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.

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.

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.

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.

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.

Management of ductal spasm in a neonate with pulmonary atresia and an intact ventricular septum during cardiac catheterization: A case report.

BACKGROUND: Ductal spasm is a rare but life-threatening complication of cardiac catheterization in neonates with pulmonary atresia and an intact ventricular septum. In patients with ductal-dependent pulmonary blood flow, ductal spasm may lead to refractory hypoxemia and severe hemodynamic instability, which need to be treated in perfect order. CASE SUMMARY: We present a male infant with a gestational age of 39 wk, and his fetal echocardiography showed pulmonary atresia. At 28 d of age, transcatheter pulmonary valvuloplasty with balloon dilatation was performed. Two hours after the operation, the patient's pulse oxygen saturation continued to decrease. The patient was then transferred to receive cardiac catheterization. During catheterization, the invasive blood pressure and pulse oxygen saturation suddenly decreased, and repeated aortography revealed partial occlusion of the ductus arteriosus. It no longer changed when pulse oxygen saturation rose to 51% after approximately 20 min of maintenance therapy. Therefore, a ductal stent was used for implantation. Hemodynamics and hypoxemia were improved. CONCLUSION: We should know that ductal spasm may occur during pulmonary atresia and intact ventricular septum cardiac catheterization. Understand the pathophysiology of ductal-dependent pulmonary blood flow and make comprehensive perioperative preparations essential to deal with hemodynamic disorders caused by ductal spasm.

Considerations of single-lung ventilation in neonatal thoracoscopic surgery with cardiac arrest caused by bilateral pneumothorax: A case report.

BACKGROUND: Tension pneumothorax of the contralateral lung during single-lung ventilation (SLV) combined with artificial pneumothorax can cause cardiac arrest due to bilateral pneumothorax. If not rapidly diagnosed and managed, this condition can lead to sudden death. We describe the emergency handling procedures and rapid diagnostic methods for this critical emergency situation. CASE SUMMARY: We report a case of bilateral pneumothorax in a neonatal patient who underwent thoracoscopic esophageal atresia and tracheoesophageal fistula repair under the combined application of SLV and artificial pneumothorax. The patient suffered sudden cardiac arrest and received emergency treatment to revive her. The recognition of dangerous vital sign parameters, rapid evacuation of the artificial pneumothorax, and initiation of lateral position cardiopulmonary resuscitation while simultaneously removing the endotracheal tube to the main airway are critically important. Moreover, even though the sinus rhythm was restored, the patient's continued tachycardia, reduced pulse pressure, and depressed pulse oximeter waveform were worrisome. We should highly suspect the possibility of pneumothorax and use rapid diagnostic methods to make judgment calls. Sometimes thoracoscopy can be used for rapid examination; if the mediastinum is observed to be shifted to the right, it may indicate tension pneumothorax. This condition can be immediately relieved by needle thoracentesis, ultimately allowing the safe completion of the surgical procedure. CONCLUSION: Bilateral pneumothorax during SLV combined with artificial pneumothorax is rare but can occur at any time in neonatal thoracoscopic surgery. Therefore, anesthesiologists should consider this possibility, be alert, and address this rare but critical complication in a timely manner.

Impact of hyperbilirubinemia associated acute kidney injury on chronic kidney disease after aortic arch surgery: a retrospective study with follow-up of 1-year.

BACKGROUND: Hyperbilirubinemia (HB) is a serious complication in aortic arch surgery, which is associated with acute kidney injury (AKI). The association between HB and chronic kidney disease (CKD) is unknown. The aim of this study was to investigate the impact of HB associated AKI on CKD after aortic arch surgery. METHODS: We reviewed 284 patients who underwent aortic arch surgery from 2016 to 2020 in our hospital. AKI was defined as a 50% increase in sCr from baseline value within the first 7 postoperative days. HB was defined as total bilirubin > 51.3 µmol/L. Patients were divided into 3 groups based on AKI and HB: HB associated AKI (HB-AKI) group (AKI patients suffered HB within the first 7 postoperative days); AKI without HB group and Non-AKI group. RESULTS: Follow-up for 204 patients ranged from 3 to 12 months. Kaplan-Meier analysis showed that the 1-year cumulative incidence of CKD was highest in HB-AKI (32.6%) than AKI without HB (17.8%) and Non-AKI (7.4%, log-rank test, p < 0.001), and the incidence of CKD was higher in HB group than that in Non-HB group (26.7% vs. 13.9%, log-rank test, p = 0.015). Preoperative sCr (HR 1.010, 95% CI 1.004-1.016, p = 0.001), AKI without HB (HR 2.887, 95% CI 1.133-7.354, p = 0.026) and HB-AKI (HR 4.490, 95% CI 1.59-12.933, p = 0.005) were associated with CKD during 1-year follow-up. CONCLUSIONS: Patients suffering HB associated AKI were at more increased odds of CKD than patients suffering AKI without HB after aortic arch surgery.

Association between cumulative serum urate and development of diabetes type II: the Kailuan Study.

OBJECTIVE: To explore whether cumulative serum urate (cumSU) is correlated with diabetes type II mellitus incidence. METHODS: In this study, we recruited individuals participating in all Kailuan health examinations from 2006 to 2013 without stroke, cancer, gestation, myocardial infarction, and diabetes type II diagnosis in the first three examinations. CumSU was calculated by multiplying the average serum urate concentration and the time between the two examinations (umol/L × year). CumSU levels were categorized into five groups: Q1-Q5. The effect of cumSU on diabetes type II incidence was estimated by logistic regression. RESULTS: A total of 36,277 individuals (27,077 men and 9200 women) participated in the final analysis. The multivariate logistic regression model showed the odds ratios (95% confidence intervals) of diabetes type II from Q1 to Q5 were 1.00 (reference), 1.25 (1.00 to 1.56), 1.43 (1.15 to 1.79), 1.49 (1.18 to 1.87), and 1.80 (1.40 to 2.32), respectively. Multivariable odds ratios per 1-standard deviation increase in cumSU were 1.26 (1.17 to 1.37) in all populations, 1.20 (1.10 to 1.32) for men, and 1.52 (1.27 to 1.81) for women, respectively. CONCLUSIONS: CumSU is a significant risk factor for diabetes type II. Individuals with higher cumSU, especially women, are at a higher risk of diabetes type II independent of other known risk factors.Key Points• Cumulative exposure to serum urate is a significant risk factor for diabetes type II.• Individuals with higher cumSU, especially women, are at a higher risk of diabetes type II.

Hyperbilirubinemia Induces Pro-Apoptotic Effects and Aggravates Renal Ischemia Reperfusion Injury.

AIMS: Hyperbilirubinemia is associated with postoperative acute kidney injury in patients undergoing cardiac surgeries. A high concentration of bilirubin could induce oxidative stress and cell apoptosis. The aim of this study was to investigate whether hyperbilirubinemia aggravated the renal tubule cells injury and the pro-apoptotic potential of bilirubin on renal ischemia reperfusion injury (RIRI). METHODS: The human proximal tubular epithelial cell line HK-2 cells were challenged with a gradient concentration of bilirubin for 24 h. Cell injury was assessed by flow cytometry and MTT assay. Bilirubin was injected intraperitoneally into male Sprague-Dawley rats once every 12 h (100 mg/kg), 3 times in total. The same solvent volume without bilirubin powder was used as vehicle in non-bilirubin injection groups. The RIRI surgical procedure was a bilateral renal pedicles clamping (45 min) followed by 30 h reperfusion. The rats were divided into 4 groups: negative control (NC), similar surgical procedures without clamping; Bil, bilirubin injection for 36 h, then rats were sacrificed; RIRI, RIRI surgical procedures; Bil + RIRI, RIRI applied 6 h later than the first bilirubin injection, rats were sacrificed after another 30 h. RESULTS: In vitro, bilirubin induced cell apoptosis and significantly decreased the cell viability of HK-2 cells. Bilirubin induced the active caspase 3 and phosphorylation of p38 in HK-2 cells. In vivo, serum creatinine was higher in Bil + RIRI compared with RIRI (p < 0.01). The tubular injury scores of hematoxylin and eosin and tubular necrosis scores of periodic acid-Schiff were higher in Bil + RIRI than these in RIRI (All p < 0.05). The number of Tunel-positive nuclei was higher in Bil + RIRI compared to RIRI (p < 0.001). The active caspase 3 and phosphorylation of p38 were higher and the Bcl2 was lower in Bil + RIRI compared to RIRI. Moreover, the apoptosis level was higher in Bil compared to NC. CONCLUSIONS: Our results reveal that the hyperbilirubinemia induces pro-apoptotic effects and aggravates RIRI.

Association of serum uric acid and risk of hypertension in adults: a prospective study of Kailuan Corporation cohort.

Whether hyperuricemia is an independent risk factor for hypertension in adults is still under debate. To determine the association between serum uric acid and risk of hypertension in the Chinese population, we conducted a prospective study using the "Kailuan Corporation cohort." A total of 39,233 adult subjects with available data on serum uric acid were enrolled from 2006 to 2007. Subjects with established hypertension were excluded and were then grouped based on the gender and baseline quartile serum uric acid into F1-4 for women and M1-4 for men with F1 and M1 being the lowest quartiles. Incidence of newly described primary hypertension was reevaluated in 2010-2011. The median (interquantile range) baseline uric acid (UA) was 290 (243-344) µmol/L in men and 230 (194-274) µmol/L in women. During a 4-year follow-up period, 12,844 subjects (31.31 %) were newly diagnosed with hypertension. The incidence of hypertension was 14.36, 16.57, 19.06, and 22.35 % in F1 to F4 and 33.64, 33.97, 36.54, and 40.74 % in M1 to M4, respectively. Multiple logistic regression analysis showed that the odds ratios (ORs) of incident hypertension were 1.17 [95 % confidence interval (CI) 1.00-1.37, P = 0.055], 1.24 (95 % CI 1.06-1.45, P = 0.009), and 1.20 (95 % CI 1.02-1.41, P = 0.027) in F2 to F4 compared to the F1 and 0.98 (95 % CI 0.91-1.05, P = 0.534), 1.05 (95 % CI 0.98-1.13, P = 0.190), and 1.13 (95 % CI 1.05-1.22, P = 0.002) in M2 to M4 compared to the M1. Elevated level of serum uric acid is associated with an increased risk of hypertension in adults.

Glycan Biomarkers for Rheumatoid Arthritis and Its Remission Status in Han Chinese Patients.

Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p < 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA.

Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome.

OBJECTIVE: Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case-control study to determine whether SLE is associated with altered IgG glycosylation. METHODS: Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). RESULTS: Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity). CONCLUSION: The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.