Trends and disparities in non-communicable diseases in the Western Pacific region.

The WHO Western Pacific region bears disproportionate deaths from non-communicable diseases (NCDs), with increased overall NCD proportional mortality over the past two decades. The disease burden of mental health increased, resulting from rapid ageing, enhanced stress, and the COVID-19 pandemic, but it was largely neglected. The highly diverse cultures, religions, political systems, socioeconomic contexts, lifestyles, and environmental factors probably have led to massive disparities across countries in NCD mortality, risk factors, and NCD management. Geographically, East Asia had the lowest NCD mortality whilst Pacific islands had the highest. Economic booms, ageing, nutrition transition, social stress, prevalent tobacco use, and fast-increasing obesity and hyperglycaemia are important drivers of NCDs. Men tended to have more adverse behavioural and metabolic risk factors. Rural residents are catching up with their urban counterparts in metabolic risk factors and conditions. Sustainable strategies tailored to NCD patterns are needed to fight the NCD epidemic and related disparities.

Integrated analysis of the lncRNA-associated competing endogenous RNA network in salt sensitivity of blood pressure.

Accumulating evidence showed that competing endogenous RNA (ceRNA) mechanism plays a pivotal role in salt sensitivity of blood pressure (SSBP). We constructed a ceRNA network based on SSBP-related differently expressed lncRNAs (2), mRNAs (73) and miRNAs (18). Bioinformatic analyses were utilized to analyze network and found network genes participate in biological pathways related to SSBP pathogenesis such as regulation of nitric oxide biosynthetic process (GO:0045,428) and cellular response to cytokine stimulus (GO:0071,345). Fourteen candidate ceRNA pathways were selected from network to perform qRT-PCR validation and found nine RNAs (KCNQ1OT1, SLC8A1-AS1, IL1B, BCL2L11, KCNJ15, CX3CR1, KLF2, hsa-miR-362-5p and hsa-miR-423-5p) differently expressed between salt-sensitive (SS) and salt-resistant (SR) groups (P < 0.05). Four ceRNA pathways were further validated by luciferase reporter assay and found KCNQ1OT1→hsa-miR-362-5p/hsa-miR-423-5p→IL1B pathways may influence the pathogenic mechanism of SS. Our findings suggested the ceRNA pathway and network may affect SS occurrence mainly through endothelial dysfunction and inflammatory activation.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

The mediation effect of lipids, blood pressure and BMI between air pollutant mixture and atherosclerotic cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: The combine effect of air pollutant mixture on atherosclerotic cardiovascular disease (ASCVD) remain undefined. This study aims to explore the association between long-term exposure of air pollutants and ASCVD, focusing on the mediating role of lipids, blood pressure and BMI. METHODS: This study was based on the CHCN-BTH cohort study. The annual concentrations of air pollutants and PM2.5 constituents were sourced from in the Tracking Air Pollution in China (TAP) and ChinaHighAirPollutants (CHAP) datasets from 2014 to 2019. A Cox mixed-effects model was used to investigate the associations between long-term exposure of air pollutants and ASCVD. The combined impact of the air pollutant mixture was assessed using Quantile g-Computation. Stratified, sensitivity, and mediation analyses were conducted. RESULTS: A total of 27,134 participants aged 18-80 were recruited in the present study. We found that each IQR increase of PM2.5, PM1, NO2, O3, BC, SO42-, and OM were significantly associated with the incidence of ASCVD, the hazard ratios (HRs) and 95 % confidence interval (CI) were 1.55 (1.35, 1.78), 1.46 (1.27, 1.67), 1.30 (1.21, 1.39), 1.66 (1.41,1.95), 2.14 (1.63, 2.83), 1.65 (1.25, 2.17) and 1.92(1.52, 2.45), respectively. The combined effect of air pollutant mixture on ASCVD was 1.79 (1.46, 2.20), PM2.5 contributed 83.3 % to this combined effect. Mediation effect models suggested that air pollutants and ASCVD might be mediated through SBP, DBP, HDL-C, LDL-C, hsCRP and BMI (mediation proportion range from 1.3 % to 26.1 %), Notably, HDL-C played mediation roles of 11.3 % (7.0 %, 18.4), 26.1 % (17.7 %, 38.1 %) and 25.4 % (15.4, 47.7 %) in the effects of long-term exposure to PM2.5, PM1 and OM on ASCVD, respectively. CONCLUSIONS: Long-term, high-level air pollutant exposure was significantly associated with an elevated risk of ASCVD, particularly for PM2.5. Blood pressure, lipids and BMI, especially HDL-C, may mediate the effects of air pollutants exposure on ASCVD.

Associations between depressive, anxiety, stress symptoms and elevated blood pressure: Findings from the CHCN-BTH cohort study and a two-sample Mendelian randomization analysis.

BACKGROUND: We aimed to determine whether depressive, anxiety, stress symptoms were associated with the risk of elevated blood pressure by performing longitudinal cohort and Mendelian Randomization (MR) analyses. METHODS: We used data from the Cohort Study on Chronic Disease of Community Natural Population in the Beijing-Tianjin-Hebei region (CHCN-BTH) from 2017 to 2021. The Depression-Anxiety-Stress Scale was used to evaluate the depressive, anxiety, stress symptoms. The longitudinal associations between depressive, anxiety, stress symptoms and elevated blood pressure were estimated using Cox proportional regression models. Two-sample MR analysis was performed using the Inverse-variance weighted (IVW), weighted median, and MR-Egger to explore the causal relationships between depressive, anxiety, stress symptoms and elevated blood pressure. RESULTS: In total, 5624 participants were included. The risk of SBP ≥ 140 mmHg or DBP ≥ 90 mmHg was significantly higher in participants with baseline anxiety symptoms (HR = 1.48, 95 % CI: 1.03 to 2.12, P = 0.033; HR = 1.56, 95 % CI: 1.05 to 2.32, P = 0.028), especially in men and individuals with higher educational levels, independent of baseline depression and anxiety at the two-year follow-up. The two-sample MR analysis showed positive associations between depressive, anxiety, stress symptoms and elevated blood pressure. LIMITATION: Self-reported mental health symptoms, relatively shorter follow-up duration and the European-derived genome-wide association study data for MR analysis. CONCLUSIONS: Anxiety symptoms were positively associated with elevated blood pressures in the longitudinal analysis independent of depression, stress, and other confounders. The results were verified in MR analysis, providing evidence for causal effects of anxiety symptoms on the risk of elevated blood pressure.

Combined effects of ambient air pollution and PM2.5 components on renal function and the potential mediation effects of metabolic risk factors in China.

Growing evidence links long-term air pollution exposure with renal function. However, little research has been conducted on the combined effects of air pollutant mixture on renal function and multiple mediation effects of metabolic risk factors. This study enrolled 8996 adults without chronic kidney disease (CKD) at baseline from the CHCN-BTH cohort study. Three-year exposure to air pollutants [particulate matter ≤ 2.5 µm (PM2.5), PM10, PM1, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)] and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-) and organic matter (OM)] were assessed using well-validated machine learning methods. Linear mixed models were applied to investigate the associations between air pollutants and estimated glomerular filtration rate (eGFR). Quantile G-computation was used to assess the combined effects of pollutant mixtures. Causal mediation analysis and Bayesian mediation analysis were employed to estimate the mediation effects of metabolic risk factors. An interquartile range increases in BC (-0.256, 95 %CI: -0.331, -0.180) and OM (-0.603, 95 %CI: -0.810, -0.397) were significantly associated with eGFR decline; while O3 (1.151, 95 %CI: 0.813, 1.489), PM10 (0.721, 95 %CI: 0.309, 1.133), NH4+ (0.990, 95 %CI: 0.638, 1.342), and NO3- (0.610, 95 %CI: 0.405, 0.815) were associated with higher eGFR. The combined effect of the PM2.5 component mixture was found to be associated with lower eGFR (-1.147, 95 % CI: -1.456, -0.839), with OM contributing 72.4 % of the negative effect. Univariate mediation analyses showed that high-density lipoprotein (HDL) mediated 7.1 %, 6.9 %, and 6.1 % effects of O3, BC, and OM, respectively. However, these mediation effects were not significant in Bayesian mediation analysis. These findings suggest the effect of the PM2.5 component mixture on eGFR decline and the strong contribution of OM. Metabolic risk factors may not mediate the effects of air pollutants. Further study is warranted to clarify the potential mechanisms involved.

Association of long-term exposure to air pollutant mixture and incident cardiovascular disease in a highly polluted region of China.

Despite growing evidence that links long-term air pollution exposure to cardiovascular disease (CVD), the combined effects of air pollutants and particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) components are still limited. A prospective cohort study was performed based on the Cohort Study on Chronic Disease of the Community Natural Population in the Beijing-Tianjin-Hebei Region (CHCN-BTH) to assess the association of long-term air pollutants with incident CVD and the combined effect of the air pollutants mixture among 26,851 adults. Three-year residential exposure to air pollutants (PM2.5, O3, PM10, PM1, NO2, SO2 and CO) and PM2.5 components [black carbon (BC), NH4+, SO42-, NO3- and organic matter (OM)] were calculated based on well-validated models. Proportional hazard models were applied to assess the association of air pollutants with incident CVD. Quantile g-Computation was used to examine the combined effect of the pollutant mixture. During the 56,090 person-years follow-up, 629 participants reported incident CVD. Adjusted hazard ratios with 95% confidence intervals (CIs) of CVD per interquartile range increase in O3, PM2.5, PM1, NO2, BC, and OM concentrations were 4.52 (95%CI: 2.61, 7.83), 2.39 (95%CI: 1.83, 3.13), 2.37 (95%CI: 1.20, 4.70), 1.36 (95%CI: 1.19, 1.56), 3.84 (95%CI: 2.38, 6.18), and 3.07 (95%CI: 2.01, 4.69), respectively. In multi-pollutant models, the combined effect of air pollutant mixture on incident CVD was 2.37 (95%CI: 2.30, 2.44). PM2.5 and O3 contributed 54.3% and 44.5% of the combined effect of the air pollutant mixture, respectively. After using PM2.5 components instead of PM2.5 as part of the mixture, OM drove 55.2% of the combined effect. The findings indicated associations of air pollutant mixtures with CVD incidence. PM2.5 (especially OM) and O3 might strongly contribute to air pollutant mixtures that lead to incident CVD.

Association of Serum Metabolites and Salt Sensitivity of Blood Pressure in Chinese Population: The EpiSS Study.

BACKGROUND: To identify novel metabolites associated with salt sensitivity of blood pressure (SSBP) in Chinese Han population. METHODS: A case-control study was conducted with 25 salt sensitive (SS) and 26 salt resistant (SR) participants, which was selected from the Systems Epidemiology Study on Salt Sensitivity of Blood Pressure (EpiSS) study. The modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was conducted to identify SS. Untargeted, ultra-high performance liquid chromatograph-high resolution mass spectrometer (UPLC-HRMS) was conducted and orthogonal partial least squares-discriminate analysis (OPLS-DA) and multivariable logistic regression model were used to screen the metabolites related to SS, mixed linear regressions models were used to examined the association of SSBP with metabolites during saline load period and diuresis shrinkage period. Receiver operating characteristic (ROC) curve analysis was performed. The area under the curve's (AUC) sensitivity and specificity were calculated to identified metabolites biomarkers for SS. RESULTS: There were 39 differentially expressed metabolites (DE-metabolites) between SS and SR. Thirty-five and four of DE-metabolites were inversely or positively associated with SS, respectively. Four biochemical pathways demonstrated significant enrichment for identified metabolites. In single-metabolite analyses, L-Glutamine displayed the best diagnostic performance (AUC = 0.88, 95% CI: 0.78-0.97). In multi-metabolites analyses, L-Glutamine + Cholesterol ester 22:5n6 combination showed the best diagnostic performance (AUC = 0.96, 95% CI: 0.91-1.00). Adjusted for traditional risk factors, L-Glutamine and Cholesterol ester 22:5n6 explained an additional 38.3% of SS susceptibility. CONCLUSIONS: This study provide potential evidence for clarifying the mechanism of SS and provide novel biological insights into salt sensitive hypertension.

Depression among schoolchildren and adolescents aged 9-17 years during the outbreak of COVID­19 in Beijing: a cross-sectional online survey.

The COVID-19 outbreak and related confinement have highly impacted psychological health among children and adolescents. This study aimed to explore the potential risk factors for depression among primary and middle school students and provide advices for psychological interventions during the outbreaks. An online cross-sectional survey was conducted among 18 primary and middle school students via quota sampling in Beijing during March 2020. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess depression. Differences between characteristics and depression were examined by chi-square tests. Multivariate logistic regression was used to reveal the potential risk factors for depression. A total of 7377 participants were included. The proportion of depression was 29.7%. Students in rural areas, with higher school categories, in graduating grades, with poor or excessive sleep duration, and without daily exercise were associated with a higher proportion of depression. Furthermore, students with a higher knowledge performance of COVID-19 showed a lower proportion of depression (odds ratio [OR] = 0.900, 95% confidence intervals [95% CI]: 0.888-0.913). Students who worried about academic performance (OR = 1.919, 95% CI: 1.718-2.144) or COVID-19 infection (OR = 1.450, 95% CI: 1.268-1.658) exhibited a high proportion of depression. The proportion of depression among primary and middle school students was negatively associated with the knowledge score and positively associated with their worry. Our findings suggest that psychological intervention might be more necessary for students with specific characteristics.

Serum lipoprotein (a) associates with the risk of renal function damage in the CHCN-BTH Study: Cross-sectional and Mendelian randomization analyses.

Background: Evidence regarding the effects of lipoprotein (a) [lp(a)] and renal function remains unclear. The present study aimed to explore the causal association of serum lp(a) with renal function damage in Chinese general adults. Methods: A total of 25343 individuals with available lp(a) data were selected from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin, and Hebei (CHCN-BTH). Five renal function indexes [estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), high-sensitivity C-reactive protein(CRPHS)] were analyzed. The restricted cubic spline (RCS) method, logistic regression, and linear regression were used to test the dose-response association between lp(a) and renal function. Stratified analyses related to demographic characteristics and disease status were performed. Two-sample Mendelian randomization (MR) analysis was used to obtain the causal association of lp(a) and renal function indexes. Genotyping was accomplished by MassARRAY System. Results: Lp(a) levels were independently associated with four renal function indexes (eGFR, Scr, BUN, CRPHS). Individuals with a higher lp(a) level had a lower eGFR level, and the association with Scr estimated GFR was stronger in individuals with a lower lp(a) level (under 14 mg/dL). . The association was similar in individuals regardless of diabetes or hypertension. MR analysis confirmed the causal association of two renal function indexes (Scr and BUN). For MR analysis, each one unit higher lp(a) was associated with 7.4% higher Scr (P=0.031) in the inverse-variance weighted method. But a causal effect of genetically increased lp(a) level with increased eGFR level which contrasted with our observational results was observed. Conclusion: The observational and causal effect of lp(a) on Scr and BUN were founded, suggesting the role of lp(a) on the risk of renal function damage in general Chinese adults.

SNPs in lncRNA KCNQ1OT1 Modulate Its Expression and Confer Susceptibility to Salt Sensitivity of Blood Pressure in a Chinese Han Population.

Long noncoding RNA (lncRNA) plays an important role in cardiovascular diseases, but the involvement of lncRNA in salt sensitivity of blood pressure (SSBP) is not well-known. We aimed to explore the association of sixteen single-nucleotide polymorphisms (SNPs) in five lncRNA genes (KCNQOT1, lnc-AGAP1-8:1, lnc-IGSF3-1:1, etc.) with their expression and susceptibility to SSBP. A two-stage association study was conducted among 2057 individuals. Quantified expression of the lncRNA was detected using real-time PCR. Genotyping was accomplished using the MassARRAY System. The expression quantitative tra2it loci test and the generalized linear model were utilized to explore the function of SNPs. One-sample Mendelian randomization was used to study the causal relationship between KCNQOT1 and SSBP. Significant effects were observed in KCNQ1OT1 expressions on the SSBP phenotype (p < 0.05). Rs10832417 and rs3782064 in KCNQ1OT1 may influence the secondary structure, miRNA binding, and expression of KCNQ1OT1. Rs10832417 and rs3782064 in KCNQ1OT1 were identified to be associated with one SSBP phenotype after multiple testing corrections and may be mediated by KCNQ1OT1. One-sample Mendelian randomization analyses showed a causal association between KCNQ1OT1 and SSBP. Our findings suggest that rs10832417 and rs3782064 might be associated with a lower risk of SSBP through influencing the KCNQ1OT1 secondary structure and miRNA binding, resulting in changes in KCNQ1OT1 expression.

Higher Potassium Intake and Lower Sodium Intake May Help in Reducing CVD Risk by Lowering Salt Sensitivity of Blood Pressure in the Han Chinese Population.

Sodium (Na) reduction with a parallel supplemental potassium (K) intake can prevent cardiovascular diseases (CVDs). The relationship of the urinary Na/K ratio and salt sensitivity of blood pressure (SSBP) with CVDs is not clearly explained. We assumed that the SSBP mediates the relationship between the Na/K ratio and CVDs. In total, 2055 subjects who had 24 h urine collected and SSBP determined were included in this study. CVD risk was estimated using the China-PAR equation. MediationMultivariate logistic regression was used to explore the associations between the Na/K ratio or SSBP with CVD risk. Mediation analysis using a logistic regression model was performed. Both the urinary Na/K ratio and SSBP were related to the estimated CVD risk (p < 0.05). The mediation analysis found that SSBP mediated approximately 12% of the association between Na/K ratio and CVD risk. Our findings indicate that higher K intake and lower Na intake may help in preventing CVD risk by reducing SSBP risk in individuals with normotension or stage-one hypertension.

Associations of long-term ambient air pollution and traffic-related pollution with blood pressure and hypertension defined by the different guidelines worldwide: the CHCN-BTH study.

The assessment of the generalization of the strict hypertension definition in the 2017 ACC/AHA Hypertension Guideline from environmental condition remains sparse. The aims of this study are to investigate and compare the associations of ambient air pollution and traffic-related pollution (TRP) with hypertension defined by the different criteria. A total of 32,135 participants were recruited from the baseline survey of the CHCN-BTH in 2017. We defined hypertension as SBP/DBP ≥ 140/90 mmHg according to the hypertension guidelines in China, Japan, Europe and ISH (traditional criteria) and defined as SBP/DBP ≥ 130/80 mmHg according to the 2017 ACC/AHA Hypertension Guideline (strict criteria). A two-level generalized linear mixed models were applied to investigate the associations of air pollutants (i.e. PM2.5, SO2, NO2) and TRP with blood pressure (BP) measures and hypertension. Stratified analyses and two-pollutant models were also performed. The stronger associations of air pollutants were found in the hypertension defined by the strict criteria than that defined by the traditional criteria. The ORs per an IQR increase in PM2.5 were 1.17 (95% CI: 1.09, 1.25) for the strict criteria and 1.14 (95% CI: 1.06, 1.23) for the traditional criteria. The similar conditions were also observed for TRP. The above results were robust in both stratified analyses and two-pollutant models. Our study assessed the significance of the hypertension defined by the strict criteria from environmental aspect and called attention to the more adverse effects of air pollution and TRP on the earlier stage of hypertension.

Sensitive inflammatory biomarkers of acute fine particulate matter exposure among healthy young adults: Findings from a randomized, double-blind crossover trial on air filtration.

The short-term alteration of peripheral cytokines may be an early adverse health effect of PM2.5 exposure and may be further associated with cardiovascular disease. We conducted a randomized, double-blind crossover trial using true or sham air filtration among 54 healthy college students in Beijing to investigate the potential benefits of short-term indoor air filtration and the adverse health effects of time-weighted personal PM2.5 exposure through inflammatory cytokines. The participants randomly received true or sham air filtration intervention for a week, and the treatment was changed after a two-week washout period. Peripheral blood samples were collected after each intervention period to measure 38 inflammatory cytokines. A linear mixed-effects model was applied to estimate the impacts of air purification or a 10 µg/m3 PM2.5 exposure increase on cytokines. Lag effects of PM2.5 exposure were analyzed using single-day and moving average lag models. Air filtration reduced indoor and time-weighted average personal PM2.5 concentrations by 69.0% (from 33.6 to 10.4 µg/m3) and 40.3% (from 40.6 to 24.3 µg/m3), respectively. We observed a significant association of PM2.5 exposure with growth-regulated alpha protein (GRO-α) of -11.3% (95%CI: 17.0%, -5.4%). In the lag models, significant associations between personal PM2.5 exposure and interleukin-1 receptor antagonist (IL-1Ra), monocyte chemotactic protein (MCP-1), and eotaxin were obtained at lag0, while associations with cytokines including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein-1ß (MIP-1ß), IL-4, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were noted at relatively long lagged exposure windows (lag5-lag6). No significant alteration in cytokines was observed under true air filtration intervention. Our study indicates the effectiveness of air filtration on indoor PM2.5 reduction. PM2.5 exposure may decrease GRO-α levels and change different cytokine levels time-varyingly. Further study is still needed to explore the mechanisms of PM2.5 exposure on the inflammatory response.

Impact of lipoprotein(a) level on cardiometabolic disease in the Chinese population: The CHCN-BTH Study.

BACKGROUND: The emergence of promising compounds to lower lipoprotein(a) [Lp(a)] has increased the need for a precise characterisation and comparability assessment of Lp(a)-associated cardiometabolic disease risk. This study aimed to evaluate the distribution of Lp(a) levels in a Chinese population and characterise the association with cardiometabolic diseases. METHODS: We assessed data from individuals from the Cohort Study on Chronic Diseases of the General Community Population in the Beijing-Tianjin-Hebei Region project. All Lp(a) measurements were performed in the same hospital. The cardiometabolic diseases considered were coronary heart disease (CHD), stroke, hypertension and type 2 diabetes (T2DM). RESULTS: A total of 25343 individuals were included in the study. The median level of Lp(a) was 11.9 mg/dl (IQR 5.9 to 23.7 mg/dl), and higher Lp(a) levels showed a significant concentration-dependent association with CHD risk. Individuals with Lp(a) levels lower than the 25th percentile were at increased risk of hypertension (OR: 1.15, 95% CI: 1.06-1.25) and T2DM (OR: 1.15, 95% CI: 1.03-1.28); however, Lp(a) levels were not significantly associated with stroke. The addition of Lp(a) levels to the prognostic model led to a marginal but significant C-index, integrated discrimination improvement and net reclassification improvement. CONCLUSIONS: In this large sample size study, we observed that elevated Lp(a) levels were significantly associated with CHD. Furthermore, we found that the lowest Lp(a) levels were also significantly associated with hypertension and T2DM. These results provide evidence for differential approaches to higher levels of Lp(a) in individuals with different cardiometabolic diseases.

Association of Circulating Biomarkers of lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 with Salt Sensitivity of Blood Pressure in Chinese Population.

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) could play biological roles in cardiovascular diseases. We investigated whether lncRNAs can serve as biomarkers for salt sensitivity of blood pressure (SSBP). Participants were divided into salt-sensitive (SS) and salt-resistant (SR) ones by oral saline test. LncRNAs were tested by microarray (N = 20) and two-stage qRT-PCR (N = 89 and 228). We identified five differently expressed lncRNAs (lnc-IGSF3-1:1, SCOC-AS1, SLC8A1-AS1, KCNQ1OT1, and lnc-GNG-10-3:1) between SS and SR. In single-lncRNA analyses, lnc-IGSF3-1:1 displayed better diagnostic performance in hypertensive patients (AUC = 0.840), while SCOC-AS1 in normotensive (AUC = 0.810). In multi-lncRNA analyses, lnc-IGSF3-1:1 + SCOC-AS1 + SLC8A1-AS1 combination showed the best diagnostic performance in hypertensive (AUC = 0.853) and normotensive groups (AUC = 0.873). We constructed a lncRNA-mRNA-GO-KEGG-disease network by bioinformatic analysis; lnc-IGSF3-1:1 and SLC8A1-AS1 were identified as hub biomarkers. Our findings suggest that lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 may represent as genetic susceptible biomarkers for SSBP, and had different SS diagnostic performance in hypertensive patients and normotensive individuals.

Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators.

Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes (P < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction (P < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects (P < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects (P < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators.

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study.

BACKGROUND AND AIMS: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP). METHODS AND RESULTS: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), ß (95%CI) for mean arterial pressure change (ΔMAP1), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q1), the OR (95%CI) for SS in Q3 and Q4 were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the ß (95%CI) for ΔMAP1 was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers. CONCLUSION: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.

Association of long-term exposure to ambient particulate pollution with stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline and cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: Evidence regarding the effects of ambient air pollution on new stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline remains sparse. OBJECTIVES: To investigate the association of long-term exposure to ambient PM2.5 with stage 1 hypertension and to explore the mediating and modifying effects of PM2.5 on cardiovascular disease (CVD). METHODS: A total of 32,135 participants aged 18-80 years were recruited in 2017. The three-year (2014-2016) average PM2.5 concentrations were assessed by a spatial statistical model. Blood pressure (BP) was divided into four categories according to the 2017 ACC/AHA Hypertension Guideline: normal BP (SBP<120 mmHg and DBP<80 mmHg), elevated BP (SBP 120-129 mmHg and DBP<80 mmHg), stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg), and stage 2 hypertension (SBP≥140 mmHg or DBP≥90 mmHg or taking antihypertensive medications). The associations of PM2.5 with BP categories were estimated by two-level generalized linear mixed models. Analyses stratified by age, mediation and interaction analyses of PM2.5 and stage 1 hypertension with CVD were performed. RESULTS: We detected a positive significant association between long-term exposure to PM2.5 and stage 1 hypertension. Compared to normal BP, the OR was 1.05 (95% CI: 1.02, 1.08) per 10 µg/m3 increase in PM2.5. The association was stronger than that of elevated BP but weaker than that of stage 2 hypertension. Stage 1 hypertension only partially mediated the association between PM2.5 and CVD, and the mediation proportions ranged from 1.55% to 11.00%. However, it modified the association between PM2.5 and CVD, which was greater in participants with stage 1 hypertension (OR: 1.66; 95% CI: 1.43, 1.93) than in participants with normal BP (OR: 1.32; 95% CI: 1.11, 1.57), with Pinteraction<0.001. In the analysis stratified by age, the above associations were age-specific, and significant associations were only observed in the young and middle-aged (<60 years) groups. CONCLUSIONS: Long-term exposure to ambient PM2.5 was significantly associated with stage 1 hypertension. This earlier stage of hypertension may be a trigger BP range for adverse effects of air pollution in the development of hypertension and CVD, especially in young and middle-aged individuals.

Elevated lipoprotein(a) and risk of coronary heart disease according to different lipid profiles in the general Chinese community population: the CHCN-BTH study.

BACKGROUND: To evaluate the contributions of elevated lipoprotein(a) [Lp(a)] to the risk of coronary heart disease (CHD) in the general Chinese community population according to different lipid profiles. METHODS: We recruited individuals aged over 18 years from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) using a stratified, multistage cluster sampling method. Data were collected through questionnaire surveys, anthropometric measures and laboratory tests. Restricted cubic spline (RCS) functions, multivariate logistic regression, sensitivity analyses and stratified analyses were used to evaluate the association between Lp(a) and CHD. RESULTS: A total of 25,343 participants were included, with 1,364 (5.38%) identified as having CHD. Elevated Lp(a) levels were linearly related to an increased risk of CHD (Poverall-association<0.0001 and Pnonlinear-association=0.8468). Multivariate logistic regression analysis indicated that subjects with Lp(a) ≥300 mg/L had a higher risk of CHD [OR (95% CI): 1.36 (1.17, 1.57)] than did individuals with Lp(a) <300 mg/L. Compared with individuals with Lp(a) <119.0 mg/L (<50th percentile), the ORs (95% CI) for CHD in the 51st-80th, 81st-95th and >95th percentiles were 1.07 (0.93, 1.23), 1.26 (1.07, 1.50) and 1.68 (1.30, 2.17), respectively (P for trend <0.0001). This association was also found among the subgroup of subjects without dyslipidemia, including those with normal total cholesterol (TC) (<6.2 mmol/L), triglycerides (TG) (<2.3 mmol/L), high-density lipoprotein cholesterol (HDL-C) (≥1.0 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (<4.1 mmol/L). Elevated Lp(a) and dyslipidemia significantly contributed to a higher risk of CHD with synergistic effects. Stratified analyses showed that elevated Lp(a) concentrations were significantly associated with an increased risk of CHD in the subgroups of individuals who were noncurrent drinkers, overweight individuals, individuals with hypertension, individuals who engaged in moderate physical activity, those without diabetes mellitus and individuals in Beijing and Tianjin. CONCLUSIONS: Elevated Lp(a) concentrations were linearly associated with a higher risk of CHD in the general Chinese community population, especially in normolipidemic subjects. Both dyslipidemia and elevated Lp(a) independently or synergistically contributed to the risk of CHD. Our results suggest that more attention should be paid to the levels of Lp(a) in normolipidemic subjects, which may be an early predictor of CHD.