The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.

Ideal physical activity in association with incident ankylosing spondylitis: a community-based, prospective cohort study.

OBJECTIVES: Only limited risk factors for ankylosing spondylitis (AS) have been identified to date. Therefore, we aimed to explore whether cardiovascular health (CVH) behaviours and factors are associated with the risk of developing AS. METHODS: Patients with incident AS were identified in cohorts from two ongoing prospective studies. Assessments were made of the association of AS with individual baseline cardiovascular health lifestyle behaviours (including smoking status, body mass index, physical activity and diet) and cardiovascular health factors (including total cholesterol levels, blood pressure levels and fasting plasma glucose levels), and with a cardiovascular health metric determined by the number of ideal behaviours and factors. Cox regression analysis was used for the estimation of hazard ratios (HRs) for AS. RESULTS: Among 124,303 participants, incident AS was identified in 53 individuals within the 8 years of follow-up. For participants with ideal physical activity (>80 min/week) the HR was 0.21 (95% CI 0.05-0.89) compared with participants without ideal physical activity after adjusting for potential confounders. No signi cant risk of developing AS was associated with baseline smoking, diet, body mass index, blood pressure, fasting blood glucose or total cholesterol status, nor did cardiovascular health metrics. CONCLUSIONS: Adherence to ideal physical activity may reduce the risk of developing AS.

Longitudinal Study of Brachial-Ankle Pulse Wave Velocity and Change in Estimated Glomerular Filtration Rate among Chinese Adults.

BACKGROUND AND OBJECTIVES: Studies on the association between arterial stiffness and kidney function have generated inconsistent results. Whether arterial stiffness is linked to decline in renal function warrants further study. This study aimed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and longitudinal change in estimated glomerular filtration rate (eGFR) among Chinese adults. METHODS: In this longitudinal study, 8,264 participants in a community-based cohort had baPWV measured in 2010-2011 and were followed in subsequent surveys through to 2016. During each survey visit, fasting blood samples were collected for serum creatinine and eGFR was calculated. Participants were divided into 5 groups (Q1-Q5) by baPWV quintile. The association between baPWV and longitudinal changes in eGFR was assessed using generalized estimating equation models. RESULTS: A total of 8,045 participants were included in the final analysis. The average age was 54 ± 12 years (age range 24-97 years), and mean eGFR was 93.0 ± 18.6 mL/min/1.73 m2. There was an inverse linear association between baseline baPWV and eGFR change rate (p < 0.001). Compared with Q1 (lowest) group, the mean differences and 95% CI in eGFR decrease rate among Q2-Q5 groups were -0.23 (-0.62, 0.16), -0.67 (-1.06, -0.28), -1.11 (-1.50, -0.72), and -1.30 (-1.69, -0.92) mL/min/1.73 m2 per year, respectively, after adjustment for age, gender, and other potential confounders (p trend < 0.0001). For each 100 cm/s increase in baPWV at baseline, the fully adjusted mean difference in eGFR decrease rate was -0.14 mL/min/1.73 m2 per year (95% CI -0.18, -0.10; p < 0.0001). Compared with participants with baPWV < 1,400 cm/s, the fully adjusted mean difference in eGFR decrease rate was -0.92 mL/min/1.73 m2 per year (95% CI -1.18, -0.66) for those with baPWV ≥ 1,400 cm/s (p < 0.0001). CONCLUSIONS: Participants with a higher baPWV at baseline had a greater decrease in eGFR over time. Future studies could examine the relationship between baPWV and decline in renal function in higher risk cohorts, and its potential role in targeting reno-protective interventions to those who may benefit from them most.

Habitually skipping breakfast is associated with chronic inflammation: a cross-sectional study.

OBJECTIVE: We examined whether breakfast frequency was associated with chronic inflammatory, as assessed by high-sensitivity C-reactive protein (CRP) concentration. DESIGN: Cross-sectional study. SETTING: Kailuan community, China. PARTICIPANTS: Included were 70 092 Chinese adults without CVD and cancer in 2014 with CRP concentrations <10 mg/l, when breakfast frequency was assessed via a questionnaire, and plasma CRP concentration was measured. RESULTS: Breakfast frequency was associated with CRP concentration (P-trend < 0·001). The adjusted mean CRP was 1·33 mg/l (95 % CI 1·23, 1·44) for the 'no breakfast' group and 1·07 mg/l (95 % CI 1·0, 1·14) for the 'breakfast everyday' group (P-difference < 0·001), adjusting for age, sex, diet quality, total energy, obesity, education, occupation, marital status, smoking, alcohol consumption, blood pressure, sleep parameters, fasting blood glucose and lipid profiles. Consistently, the adjusted OR for CRP ≥ 1·0 mg/l and CRP ≥ 3·0 mg/l were 1·86 (95 % CI 1·73, 2·00) and 1·27 (95 % CI 1·15, 1·40), respectively, when comparing these two breakfast consumption groups (P-trend < 0·001 for both). The associations were more pronounced among older adults, relative to those who were younger (P-interaction < 0·001). Significant association between breakfast skipping and elevated CRP concentration was observed in those with poor diet quality, but not those with good diet quality. CONCLUSIONS: Habitually skipping breakfast is associated with elevated concentrations of CRP. Future prospective studies including repeated assessment of inflammatory biomarkers and a collection of detailed information on type and amount of breakfast foods are warranted.

NAF1 rs4691896 Is Significantly Associated with Coal Workers' Pneumoconiosis in a Chinese Han Population: A Case-Control Study.

BACKGROUND Previous studies have demonstrated the important role of genetic predisposition in coal workers' pneumoconiosis (CWP) in addition to environmental factors. The pathogenesis of pulmonary fibrosis disease is related to telomere activity. We performed this study to assess the association between genetic variants of telomere-related genes and the risk of CWP. MATERIAL AND METHODS We enrolled 652 CWP Chinese Han patients and 648 dust-exposed controls in this case-control design study, genotyping 8 single-nucleotide polymorphisms (SNPs) including TERT (rs2736100), TERC (rs10936599 and rs12696304), and NAF1 (rs7675998, rs3822304, rs12331717, rs936562 and rs4691896) using the Sequenom MassARRAY system. RESULTS We identified a significant allele association between NAF1 rs4691896 and CWP by comparing patients with controls (22.0% vs. 13.0%, odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.54-2.33, Pc=1.14×10⁻8). The genotype frequency of rs4691896 differed significantly between the patients and controls (Pc=1.49×10⁻8). In addition, rs4691896 was correlated with CWP in an additive genetic model (OR: 1.96, 95% CI: 1.58-2.44, Pc=8.96×10⁻9) and a dominant model (OR: 2.15, 95% CI: 1.70-2.73, Pc=2.39×10⁻9). CONCLUSIONS Our study for the first time demonstrates an association between a telomere-related gene (NAF1) and CWP in a Chinese Han population, and provides valuable insight to further understand the possible pathogenetic mechanism of fibrosis in CWP.

Association of single nucleotide polymorphisms in the CYBA gene with coal workers' pneumoconiosis in the Han Chinese population.

Coal workers' pneumoconiosis (CWP) is caused by long-term exposure to inhaled coal dust; it is likely influenced by the interaction between environmental factors and multiple susceptibility genes, such as the CYBA (cytochrome b-245α polypeptide) gene that has recently been identified to be involved in the genetic susceptibility for several pulmonary diseases. The aim of this case-control study was to explore the association between CYBA gene polymorphisms and the development of CWP in coal miners belonging to the Han ethnic group in China. Single nucleotide polymorphisms (SNPs) rs7195830, rs13306296, rs4673, rs9932581, and rs16966671 of the CYBA gene were analyzed in CWP patients (n = 652) and dust-exposed control subjects (n = 648) using the matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) on the Sequenom MassARRAY® platform (Sequenom, San Diego, CA, USA). Results from the present study showed a strong allele association between CWP patients and the CYBA SNP rs7195830 polymorphism (p < .001, OR = 1.550). Using the additive and the dominant model, the CYBA SNP rs7195830 polymorphism also showed significant associations with CWP patients (p < .001, OR = 1.621; p = .003, OR = 1.711, respectively). No statistically significant difference was demonstrated in either the allele or genotype frequencies of the other four examined SNPs (rs13306296, rs4673, rs9932581, and rs16966671) between the CWP group and dust-exposed control group (all p > .05). The present study is the first to have demonstrated an association between CYBA (rs7195830) polymorphism and the risk of developing CWP in subjects belong to the Han ethnic group in China and provides further clues for research into the pathogenesis of CWP.

Prevalence and risk factors of hyperuricemia: results of the Kailuan cohort study.

OBJECTIVE: The objective of this study is to determine the serum uric acid (SUA) level and the prevalence of hyperuricemia (HUA) in Chinese population. METHODS: We conducted a cross-sectional study among 100,226 employees (79.9% male) of the Kailuan Group using physical examination data in 2006-2007. HUA was defined as SUA >356.9 µmol/L (6.0 mg/dL) for women and SUA >416.4 µmol/L (7.0 mg/dL) for men. We investigated crude and age adjusted HUA prevalence and compared characteristics of subjects with and without HUA in men and women using multivariate logistic regression. RESULTS: SUA levels were 244.9 ± 71.5 µmol/L in women and 302.0 ± 83.5 µmol/L in men. About 8290 (8.27%) subjects were diagnosed with HUA. Age-adjusted prevalence of HUA was 8.02% in the total sample (6.87% in women and 8.57% in men). The SUA level and HUA prevalence showed U-shaped or J-shaped associations with age. Multivariate logistic regression revealed age, waist circumference, total cholesterol, triglyceride, hypertension and non-alcoholic fatty liver disease history, prolonged sitting, alcohol consumption, and oral diuretics were independent risk factors of HUA, while long sleep duration was protective against HUA. CONCLUSIONS: The prevalence of HUA is 6.87% and 8.57% in Chinese women and men. HUA is likely related with life style and metabolic disorders.

The impact of rheumatoid arthritis on work capacity in Chinese patients: a cross-sectional study.

OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.

[The effects of exposure to the famine during early life with elevated resting heart rate in the adult].

OBJECTIVE: To investigate the association between exposure to the famine during early life and elevated resting heart rate (RHR) in adulthood. METHOD: From June 2006 to October 2007, the employees of kailuan group who took part in the health examination were selected. Of those, 18 619 cases who was born during October 1, 1956 to September 30, 1964 in Hebei province were finally included in the analysis based on the inclusion and exclusion criteria. All the subjects were received questionnaire survey, smoking and drinking, physical examination, Lab examination and the measurement of RHR. The subjects of famine exposure group (3 190 cases) were born from October 1, 1959 to September 30, 1961, semi-exposure group (3 851 cases) were born from October 1, 1958 to September 30, 1959 and from October 1, 1961 to September 30, 1962, control group (11 578 cases) were born from October 1, 1956 to September 30, 1958 and from October 1, 1962 to September 30, 1964. The RHR and the detection rate of elevated RHR were compared among the three groups. The Multivariate logistic regression model was used to analyze the association between of exposure to famine during early life and elevated RHR in adulthood. RESULTS: The RHR level was higher in famine exposure group and semi-exposed group than control group, which were (74.34 ± 9.71), (74.41 ± 9.48) and (73.90 ± 9.45) beat per minute (bpm) (P values were 0.003 and 0.020, respectively). In all of the subjects. The results of multivariate logistic regression showed that exposure of famine during early life increased the risk of elevated RHR in adulthood after adjustment for age, gender and other confounders (OR = 1.10, 95% CI: 1.01-1.21). In men, exposure of famine during early life also increased the risk of elevated RHR in adulthood (OR = 1.15, 95% CI: 1.04-1.28); In women, there was no association between the famine exposure and elevated RHR (OR = 0.92, 95% CI: 0.74-1.14). CONCLUSION: Exposure of famine during early life increases the risk of elevated RHR in adulthood. This negative effect existed mainly in the male.

Association between cardiac conduction block and cardiovascular disease and all-cause mortality: The kailuan study.

BACKGROUND: Although bundle branch block and atrioventricular block are recognized to be association with cardiovascular disease (CVD) and mortality, the relationship between cardiac conduction block (CCB) and both CVD and all-cause mortality has yet to be explored. AIMS: To explore the relationship between CCB and CVD and all-cause mortality. METHODS AND RESULTS: We included 145,805 subjects (mean age 49.7 years, 81.2% males) from the kailuan study. CCB was diagnosed through a 12­lead electrocardiograph (ECG). Mortality and CVD events were ascertained through multiple sources, including a municipal social insurance institution, hospital records, death certificates, and regular active follow-ups. After a mean follow-up of 12.5 years, 18,301 cases developed all-cause mortality. After excluding 4443 subjects with CVD presence at baseline, 13,208 cases of CVD occurred among the 141,362 study subjects during follow-up. Compared with non-CCB group, the cumulative incidence of CVD and all-cause mortality for CCB group was 18.38% VS 12.14% and 33.45% VS 14.18%, respectively. The multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) with CCB group were 1.25(1.17-1.34) for CVD, and 1.31(1.25-1.38) for all-cause mortality. Additionally, there were generally stronger associations for CCB with all-cause mortality and CVD in younger participants compared with their older counterparts (Ps-interaction <0.001). CONCLUSION: CCB can increase the risk of CVD and all-cause mortality in the general population. Our findings highlight the importance of strategies for preventing CCB to reduce the risk of CVD and mortality.

Distinct uric acid trajectories are associated with incident cardiac conduction block.

BACKGROUND: The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. METHODS: A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. RESULTS: We categorized three observed discrete trajectories of UA during 2006-2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16-1.47) and 1.86 (1.56-2.22), and HRs of atrioventricular block were 1.39 (1.12-1.72) and 2.90 (2.19-3.83), and HRs of bundle branch blocks were 1.27 (1.10-1.47) and 1.43 (1.13-1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. CONCLUSIONS: The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.

The Combination of Hyperuricemia and Elevated High-Sensitivity C-Reactive Protein Increased the Risk of Cardiac Conduction Block.

Objective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP. Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP>3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB. Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22-1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27-2.77), and right bundle branch block (HR:1.47, 95% CI:1.02-2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP. Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP.

Associations of uric acid with the risk of cardiovascular disease and all-cause mortality among individuals with chronic kidney disease: the Kailuan Study.

AIMS: The relationship between uric acid (UA) concentrations and the risk of cardiovascular disease (CVD), especially for subtypes of CVD among individuals with chronic kidney disease (CKD) is not well understood. This study aimed to investigate whether uric acid concentration was associated with subtypes of CVD and all-cause mortality among individuals with CKD. METHODS: A total of 27,707 individuals with CKD, free of CVD at recruitment from the Kailuan Study, were included. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 11-12 years, we documented 674 myocardial infarctions, 1197 heart failures, 2406 strokes, and 5676 total deaths. Among participants with CKD, compared with those in the lowest tertile of UA, the HRs (95% CIs) of participants in the highest UA tertile were 1.38 (1.13-1.67) for myocardial infarction, 1.60 (1.38-1.85) for heart failure, 1.01 (0.91-1.12) for stroke, and 1.29 (1.21-1.38) for all-cause mortality. Subgroup analyses showed that the associations between UA and heart failure and all-cause mortality were stronger in individuals with eGFR <45 mL/min/1.73m2 compared to their counterparts (Pinteraction<0.05). Additionally, the association between UA and all-cause mortality was stronger among individuals without diabetes than those with diabetes (Pinteraction<0.05). CONCLUSIONS: In individuals with CKD, a higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality, following a dose-response relationship. Our data underscore the importance of UA screening among individuals with CKD for CVD and premature death prevention.

This study investigated the relationship between uric acid (UA) concentrations and the risk of cardiovascular disease and all-cause mortality in individuals with chronic kidney disease (CKD) using the Kailuan Study. A higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality among individuals with CKD, following a dose-response manner.The associations between concentrations of UA and the risk of heart failure and all-cause mortality were more pronounced in individuals with severe kidney impairment (estimated glomerular filtration rate <45 mL/min/1.73m2). Furthermore, the association between UA and all-cause mortality was stronger among individuals without diabetes compared to those with the condition.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS).

BACKGROUND: Serum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. METHODS: Data are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. RESULTS: A total of 1014 participants aged 25-83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. CONCLUSION: SUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. TRIAL REGISTRATION: The KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Upregulated microRNA-155 expression in peripheral blood mononuclear cells and fibroblast-like synoviocytes in rheumatoid arthritis.

OBJECTIVE: This study was to screen for the miRNAs differently expressed in peripheral blood mononuclear cells (PBMC) of RA, to further identify the expression of miR-155 in RA PBMC and fibroblast-like synoviocytes (FLS), and to evaluate the function of miR-155 in RA-FLS. METHODS: Microarray was used to screen for differentially expressed miRNAs in RA PBMC. miR-155 expression in PBMC and FLS of RA were identified by real-time PCR. Enforced overexpression and downexpression of miR-155 were used to investigate the function of miR-155 in RA-FLS. Expression of IKBKE which was previously identified as the actual target of miR-155 was examined by Western blot and real-time PCR in RA-FLS. RESULTS: miR-155 levels were increased in both PBMC and FLS of RA and could be induced by TNF- α . Upregulation of miR-155 decreased MMP-3 levels and suppressed proliferation and invasion of RA-FLS. Inverse relationship between the expressions of miR-155 and the MMPs production-related protein IKBKE was found. CONCLUSION: An inflammatory milieu may alter miRNA expression profiles in rheumatoid arthritis. miR-155 is upregulated in RA-FLS, and it may be a protective factor against the inflammatory effect in part by attenuating expression of IKBKE.

High levels of high-sensitivity C reactive protein to albumin ratio can increase the risk of cardiovascular disease.

BACKGROUND: The high levels of C reactive protein (CRP) to albumin ratio (CAR) is thought to increase the risk of poor outcomes for cancer and cardiovascular disease (CVD). However, the association between CAR and CVD in the Chinese community population has not been investigated. OBJECTIVE: The aim of this study was to investigate the association between CAR and CVD in the Chinese community population. METHODS: A total of 62 067 participants without a history of CVD or cancer were included in this study. Kaplan-Meier survival curves were used to calculate the cumulative incidence of endpoint events in CAR quartile groups, and the results were tested by log-rank test. Fine-Gray model was used to analyse the competing risk of death. C-index, Net Reclassification Index (NRI) and Integrated Discrimination Improvement Index (IDI) of different indicators were calculated to distinguish the predictive performance of different indicators. RESULTS: During an average follow-up period of 10.3±2.1 years, 4025 participants developed CVD. In multivariable Cox regression analysis, compared with Q1 group, model 3 showed that the hazard ratio (HR) (95% confidence interval (95%CI)) of CVD in Q4 group was 1.26 (1.15 to 1.38) (p<0.01), and the HR (95% CI) per 1 SD increase was 1.06 (1.03 to 1.08) (p<0.01). The C-index, continuous NRI and IDI for predicting 10-year CVD were 73.48%, 0.1366 (0.1049 to 0.1684) (p<0.01) and 0.0002 (0.0001 to 0.0004) (p<0.01), respectively, which were higher than those of hs-CRP (C-index:0.7344, NRI:0.0711, IDI: 0.0001) and albumin (C-index:0.7339, NRI: -0.0090, IDI: 0.0000). CONCLUSION: High levels of CAR can increase the risk of CVD and the predictive performance of CAR for CVD is better than that of hs-CRP or albumin alone.

The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. METHODS: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010-2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. RESULTS: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. CONCLUSIONS: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.

Distinct WBC Trajectories are Associated with the Risks of Incident CVD and All-Cause Mortality.

AIMS: To examine the trajectory of white blood cell (WBC) and their potential impacts on cardiovascular disease (CVD) and all-cause mortality (ACM) risks. METHODS: This prospective cohort included 61,666 participants without CVD on or before June 1, 2012. Latent mixture modeling was used to identify WBC trajectories in 2006-2012 as predictors of CVD and ACM. Incident CVD and ACM in 2012-2019 were the outcomes. Cox proportional hazards models were fitted to analyze the risks of incident CVD and ACM. RESULTS: According to WBC ranges and dynamics, five distinct WBC trajectories were identified: low-stable (n=18,432), moderate-stable (n=26,656), elevated-stable (n=3,153), moderate-increasing (n=11,622), and elevated-decreasing (n=1,803). During 6.65±0.83 years of follow-up, we documented 3773 incident CVD cases and 3304 deaths. Relative to the low-stable pattern, the moderate-increasing pattern was predictive of an elevated risk of CVD (HR=1.36, 95% CI: 1.24-1.50), especially acute myocardial infarction (AMI) (HR=1.91, 95% CI: 1.46-2.51), while the elevated-stable pattern was predictive of an elevated risk of ACM (HR=1.77, 95% CI: 1.52-2.06). Among participants with hs-CRP ＜2 mg/L or ≥2 mg/L, similar associations were observed between the moderate-increasing pattern with CVD (HR=1.41, 95% CI: 1.24-1.61) and ACM (HR=1.54, 95% CI: 1.18-2.01, HR=1.89, 95% CI: 1.57-2.29, respectively). CONCLUSIONS: We found that distinct WBC trajectories were differentially associated with CVD and ACM risks in Chinese adults.

Altered cerebral blood flow and white matter during wakeful rest in patients with obstructive sleep apnea: a population-based retrospective study.

OBJECTIVES: To explore changes in cerebral blood flow (CBF) and white matter during wakeful rest in patients with obstructive sleep apnea (OSA). METHODS: The subjects comprised OSA patients and age- and sex-matched non-sleep apnea (NSA) subjects from December 2020 to December 2021. All subjects underwent structural and arterial spin labeling MRI examinations using a 3.0 T MRI scanner. Intergroup differences in regional and global CBF and white matter hyperintensities (WMHs) were analyzed. RESULTS: In this study, 100 (74 males) of 750 (439 males) subjects were diagnosed with OSA, so the prevalence of OSA in the general population was 13.3% (100/750), with 16.9% (74/439) in males and 8.4% (26/311) in females. Excluding four patients with incomplete imaging data, 96 OSA patients and 103 age- and sex-matched NSA subjects were included. At global level, OSA patients showed significantly decreased CBF values in gray matter and whole brain compared to NSA subjects (gray matter: p = 0.010; whole brain: p = 0.021). No significant difference in CBF values was found in WM between the two groups (p = 0.250). At regional level, compared with NSA subjects, patients with OSA exhibited significantly decreased regional CBF values mainly in right parietal lobe and right temporal lobe. Moreover, OSA patients had significantly higher WMHs burden than NSA subjects (p = 0.017). CONCLUSIONS: OSA patients exhibit decreased global and regional CBF values and increased WMHs burden. ADVANCES IN KNOWLEDGE: These findings provide a basis for exploring neuropathological changes of OSA and for early and appropriate treatment.

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment.

BACKGROUND: Hypertension and enlarged perivascular spaces (EPVS) are thought to be associated with cognitive impairment. However, the correlations among hypertension, EPVS, and cognitive impairment have not been studied yet. We aimed to investigate the relationships between cumulative blood pressure (cBP) exposure with EPVS and cognitive impairment and whether EPVS may mediate the relationship between cBP and cognitive impairment. METHODS: A total of 1507 subjects from the Kailuan prospective cohort study were enrolled. cBP was calculated from 2006 to 2022. The effects of cBP, EPVS scores, and cognitive impairment were evaluated using a logistic regression model. The relationships among cBP, EPVS score, and cognitive impairment were analyzed using a mediation model. RESULTS: An increase in cBP was positively correlated with an increase in EPVS score. For every SD increase in cBP, the odds ratios (95% CI) of increased EPVS score of the centrum semiovale were 1.67 (1.43-1.95), 1.63 (1.4-1.9), and 1.35 (1.17-1.56), respectively; the odds ratios (95% CI) of increased EPVS score of the basal ganglia were 1.83 (1.56-2.15), 2.01 (1.7-2.36), and 1.31 (1.13-1.52), respectively; and the odds ratios (95% CI) of developing cognitive impairment were 1.28 (1.06-1.53), 1.13 (0.95-1.34), and 1.28 (1.07-1.5), respectively. Basal ganglia-EPVS score accounted for 10.46% to 18.32% of the mediating effects on the relationships of cBP/SD with cognitive impairment. CONCLUSIONS: High cBP exposure was an independent risk factor for EPVS, and basal ganglia-EPVS score mediated the effects of cBP on cognitive impairment. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ChiCTR-TNRC-11001489.