chinese cohorts with 14 123 and 70 838 participants. Furthermore, model performance was compared with the Pooled Cohort Equations reported in the American College of Cardiology/American Heart Association guideline. RESULTS: Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants, 1048 subjects developed a first ASCVD event. Sex-specific equations had C statistics of 0.794 (95% confidence interval, 0.775-0.814) for men and 0.811 (95% confidence interval, 0.787-0.835) for women. The predicted rates were similar to the observed rates, as indicated by a calibration χ2 of 13.1 for men (P=0.16) and 12.8 for women (P=0.17). Good internal and external validations of our equations were achieved in subsequent analyses. Compared with the Chinese equations, the Pooled Cohort Equations had lower C statistics and much higher calibration χ2 values in men. CONCLUSIONS: Our project developed effective tools with good performance for 10-year ASCVD risk prediction among a Chinese population that will help to improve the primary prevention and management of cardiovascular disease.

Mortality attributable to smoking in China.

BACKGROUND: Smoking is a risk factor for many diseases and has been increasingly prevalent in economically developing regions of the world. We aimed to estimate the number of deaths attributable to smoking in China. METHODS: We conducted a large, prospective cohort study in a nationally representative sample of 169,871 Chinese adults who were 40 years of age or older. Investigators for the China National Hypertension Survey collected data on smoking and other risk factors at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 and 2000, with a response rate of 93.4%. We used multivariable-adjusted relative risk, prevalence of smoking, mortality, and population size in each age group, stratified according to sex, to calculate the number of deaths attributable to smoking in 2005. RESULTS: There was a significant, dose-response association between pack-years smoked and death from any cause in both men and women after adjustment for multiple risk factors (P<0.001 for trend). We estimated that in 2005, a total of 673,000 deaths (95% confidence interval [CI], 564,700 to 781,400) were attributable to smoking in China: 538,200 (95% CI, 455,800 to 620,600) among men and 134,800 (95% CI, 108,900 to 160,800) among women. The leading causes of smoking-related deaths were as follows: cancer, 268,200 (95% CI, 214,500 to 321,900); cardiovascular disease, 146,200 (95% CI, 79,200 to 213,100); and respiratory disease, 66,800 (95% CI, 20,300 to 113,300). CONCLUSIONS: Our study documents that smoking is a major risk factor for mortality in China. Continued strengthening of national programs and initiatives for smoking prevention and cessation is needed to reduce smoking-related deaths in China.

Causal associations of alcohol consumption with cardiovascular diseases and all-cause mortality among Chinese males.

BACKGROUND: The causal effects of moderate alcohol consumption on cardiovascular diseases (CVDs) are continuously debated, especially on coronary artery disease (CAD). OBJECTIVES: We aimed to explore the causal associations of alcohol consumption with CVDs and all-cause mortality among Chinese males. METHODS: A prospective cohort study was conducted in 40,386 Chinese males, with 17,676 being genotyped for the rs671 variant in the aldehyde dehydrogenase 2 (ALDH2) gene. A Cox proportional hazards model was conducted to estimate the effects of self-reported alcohol consumption. Mendelian randomization (MR) analysis was performed to explore the causality using rs671 as an instrumental variable. RESULTS: During the follow-up of 303,353 person-years, 2406 incident CVDs and 3195 all-cause mortalities were identified. J-shaped associations of self-reported alcohol consumption with incident CVD and all-cause mortality were observed, showing decreased risks for light (≤25 g/d) and moderate drinkers (25-≤60 g/d). However, MR analyses revealed a linear association of genetically predicted alcohol consumption with the incident CVD (P-trend = 0.02), including both CAD (P-trend = 0.03) and stroke (P-trend = 0.02). The HRs (95% CIs) for incident CVD across increasing tertiles of genetically predicted alcohol consumption were 1 (reference), 1.18 (1.01, 1.38), and 1.22 (1.03, 1.46). After excluding heavy drinkers, the risk of incident CVD and all-cause mortality was increased by 27% and 20% per standard drink increment of genetically predicted alcohol consumption, respectively. CONCLUSIONS: Our analyses extend the evidence of the harmful effect of alcohol consumption to total CVD (including CAD) and all-cause mortality, highlighting the potential health benefits of lowering alcohol consumption, even among light-to-moderate male drinkers.

Classical risk factors of cardiovascular disease among Chinese male steel workers: a prospective cohort study for 20 years.

BACKGROUND: Cardiovascular disease (CVD) constitutes a major public health problem in China and worldwide. We aimed to examine classical risk factors and their magnitudes for CVD in a Chinese cohort with over 20 years follow-up. METHODS: A cohort of 5092 male steelworkers recruited from 1974 to 1980 in Beijing of China was followed up for an average of 20.84 years. Cox proportional-hazards regression model were used to evaluate the risk of developing a first CVD event in the study participants who were free of CVD at the baseline. RESULTS: The multivariable-adjusted hazard ratio (HR) associated with every 20 mmHg rise in systolic blood pressure (SBP) was 1.63 in this Chinese male population, which was higher than in Caucasians. Compared to non-smokers, men who smoked not less than one-pack-a-day had a HR of 2.43 (95% confidence interval [CI], 1.75-3.38). The HR (95% CI) for every 20 mg/dl increase in total serum cholesterol (TC) and for every point rise in body mass index (BMI) was 1.13 (1.04-1.23) and 1.06 (1.02-1.09), respectively. CONCLUSIONS: Our study documents that hypertension, smoking, overweight and hypercholesterolemia are major conventional risk factors of CVD in Chinese male adults. Continued strengthening programs for prevention and intervention on these risk factors are needed to reduce the incidence of CVD in China.

Mortality from suicide and other external cause injuries in China: a prospective cohort study.

BACKGROUND: Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China. METHODS: A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded. RESULTS: Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29-3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries. CONCLUSIONS: External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted.

Validating World Health Organization cardiovascular disease risk charts and optimizing risk assessment in China.

BACKGROUND: World Health Organization (WHO) released region-specific cardiovascular disease (CVD) risk prediction charts recently, but the extent to which the charts can apply to Chinese population is unknown. We aimed to validate the WHO CVD risk charts for East Asia, and evaluate their practicability combining with China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equations among Chinese adults. METHODS: The China-PAR cohort with 93,234 participants aged 40-80 years was followed up during 1992-2015, including 29,337 participants from three sub-cohorts with follow-up period of over 10 years. We validated the WHO CVD risk charts using the China-PAR cohort by assessment of the predicted number of events, C index, calibration χ², and calibration plots, further elaborated the concordance between the China-PAR equations and the WHO risk charts. FINDINGS: During an average follow-up of 13•64 years, 1849 incident CVD cases were identified from 29,337 participants. Both the laboratory-based and non-laboratory-based charts overestimated CVD events by 59% and 58% in men, and by 72% and 85% in women, respectively. However, 92% of participants identified as high risk by the China-PAR equations could be successfully detected by the laboratory-based charts at the cut-off point of 10%. We also observed that the non-laboratory-based charts demonstrated the poor performance for diabetic population, with high proportion of high-risk individuals (17% for men, 31% for women) would be missed. INTERPRETATION: Although the WHO CVD risk charts for East Asia apparently overestimated CVD risk among Chinese population, they could be pragmatic pre-selection tools, as potential supplement to the China-PAR equations. The widespread use of the WHO risk charts along with the China-PAR equations might facilitate the implementation of the risk-based CVD prevention in China. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population.

OBJECTIVE: To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke. METHODS: Using a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals. RESULTS: During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%-27.7%) and 13.6% (95% CI 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%-49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%). CONCLUSIONS: Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that metaPRS is predictive of stroke risk.

Premature deaths attributable to blood pressure in China: a prospective cohort study.

BACKGROUND: Hypertension is a major global-health challenge because of its high prevalence and concomitant risks of cardiovascular disease. We estimated premature deaths attributable to increased blood pressure in China. METHODS: We did a prospective cohort study in a nationally representative sample of 169,871 Chinese adults aged 40 years and older. Blood pressure and other risk factors were measured at a baseline examination in 1991 and follow-up assessment was done in 1999-2000. Premature death was defined as mortality before age 72 years in men and 75 years in women, which were the average life expectancies in China in 2005. We calculated the numbers of total and premature deaths attributable to blood pressure using population-attributable risk, mortality, and the population size of China in 2005. FINDINGS: Hypertension and prehypertension were significantly associated with increased all-cause and cardiovascular mortality (p<0.0001). We estimated that in 2005, 2.33 million (95% CI 2.21-2.45) cardiovascular deaths were attributable to increased blood pressure in China: 2.11 million (2.03-2.20) in adults with hypertension and 0.22 million (0.19-0.25) in adults with prehypertension. Additionally, 1.27 million (1.18-1.36) premature cardiovascular deaths were attributable to raised blood pressure in China: 1.15 million (1.08-1.22) in adults with hypertension and 0.12 million (0.10-0.14) in adults with prehypertension. Most blood pressure-related deaths were caused by cerebrovascular diseases: 1.86 million (1.76-1.96) total deaths and 1.08 million (1.00-1.15) premature deaths. INTERPRETATION: Increased blood pressure is the leading preventable risk factor for premature mortality in the Chinese general population. Prevention and control of this condition should receive top public-health priority in China. FUNDING: American Heart Association (USA); National Heart, Lung, and Blood Institute, National Institutes of Health (USA); Ministry of Health (China); and Ministry of Science and Technology (China).

Blood pressure, body mass index and risk of cardiovascular disease in Chinese men and women.

BACKGROUND: It is still uncertain whether increased blood pressure (BP) has a stronger effect on the risk of cardiovascular disease (CVD) in lean persons than in obese persons. We tested it using a data set collected from a large cohort of Chinese adults. METHODS: Systolic and diastolic BP, body mass index (BMI) and other variables were measured in 169,871 Chinese men and women > or = 40 years of age in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Data were analyzed with Cox proportional hazards models. RESULTS: After adjusted for age, sex, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, we found that the effects of systolic or diastolic BP on risk of CVD generally increased with the increasing BMI levels (underweight, normal, overweight, and obese). For example, hazard ratios (HRs) and 95% confidence interval (CI) per 1- standard deviation (SD) increase in systolic BP within corresponding BMI levels were 1.27(1.21-1.33), 1.45(1.41-1.48), 1.52 (1.45-1.59) and 1.63 (1.51-1.76), respectively. Statistically significant interactions (P < 0.0001) were observed between systolic BP, diastolic BP and BMI in relation to CVD. In baseline hypertensive participants we found both obese men and women had higher risk of CVD than normal-weight persons. The multivariate-adjusted HRs(95%CI) were 1.23(1.03-1.47) and 1.20(1.02-1.40), respectively. CONCLUSION: Our study suggests that the magnitude of the association between BP and CVD generally increase with increasing BMI. Hypertension should not be regarded as a less serious risk factor in obese than in lean or normal-weight persons in Chinese adults.

The effect of total cholesterol on myocardial infarction in Chinese male hypertension population.

OBJECTIVE: Total cholesterol (TC) is an important risk factor for myocardial infarction (MI), but the effect of TC on MI in Chinese male hypertension population has not been well documented. We conducted a prospective cohort study to determine the incidence and relative risk for MI across a wide range of TC levels in Chinese male hypertension population. METHODS: A cohort of 5298 male employees aged 18-74 years recruited from Capital Steel and Iron Company in Beijing of China in 1974-1980 was followed up for an average of 20.84 years. A total of 122 incident MI cases were identified during the period of follow-up. RESULTS: The incidence of MI among participants with elevated TC and those with desirable TC in male non-hypertension population was 137.20 and 63.81 per 100,000 person-years, respectively; and the corresponding incidence in male hypertension population was 279.80 and 130.96 per 100,000 person-years, respectively. After adjustment for important covariables, 10.38%, 16.71%, and 23.80% of MI cases were attributable to hypertension, elevated TC, and hypertension plus elevated TC, respectively. In male hypertension population, the multivariate adjusted hazard ratios of MI were 1.21, 2.39, 3.38, and 3.95 for participants with TC level of 5.17-5.68, 5.69-6.20, 6.21-6.71, and > or = 6.72 mmol/L, compared with those with TC < 5.17 mmol/L. The corresponding population attributable risks were 2.92%, 9.20%, 8.87%, and 9.84%, respectively. CONCLUSION: Elevated TC is an important independent risk factor of MI both in male non-hypertension and hypertension populations. There is a linear association between TC level and MI incidence in Chinese male hypertension population.

Long-Term Exposure to Fine Particulate Matter and Cardiovascular Disease in China.

BACKGROUND: Evidence of the effects of long-term fine particulate matter (PM2.5) exposure on cardiovascular diseases (CVDs) is rare for populations exposed to high levels of PM2.5 in China and in other countries with similarly high levels. OBJECTIVES: The aim of this study was to assess the CVD risks associated with long-term exposure to PM2.5 in China. METHODS: A nationwide cohort study, China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China), was used, with 116,972 adults without CVD in 2000 being included. Participants were followed until 2015. Satellite-based PM2.5 concentrations at 1-km spatial resolution during the study period were used for exposure assessment. A Cox proportional hazards model with time-varying exposures was used to estimate the CVD risks associated with PM2.5 exposure, adjusting for individual risk factors. RESULTS: Annual mean concentrations of PM2.5 at the China-PAR sites ranged from 25.5 to 114.0 µg/m3. For each 10 µg/m3 increase in PM2.5 exposures, the multivariate-adjusted hazard ratio was 1.251 (95% confidence interval: 1.220 to 1.283) for CVD incidence and 1.164 (95% confidence interval: 1.117 to 1.213) for CVD mortality. The slopes of concentration-response functions of PM2.5 exposure and CVD risks were steeper at high PM2.5 levels. In addition, older residents, rural residents, and never smokers were more prone to adverse effects of PM2.5 exposure. CONCLUSIONS: This study provides evidence that elevated long-term PM2.5 exposures lead to increased CVD risk in China. The effects are more pronounced at higher PM2.5 levels. These findings expand the current knowledge on adverse health effects of severe air pollution and highlight the potential cardiovascular benefits of air quality improvement in China and other low- and middle-income countries.

Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project.

AIMS: The role of tea consumption in the primary prevention of atherosclerotic cardiovascular disease remains unclear in cohort studies. This prospective cohort study aimed to investigate the associations of tea consumption with the risk of atherosclerotic cardiovascular disease and all-cause mortality. METHODS: We included 100,902 general Chinese adults from the project of Prediction for ASCVD Risk in China (China-PAR) in 15 provinces across China since 1998. Information on tea consumption was collected through standardized questionnaires. Outcomes were identified by interviewing study participants or their proxies, and checking hospital records and/or death certificates. Cox proportional hazard regression models were used to calculate hazard ratios and their corresponding 95% confidence intervals related to tea consumption. RESULTS: During a median follow-up of 7.3 years, 3683 atherosclerotic cardiovascular disease events, 1477 atherosclerotic cardiovascular disease deaths, and 5479 all-cause deaths were recorded. Compared with never or non-habitual tea drinkers, the hazard ratio and 95% confidence interval among habitual tea drinkers was 0.80 (0.75-0.87), 0.78 (0.69-0.88), and 0.85 (0.79-0.90) for atherosclerotic cardiovascular disease incidence, atherosclerotic cardiovascular disease mortality, and all-cause mortality, respectively. Habitual tea drinkers had 1.41 years longer of atherosclerotic cardiovascular disease-free years and 1.26 years longer of life expectancy at the index age of 50 years. The observed inverse associations were strengthened among participants who kept the habit during the follow-up period. CONCLUSION: Tea consumption was associated with reduced risks of atherosclerotic cardiovascular disease and all-cause mortality, especially among those consistent habitual tea drinkers.

Associations of long-term exposure to ambient PM2.5 with mortality in Chinese adults: A pooled analysis of cohorts in the China-PAR project.

BACKGROUND: The concentration-response relationship between mortality and long-term exposure to fine particulate matter (PM2.5) has not been fully elucidated, especially at high levels of PM2.5 concentrations. OBJECTIVE: We aimed to evaluate chronic effects of ambient PM2.5 exposure on deaths among Chinese adults in high-exposure settings. METHODS: Participants of the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) project were included from four prospective cohorts among Chinese adults aged ≥18 years old. The overall follow-up rate of the four cohorts was 93.4% until the recent follow-up survey that ended in 2015. The average of satellite-based PM2.5 concentrations during 2000-2015 at 1-km spatial resolution was assigned to each participant according to individual residence addresses. Based on the pooled analysis of individual data from the four cohorts, a Cox proportional hazards model was used to estimate the hazard ratio (HR) and corresponding 95% confidence intervals (95% CIs) for the association of PM2.5 exposure with mortality after multivariate adjustment. RESULTS: A total of 116,821 participants were eligible in the final analysis. During a mean of 7.7 years of follow-up, 6,395 non-accidental deaths and 2,507 cardio-metabolic deaths occurred. The mean of PM2.5 concentration was 64.9 µg/m3 ranging from 31.2 µg/m3 to 97.0 µg/m3. For each 10 µg/m3 increment in PM2.5, the HR was 1.11 (95% CI: 1.08-1.14) for non-accidental mortality and 1.22 (95% CI: 1.16-1.27) for cardio-metabolic mortality. In addition, a weak exponential curve for the concentration-response association between mortality and PM2.5 was observed among Chinese adults. CONCLUSIONS: Our study provided important evidence of the long-term effects of PM2.5 exposure on deaths among Chinese adults. The findings expand our knowledge on concentration-response relationship in high-exposure environments, which is essential to address the urgent challenge of reducing the disease burden attributable to PM2.5 exposure in rapidly industrializing countries such as China.

Hypertension subtype and risk of cardiovascular disease in Chinese adults.

BACKGROUND: We examined the relationship between hypertension subtype and cardiovascular disease incidence and mortality in Chinese adults. METHODS AND RESULTS: We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged >or=40 years. Data on systolic (SBP) and diastolic blood pressure (DBP) and other variables were obtained at a baseline examination in 1991 with the use of standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Hypertension subtypes were defined as combined systolic and diastolic hypertension (SBP >or=140 and DBP >or=90 mm Hg), isolated systolic hypertension (SBP >or=140 and DBP <90 mm Hg), isolated diastolic hypertension (SBP <140 and DBP >or=90 mm Hg), and 2 categories of treated hypertension (SBP <140 and DBP <90 mm Hg or SBP >or=140 and/or DBP >or=90 mm Hg). After participants with missing BP values were excluded, 169 577 adults were included in the analyses. Compared with normotensives, relative risks (95% CIs) of cardiovascular disease incidence and mortality were 2.73 (2.60 to 2.86) and 2.53 (2.39 to 2.68) for combined systolic and diastolic hypertension, 1.78 (1.69 to 1.87) and 1.68 (1.58 to 1.78) for isolated systolic hypertension, 1.59 (1.43 to 1.76) and 1.45 (1.27 to 1.65) for isolated diastolic hypertension, 2.01 (1.64 to 2.48) and 1.61 (1.28 to 2.03) for treated hypertension with SBP <140 and DBP <90 mm Hg, and 3.37 (3.07 to 3.69) and 2.88 (2.60 to 3.19) for treated hypertension with SBP >or=140 and/or DBP >or=90 mm Hg, respectively, after adjustment for important covariables. CONCLUSIONS: Our results indicate that all hypertension subtypes are associated with significantly increased risk of cardiovascular disease in Chinese adults. Primary prevention of hypertension should be a public health priority in the Chinese population.

Genetic variants of cGMP-dependent protein kinase genes and salt sensitivity of blood pressure: the GenSalt study.

Genetic mechanisms involved in the susceptibility to salt sensitivity have not been completely clarified. This study aimed to comprehensively examine the association between genetic variants in the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG/PRKG) genes and blood pressure (BP) responses to dietary sodium intervention in a Chinese population. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive association of 213 tag single-nucleotide polymorphisms (SNPs) in two PRKG genes (PRKG1 and PRKG2) with salt sensitivity phenotypes. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing. Mean systolic BP response to low-sodium intervention significantly decreased with the number of minor T allele of marker rs10997916 in PRKG1 (P = 2.4 × 10-5). Mean systolic BP responses (95% confidence interval) among those with genotypes CC, CT, and TT were -5.6 (-6.0, -5.3), -3.7 (-4.7, -2.8), and -1.3 (-4.6, 2.0) mmHg, respectively, during the low-sodium intervention. Gene-based analyses demonstrated that PRKG1 was significantly associated with systolic BP response to low-sodium intervention (P = 1.2 × 10-3), whereas PRKG2 was nominally significantly associated with diastolic BP responses to high-sodium intervention (P = 2.6 × 10-2). The current study suggested a significant association of genetic variants in the PRKG genes with variation of BP response to dietary sodium intake in Han Chinese population. These novel findings merit further replication in future.