Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

Adverse associations of sedentary behavior with cancer incidence and all-cause mortality: A prospective cohort study.

BACKGROUND: Inconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality, and evidence from the Chinese population is scarce. This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity (MVPA) on these relationships. METHODS: We included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire. Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for cancer and mortality were estimated using Cox proportional hazards regression models. RESULTS: During 559,002 person-years of follow-up, 2388 cancer events, 1571 cancer deaths, and 4562 all-cause deaths were recorded. Sedentary behavior was associated with increased risk of developing cancer and deaths in a dose-response manner. The multivariable-adjusted HRs (95%CIs) were the following: HR = 1.16, 95%CI: 1.01‒1.33; HR = 1.24, 95%CI: 1.04‒1.48; and HR = 1.15, 95%CI: 1.04‒1.28 for cancer incidence, cancer mortality, and all-cause mortality, respectively, for those having ≥10 h/day of sedentary time compared with those having <6 h/day of sedentary time. Sedentary populations (≥10 h/day) developed cancer or died 4.09 years and 2.79 years earlier, respectively, at the index age of 50 years. Failure to achieve the recommended level of MVPA may further aggravate the adverse associations, with the highest cancer and mortality risks being observed among participants with both ≥10 h/day of sedentary time and <150 min/week of MVPA. Limitations of this study include the fact that physical activity information was obtained via questionnaire instead of objective measurement and that there were insufficient incident cases for the analysis of associations between sedentary behavior and site-specific cancers. CONCLUSION: Sedentary behavior was associated with an increased risk of cancer and all-cause mortality among Chinese adults, especially for those with ≥10 h/day of sedentary time. It is necessary to reduce sedentary time, in addition to increasing MVPA levels, for the prevention of cancer and premature death.

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.

Predicting 10-Year and Lifetime Stroke Risk in Chinese Population.

Background and Purpose- Risk assessment is essential for the primary prevention of stroke. However, the current available tools derived from Chinese populations are insufficient for individualized 10-year and lifetime stroke risk prediction. Our study aims to develop and validate personalized 10-year and lifetime stroke risk equations incorporating 4 large Chinese cohorts. Methods- We used 2 prospective cohorts of 21 320 participants with similar survey protocols as the derivation cohort to develop sex-specific 10-year and lifetime stroke risk equations. Two other independent cohorts with 14 123 and 70 838 participants were used for external validation. In addition, the performance of the 10-year stroke risk equations among participants aged ≥55 years was compared with the new Framingham Stroke Risk Profile. Results- The sex-specific equations for predicting 10-year stroke risk had C statistics being 0.810 for men and 0.810 for women, with calibration χ2 being 15.0 (P=0.092) and 7.8 (P=0.550), respectively. The lifetime stroke risk equations also showed C statistics around 0.800 and calibration χ2 below 20 for both sexes. In the validation cohorts, we found good agreement between the observed and predicted stroke probabilities for both the 10-year and lifetime stroke risk equations. Further compared with the new Framingham Stroke Risk Profile, our 10-year stroke risk equations displayed better prediction capability. In addition, based on lifetime stroke risk assessment, 5.7% of study participants aged 35 to 49 years old were further reclassified as high risk, who were initially categorized as low 10-year risk. Conclusions- We developed a well-performed tool for predicting personalized 10-year and lifetime stroke risk among the Chinese adults, which will facilitate the further identification of high-risk individuals and community-based stroke prevention 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.

Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

OBJECTIVES: To explore synergistic effect between angiotensin II receptor blockers (ARBs) and statins on Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. METHODS: This study was a 2 × 2 factorial randomized, prospective, double-blind, placebo-controlled trial. One hundred and fifty nine hypertensive patients with carotid atherosclerosis were randomized to the administration of control group, telmisartan group, rosuvastatin group, and combination group (telmisartan plus rosuvastatin) base on hydrochlorothiazide treatment. Carotid ultrasonography, parameters of Th17/Treg functional axis, interleukin (IL)-1ß, IL-2, interferon (IFN)-γ, hypersensitive C-reactive protein (hsCRP), monocyte chemotactic protein (MCP)-1 were evaluated. RESULTS: Blood pressure level markedly reduced in four groups. There was significantly synergistic effect of combination of telmisartan with rosuvastatin on reducing carotid imtima-media thickness (IMT), Th17 cells frequency, IL-17, IL-6, IL-23, tumor necrosis factor (TNF)-α, expression of retinoic acid receptor-related orphan receptor (ROR)γt mRNA, Th17/Treg ratio, IL-1ß, IL-2, IFN-γ, hsCRP, and MCP-1, and increasing Treg cells frequency, IL-10, transforming growth factor(TGF)-ß1, and expression of forkhead/winged helix transcription factor (Foxp3) mRNA (all P<0.05). Change rate of IMT statistical positively related to descent rates of Th17 cells frequency, IL-17, IL-6, IL-23, TNF-α, expression of RORγt mRNA, Th17/Treg ratio, IL-1ß, IL-2, IFN-γ, hsCRP, and MCP-1, and negatively related to increased rates of Treg frequency, IL-10, TGF-ß1, and expression of Foxp3 mRNA, respectively (all P<0.05). CONCLUSION: There is a synergistic effect of combination of telmisartan with rosuvastatin on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

Analysis of sex hormone genes reveals gender differences in the genetic etiology of blood pressure salt sensitivity: the GenSalt study.

BACKGROUND: We examined the association between 799 single-nucleotide polymorphisms in 39 sex hormone genes and blood pressure (BP) responses to a dietary-sodium intervention. METHODS: A 7-day low-sodium feeding study (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. RESULTS: Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453, rs9371562, rs9397459, and rs9383951. For example, mean diastolic blood pressure (DBP) responses to low-sodium intervention (95% confidence interval) were -2.67 (-3.13, -2.22) mm Hg among those with the rs9397453 C/C genotype, -1.23 (-1.98, -0.48) mm Hg among those with the C/T genotype, and 0.08 (-2.31, 2.47) mm Hg among those with the T/T genotype (P = 1×10(-4); false discovery rate (FDR)-q = 0.04). Mean DBP responses to high sodium according to the rs9397453 genotypes were 1.46 (1.03, 1.89) mm Hg among those with C/C, 0.19 (-0.54, 0.91) mm Hg among those with C/T, and -1.10 (-2.82, 0.61) mm Hg among those with T/T (P = 2×10(-4); FDR-q = 0.04). Similar trends were noted for the association between these ESR1 variants and SBP responses to the dietary intervention. There were no significant associations between sex hormone gene variants and salt sensitivity in women, with genotype-gender interactions noted for the ESR1 markers that achieved significance in men. CONCLUSIONS: We identified strong, consistent associations between ESR1 gene variants and salt sensitivity in men. Our results support a gender-specific role for ESR1 in the etiology of this complex trait.

Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

Correlation of peripheral Th17 cells and Th17-associated cytokines to the severity of carotid artery plaque and its clinical implication.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Th17 cells reportedly play important roles in the development of inflammatory and autoimmune diseases. In this study, we investigated the contributions of circulating Th17 cells and plasma Th17-associated cytokines to carotid artery plaques. METHODS: Based on carotid artery ultrasonography, 280 atherosclerosis patients were categorized both by: (1) 4 levels for extent and severity of plaques (Level 1=least severe; Level 4=most severe) and (2) 5 groups for ultrasound features of carotid artery plaques (none, flat, soft, hard, ulcerated). Peripheral blood Th17 cell frequencies and plasma concentrations of Th17-associated cytokines (IL-17, IL-6, and TNF-α) were also determined. RESULTS: For groups categorized by the extent and severity of carotid artery plaques, Th17 cell frequencies, common carotid artery intima-media thickness (CCA-IMT), and Crouse scores were significantly increased in higher level groups (Levels 3 and 4) than in lower level groups (Levels 1 and 2), and plasma concentrations of IL-17, IL-6, and TNF-α increased with increased levels of plaque severity. The same pattern was found for groups categorized by ultrasound features of carotid artery plaques. The results of Pearson correlation and multiple linear regression analyses showed that both CCA-IMT and Crouse scores for carotid artery plaques were significantly and positively correlated with Th17 cell frequencies and plasma Th17-associated cytokine concentrations. CONCLUSION: These results suggest that increased frequencies of circulating Th17 cells and Th17-associated cytokines are correlated to the severity and progression of carotid artery plaques.

Prevalence of prehypertension and hypertension in a Chinese rural area from 1991 to 2007.

Shandong Province is located in the east of China. The province is characterized by robust economic development, with a rural population accounting for 56% of the total population. However, no data are available regarding temporal changes in the prevalence, awareness, treatment and control of hypertension among this population. Three independent cross-sectional surveys were performed in 1991 (n=8359), 2002 (n=18922) and 2007 (n=20167) in the rural area population, aged 35-74 years. The sampling included a survey on blood pressure and associated risk factors. Although the rate of smoking and alcohol consumption decreased significantly from 1991 to 2007, the prevalence of overweight and obesity increased, whereas that of high-strength physical activity decreased remarkably. In 1991, 2002 and 2007, the prevalence of prehypertension was 33.8, 61.5 and 54.6%, respectively. The prevalence of hypertension was 20.4, 24.5 and 30.6%, respectively. Overall, the rate of hypertension awareness, treatment and control showed a steady increase over the 16-year period, although the control rate of hypertension is still far from being satisfactory. In conclusion, among the Chinese rural population, the prevalence of prehypertension and hypertension increased significantly from 1991 to 2007. Public health programs are required to improve this situation in Chinese rural populations.

[A cohort study on the predictive value of factors influencing cardio-cerebro vascular death among people over 40 years of age].

OBJECTIVE: To explore the factors influencing cardio-cerebro vascular death events among people over 40 years of age in Shandong area, China. METHODS: Baseline survey was carried out in 1991. A total number of 11,008 adults over 40 years old had been studied in Shandong province. Data on cardiocerebro death was collected. The correlation between influencing factors and cardio-cerebro vascular death events was analyzed by Cox regression model. RESULTS: Totally, 434 cardio-cerebro death events occurred among the 11,008 subjects during the 8-year follow-up study. Cardio-cerebro death events were related to systolic blood pressure, diastolic blood pressure, smoking, stroke history and age. Data from Cox regression analysis showed that the relative risk (RR) for cardio-cerebro vascular death events increased by 2.862 [95% confidence interval (CI): 1.976-4.144] times for those people having stroke history. When systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardio-cerebro vascular death events increased by 1.171 (95% CI: 1.033-1.328), 1.214 (95% CI: 1.044-1.413) respectively. it was found that a 1.239 (95% CI: 1.088-1.553) times higher in smokers than non-smokers on relative risk for cardio-cerebro vascular death events. However, the predictive values of the influencing factors for cardio-cerebro vascular death were different among population of different years of age. The relative risk for cardio-cerebro vascular death events increased by 1.366 (95% CI: 1.102-1.678) times for each 10 mm Hg increase of diastolic blood pressure in 40-59 years old population. However, the effect was taken place by systolic blood pressure in 60-74 years old population,with a relative risk of 1.201 (95% CI: 1.017-1.418) for each 10 mm Hg increase. Age seemed the only significant factor for cardio-cerebro vascular death events on population aged more than 75 years old. Conclusion The predictive values of the risk factors were different among age groups. The different risk factors should be taken care according to the difference of age.

[A study on K469E polymorphism of ICAM1 gene and ICAM1 plasma level in patients with coronary heart disease].

OBJECTIVE: To study the linkage between K469E polymorphism of intercellular adhesion molecule 1(ICAM1) gene with ICAM1 plasma level and coronary heart disease (CHD) in Han population of China. METHODS: One hundred and sixty-four controls without CHD and 160 patients with CHD were enrolled in our study. By nested PCR with allele-specific oligonucleotide primers, all patients and controls were genotyped for the ICAM1 polymorphism. And the ICAM1 plasma level was measured by ELISA. RESULTS: In the patients with CHD, both K allele frequency and the plasma level of ICAM1 were higher than those in control (P<0.05). The individual with K allele had higher plasma level of ICAM1 than that without K allele (344.34+/-128.59 microg/L vs 303.54+/-108.74 microg/L, P=0.008). K allele enhanced the risk of CHD (P<0.01, OR=2.158, 95%CI: 1.250-3.727). There was the K allele cooperation with smoking in influencing the risk of CHD. CONCLUSION: There is the polymorphism of ICAM1 K469E gene in Han population of China, and the K allele may be a genetic factor influencing the risk of CHD.

[Relationship between fibrinogen B beta gene FGB -455G/A polymorphism and atherosclerotic cerebral infarction].

OBJECTIVE: To explore the distribution of fibrinogen (FGB) B beta polymorphism in Chinese Han population and the association of the polymorphisms with the occurrence of atherosclerotic cerebral infarction (ACI). METHODS: The B beta gene FGB -455G/A polymorphism was identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 132 patients with ACI and 148 healthy controls matching on age and sex. Turbidimetric assays were performed to measure the plasma fibrinogen levels of all cases. RESULTS: The plasma fibrinogen level in ACI group (3.42+/-0.52 g/L), was significantly higher than that in the controls (2.96+/-0.42g/L), P<0.001. The A allele was associated with the elevated plasma fibrinogen levels in both patients and controls. Among the A allele carriers, smokers had significantly higher plasma fibrinogen levels than did the non-smokers (P<0.05). The distribution of B beta gene FGB -455G/A polymorphism was in accordance with the Hardy-Weinberg equilibrium (P>0.05). The A allelic frequency in ACI group (0.258) was significantly higher than that in the control group (0.152) (P<0.05). Logistic regression analysis showed that the cases carrying A allele (GA+AA genotype) had 1.653 times the risk of ACI. CONCLUSION: The study demonstrates that A allele of the B beta gene FGB -455G/A polymorphism may be a susceptible predictor of the occurrence of ACI, particularly in smokers.