Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Association between hypertriglyceridemic-waist phenotype and circadian syndrome risk: a longitudinal cohort study.

Recently, circadian syndrome (CircS) has been proposed as a new predictor of cardiometabolic risk. We aimed to investigate the relationship between the hypertriglyceridemic-waist phenotype and its dynamic status with CircS in China. We conducted a two-stage study based on the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Multivariate logistic regression models in cross-sectional analysis and Cox proportional hazards regression models in longitudinal analysis were used to estimate the associations of hypertriglyceridemic-waist phenotypes with CircS and its components. We then applied multiple logistic regression analysis to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) for CircS risk by transformation into the hypertriglyceridemic-waist phenotype. A total of 9863 participants were included in the cross-sectional analysis and 3884 participants in the longitudinal analysis. Compared with normal waist circumference (WC) and normal triglyceride (TG) level (NWNT), CircS risk was increased with enlarged WC and high TG level (EWHT) (hazard ratio (HR) 3.87 [95% CI: 2.38, 5.39]). Similar results were observed in subgroup analyses by sex, age, smoking status, and drinking status. During follow-up, CircS risk was increased in group K (stable EWNT during follow-up) (OR 9.97 [95% CI: 6.41, 15.49]) compared with group A (stable NWNT during follow-up), while group L (baseline enlarged WC and normal TG level transformed to follow-up EWHT) had the highest risk of CircS (OR 116.07 [95% CI: 72.77, 185.14]). In conclusion, the hypertriglyceridemic-waist phenotype and its dynamic status were associated with the risk of developing CircS in Chinese adults.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

Identification of Metabolism-Related Proteins as Biomarkers of Insulin Resistance and Potential Mechanisms of m6A Modification.

BACKGROUND: Insulin resistance (IR) is a major contributing factor to the pathogenesis of metabolic syndrome and type 2 diabetes mellitus (T2D). Adipocyte metabolism is known to play a crucial role in IR. Therefore, the aims of this study were to identify metabolism-related proteins that could be used as potential biomarkers of IR and to investigate the role of N6-methyladenosine (m6A) modification in the pathogenesis of this condition. METHODS: RNA-seq data on human adipose tissue were retrieved from the Gene Expression Omnibus database. The differentially expressed genes of metabolism-related proteins (MP-DEGs) were screened using protein annotation databases. Biological function and pathway annotations of the MP-DEGs were performed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Key MP-DEGs were screened, and a protein-protein interaction (PPI) network was constructed using STRING, Cytoscape, MCODE, and CytoHubba. LASSO regression analysis was used to select primary hub genes, and their clinical performance was assessed using receiver operating characteristic (ROC) curves. The expression of key MP-DEGs and their relationship with m6A modification were further verified in adipose tissue samples collected from healthy individuals and patients with IR. RESULTS: In total, 69 MP-DEGs were screened and annotated to be enriched in pathways related to hormone metabolism, low-density lipoprotein particle and carboxylic acid transmembrane transporter activity, insulin signaling, and AMPK signaling. The MP-DEG PPI network comprised 69 nodes and 72 edges, from which 10 hub genes (FASN, GCK, FGR, FBP1, GYS2, PNPLA3, MOGAT1, SLC27A2, PNPLA3, and ELOVL6) were identified. FASN was chosen as the key gene because it had the highest maximal clique centrality (MCC) score. GCK, FBP1, and FGR were selected as primary genes by LASSO analysis. According to the ROC curves, GCK, FBP1, FGR, and FASN could be used as potential biomarkers to detect IR with good sensitivity and accuracy (AUC = 0.80, 95% CI: 0.67-0.94; AUC = 0.86, 95% CI: 0.74-0.94; AUC = 0.83, 95% CI: 0.64-0.92; AUC = 0.78, 95% CI: 0.64-0.92). The expression of FASN, GCK, FBP1, and FGR was significantly correlated with that of IGF2BP3, FTO, EIF3A, WTAP, METTL16, and LRPPRC (p < 0.05). In validation clinical samples, the FASN was moderately effective for detecting IR (AUC = 0.78, 95% CI: 0.69-0.80), and its expression was positively correlated with the methylation levels of FASN (r = 0.359, p = 0.001). CONCLUSION: Metabolism-related proteins play critical roles in IR. Moreover, FASN and GCK are potential biomarkers of IR and may be involved in the development of T2D via their m6A modification. These findings offer reliable biomarkers for the early detection of T2D and promising therapeutic targets.

Occupational stress is associated with insulin resistance and incident type 2 diabetes: A prospective cohort study of functional community.

BACKGROUND: To exploit the association of occupational stress with the development of insulin resistance (IR) and type 2 diabetes (T2D) in a Chinese population-based cohort. METHODS: A total of 6109 participants from a functional community cohort in Beijing were enrolled in 2015 and followed up until 2021. Copenhagen Psychosocial Questionnaire (COPSOQ) were used to evaluate occupational stress. RESULTS: At baseline, increase values of all five scales of COPSOQ and total COPSOQ were significantly associated with IR. During an average 5.63 y follow-up, 732 individuals developed T2D. Increasing in values of "Demands at work", "Insecurity at work", "Job satisfaction" and total COPSOQ were significantly associated with incident T2D (P < 0.01). Mediation analysis showed that subjectively perceived occupational stress promoted T2D mainly by affecting plasma cortisol and the mediation effects of HOMA-IR, SBP, DBP, TG, Urea and UA were significant on the association between cortisol and incident T2D, with proportion mediated of 37.1%, 8.12%, 2.02%, 2.94%, 2.35% and 2.70%. CONCLUSION: Occupational stress was independently associated with the development of IR and T2D. IR, BP, TG, Urea and UA all partly mediated the association between occupational stress and incident T2D.

Associations between long-term exposure to ambient fine particulate pollution with the decline of kidney function and hyperuricemia: a longitudinal cohort study.

Evidence of associations between ambient fine particulate matter (PM2.5) and risks of decline of kidney function and hyperuricemia is limited. We aimed to investigate the associations between long-term exposure to PM2.5 with decline of kidney function and hyperuricemia in China. We conducted a two-stage study based on China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Cox proportional hazard regression models and restricted cubic splines were used to evaluate the associations of PM2.5 with risks of decline of kidney function and hyperuricemia. Latent class trajectory models (LCTM) were used to identify trajectories of PM2.5 from 2011 to 2015 in the sensitivity analysis. A total of 9760 participants were included in baseline analysis, and 5902 participants were in follow-up analysis. PM2.5 was associated with the risks of decline of kidney function [hazard ratio (HR): 2.14; 95% confidence interval (CI): (1.03, 4.44)] and hyperuricemia [HR 1.40 (95% CI: 1.10, 1.79)] in the second quartile group versus the lowest quartile group of PM2.5. We also observed nonlinear relationships between PM2.5 and the risks of the decline of kidney function and hyperuricemia (Pnon-linear < 0.001). In sensitivity analysis, four trajectory groups were identified. "Maintaining a high PM2.5" [odds ratio (OR): 2.20; 95%CI: (1.78, 2.73)] and "moderately high starting PM2.5 then steadily decreased" [OR (95%CI): 5.15 (1.55, 16.13)] were associated with hyperuricemia risk, using "low starting PM2.5 then steadily decreased" trajectory as reference. In conclusion, improved air quality is essential for prevention of decline of kidney function and hyperuricemia.

Associations of waist-to-height ratio with the incidence of type 2 diabetes and mediation analysis: Two independent cohort studies.

AIM: To assess the relationship between waist-to-height ratio (WHtR) and the incidence of type 2 diabetes (T2D)/impaired fasting glucose (IFG) and to explore to what extent these associations are mediated by blood pressure, lipids and other indicators related to liver and kidney metabolism. MATERIALS AND METHODS: This study was based on a functional community cohort included 6109 participants which were divided into two sub-cohorts. One sub-cohort included participants with normal fasting glucose (n = 5563), another included IFG individuals at baseline (n = 546). Cox regression models were used to evaluate the relationships of WHtR with T2D/IFG. Four-year time-dependent receiver operating characteristic (ROC) curve and area under curve (AUC) were calculated to estimate the discriminatory power of WhtR and other anthropometric indices on T2D. Mediation analysis was performed to estimate which risk factors mediate the association between WHtR and T2D. RESULTS: Significant positive associations were found between WHtR and the incidence of T2D/IFG in both sub-cohort. WhtR was a useful predictor of T2D (P < 0.05). Mediation analysis showed that HOMA-IR (0.45 %), SBP (5.10 %), triglycerides (11.02 %), creatinine (9.36 %) and combined kidney indicators (17.48 %) partly mediated the effect of WHtR on T2D in men. For women, this association was partly mediated by SBP (13.86 %), HDL (24.54 %), ALT (6.29 %), UA (22.58 %) and combined kidney indicators (39.51 %). CONCLUSIONS: WHtR was an independent risk factor for the development of T2D and IFG. This association was partly mediated by HOMA-IR, SBP, lipids and other liver and kidney metabolism indicators.

Association of serum uric acid with the risk of developing hypertension: A prospective cohort study with mediation analysis.

Elevated serum uric acid (SUA) is associated with the incidence of hypertension, but whether relevant metabolic factors have mediating effects is not certain. Our study was based on a functional community cohort established in Beijing. In 2015, a total of 7482 individuals without hypertension were recruited and followed up until 2019. Multivariate logistic regression analysis was used to investigate the association between SUA and hypertension. Cross-lagged panel analysis and mediation analysis were used to explore the effects of metabolic factors on the association between SUA and incident hypertension. During the average 4-year follow-up, the cumulative incidence of hypertension was 10.9% (n = 580). SUA was an independent risk factor for hypertension, and the RRs (95% CI) for subjects with baseline SUA levels in quartile 2, quartile 3 and quartile 4 were 1.20 (0.88-1.63), 1.50 (1.10-2.05), and 1.57 (1.11-2.22) compared to those in quartile 1, respectively. The cross-lagged panel analysis showed that the increases in Cr, TG, LDL, ALT, AST and WBC occurred after SUA increased (P < 0.001). Among these factors, TG, WBC and ALT played an intermediary role in both men (TG: 14.76%; WBC: 11.61%; ALT: 15.93%) and women (TG: 14.55%; WBC: 8.55%; ALT: 6.89%). The elevated SUA concentration was an independent risk factor for hypertension in the Chinese population, and TG, WBC and ALT had important mediating effects on the association between SUA and hypertension.

Association between surrogate indicators of insulin resistance and risk of type 2 diabetes combined with hypertension among Chinese adults: two independent cohort studies.

BACKGROUND: Type 2 diabetes (T2D) combined with hypertension has a higher risk of developing cardiovascular diseases. This study aimed to investigate the relationships between the surrogate indicators of insulin resistance (TyG, TG/HDL, and Mets-IR) with the risk of T2D combined with hypertension. METHODS: This study is based on a functional community cohort from Beijing and the China Health and Retirement Longitudinal Study, comprising 4234 and 4658 participants respectively. Cox proportional hazards models and restricted cubic spline regression were performed to assess the link between TyG, TG/HDL, and Mets-IR with T2D combined with hypertension. The cross-lagged panel analysis and the mediation analysis were used to examine the temporal relationship between insulin resistance and obesity and their temporal relationship with follow-up T2D combined with hypertension. RESULTS: In multivariable-adjusted models, higher TyG was associated with a higher risk of developing T2D combined with hypertension, the hazard ratios (95% confidence interval) were 3.46 (2.43-4.93) and 2.02 (1.67-2.44), in two cohorts respectively. A similar positive association was shown for Mets-IR, the hazard ratios (95% confidence interval) were 1.04 (1.03-1.06) and 1.05 (1.03-1.07), in two cohorts respectively. However, the association between TG/HDL with T2D combined with hypertension was different in two cohorts. The restricted cubic spline regression showed a linear association between TyG and T2D combined with hypertension (P-nonlinear > 0.05). The cross-lagged path coefficient from baseline BMI to follow-up TyG index was significantly greater than the path coefficient from baseline TyG to follow-up BMI. TyG partially mediated the effect of BMI on the risk of T2D combined with hypertension and the percentage of mediated association was estimated at 41.58% and 48.41% in two cohorts, respectively. CONCLUSION: These findings indicated positive associations between TyG and Mets-IR with the risk of T2D combined with hypertension in two cohorts. In addition, BMI change may precede TyG index change, and the TyG index plays a mediating role in BMI induced T2D combined with hypertension.

Short-term effects of gaseous air pollutants on outpatient visits for respiratory diseases: a case-crossover study in Baotou, China.

Air pollution is a major public health problem throughout the world. Although there have been several studies in this field, most of them have focused on particulate matter and only covered a few key cities. This study aimed to assess a potential association between exposure to gaseous air pollutants and outpatient visits for respiratory diseases in Baotou, China. Daily outpatient visits for respiratory diseases and daily averages of air pollutants and meteorological parameters from 2015 to 2020 were obtained. Time-stratified case-crossover design and restricted cubic splines were used to perform the analyses. Stratified analyses were performed in different hospital departments and districts. Significant association between the concentrations of air pollutants and outpatient visits for respiratory diseases was observed. The odds ratios of outpatient visits for respiratory diseases associated with per 10 µg/m3 increases in concentrations of NO2 and SO2, and per 10 mg/m3 increases in concentrations of CO were 1.033 (95% CI: 1.018 to 1.049), 0.965 (95% CI: 0.954 to 0.976), and 1.038 (95% CI: 1.006 to 1.071), respectively. Short-term exposure to NO2, SO2, and CO was positively associated with outpatient visits for respiratory diseases, with stronger effects among children. The relationship between O3 and respiratory diseases varied at different concentrations.

Gender-specific predictive ability for the risk of hypertension incidence related to baseline level or trajectories of adiposity indices: a cohort study of functional community.

BACKGROUND: Early prevention of hypertension is important for global cardiovascular disease morbidity and mortality. This study aims to explore better predictors for hypertension incidence related to baseline level or trajectories of adiposity indices, as well as the gender-specific effect. METHODS: 6085 subjects from a functional community cohort in urban Beijing participated in our study. Restricted cubic splines were used to estimate nonlinear associations of body mass index (BMI) and waist-to-height ratio (WHtR) as continuous variable with risk of hypertension. Stepwise logistic regression model was performed to estimate the relative risks (RRs) of adiposity indices and metabolic status, adjusted for covariates. Nomogram models and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of BMI trajectory groups and WHtR trajectory groups on hypertension incidence. Further, all analysis were performed by gender. RESULTS: The risk of hypertension incidence was related to BMI trajectory groups (persistent overweight: RR = 1.88, 95% CI: 1.48-2.37; persistent obesity: RR = 2.79, 95% CI: 2.18-3.56; persistent the highest: RR = 4.30, 95% CI: 3.20-5.78) and WHtR trajectory groups (persistent medium: RR = 2.69, 95% CI: 2.07-3.50; persistent high: RR = 3.85, 95% CI: 2.92-5.09; increasing to higher: RR = 7.00, 95% CI: 4.96-9.89). In total population, BMI trajectories and WHtR trajectories showed similar ability to predict the risk of hypertension incidence with AUC 0.723 and 0.726, respectively. After stratified by gender, both BMI trajectories and WHtR trajectories showed higher power in female than male (BMI trajectories: 0.762 vs. 0.661; WHtR trajectories: 0.768 vs. 0.661). CONCLUSIONS: BMI and WHtR trajectories have higher predictive power for hypertension incidence compared to baseline data. Females are more vulnerable to obesity than males.

Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study.

BACKGROUND AND AIMS: There is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study. METHODS AND RESULTS: The study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose-response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose-response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14-2.04), 1.86 (1.40-2.46), and 2.55 (1.94-3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08-1.90), 1.59 (1.20-2.12), and 1.69 (1.26-2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025). CONCLUSION: IR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.

Association of household solid fuel use and long-term exposure to PM2.5 with arthritis in middle-aged and older population in China: A cohort study.

Air pollutants are common modifiable risk factors for arthritis. To explore the longitudinal effects of air pollution on arthritis based on a cohort study in middle-aged and elder people of China. Data was obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 7449 participants aged 45 years and older were involved in our study. The generalized linear mixed models were conducted to examine the separate and joint effects of household air pollution and outdoor air pollution on arthritis, respectively. We found a strong significant association between air pollution and arthritis incidence. Individuals cooking primarily with solid fuel were more likely in higher risk of arthritis compared with cleaner fuel (OR= 1.15; 95% CI: 1.08-1.23). The group-based trajectory model identified four trajectory groups, compared with group "High-Decreasing rapidly", adjusted ORs of incident arthritis for group "Middle-Decreasing moderately", "Low-Decreasing slowly" and "Low-Stably" were 1.36 (95% CI, 1.03-1.79), 1.36 (95% CI, 1.01-1.83) and 1.81 (95% CI, 1.30-2.52), respectively. These associations were generally higher in participants younger than 65 years. In addition, solid fuel use and PM2.5 exposure had additive and multiplicative effects on arthritis. The results suggested that solid fuel use and long-term PM2.5 exposure were associated with a higher incidence of arthritis. Therefore, it is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to reduce PM2.5 concentration.