Aims To quantify the association of combined sleep behaviours and genetic susceptibility with the incidence of cardiovascular disease (CVD). Methods and results This study included 385 292 participants initially free of CVD from UK Biobank. We newly created a healthy sleep score according to five sleep factors and defined the low-risk groups as follows: early chronotype, sleep 7–8 h per day, never/rarely insomnia, no snoring, and no frequent excessive daytime sleepiness. Weighted genetic risk scores of coronary heart disease (CHD) or stroke were calculated. During a median of 8.5 years of follow-up, we documented 7280 incident CVD cases including 4667 CHD and 2650 stroke cases. Compared to those with a sleep score of 0–1, participants with a score of 5 had a 35% (19–48%), 34% (22–44%), and 34% (25–42%) reduced risk of CVD, CHD, and stroke, respectively. Nearly 10% of cardiovascular events in this cohort could be attributed to poor sleep pattern. Participants with poor sleep pattern and high genetic risk showed the highest risk of CHD and stroke. Conclusion In this large prospective study, a healthy sleep pattern was associated with reduced risks of CVD, CHD, and stroke among participants with low, intermediate, or high genetic risk.

Rationale: In observational studies, type 2 diabetes mellitus (T2D) has been associated with an increased risk of hypertension, and vice versa; however, the causality between these conditions remains to be determined. Objectives: This population-based prospective cohort study sought to investigate the bidirectional causal relations of T2D with hypertension, systolic and diastolic blood pressure (BP) using Mendelian randomization (MR) analysis. Methods and Results: After exclusion of participants free of a history of heart failure, cardiovascular disease, cardiac procedures, and non-T2D diabetes mellitus, a total of 318 664 unrelated individuals with qualified genotyping data of European descent aged 37 to 73 from UK Biobank were included. The genetically instrumented T2D and hypertension were constructed using 134 and 233 single nucleotide polymorphisms, respectively. Seven complementary MR methods were applied, including inverse-variance weighted method, 2 median-based methods (simple and weighted), MR-Egger, MR-robust adjusted profile scores, MR-Pleiotropy Residual Sum and Outlier, and multivariate MR. The genetically instrumented T2D was associated with risk of hypertension (odds ratio, 1.07 [95% CI, 1.04–1.10], P =3.4×10 −7 ), whereas the genetically determined hypertension showed no relationship with T2D (odds ratio, 0.96 [0.88–1.04], P =0.34). Our MR estimates from T2D to BP showed that the genetically instrumented T2D was associated with a 0.67 mm Hg higher systolic BP (95% CI, 0.41–0.93, P =5.75×10 –7 ) but not with a higher diastolic BP. There was no clear evidence showing a causal effect of elevated systolic BP or diastolic BP on T2D risk. Positive pleiotropic bias was indicated in the hypertension→T2D relation (odds ratio, of MR-Egger intercept 1.010 [1.004–1.016], P =0.001) but not from T2D to hypertension (1.001 [0.998–1.004], P =0.556). Conclusions: T2D may causally affect hypertension, whereas the relationship from hypertension to T2D is unlikely to be causal. These findings suggest the importance of keeping an optimal glycemic profile in general populations, and BP screening and monitoring, especially systolic BP, in patients with T2D.

IntroductionNumerous studies have reported a strong inverse association between BMI and physical activity in western populations. Recently, the association between BMI and physical activity has been considered bidirectional. This study aimed to examine the associations of body mass index (BMI) with physical activity and sedentary behavior and to explore whether those associations were modified by socio-demographic characteristics.Materials and MethodsWe conducted a multistage random sampling survey in three districts of Hangzhou, China, in 2012. The International Physical Activity Questionnaire long form was used to collect data regarding physical activity and sedentary behavior. A multilevel mixed-effects regression model was used to assess the associations of BMI with physical activity and sedentary behavior.ResultsA total of 1362 eligible people (624 men and 738 women, ages 23-59 years) completed the survey. People who are young or middle-aged and have the highest education level are the most inactive. Significant differences in the associations between physical activity and BMI across socio-demographic groups were identified (sex*BMI, P=0.018; age*BMI, P<0.001; education level*BMI, P=0.030). Women or individuals older than 50 had a higher level of physical activity with increasing BMI. There was no statistically significant association between BMI and sedentary behavior (P=0.450).ConclusionsThe associations between BMI and physical activity were modified by sex, age, and education level in Hangzhou, China.

Objectives:We aimed to prospectively examine the associations of total, domain-specific, and intensity-specific physical activity with all-cause and cardiovascular mortality among Chinese hypertensive adults.Methods:We performed a prospective cohort study in 150 391 hypertensive participants aged 30–79 years from the China Kadoorie Biobank study of 512 891 participants recruited from 10 diverse areas across China during 2004–2008. Participants with heart disease, stroke, chronic obstructive pulmonary disease, and cancer at baseline were excluded.Results:During 1069 863 person-years of follow-up (median 7.1 years), a total of 5332 men and 4384 women died. Compared with hypertensive participants in the lowest level of total physical activity, the hazard ratios for all-cause mortality were 0.80 (0.76–0.84), 0.69 (0.65–0.73), and 0.67 (0.62–0.72) for those in quartiles 2–4 (Ptrend < 0.001), respectively. Inverse associations were also observed for cardiovascular mortality. Being active in occupational, domestic, and leisure time were associated with lower risk of all-cause and cardiovascular mortality. However, the adjusted ratio for active commuting was 1.08 (1.02–1.15) for all-cause mortality. High levels of low-intensity, moderate-intensity, and vigorous-intensity physical activity were consistently associated with lower risks of all-cause and cardiovascular mortality.Conclusion:Among Chinese hypertensive adults, a higher level of physical activity reduces all-cause and cardiovascular mortality, independent of intensities of physical activity. Not only leisure-time but also occupational and domestic physical activities were benefited.

BackgroundActive commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population.Methods and ResultsA total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self‐reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow‐up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84–0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74–0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84–1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity.ConclusionsIn urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

Allergic asthma is a chronic inflammatory disease mediated by Th2 cell immune responses. Currently, immunotherapies based on immune deviation are attractive, preventive, and therapeutic strategies for asthma. Many studies have shown that intracellular bacterial infections such as mycobacteria and their components can suppress asthmatic reactions by enhancing Th1 responses, while helminth infections and their proteins can inhibit allergic asthma via immune regulation. However, some helminth proteins such as SmP40, the major egg antigen of Schistosoma mansoni, are found as Th1 type antigens. Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions.Keywords: Asthma r peptides r Schistosoma japonicum r SjP40 r Th1 epitope Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAllergic asthma is a chronic airway disorder characterized by reversible airflow obstruction, increased allergen-specific IgE production, and predominant eosinophilic airway inflammation [1]. From immunology point of view, the pathology in asthma occurs Correspondence: Dr. Peimei Liu e-mail: liupeimei63@126.com as a consequence of increased Th2 type immune responses, especially overproduction of IL-4, IL-5, and IL-13 by allergen-specific CD4 + T helper (Th) cells [2,3].The prevalence of allergy and asthma has increased markedly over the past decades world-wide, not only in developed but also developing areas [4,5]. The reason for this dramatic increase * These authors contributed equally to this work. Eur. J. Immunol. 2016Immunol. . 46: 1203Immunol. -1213 remains unclear. It was believed that an insufficient stimulation of the Th1 responses due to limited exposure to bacterial and viral pathogens could not counterbalance the expansion of Th2 responses resulting in predisposition of allergy. However, the distorted Th1/Th2 balance could not explain the simultaneous increase in several Th1-mediated auto-immune diseases together with the increase in allergic disorders in the same countries. Then it is suggested that more vital microbial exposures, such as chronic infections (helminthes) and commensals seem to be important to prevent the development of hyperinflammatory responses [6]. Therefore, the induction of a strong regulatory network (tolerogenic DC, Treg, Breg, Tr-1, Tr-3) and Th1 responses by these microbes is an important factor in controlling the diseases.Immunotherapy based on immune deviation is an effective strategy to treat or prevent allergic asthma. Live and dead bacteria, parasite, or bacterial components such as purified protein derivative from Mycobacterium tuberculosis have shown potential to prote...

ObjectiveThe application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson’s disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system.DesignPopulation-based prospective cohort study.SettingThe China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline.Primary and secondary outcome measuresIncident events of predefined major vascular and non-vascular diseases.ResultsIn multivariable-adjusted analyses, participants having bowel movements ‘more than once a day’ had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group (‘once a day’). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF (‘less than three times a week’) was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35).ConclusionBMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered.

Background and Purpose Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. Methods The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. Results About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed ( P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. Conclusions Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.