Shuohua Chen

The effect of air pollution on human physiological function in China: a longitudinal study

Abstract Background Air pollution has been identified as a terrible environmental problem in China. However, no study has systematically assessed whether air pollution has adverse effects on human physiological function. Methods This study was based on longitudinal data collected by the Kailuan Cohort Study, which was conducted in the area of Kailuan community, Tangshan City, China. 11 hospitals were responsible for the health care of the community. We only used cohort data between 2006 and 2008, as we only had these two years air pollution data. We assessed each participant twice with a standardised questionnaire assessment, health examination, and laboratory assessment. The health examination and laboratory assessment included heart function, renal function, haematopoietic function, metabolic endocrine function, liver function, and inflammatory response function. The questionnaire collected individual characteristics (age, sex, weight, height, smoking status, drinking status, physical activity, dietary salt intake, financial income, work type, education level, and medical history, etc). Community level of daily concentrations of particles (PM 10 ), sulphur dioxide (SO 2 ) and nitrogen dioxide (NO 2 ) was provided by the Tangshan Environmental Monitoring Centre. We used generalised additive mixed models to examine the effects of community level of daily air pollutants on physiological function, while controlling for random effects of participants and other potential confounders. This study was approved by the University of Queenslands behaviour and social sciences ethical review committee (2014001075). Written informed consent was obtained for each participant. Findings Out of the 155u2009418 residents, 101u2009510 (65·31%; 81u2009110 (82%) men and 20u2009400 women) who provided a written informed consent, were enrolled in the Kailuan study since 2006. We followed up 27u2009685 participants twice between 2006 and 2008. Age ranged from 18 to 90 years, with mean of 47 years (SD 11·3). About 60% of the participants were not smokers or drinkers in 2006. The prevalence of diabetes was 7·7% in 2006, and 20·9% of participants had a history of hypertension. Increased concentrations of PM 10 , SO 2 , and NO 2 were significantly associated with decreases in all categories of physiological function, such as increase in heart rate and blood pressure (heart function), increase in urine creatinine and urea (renal function), decrease in haemoglobin and white blood cell (hematopoietic function), increase in cholesterol, low-density lipoprotein, high-density lipoprotein, and the ratio of low-density lipoprotein to high-density lipoprotein (metabolic endocrine function), increase in serum albumin, glutamic-pyruvic transaminase, and total bilirubin (liver function), and increase in C-reactive protein (inflammatory response function). Generally, elderly people, women, and people who were overweight were more susceptible to air pollution than young people, men, and people who were normal weight. Interpretation Air pollution could systemically damage human physiological function. Effective air pollution control is essential for disease prevention. We used community level of air pollution to estimate individual exposures rather than personal air pollution exposure data. This may underestimate the effects of air pollutants on physiological function. Funding University of Queensland Research Fellowship (YG). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients.

Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 × 107 to 3.0 × 1012 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 × 1012u2009VP and transient grade IV thrombocytopenia at the dose of 3.0 × 1012u2009VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4+ and CD8+ T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study

BACKGROUNDnTo investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes.nnnMETHODSnThe prospective analysis included 73,357 participants of the Kailuan cohort (57,719 men and 15,638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models.nnnRESULTSnDuring 4 years of follow-up, 17,463 incident IFG cases and 4,649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8).nnnCONCLUSIONnFaster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes.

Resting Heart Rate and Risk of Cardiovascular Diseases and All-Cause Death: The Kailuan Study

Background Resting heart rate (RHR) predicts both cardiovascular and noncardiovascular death in different populations. However, the results of the association between RHR and cardiovascular diseases (CVDs) are inconsistent, especially for each subtype of CVDs. Objective The aim of this study was to prospectively explore the relationship between RHR and CVDs including myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke and all-cause death in a general population. Methods The Kailuan study is a prospective longitudinal cohort study on cardiovascular risk factors and cardiovascular or cerebrovascular events. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results We analyzed 92,562 participants (18–98 years old) in the Kailuan Study. CVDs were developed in 1,903 people during follow-ups. In multivariate analysis with adjustment for major traditional cardiovascular risk factors, HRs of the highest quintile group compared with the lowest quintile group of RHR for all-cause CVDs, MI, any stroke, ischemic stroke, hemorrhagic stroke, and all-cause death were 1.03 (95% CI, 0.98–1.07), 1.10 (95% CI, 1.01–1.20), 1.01 (95% CI, 0.97–1.06), 1.02 (95% CI, 0.96–1.07), 1.01 (95% CI, 0.92–1.11) and 1.18, (95% CI, 1.13–1.23), respectively. Conclusions The elevated RHR was independently associated with the increased risk for MI and all-cause death, but not for all-cause CVDs, any stroke, ischemic stroke, nor hemorrhagic stroke. This indicates that the elevated RHR might be a risk marker for MI and all-cause death in general populations.

Risk factors for probable REM sleep behavior disorder: A community-based study.

Objective: To examine risk factors for REM sleep behavior disorder (RBD) in a large-scale community-based study. Methods: This community-based study included 12,784 Chinese adults (10,556 men and 2,228 women, aged 24 years or older) who were free of Parkinson disease and dementia in 2012. Probable RBD (pRBD) status was determined by a validated questionnaire (Chinese RBD questionnaire–Hong Kong) in 2012. Potential risk factors—including age, sex, smoking, socioeconomic status, physical activity, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, serum concentrations of lipids and glucose, and chronic disease status—were assessed in 2006. Logistic regression was used to calculate odds ratios and 95% confidence intervals and to test differences in prevalence of pRBD across exposures. Results: Prevalence of pRBD was 5.9% in men and 4.1% in women. In the fully adjusted model, risk factors that were significantly associated with a higher risk of having pRBD included lower education level, coal mining and other blue collar occupation, lower physical activity level, diabetes or prediabetes, lower body mass index, head injury, higher low-density lipoprotein level, and chronic olfactory and taste dysfunction. In sensitivity analyses, restricting to pRBD cases with symptom onset within 1 year or excluding coal miners or those with history of head injury generated similar results. Conclusion: We found several potential risk factors for pRBD, including socioeconomic status, head injury, olfactory and taste dysfunction, and various cardiovascular risk factors. Future prospective studies to establish the temporal relationship between these potential risk factors and RBD are warranted.

Cardiovascular Health Score and the Risk of Cardiovascular Diseases

In 2010 the American Heart Association proposed a definition of ideal health behaviors and health factors to measure cardiovascular health, from which Huffman et al. created the Cardiovascular Health Score (CVH score) to estimate these metrics on an individual level. We performed a prospective cohort study among employees of the Kailuan Group Corporation, who underwent a physical examination in 2006–2007 to investigate the relationship between the CVH score and the risk of cardiovascular disease (CVD). A total of 91,598 individuals free of stroke and myocardial infarction at baseline were included in the final analysis. We calculated baseline CVH score for each metric (poor=0, intermediate=1, ideal=2 points; range=0–14 points for all seven metrics) and categorized them into three groups: inadequate (0–4 points), average (5–9 points), and optimum (10–14 points). Incidence of total number of CVD events, myocardial infarction, and stroke was analyzed among these three groups and each incremental point on the CVH score. During an average 6.81 years of follow-up, there were 3276 CVD events, 2579 strokes and 747 myocardial infarction occurred. After adjusting for several confounding factors, each better health category of the CVH score was associated with reduced odds of 47% for all CVD events, and each point higher on the CVH score was associated with reduced odds of 18%. Similar trends were detected in the risks for myocardial infarction and stroke. A higher CVH score is therefore a protective factor for CVD, myocardial infarction, and stroke.

Homocysteine as a Risk Factor for Hypertension: A 2-Year Follow-Up Study

Homocysteine (Hcy) is regarded as a risk factor for hypertension, but research on the causal relationship between Hcy and hypertension is limited. In the present study, we prospectively tracked the blood pressure progression of a normotensive population with different Hcy levels over a 2-year period. The incidence of hypertension with increasing Hcy quartiles produced an approximately U-shaped curve, with significance in males. Compared with the third quartile, the risk of hypertension in the first and second quartiles was increased by 1.55 (95% confidence interval [CI] 1.154–2.081) fold and 1.501 (95% CI 1.119–2.013) fold, respectively, with the increase being more significant in males. In conclusion, Hcy is related to hypertension incidence with the results approximating an U-shaped curve. Low Hcy levels might also increase the risk of hypertension.

Association of Ideal Cardiovascular Metrics and Serum High-Sensitivity C-Reactive Protein in Hypertensive Population

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of cardiovascular disease. However, ideal cardiovascular health indicates lower risk of cardiovascular disease. This study aimed to investigate the effect of ideal cardiovascular health behaviors and health factors on hs-CRP levels among a hypertensive population. From 2006 to 2007, a cross-sectional study was conducted to survey 41,476 hypertensive subjects among the employees of Kailuan Corporation. Data from unified questionnaires and blood biochemical examinations were collected. The effects of ideal cardiovascular health behaviors and health factors on hs-CRP levels were evaluated through multivariate logistic regression analysis. A negative correlation was observed between hs-CRP levels and the number of ideal cardiovascular health metrics. The mean hs-CRP levels of subjects with zero to one, two, three, and four to six ideal cardiovascular health metrics were 1.11, 0.96, 0.90, and 0.80 mg/L, respectively (P<0.01). Multivariate logistic regression analysis revealed that after adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, the risks for subjects with two, three, and four to six ideal health metrics with serum hs-CRP >3 mg/L were lower than those with zero to one ideal health metrics, with corresponding odd ratios of 0.86 (95%CI: 0.79–0.93, P<0.01), 0.76 (95%CI: 0.69–0.83, P<0.01), and 0.68 (95%CI: 0.64–0.75, P<0.01), respectively. This finding suggests that ideal cardiovascular health behaviors and health factors were related to decreased hs-CRP levels in a hypertensive population. Clinical Trial Registration Unique identifier: ChiCTR-TNC-11001489.

Cumulative Exposure to Ideal Cardiovascular Health and Incident Diabetes in a Chinese Population: The Kailuan Study

Background It is unclear whether ideal cardiovascular health (CVH), and particularly cumulative exposure to ideal CVH (cumCVH), is associated with incident diabetes. We aimed to fill this research gap. Methods and Results The Kailuan Study is a prospective cohort of 101 510 adults aged 18 to 98 years recruited in 2006–2007 and who were subsequently followed up at 2‐ (Exam 2), 4‐ (Exam 3), and 6 (Exam 4)‐year intervals after baseline. The main analysis is restricted to those individuals with complete follow‐up at all 4 examinations and who had no history of diabetes until Exam 3. Cumulative exposure to ideal CVH (cumCVH) was calculated as the summed CVH score for each examination multiplied by the time between the 2 examinations (score×year). Logistic regression models were used to assess the association between cumCVH and incident diabetes. In fully adjusted models, compared with the lowest quintile of cumCVH, individuals in the highest quintile had ~68% (95% confidence interval [CI] 60‐75) lower risk for incident diabetes (compared with 61% [95% CI 52‐69] lower risk when using baseline CVH). Every additional year lived with a 1‐unit increase in ideal CVH was associated with a 24% (95% CI 21‐28) reduction in incident diabetes. Conclusions Ideal CVH is associated with a reduced incidence of diabetes, but the association is likely to be underestimated if baseline measures of CVH exposure are used. Measures of cumulative exposure to ideal CVH are more likely to reflect lifetime risk of diabetes and possibly other health outcomes. Clinical Trial Registration URL: https://www.chictr.org. Unique identifier: ChiCTRTNC‐11001489.

The product of resting heart rate times blood pressure is associated with high brachial-ankle pulse wave velocity.

Objective To investigate potential associations between resting heart rate, blood pressure and the product of both, and the brachial-ankle pulse wave velocity (baPWV) as a maker of arterial stiffness. Methods The community-based “Asymptomatic Polyvascular Abnormalities in Community (APAC) Study” examined asymptomatic polyvascular abnormalities in a general Chinese population and included participants with an age of 40+ years without history of stroke and coronary heart disease. Arterial stiffness was defined as baPWV≥1400 cm/s. We measured and calculated the product of resting heart rate and systolic blood pressure (RHR-SBP) and the product of resting heart rate and mean arterial pressure (RHR-MAP). Results The study included 5153 participants with a mean age of 55.1±11.8 years. Mean baPWV was 1586±400 cm/s. Significant (P<0.0001) linear relationships were found between higher baPWV and higher resting heart rate or higher arterial blood pressure, with the highest baPWV observed in individuals from the highest quartiles of resting heart rate and blood pressure. After adjusting for confounding parameters such as age, sex, educational level, body mass index, fasting blood concentrations of glucose, blood lipids and high-sensitive C-reactive protein, smoking status and alcohol consumption, prevalence of arterial stiffness increased significantly (P<0.0001) with increasing RHR-SBP quartile (Odds Ratio (OR): 2.72;95%Confidence interval (CI):1.46,5.08) and increasing RHR-MAP (OR:2.10;95%CI:1.18,3.72). Similar results were obtained in multivariate linear regression analyses with baPWV as continuous variable. Conclusions Higher baPWV as a marker of arterial stiffness was associated with a higher product of RHR-SBP and RHR-MAP in multivariate analysis. In addition to other vascular risk factors, higher resting heart rate in combination with higher blood pressure are risk factors for arterial stiffness.