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.

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.

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.

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.

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.

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.

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.

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.

Long-Term Exposure to Fine Particulate Matter and Hypertension Incidence in China.

The risk of incident hypertension associated with long-term exposure to fine particulate matter (PM2.5) was still unclear by studies conducted in North America and Europe, and this relationship has rarely been quantified at higher ambient concentrations typically found in developing countries. We aimed to investigate the association between PM2.5 and incident hypertension using the large-scale prospective cohorts in China. We included 59 456 participants without hypertension aged ≥18 years from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. Data on ambient PM2.5 at participants' residential address were obtained during 2004 to 2015 using a satellite-based spatial-temporal model. Hazard ratios and 95% CIs were calculated for incident hypertension using stratified Cox proportional hazards models with adjustment of potential confounders. The findings indicated that average PM2.5 concentration from 2004 to 2015 at study participants' address was 77.7 µg/m3. During the follow-up of 364 947 person-years, we identified 13 981 incident hypertension cases. Compared with the lowest quartile exposure of PM2.5, participants in the highest quartile had an increased risk of incident hypertension with a hazard ratio (95% CI) of 1.77 (1.56-2.00). Each 10 µg/m3 increment of PM2.5 concentration could increase 11% risk of hypertension (hazard ratio, 1.11; 95% CI, 1.05-1.17). This cohort study provided the first evidence from China that long-term exposure to PM2.5 was independently associated with incident hypertension at relatively high ambient concentrations. Stringent strategies on PM2.5 pollution control are warranted to improve the air quality and contribute to the reduction of disease burden of hypertension in China.

Long-term exposure to ambient fine particulate matter and incidence of diabetes in China: A cohort study.

BACKGROUND: Diabetes caused substantial economic and health burden worldwide. However, the associations between air pollution and diabetes incidence were rarely reported in the developing countries, especially in China with relatively high PM2.5 concentrations. OBJECTIVES: A cohort-based study was conducted to assess the diabetes incidence associated with long-term exposure to ambient PM2.5. METHODS: We collected individual health data and risk factors from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR Project) from 15 provinces over China. Diabetes was defined as fasting glucose levels ≥7.0 mmol/L at the follow-ups and/or the use of insulin or oral hypoglycemic agents and/or diagnosed medical history of diabetes during 2004 to 2015. Individual-level PM2.5 exposures were estimated from satellite-based PM2.5 concentrations (10 km spatial resolution) during the study period. Cox proportional hazards models with random intercepts of each cohort and region were employed to estimate the diabetes incidence attributable to PM2.5, after the adjustment for age, gender, body mass index, smoking status, education, work-related physical activity level, hypertension, urbanicity, county-level averaged years of education, and long-term levels of temperature and relative humidity. RESULTS: A total of 88,397 subjects were analyzed with 580,928 person-years of follow-up after 2004, among which 6439 new cases of diabetes were observed. The mean age of the subjects was 51.7 years at baseline. For an increase of 10 µg/m3 in long-term PM2.5 exposure, the multivariable-adjusted percent increase in the diabetes incidence was estimated to be 15.66% (95% confidence interval: 6.42%, 25.70%). The adverse effects of PM2.5 were larger among females, rural subjects, non-smokers, normotensives, subjects younger than 65 years and subjects with body mass index <25 kg/m2. CONCLUSIONS: Our findings provided evidence for the association of long-term exposure to PM2.5 with diabetes incidence in China. A sustained improvement of air quality will benefit the reduction for diabetes epidemic in China.

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.

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.

Long term exposure to ambient fine particulate matter and incidence of stroke: prospective cohort study from the China-PAR project.

OBJECTIVE: To study the effect of long term exposure to ambient fine particulate matter of diameter ≤2.5 µm (PM2.5) on the incidence of total, ischemic, and hemorrhagic stroke among Chinese adults. DESIGN: Population based prospective cohort study. SETTING: Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project carried out in 15 provinces across China. PARTICIPANTS: 117 575 Chinese men and women without stroke at baseline in the China-PAR project. MAIN OUTCOME MEASURES: Incidence of total, ischemic, and hemorrhagic stroke. RESULTS: The long term average PM2.5 level from 2000 to 2015 at participants' residential addresses was 64.9 µg/m3, ranging from 31.2 µg/m3 to 97.0 µg/m3. During 900 214 person years of follow-up, 3540 cases of incident stroke were identified, of which 63.0% (n=2230) were ischemic and 27.5% (n=973) were hemorrhagic. Compared with the first quarter of exposure to PM2.5 (<54.5 µg/m3), participants in the highest quarter (>78.2 µg/m3) had an increased risk of incident stroke (hazard ratio 1.53, 95% confidence interval 1.34 to 1.74), ischemic stroke (1.82, 1.55 to 2.14), and hemorrhagic stroke (1.50, 1.16 to 1.93). For each increase of 10 µg/m3 in PM2.5 concentration, the increased risks of incident stroke, ischemic stroke, and hemorrhagic stroke were 13% (1.13, 1.09 to 1.17), 20% (1.20, 1.15 to 1.25), and 12% (1.12, 1.05 to 1.20), respectively. Almost linear exposure-response relations between long term exposure to PM2.5 and incident stroke, overall and by its subtypes, were observed. CONCLUSIONS: This study provides evidence from China that long term exposure to ambient PM2.5 at relatively high concentrations is positively associated with incident stroke and its major subtypes. These findings are meaningful for both environmental and health policy development related to air pollution and stroke prevention, not only in China, but also in other low and middle income countries.

Ideal cardiovascular health and incidence of atherosclerotic cardiovascular disease among Chinese adults: the China-PAR project.

Existing evidence on the relationship between cardiovascular health (CVH) metrics and cardiovascular disease (CVD) was primarily derived from western populations. We aimed to evaluate the benefits of ideal CVH metrics on preventing incident atherosclerotic CVD (ASCVD) in Chinese population. This study was conducted among 93,987 adults from the China-PAR project (Prediction for ASCVD Risk in China) who were followed up until 2015. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVH metrics for the risk of ASCVD, including coronary heart disease (CHD), stroke and ASCVD death. We further estimated the population-attributable risk percentage (PAR%) of these metrics in relation to each outcome. We observed gradient inverse associations between the number of ideal CVH metrics and ASCVD incidence. Compared with participants having ≤2 ideal CVH metrics, the multivariable-adjusted HRs (95% CIs) of ASCVD for those with 3, 4, 5, 6 and 7 ideal CVH metrics were 0.83 (0.74-0.93), 0.66 (0.59-0.74), 0.55 (0.48-0.61), 0.44 (0.38-0.50) and 0.24 (0.18-0.31), respectively (P for trend <0.0001). Approximately 62.1% of total ASCVD, 38.7% of CHD, 66.4% of stroke, and 60.5% of ASCVD death were attributable to not achieving all the seven ideal CVH metrics. After adjusting effects of ideal health factors, having four ideal health behaviors could independently bring adults health benefits in preventing 17.4% of ASCVD, 18.0% of CHD, 16.7% of stroke, and 10.1% of ASCVD death. Among all the seven CVH metrics, to keep with ideal blood pressure (BP) implied the largest public health gains against various ASCVD events (PAR% between 33.0% and 47.2%), while ideal diet was the metric most difficult to be achieved in the long term. Our study indicates that the more ideal CVH metrics adults have, the less ASCVD burden there is in China. Special efforts of health education and behavior modification should be made on keeping ideal BP and dietary habits in general Chinese population to prevent the epidemic of ASCVD.

Predicting lifetime risk for developing atherosclerotic cardiovascular disease in Chinese population: the China-PAR project.

Evidence on the lifetime risk for atherosclerotic cardiovascular disease (ASCVD) is insufficient; yet, estimating an individual's lifetime risk allows for a comprehensive assessment of ASCVD burden. We developed and validated lifetime risk prediction equations for ASCVD using four large and ongoing prospective cohorts of Chinese, the China-PAR project (Prediction for ASCVD Risk in China). Sex-specific equations were developed using two cohorts (as the derivation cohort) of 21,320 participants. Two other independent cohorts with 14,123 and 70,838 participants were used for their external validation, respectively. We evaluated both calibration and discrimination measures for model performance. Furthermore, we estimated ASCVD-free years lost or excess absolute risk attributable to high 10-year risk (≥10.0%) and/or high lifetime risk (≥32.8%). After 12.3 years' follow-up of the derivation cohort, 1048 ASCVD events and 1304 non-ASCVD deaths were identified. Our sex-specific equations had good internal validation, with discriminant C statistics of 0.776 (95% confidence interval [CI]: 0.757-0.794) and 0.801 (95% CI: 0.778-0.825), and calibration χ2 of 9.2 (P = 0.418) and 5.6 (P = 0.777) for men and women, respectively. Good external validation was also demonstrated with predicted rates closely matched to the observed ones. Compared with men having both low 10-year and low lifetime risk, men would develop ASCVD 3.0, 4.6 and 8.6 years earlier if they had high 10-year risk alone, high lifetime risk alone, or both high 10-year and high lifetime risk at the index age of 35 years, respectively. We developed well-performed lifetime risk prediction equations that will help to identify those with the greatest potential to avert ASCVD burden after implementation of innovative clinical and public health interventions in China.

Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study.

BACKGROUND: A resequencing study of renal epithelial sodium channel (ENaC) genes was conducted to identify rare variants associated with blood pressure (BP) salt-sensitivity. METHODS: The Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low-sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive and 300 most salt-resistant GenSalt participants were selected for the resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were resequenced using capillary-based sequencing methods. Traditional burden tests were utilized to examine association between rare variants and BP salt-sensitivity. Associations of low-frequency and common variants were tested using single-marker analyses. RESULTS: Carriers of SCNN1A rare variants had a 0.52 [95% confidence interval (CI): 0.32-0.85] decreased odds of BP salt-sensitivity compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt-sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In single-marker analyses, 3 independent common variants in SCNN1A, rs11614164, rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni correction (P = 4.4 × 10-4, 1.1 × 10-8, and 1.3 × 10-3). Each copy of the minor allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23-1.52) increased odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and rs3741914 was associated with 0.68-fold (95% CI: 0.55-0.84) and 0.69-fold (95% CI: 0.54-0.86) decreased odds of salt-sensitivity, respectively. CONCLUSIONS: This study demonstrated for the first time a relationship between rare variants in the ENaC pathway and BP salt-sensitivity. Future replication and functional studies are needed to confirm the findings in this study. CLINICAL TRIAL REGISTRY: Trial Number NCT00721721.

Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).

We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (P=2.7×10-8, 9.8×10-8, and 6.4×10-6, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (P=1.4×10-3, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (P=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension.

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.