Impaired kidney function and the risk of all-cause mortality and cardiovascular disease among Chinese hypertensive adults: Using three different equations to estimate the glomerular filtration rate.

OBJECTIVES: We aimed to seek accurate assessments of the glomerular filtration rate (GFR) in a Chinese hypertensive population to identify individuals at high risk for chronic kidney disease (CKD) progression. Then, the risk of cardiovascular disease (CVD) and all-cause death due to kidney injury were further investigated under appropriate GFR-estimation equations. METHODS: In this prospective follow-up cohort study of 10,171 hypertensive patients, we compared the discrimination power of a trio of GFR-estimation equations using Harrell's C-index, measuring the model fit by calculating the Akaike information criterion. Univariate and multivariable logistic regression analyses were respectively used to calculate the hazard ratio (HR) and 95% confidence interval [CI] values for CKD progression. In addition, we also assessed the risk of CVD and all-cause death with impaired renal function using multivariable-adjusted Cox regression models. RESULTS: The Modification of Diet in Renal Disease (MDRD) equation showed the highest C-index range for the predicted probability of CKD progression in the fully adjusted model. During MDRD analysis, a low eGFR (60-89 mL/min/1.73m2 or < 60 mL/min/1.73m2) was an independent risk factor for CVD, especially stroke (1.28 [95% CI, 1.05-1.55] and 1.89 [95% CI, 1.08-3.31]), as well as all-cause mortality (1.28 [95% CI, 1.09-1.50] and 1.68 [95% CI, 1.01-2.78]). CONCLUSIONS: The MDRD equation seems to be more suitable for screening CKD progression in Chinese hypertensive populations, targeting potential risk factors for effective prevention to reduce renal impairment so as to further limit CVD morbidity and mortality.

CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema.

Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)-induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.

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.

The aberrant cross-talk of epithelium-macrophages via METTL3-regulated extracellular vesicle miR-93 in smoking-induced emphysema.

Cigarette smoke (CS), a complex chemical indoor air pollutant, induces degradation of elastin, resulting in emphysema. Aberrant cross-talk between macrophages and bronchial epithelial cells is essential for the degradation of elastin that contributes to emphysema, in which extracellular vesicles (EVs) play a critical role. The formation of N6-methyladenosine (m6A) is a modification in miRNA processing, but its role in the development of emphysema remains unclear. Here, we established that production of excess mature microRNA-93 (miR-93) in bronchial epithelial cells via enhanced m6A modification was mediated by overexpressed methyltransferase-like 3 (METTL3) induced by CS. Mature miR-93 was transferred from bronchial epithelial cells into macrophages by EVs. In macrophages, miR-93 activated the JNK pathway by targeting dual-specificity phosphatase 2 (DUSP2), which elevated the levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 12 (MMP12) and induced elastin degradation, leading to emphysema. These results demonstrate that METTL3-mediated formation of EV miR-93, facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 may use as a novel risk biomarker for CS-induced emphysema.

Effect of group cognitive behavioural therapy on psychological stress and blood glucose in people with type 2 diabetes mellitus: A community-based cluster randomized controlled trial in China.

OBJECTIVE: To assess whether group cognitive behavioural therapy (GCBT) delivered by general practitioners reduces anxiety and depression and improves glycaemic levels in adults with type 2 diabetes mellitus. METHODS: We conducted a community-based cluster randomized controlled trial in adults with type 2 diabetes mellitus from 48 communities in China. Participants received either GCBT plus usual care (UC) or UC only. General practitioners were trained in GCBT before intervention in the intervention group. The primary outcome was glycated haemoglobin (HbA1c ) concentration. Outcome data were collected from all participants at baseline, 2 months, 6 months and 1 year. The secondary outcomes were depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (General Anxiety Disorder questionnaire; GAD-7). RESULTS: The GCBT group showed greater improvement in GAD-7 and PHQ-9 scores, respectively, than the UC group after 2 months post-baseline (T = -6.46, p < 0.0001; T = -5.29, p < 0.001), 6 months (T = -4.58, p < 0.001; T = -4.37, p < 0.001) and 1 year post-intervention (T = -3.91, p < 0.001; T = -3.57, p < 0.001). There was no difference in HbA1c values between the GCBT and UC groups at 2 months while the values were lower in the GCBT group at 6 months and 1 year (T = -6.83, p < 0.001; T = -4.93, p < 0.001, respectively). Subgroup analysis indicated a long-term effect of GCBT only for mild and moderate anxiety and mild depression groups. Similarly, HbA1c values reduced only in the mild and moderate anxiety and the mild depression groups. CONCLUSIONS: General practitioners can deliver GCBT interventions. GCBT plus UC is superior to UC for reducing mild/moderate anxiety and depression, and improving glycaemic levels. TRIAL REGISTRATION: Chinese clinical trials registration (ChiCTR-IOP-16008045).

Effects of cognitive behavioral therapy on sleep disturbances and quality of life among adults with type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND AND AIMS: Cognitive behavioral therapy (CBT) is recommended as the first-line nonpharmacotherapy for sleep complaints. However, there are no studies that tested CBT for improving sleep quality and increasing quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to test the effect of CBT on sleep disturbances and QOL in patients with T2DM. METHODS AND RESULTS: In total, 187 participants with T2DM and comorbid poor sleep quality were included in the analysis with the control group of 93 receiving usual care (UC) only and the intervention group of 94 receiving CBT with aerobic exercise plus UC, The Pittsburgh Sleep Quality Index (PSQI), the Diabetes-Specific Quality of Life Scale (DSQLS) and the glycated hemoglobin (HbA1C) values were collected at baseline, after the 2-month intervention, and 6 months of follow-up. The CBT group had 3.03 points lower PSQI scores (95% confidence interval [CI]: 2.07-4.00, P < 0.001) and 7.92 points lower total DSQLS scores (95% CI: 4.98-10.87, P < 0.001) than the control group after 6-month follow-up. No difference was found in HbAlc between the two groups (t = -0.47, P = 0.64) after 2-month intervention, while the CBT group had 0.89 units lower HbAlc (95% CI: 0.49-1.28, P < 0.001) than the control group after 6-month follow-up. CONCLUSION: CBT is effective for sleep disturbances and can also improve sleep quality, increase QOL, and decrease glycemic levels in participants with T2DM. TRIAL REGISTRATION: Chinese Clinical Trials Registration (Practical study of the appropriate technique for improvement of quality of life of the patients with type 2 diabetes in communities: ChiCTR-IOP-16008045).

MALAT1 via microRNA-17 regulation of insulin transcription is involved in the dysfunction of pancreatic ß-cells induced by cigarette smoke extract.

Cigarettes contain various chemicals with the potential to influence metabolic health. Exposure to cigarette smoke causes a dysfunction in pancreatic ß-cells and impairs insulin production. However, the mechanisms for cigarette smoke-induced reduction of insulin remain largely unclear. Data from 558 patients with diabetes showed that, with smoking pack-years, homeostatic model assessment (HOMA)-ß (a method for assessing ß-cell function) decreased and that HOMA of insulin resistance increased. For ß-cells (MIN6), cigarette smoke extract (CSE) increased the levels of thioredoxin-interacting protein (TXNIP) and the long noncoding (lnc)RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and downregulated the levels of the transcription factor, mafA, and microRNA (miR)-17. MALAT1, one of four lncRNAs predicted to regulate miR-17, was knocked down by small interfering RNA (siRNA). For these cells, an miR-17 mimic inhibited TXNIP and enhanced the production of insulin. Knockdown of MALAT1 induced an increase in miR-17, which suppressed TXNIP and promoted the production of insulin. In the sera of patients with diabetes who smoked, there were higher MALAT1 levels and lower miR-17 levels than in the sera of nonsmokers. Thus, CSE inhibits insulin production by upregulating TXNIP via MALAT1-mediated downregulation of miR-17, which provides an understanding of the processes involved in the reduced ß-cells function caused by cigarette smoke.

Depression among the general adult population in Jiangsu Province of China: prevalence, associated factors and impacts.

PURPOSE: This study aimed to assess the prevalence of depression and to investigate its associated factors and impacts on daily life functioning among the general adult population in Jiangsu Province of China. METHODS: As part of the Jiangsu Provincial Survey on Chronic Disease and Behavioural Risk Factors (2010), a sample of 8400 community residents aged ≥ 18 years were recruited. Study data were collected through a questionnaire-administered face-to-face interview. Depression was measured by the Patient Health Questionnaire. RESULTS: The estimated prevalence of depression was 0.56% (0.54% in men and 0.58% in women). Increased risk of depression was found to be associated with rural residents (OR 2.24, 95% CI 1.33-3.78) and the comorbidity of chronic diseases (OR 3.83, 95% CI 1.33-11.02). Respondents with depression reported an average of 11.75 unhealthy days caused by physical illnesses and 8.31 unhealthy days by mood problems within the previous 30 days. Depression was also found to be related to worse self-ranked health status, worse relationships with families and lower life satisfaction. CONCLUSIONS: A low prevalence of depression was found in this population of China, though it is not clear the extent to which it reflects issues related to the measurement and/or other factors of the survey. Depression was found to be related to poorer health and poorer life functioning. Further research into the link between depression and access to mental health services in rural areas is necessary. Meanwhile, depression among chronic disease patients should be addressed in clinical settings, health plans and resources allocation.

Accuracy of self-reported height, weight, and waist circumference in a general adult Chinese population.

BACKGROUND: Self-reported height, weight, and waist circumference (WC) are widely used to estimate the prevalence of obesity, which has been increasing rapidly in China, but there is limited evidence for the accuracy of self-reported data and the determinants of self-report bias among the general adult Chinese population. METHODS: Using a multi-stage cluster sampling method, 8399 residents aged 18 or above were interviewed in the Jiangsu Province of China. Information on self-reported height, weight, and WC, together with information on demographic factors and lifestyle behaviors, were collected through structured face-to-face interviews. Anthropometrics were measured by trained staff according to a standard protocol. RESULTS: Self-reported height was overreported by a mean of 1.1 cm (95 % confidence interval [CI]: 1.0 to 1.2). Self-reported weight, body mass index (BMI), and WC were underreported by -0.1 kg (95 % CI: -0.2 to 0.0), -0.4 kg/m(2) (95 % CI: -0.5 to -0.3) and -1.5 cm (95 % CI: -1.7 to -1.3) respectively. Sex, age group, location, education, weight status, fruit/vegetable intake, and smoking significantly affected the extent of self-report bias. According to the self-reported data, 25.5 % of obese people were misclassified into lower BMI categories and 8.7 % of people with elevated WC were misclassified as normal. Besides the accuracy, the distribution of BMI and WC and their cut-off point standards for obesity of a population affected the proportion of obesity misclassification. CONCLUSION: Amongst a general population of Chinese adults, there was rather high proportion of obesity misclassification using self-reported weight, height, and WC data. Self-reported anthropometrics are biased and misleading. Objective measurements are recommended.

Epigenetic silencing of microRNA-218 via EZH2-mediated H3K27 trimethylation is involved in malignant transformation of HBE cells induced by cigarette smoke extract.

Abnormal expression of miRNAs has been implicated in the pathogenesis of human lung cancers, most of which are attributable to cigarette smoke. The mechanisms of action, however, remain obscure. Here, we report that there are decreased expression of miR-218 and increased expression of EZH2 and H3K27me3 during cigarette smoke extract (CSE)-induced transformation of human bronchial epithelial (HBE) cells. Depletion of EZH2 by siRNA or by the EZH2 inhibitor, 3-deazaneplanocin A, attenuated CSE-induced decreases of miR-218 levels and increases of H3K27me3, which epigenetically controls gene transcription, and BMI1, an oncogene. Furthermore, ChIP assays demonstrated that EZH2 and H3K27me3 are enriched at the miR-218-1 promoter in HBE cells exposed to CSE, indicating that EZH2 mediates epigenetic silencing of miR-218 via histone methylation. In addition, miR-218 directly targeted BMI1, through which miR-218 ablates cancer stem cells (CSCs) self-renewal in transformed HBE cells. In CSE-transformed HBE cells, the protein level of Oct-4 and mRNA levels of CD133 and CD44, indicators of the acquisition of CSC-like properties, were reduced by over-expression of miR-218, and over-expression of miR-218 decreased the malignancy of transformed HBE cells. Thus, we conclude that epigenetic silencing of miR-218 via EZH2-mediated H3K27 trimethylation is involved in the acquisition of CSC-like properties and malignant transformation of HBE cells induced by CSE and thereby contributes to the carcinogenesis of cigarette smoke.

Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China.

We carry out a study to analyze the relation between polymorphisms of GSTT1, GSTM1 and the capacity of arsenic methylation in a human population exposed to arsenic in drinking water. 230 randomly chose subjects were divided into four subgroups based on the arsenic levels, and then the associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic were investigated. The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (TAs) in urine were higher in males than that in females. Moreover, the levels of iAs and TAs in urine in the subjects with genotype of GSTM1(+) were significantly higher than those with GSTM1(-); the level of DMA in the subjects with GSTT1(+) and GSTM1(+) were higher than those with GSTT1(-) and GSTM1(-), although it is not statistically significant. Secondary methylation index (SMI) was significantly higher in the subjects with genotype of GSTT1(+) than those with GSTT1(-). The levels of TAs in urine, together with the genotypes of GSTT1/GSTM1 were associated with the levels of MMA and DMA. Our results suggested that the polymorphisms of GSTT1 and GSTM1 were associated with the methylation of arsenic, especially the levels of DMA and SMI.

[Relationship between central obesity and clustering of cardiovascular risk factors in adults of Jiangsu province].

OBJECTIVE: To explore the relationship between central obesity and cardiovascular risk factors and their clustering in adults of Jiangsu province. METHODS: Multi-stratified clustering sampling method was used to sample 8 400 residents aged 18 years and over from 14 diseases surveillance units in Jiangsu province from October to December 2010. Information was obtained with face-to-face interview, physical examination and laboratory testing. A total of 8 380 residents finished the study protocol and their data were analyzed. Central obesity was defined as waist circumference ≥ 85 cm in males or ≥ 80 cm in females. Following complex weighting of the samples, level and proportion of cardiovascular risk factors in group with different waist circumference were analyzed. RESULTS: The prevalence of central obesity among adults in Jiangsu province was 46.2%, the proportion of males and females was 46.4% and 46.1%, respectively (P > 0.05). The prevalence of center obesity varied significantly in residents with different age, area, education and occupation (all P < 0.01). The level of systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol was also significantly different in residents with different degree of waist circumference (all P < 0.01). The prevalence of hypertension, diabetes, dyslipidemia and clustering of cardiovascular risk factors increased in proportion to increasing waist circumference (all P < 0.05). Multivariate logistic regression analysis showed that the risk of hypertension, diabetes, dyslipidemia and clustering of cardiovascular risk factors was 2.2 (OR = 2.2, 95% CI: 2.0-2.4) and 4.7 (OR = 4.7, 95% CI: 3.9-5.7); 2.1 (OR = 2.1, 95% CI: 1.7-2.5) and 3.8 (OR = 3.8, 95% CI: 3.2-4.5); 2.3 (OR = 2.3, 95% CI: 1.8-2.9) and 4.1 (OR = 4.1, 95% CI: 3.2-5.3); 3.4 (OR = 3.4, 95% CI: 2.9-3.9) and 8.0 (OR = 8.0, 95% CI: 6.2-10.2) fold higher in residents with mild and severe central obesity than residents without central obesity. CONCLUSIONS: The extent of central obesity positively correlates with the prevalence of cardiovascular risk factors and their clustering in adults of Jiangsu province. Comprehensive interventions on obesity serve as an important tool to reduce the cardiovascular risk in adult Jiangshu residents.

Effectiveness of a television advertisement campaign on giving cigarettes in a chinese population.

BACKGROUND: Anti-tobacco television advertisement campaigns may convey messages on smoking-related health consequences and create norms against giving cigarettes. METHODS: Altogether, 156 and 112 slots of a television advertisement "Giving cigarettes is giving harm" were aired on Suzhou and Yizheng, respectively, over one month in 2010. Participants were recruited from 15 locations in Suzhou and 8 locations in Yizheng using a street intercept method. Overall 2306 residents aged 18-45 years completed questionnaires, including 1142 before the campaign and 1164 after, with respective response rates of 79.1% and 79.7%. Chi square tests were used to compare the difference between categorical variables. RESULTS: After the campaign, 36.0% of subjects recalled that they had seen the advertisement. Residents of Suzhou had a higher recall rate than those of Yizheng (47.6% vs. 20.6%, P < 0.001). The rate of not giving cigarettes dropped from 32.1% before the campaign to 28.5% after (P = 0.05). In the post-campaign evaluation, participants who reported seeing the advertisement were more likely not to give cigarettes in the future than those who reported not seeing the advertisement (38.7% vs. 27.5%, P < 0.001). CONCLUSIONS: Our study showed that an anti-tobacco television advertisements helped change societal norms and improve health behavior. Continuous and adequate funding of anti-tobacco media campaigns targeted at different levels of the general population is needed, in conjunction with a comprehensive tobacco control effort.

Thoracic high resolution computed tomography evaluation of imaging abnormalities of 108 lung cancer patients with different pulmonary function.

PURPOSE: Preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) belong to lung function injury. PRISm is a precursor to COPD. We compared and evaluated the different basic information, imaging findings and survival curves of 108 lung cancer patients with different pulmonary function based on high resolution computed tomography (HRCT). METHODS: This retrospective study was performed on 108 lung cancer patients who did pulmonary function test (PFT) and thoracic HRCT. The basic information was evaluated: gender, age, body mass index (BMI), smoke, smoking index (SI). The following pulmonary function findings were evaluated: forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio. The following computed tomography (CT) findings were evaluated: appearance (bronchiectasis, pneumonectasis, atelectasis, ground-glass opacities [GGO], interstitial inflammation, thickened bronchial wall), diameter (aortic diameter, pulmonary artery diameter, MPAD/AD ratio, inferior vena cava diameter [IVCD]), tumor (volume, classification, distribution, staging [I, II, III, IV]). Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. RESULTS: Compared with normal pulmonary function group, PRISm group and COPD group were predominantly male, older, smoked more, poorer lung function and had shorter survival time after diagnosis. There were more abnormal images in PRISm group and COPD group than in normal lung function group (N-C group). In PRISm group and COPD group, lung cancer was found late, and the tumor volume was larger, mainly central squamous carcinoma. But the opposite was true for the N-C group. The PRISm group and COPD group had significant poor survival probability compared with the normal lung function group. CONCLUSIONS: Considerable differences regarding basic information, pulmonary function, imaging findings and survival curves are found between normal lung function group and lung function injury group. Lung function injury (PRISm and COPD) should be taken into account in future lung cancer screening studies.

Serum creatinine levels, traditional cardiovascular risk factors and 10-year cardiovascular risk in Chinese patients with hypertension.

Background: Serum creatinine is associated with cardiovascular risk and cardiovascular events, however, the relationship between serum creatinine levels and cardiovascular risk is not well established in hypertensive population in Jiangsu Province. We aimed to evaluate the association of serum creatinine levels with traditional cardiovascular risk factors and 10-year cardiovascular risk in a Chinese hypertensive population. Methods: Participants were patients with hypertension registered and enrolled in health service centers in 5 counties or districts from January 2019 to May 2020 in Jiangsu Province of China followed strict inclusion and exclusion criteria, demographics as well as clinical indicators and disease history and lifestyle were collected. Participants were divided into four groups according to quartiles of serum creatinine levels, then the China-PAR model was used to calculate 10-year cardiovascular risk for each individual. Results: A total of 9978 participants were enrolled in this study, 4173(41.82%) were males. The blood pressure level and prevalence of dyslipidemia, elderly, current smokers and drinking as well as obesity were higher in the Q4 group than the Q1 group (all P < 0.05). Multivariable logistic regression showed that serum creatinine in the Q4 group compared with that in the Q1 group was positively associated with overweight and obesity (OR=1.432, 95% CI 1.237-1.658, P<0.001), while negatively associated with physical activity (OR=0.189, 95%CI 0.165-0.217, P<0.001), and so on. Multiple linear regression showed 10-year cardiovascular risk is positively associated with serum creatinine levels after adjusting for multiple risk factors (ß=0.432, P< 0.001). Conclusion: Serum creatinine was associated with several traditional cardiovascular risk factors and the 10-year cardiovascular risk in hypertensive patients. Creatinine-reduction and kidney-sparing therapy are essential for patients with hypertension to optimize control of cardiovascular risk.

N6-Methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2.

Epithelial cell damage-initiated chronic obstructive pulmonary disease (COPD) is implicated in regulated cell death (RCD) including ferroptosis triggered by complex gene-environment interactions. Our data showed that iron overload and ferroptosis are associated with COPD progression in COPD patients and in experimental COPD. Furthermore, we found that, in lung tissues of COPD patients, circSAV1 was associated with COPD progression by circRNA-seq screening. Knockdown of circSAV1 reversed cigarette smoke extract (CSE)-induced ferroptosis. Mechanistically, m6A-modified circSAV1 formed an RNA-protein ternary complex of circSAV1/YTHDF1/IREB2 to facilitate the translation of IREB2 mRNA. Elevated protein levels of IREB2 disrupted iron homeostasis, resulting in accumulation of a labile iron pool (LIP) and lipid peroxidation, which contribute to ferroptosis. Here we demonstrate, by use of an experimental COPD model induced by cigarette smoke (CS), that silencing of circSAV1 and the treatment with deferoxamine (DFO) blocked CS-induced ferroptosis of lung epithelial cells, which attenuated COPD progression in mice. Our results reveal that N6-methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2, indicating that circSAV1 is a mediator of ferroptosis and that circSAV1-dependent ferroptosis is a therapeutic target for COPD. In lung epithelial cell, m6A-modified circSAV1, via recruiting YTHDF1, induces the formation of a circSAV1/YTHDF1/IREB2 mRNA protein ternary complex, which promotes translation of IREB2 mRNA. Further, elevated IREB2 contributes to the accumulation of a labile iron pool (LIP) and lipid peroxidation, then triggers ferroptosis of lung epithelial cells. The ferroptosis of airway epithelial cells and alveolar epithelial cells induces airway remodeling and emphysema, respectively, which causes COPD.

Associations of outdoor fine particulate air pollution and cardiovascular disease: Results from the Prospective Urban and Rural Epidemiology Study in China (PURE-China).

BACKGROUND: Evidence on whether an excess risk of incidence and mortality of cardiovascular disease (CVD) among people exposed to a high level of ambient PM2.5 in low- and middle-income countries (LMICs) is lacking. This study aimed to investigate the associations between long-term exposure to ambient fine particulate matter<2.5 µm (PM2.5) concentrations and the risk of incidence and mortality of CVD in a large cohort study from 115 communities. METHODS: In this cohort study, we followed 42 160 adults aged 35-75 years at baseline who enrolled in the Prospective Urban and Rural Epidemiology Study conducted in China (PURE-China) between 2005 and 2009 with ambient PM2.5 estimates, and followed up until August 2021. Cox proportional hazards frailty models were used to estimate the associations between long-term mean outdoor PM2.5 concentrations and CVD events, CVD mortality, and all-cause mortality. FINDINGS: During a median follow-up period of 11.8 years, we documented 2 190 deaths, including 732 CVD deaths. There were 4 559 (10.8 %) of 42 160 participants who experienced incident total CVD, among them there were 861 myocardial infarctions (MI) and 2 338 S. The 3-year median concentration of ambient PM2.5 before the cohort commencement was 52.7 µg/m3 (interquartile range [IQR] 30.3-74.6). In full adjusted model, a 10 µg/m3 increase in PM2.5 was associated with a hazard ratio (HR) of 1.12 (95 % CI 1.11-1.14) for major CVD and 1.03 (95 % CI 1.01-1.05) for all-cause mortality. Besides, long-term PM2.5 concentrations had a significantly positive gradient association with total CVD and a similar pattern of associations with other CVD outcomes was observed. INTERPRETATION: This study demonstrated that long-term ambient PM2.5 concentrations is positively associated with increased risks of CVD in adults aged 35-70 years from China. This finding reinforces the need for policymakers to adopt more effective strategies to improve air quality.

Socioeconomic disparity in mortality and the burden of cardiovascular disease: analysis of the Prospective Urban Rural Epidemiology (PURE)-China cohort study.

BACKGROUND: Although socioeconomic inequality in cardiovascular health has long been a public health focus, the differences in cardiovascular-disease burden and mortality between people with different socioeconomic statuses has yet to be adequately addressed. We aimed to assess the effects of socioeconomic status, measured via three socioeconomic-status indicators (ie, education, occupation, and household wealth and a composite socioeconomic-status disparity index, on mortality and cardiovascular-disease burden (ie, incidence, mortality, and admission to hospital) in China. METHODS: For this analysis, we used data from the Prospective Urban Rural Epidemiology (PURE)-China cohort study, which enrolled adults aged 35-70 years from 115 urban and rural areas in 12 provinces in China between Jan 1, 2005, and Dec 31, 2009. Final follow-up was on Aug 30, 2021. Indicators of socioeconomic status were education, occupation, and household wealth; these individual indicators were also used to create an integrated socioeconomic-status index via latent class analysis. Standard questionnaires administered by trained researchers were used to obtain baseline data and were supplemeted by physical measurements. The primary outcomes were all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital. Hazard ratios (HRs) and average marginal effects were used to assess the association between the primary outcomes and socioeconomic status. FINDINGS: Of 47 931 participants enrolled in the PURE-China study, 47 278 (98·6%) had complete information on sex and follow-up. After excluding 1189 (2·5%) participants with missing data on education, household wealth, and occupation at baseline, 46 089 participants were included in this analysis. Median follow-up was 11·9 years (IQR 9·5-12·6); 26 860 (58·3%) of 46 089 participants were female and 19 229 (41·7%) were male. Having no or primary education, unskilled occupation, or being in the lowest third of household wealth was associated with a higher risk of all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital compared with having higher education, a professional or managerial occupation, or more household wealth. After adjustment for confounders, people categorised as having low integrated socioeconomic status based on the index had a higher risk of all-cause mortality (HR 1·65 [95% CI 1·42-1·92]), cardiovascular-disease mortality (2·19 [1·68-2·85]), non-cardiovascular disease mortality (1·43 [1·18-1·72]), major cardiovascular disease (1·43 [1·27-1·61]) and cardiovascular-disease admission to hospital (1·14 [1·01-1·28]) compared with people categorised as having high integrated socioeconomic status. INTERPRETATION: Socioeconomic-status inequalities in mortality and cardiovascular-disease outcomes exist in China. Targeted policies of equal health-care resource allocation should be promoted to equitably benefit people with fewer years of education and less household wealth. FUNDING: Funding sources are listed at the end of the Article.

The Role of Cumulative Mean Arterial Pressure Levels in First Stroke Events Among Adults with Hypertension: A 10-Year Prospective Cohort Study.

Background: Mean arterial pressure (MAP) has been proved to be an independent risk factor for stroke. In this study, we explored whether cumulative exposure of MAP in patients with hypertension is more associated with the occurrence of stroke. Methods: In this prospective follow-up cohort study of hypertension from June 2010 to May 2020, 9136 participants without previous stroke at recruitment were included, of whom 492 (5.4%) had a first incident stroke during the study period (418 ischemic strokes and 74 hemorrhagic strokes). The study exposure factor was cumulative MAP, and was quartered from low to high (Q1, Q2, Q3, Q4). We analyzed the risk of first stroke using multivariable adjusted Cox regression models and used stratified analysis to further explore the risk of stroke in hypertensive patients with different characteristics. Results: Increased cumulative MAP in patients with hypertension were associated with risk for ischemic stroke (HR, Q2, 1.23 [95% CI, 0.91-1.67]; Q3, 1.35 [95% CI, 1.01-1.82]; Q4, 1.55 [95% CI, 1.15-2.10]; P=0.035). Furthermore, this trend persisted after stratified analysis in men (HR, Q3, 1.76[1.10-2.82]; Q4, 2.05[1.28-3.28]), aged 60 or above (HR, Q4, 1.63[1.13-2.35]) and higher body mass index (BMI) populations (HR, Q3, 1.48[1.02-2.14]; Q4, 1.59[1.09-2.32]). In contrast, cumulative MAP was not significantly associated with stroke in women, age under 60, and non-obese individuals. Conclusion: Increased cumulative MAP is an independent risk factor of ischemic stroke in patients with hypertension. Special attention should also be paid to men, aged 60 or older, or those with a higher BMI.

The interaction effect of grip strength and lung function (especially FVC) on cardiovascular diseases: a prospective cohort study in Jiangsu Province, China.

OBJECTIVE: Lung function and grip strength (GS) are associated with cardiovascular disease (CVD), but whether these risk factors interact to affect CVD is unknown. This study aimed to explore the interactions between lung function and GS with major CVD (defined as fatal/non-fatal myocardial infarction, stroke, and heart failure) incidence. METHODS: We conducted a prospective cohort study on the Chinese population in Jiangsu Province. Cox proportional hazards models were used to explore the associations between GS, lung function, and major CVD incidence. RESULTS: A total of 5967 participants were included in our study; among them, 182 participants developed major CVD. Participants with low forced vital capacity (FVC) had a higher risk of major CVD (hazard ratio (HR) = 1.45; 95% confidence interval (CI): 1.05-2.01; P < 0.05) compared with normal FVC. The risk of major CVD incidence (HR = 0.54; 95% CI: 0.35-0.83; P < 0.01) was significantly lower in participants with high GS than in individuals with low GS. The interaction between FVC and GS for major CVD incidence (P = 0.006) was statistically significant. Compared with normal FVC participants with high GS, low FVC participants with low GS had the highest risk of major CVD incidence (HR = 2.50; 95% CI: 1.43-4.36; P < 0.01). CONCLUSION: Among people with low FVC, the risk of major CVD is lower with high GS. Participants with low FVC and low GS have the highest risk of major CVD. Therefore, more attention should be paid to the incidence of major CVD in individuals with low FVC, especially those who have lower GS.