Relationship Between Control of Cardiovascular Risk Factors and Chronic Kidney Disease Progression, Cardiovascular Disease Events, and Mortality in Chinese Adults.

BACKGROUND: Patients with chronic kidney disease (CKD) are at an elevated risk of cardiovascular disease (CVD) and premature mortality compared to the general population. OBJECTIVES: This study aimed to investigate whether the excess risk of CVD events and death among patients with CKD could be reduced or eliminated through strict control of blood pressure (systolic blood pressure: <130 mm Hg), lipids (low-density lipoprotein cholesterol: <2.6 mmol/L), and glucose (fasting blood glucose: <6.1 mmol/L). METHODS: The authors included 20,254 patients with CKD who were free of CVD or end-stage renal disease and matched them with 35,236 control individuals based on age (±2 years) and sex from the Kailuan study. RESULTS: During a median follow-up period of 12.2 to 12.8 years, 3,875 deaths, 1,888 cases of stroke, 513 cases of myocardial infarction, and 4,825 cases of CKD progression were documented. Among patients with CKD, risk factor controls showed an association with a reduction in myocardial infarction, stroke, CKD progression, and all-cause mortality risk in a dose-dependent manner. Moreover, compared to the non-CKD control individuals, having all 3 risk factors within the target ranges could theoretically eliminate the excess risk of CVD and mortality associated with CKD. Among patients with CKD who had all 3 risk factors controlled, the HRs were 0.80 (95% CI: 0.56-1.14) for myocardial infarction, 0.93 (95% CI: 0.78-1.12) for stroke, and 1.10 (95% CI: 0.98-1.24) for all-cause mortality compared to the non-CKD control individuals. CONCLUSIONS: Patients with CKD who had controlled blood pressure, lipids, and glucose showed no excess risk of death, myocardial infarction, or stroke compared to the general population.

Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73 m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CIs) for incident AF. Results: According to survey results for the range and changing pattern of eGFR during 2006-2010, four trajectories were identified: high-stable (range, 107.47-110.25 mL/min/1.73 m2; n = 11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73 m2; n = 22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73 m2; n = 7,943), and low-stable (range, 73.48-76.78 mL/min/1.73 m2; n = 20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09-2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18-3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46-3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses. Conclusion: The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.

The relation between estimated glomerular filtration rate (eGFR) within the normal or mildly impaired range and risk of atrial fibrillation (AF) in former studies is controversial, and data on longitudinal pattern of eGFR in such topic is sparse. In this cohort study, we identified 4 trajectories of eGFR in populations with normal or mildly impaired renal function. Relative to populations with high-stable pattern of eGFR, those with low-stable pattern, high-decreasing pattern and moderate-increasing pattern were associated with 128%, 92%, and 70% higher risk of AF, respectively. These findings suggested that monitoring eGFR trajectories is an important approach for AF prediction in populations with normal or mildly impaired renal function. Decreasing and consistently low eGFR trajectories within the currently designated normal or mildly impaired range may still significantly increase the risk of AF.

The effect of different levels of systolic blood pressure control on new-onset chronic kidney disease in hypertension multimorbidity.

To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP < 110 mmHg, Group 110 ≤ SBP < 120 mmHg, Group 120 ≤ SBP < 130 mmHg, Group 130 ≤ SBP < 140 mmHg, Group 140 ≤ SBP < 160 mmHg and Group SBP ≥ 160 mmHg. The outcomes were new-onset CKD, new onset proteinuria, decline in eGFR and high or very high risk of CKD. Cox proportional hazards regression was used to examine the hazard ratios (HRs) of the outcomes among SBP levels. When 110 ≤ SBP < 120 mmHg, the incidence density of new-onset CKD, new onset proteinuria and decline in eGFR were 59.54, 20.23 and 29.96 per 1000 person-years, respectively. Compared to this group, the HR (95% CI) values for the risk of new-onset CKD from Group SBP < 110 mmHg to Group SBP ≥ 160 mmHg were 1.03 (0.81-1.32), 1.04 (0.91-1.19), 1.09 (0.95-1.16), 1.16 (1.02-1.21) and 1.18 (1.04-1.24), respectively. For patients over 65 years old, the risks of outcomes were increased when SBP < 120 mmHg. The lowest HR of high or very high risk of CKD for participants with or without multimorbidity occurred when 120 ≤ SBP < 130 mmHg. The HR of new-onset CKD in hypertension multimorbidity was lowest at 110-120 mmHg. The optimal SBP level was between 120 and 130 mmHg for individuals with high or very high risk of CKD. For patients over 65 years old, the low limit of target BP is advised to be not lower than 120 mmHg.

Near-Infrared Light-Triggered NO Nanogenerator for Gas-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy to Eliminate Biofilms.

Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.

Diabetes mellitus: association of cystatin C- versus creatinine-based estimated glomerular filtration rate with mortality and cardiovascular events.

BACKGROUND: To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff), and the risk of mortality and cardiovascular (CV) events in individuals with diabetes. METHODS: Three prospective cohorts analyzed data from adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016-17 to 2020) in China, the National Health Nutrition Examination Survey (NHANES, 1999-2004 to 2019) in the USA and UK Biobank (UKB, 2006-10 to 2022) in the UK. Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. RESULTS: A total of 8129 individuals from INDEED (aged 60.7 ± 10.0 years), 1634 from NHANES (aged 62.5 ± 14.4 years) and 29 358 from UKB (aged 59.4 ± 7.3 years) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in INDEED, NHANES and UKB, respectively, had an eGFRabdiff value ≥15 mL/min/1.73 m2. During a median follow-up of 3.8 years for INDEED, 15.2 years for NHANES and 13.5 years for UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios of 0.77 and 0.82 in INDEED, 0.70 and 0.68 in NHANES, and 0.66 and 0.78 in UKB. Similar results were observed for eGFRrediff. CONCLUSIONS: eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

BACKGROUND: The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. METHODS AND RESULTS: The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. CONCLUSIONS: The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Life's Essential 8 and heart failure among patients with chronic kidney disease: the Kailuan Cohort Study.

AIMS: Patients with chronic kidney disease (CKD) are at an increased risk of developing heart failure. The American Heart Association recently released a new metric, Life's Essential 8 (LE8), for health promotion. However, evidence regarding associations between LE8 and heart failure risk among patients with CKD is scarce. METHODS AND RESULTS: A total of 16 190 patients with CKD (mean age 55.9 years), free of cardiovascular disease at recruitment from the Kailuan Study, were included. Cardiovascular health was assessed using the LE8 score. Incident heart failure events were ascertained via linkage of electronic health record data. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). There were 814 (5.0%) patients in the high LE8 criteria, with 13 180 (81.4%) in the moderate, and 2196 (13.6%) in the low LE8 category, respectively. During a median follow-up of 13.7 years, 724 incident heart failure cases were documented. Compared with the low LE8 category, the HRs (95% CIs) for heart failure were 0.58 (0.48, 0.71) for the moderate LE8 category and 0.32 (0.19, 0.54) for the high LE8 category (P for trend <0.001). In addition, the association was stronger in patients aged ≤65 years compared with their older counterparts (P for interaction = 0.01). CONCLUSION: Our data showed a strong graded inverse association between the LE8-defined cardiovascular health and the risk of heart failure among patients with CKD. Our findings support the importance of adopting the LE8 among patients with CKD to prevent heart failure.

Using the Life's Essential 8 (LE8) score, released by the American Heart Association for cardiovascular health promotion, this study investigated the relationship between cardiovascular health and the risk of heart failure in patients with chronic kidney disease (CKD) in China.Patients with CKD who had better cardiovascular health, as indicated by higher LE8 scores, had a significantly lower risk of heart failure.A stronger association between better LE8 score and lower risk of heart failure among CKD patients aged ≤65 years was observed, compared with their older counterparts.

Association between cumulative uric acid to high-density lipoprotein cholesterol ratio and the incidence and progression of chronic kidney disease.

Objective: The ratio of uric acid to high-density lipoprotein cholesterol (UHR) was related to the risk of chronic kidney disease (CKD), we aimed to investigate the association of cumulative UHR (cumUHR) with incidence and progression of CKD. Methods: Our study included a total of 49,913 participants (mean age 52.57 years, 77% males) from the Kailuan Study conducted between 2006 and 2018. Participants who completed three consecutive physical examinations were included. Cumulative UHR (cumUHR) was computed as the summed average UHR between two consecutive physical examinations, multiplied by the time between the two examinations. Participants were then categorized into four groups based on cumUHR quartiles. Subsequently, participants were further divided into a CKD group and a non-CKD group. The associations between cumUHR and CKD and it's progression were assessed by Cox proportional hazards regression models. The cumulative incidence of endpoint events was compared between the cumUHR groups using the log-rank test. The C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive performance of cumUHR. Results: After a mean follow-up of 8.0 ± 1.7 years, there were 4843 cases of new-onset CKD, 2504 of low eGFR, and 2617 of proteinuria in the non-CKD group. Within the CKD group, there were 1952 cases of decline in eGFR category, 1465 of >30% decline in eGFR, and 2100 of increased proteinuria. In the non-CKD group, the adjusted hazard ratios (HRs) and confidence intervals (CIs) in the fourth quartile were 1.484 (1.362-1.617), 1.643 (1.457-1.852), and 1.324 (1.179-1.486) for new-onset CKD, low eGFR, and proteinuria, respectively. In the CKD group, the adjusted HRs in the fourth quartile were 1.337 (1.164-1.534), 1.428 (1.216-1.677), and 1.446 (1.267-1.651) for decline in eGFR category, >30% decline in eGFR, and increase in proteinuria, respectively. In addition, we separately added a single UHR measurement and cumUHR to the CKD base prediction model and the CKD progression base prediction model, and found that the models added cumUHR had the highest predictive value. Conclusion: High cumUHR exposure was an independent risk factor for the incidence and progression of CKD, and it was a better predictor than a single UHR measurement.

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.

Association Between Arterial Stiffness and New-Onset Heart Failure: The Kailuan Study.

BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36-2.86) for the borderline AS group and 2.24 (1.49-3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02-1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.

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.

Poor Sleep Quality Is Associated with Altered Taste Perception in Chinese Adults.

BACKGROUND: Small clinical studies have suggested that individuals with insufficient sleep could experience taste dysfunction. However, this notion has not been examined in a large-scale, population-based study. OBJECTIVE: This study aimed to examine whether overall sleep quality, as assessed by insomnia, daytime sleepiness, snoring, and sleep duration, was associated with the odds of having altered taste perception in a large population-based study. DESIGN: This was a cross-sectional study that used data from a subcohort of the Kailuan study, an ongoing multicenter cohort study that began in 2006 in Tangshan City, China. PARTICIPANTS/SETTING: The participants were 11,030 adults aged 25 years or older (mean age 53.7 ± 10.7 years), who were free of neurodegenerative diseases. All the participants had undergone questionnaire assessments and medical examinations at Kailuan General Hospital from June 2012 to October 2013. MAIN OUTCOME MEASURES: Altered taste and olfactory perception were assessed via a questionnaire with two questions regarding whether participants had any problems with sense of taste or smell for ≥3 months. STATISTICAL ANALYSES PERFORMED: The association between sleep quality and altered taste/olfactory perception was examined using a logistic regression model, adjusting for age, sex, lifestyle factors (eg, obesity, smoking, alcohol intake, and physical activity) and health status (eg, lipid profiles, blood pressure, modification use, and presence of chronic diseases). RESULTS: Poor overall sleep quality was associated with a higher risk of having altered taste perception (adjusted odds ratio for low vs high sleep quality 2.03, 95% CI 1.42 to 2.91; P < 0.001). Specifically, insomnia, daytime sleepiness, and short sleep duration, but not prolonged sleep duration and snoring, were significantly associated with altered taste perception. A significant association between overall sleep quality and the risk of having altered olfactory perception was also observed (adjusted odds ratio for low vs high sleep quality 2.17, 95% CI 1.68 to 2.80; P < 0.001). CONCLUSIONS: In this population-based study, poor sleep quality was associated with a high likelihood of altered taste perception.

Relationship Between Time-Dependent Proteinuria and Risk of Stroke in Population With Different Glucose Tolerance Status.

Background Proteinuria often changes and is known as a "time-dependent exposure." The effect of time-dependent proteinuria on the risk of future stroke remains unclear. Proteinuria is often detected in patients with diabetes mellitus. The present study was designed to evaluate the association between time-dependent proteinuria and the risk of stroke in a patient cohort with different glucose tolerance status. Methods and Results A total of 82 938 participants, who were free of myocardial infarction or stroke and underwent fasting blood glucose and urinary protein measurements at baseline in the Kailuan study, were enrolled. Proteinuria was determined using urine dipstick tests at baseline and subsequent follow-ups. Time-dependent proteinuria was defined as the status of urine protein updated through the follow-up examinations, separately. Time-dependent Cox regression models were used to analyze the relationship between time-dependent proteinuria and the risk of stroke. During a median follow-up of 8.37 years, 2538 participants developed stroke. After adjusting for confounding factors, the hazard ratio (95% CI) for stroke in time-dependent proteinuria among all participants, and the normoglycemia, prediabetes, and diabetes mellitus populations were 1.68 (1.49-1.89), 1.73 (1.47-2.05), 2.15 (1.70-2.72), and 1.30 (1.03-1.65), respectively. There were interaction effects in patients with normoglycemia and prediabetes compared with those with diabetes mellitus. Findings were similar for ischemic and hemorrhagic strokes and were confirmed in sensitivity analyses. Conclusions Time-dependent proteinuria is an independent risk factor of stroke, especially in the normoglycemia and prediabetes populations.

Anemia and insomnia: a cross-sectional study and meta-analysis.

BACKGROUND: Several recent genome-wide association studies suggested insomnia and anemia may share some common genetic components. We thus examined whether adults with anemia had higher odds of having insomnia relative to those without anemia in a cross-sectional study and a meta-analysis. METHODS: Included in this cross-sectional study were 12,614 Chinese adults who participated in an ongoing cohort, the Kailuan Study. Anemia was defined as hemoglobin levels below 12.0 g/dL in women and 13.0 g/dL in men. Insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS). A total AIS score ≥6 was considered insomnia. The association between anemia and insomnia was assessed using a logistic regression model, adjusting for potential confounders such as age, sex, chronic disease status, and plasma C-reactive protein concentrations. A meta-analysis was conducted using the fixed effects model to pool results from our study and three previously published cross-sectional studies on this topic in adult populations. RESULTS: Individuals with anemia had greater odds of having insomnia (adjusted odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.03-1.70) compared with individuals without anemia. A significant association persisted after we excluded individuals with chronic inflammation, as suggested by C-reactive protein levels >1 mg/L (adjusted OR: 1.68; 95% CI: 1.22-2.32). The meta-analysis results, including 22,134 participants, also identified a positive association between anemia and insomnia (pooled OR: 1.39; 95% CI: 1.22-1.57). CONCLUSIONS: The presence of anemia was significantly associated with a higher likelihood of having insomnia in adults. Due to the nature of the cross-sectional study design, results should be interpreted with caution.

Associations of urinary epidermal growth factor and monocyte chemotactic protein-1 with kidney involvement in patients with diabetic kidney disease.

BACKGROUND: In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD. METHODS: The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD. RESULTS: In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P < 0.001; 0.82 (0.71-0.94), P = 0.005, respectively}. In the longitudinal cohort, the uEGF:MCP-1 ratio correlated more closely with the percentage change of eGFR slope (r = 0.33, P < 0.001) as compared with uEGF/Cr or uMCP-1/Cr alone. The composite endpoint was defined as end-stage renal disease or 30% reduction of eGFR. These three markers were independently associated with composite endpoint after adjusting for potential confounders [hazard ratio 0.76 (0.59-1.00), P = 0.047 for uEGF/Cr; 1.18 (1.02-1.38), P = 0.028 for uMCP-1/Cr; 0.79 (0.68-0.91), P = 0.001 for uEGF/MCP-1]. CONCLUSION: In Chinese patients, urinary EGF/MCP-1 was negatively associated with the occurrence of DKD. Moreover, uEGF/MCP-1 had a better ability to predict the composite endpoint and correlated more closely with kidney function decline in advanced DKD as compared with uEGF/Cr or uMCP-1/Cr alone.

The Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Chronic Kidney Diseases.

BACKGROUND AND OBJECTIVES: This study was to characterize the association of cumulative exposure to increased high-sensitivity C-reactive protein (hs-CRP) with chronic kidney diseases (CKD). METHODS: We included 35,194 participants with hs-CRP measured at three examinations in 2006, 2008, 2010. Participants were classified into nonexposed group (hs-CRP <3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP ≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP ≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP ≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CKD. CKD includes an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urinary protein positive. RESULTS: The study showed the risk of CKD as the number of years of exposure to hs-CRP increases. Participants in 3-exposed group had significantly increased CKD risk with hazard ratio (HR) (95% confidence interval, CI) of 1.70 (1.49-1.93), in comparison with 1.47 (1.34-1.62) for participants in the 2-exposed group, and 1.08 (1.00-1.16) for those in the 1-exposed group (p < 0.01); meanwhile, the similar and significant associations were also observed for eGFR <60 mL/min/1.73 m2, proteinuria positive, in participants of the 3-exposed group in comparison with the nonexposed group, with respective HRs (95% CI) of 1.27 (1.01-1.58) and 2.27 (1.87-2.76). CONCLUSIONS: Cumulative exposure to hs-CRP was associated with a subsequent increased risk of CKD and was of great value to risk prediction.

The effects of hypertension and diabetes on new-onset chronic kidney disease: A prospective cohort study.

The study aimed to determine the different status of hypertension and diabetes on the risk of new-onset chronic kidney disease (CKD) events in Kailuan Study. A total of 21 905 individuals were enrolled in the study. The new-onset incidents of CKD, hypertension, and diabetes were collected in the follow-ups. All the individuals were divided into five groups according to baseline and follow-up hypertension and diabetes status: baseline hypertension (BH), baseline hypertension and incidence of diabetes (BHID), baseline diabetes (BD), baseline diabetes and incidence of hypertension (BDIH), and baseline hypertension and diabetes (BHD). The risk of new-onset CKD of the five groups was calculated using the Cox regression analysis. In the median follow-up of 7.05 ± 2.59 years, the prevalence of new-onset CKD in the group of BH, BHID, BD, BDIH, and BHD were 27.1, 43.79, 25.4, 36.6, and 45.1 per 1000 years, respectively. When adjusted possible confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) of new-onset CKD were 1.50 (95% CI: 1.38-1.63), 1.25(95% CI: 1.07-1.47), and 1.52 (95% CI: 1.35-1.7) in the group of BHID, BDIH, and BHD, respectively, as referred to the BH group (P < .001). No obvious difference was observed in the group of BH and BD for the incidence of new-onset CKD. Sensitivity analysis still showed the similar results among the five groups. The study showed that the effect of simple hypertension or simple diabetes on new-onset CKD was not significantly different, but the incidence of new-onset hypertension or diabetes increased the risk of new-onset CKD. Hypertension and diabetes had a synergistic influence on the risk of new-onset CKD.

Plasma urate concentrations and possible REM sleep behavior disorder.

OBJECTIVE: To examine how urate concentrations are related to the risk of having possible REM sleep behavior disorder (pRBD) in a community-based cohort. METHODS: The study included 12,923 Chinese adults of the Kailuan Study, free of Parkinson disease (PD) and dementia. Plasma urate concentrations were measured in 2006, 2008, and 2010. Cumulative average urate concentration was used as primary exposure. In 2012, we determined pRBD status using a validated RBD questionnaire-Hong Kong (RBDQ-HK). Logistic regression analysis was performed to estimate the association between urate concentrations during 2006-2010 and odds of having pRBD in 2012 or pRBD case with symptom onset within 1 year. RESULTS: Higher average urate concentrations were associated with a lower odds of pRBD (P-trend <0.001). The adjusted odds ratio (OR), for the highest versus lowest urate quintiles, was 0.43 (95% confidence intervals (CIs) 0.32-0.57). Significant association was consistently observed when we examined the association of a single urate assessment (2006 or 2010) or the rate of change in urate concentrations during 2006-2010 with pRBD (P-trend <0.001 for all). However, restricting to pRBD onset during 2011-2012, we observed a nonsignificant trend between high urate concentration and high odds of pRBD (P-trend = 0.09). INTERPRETATION: Higher average urate concentrations were associated with a lower likelihood of having pRBD, but not new-onset pRBD. Because of its observational study design, the result should be interpreted with caution due to the possibility of residual confounding.

Changes in pulse pressure × heart rate, hs-CRP, and arterial stiffness progression in the Chinese general population: a cohort study involving 3978 employees of the Kailuan Company.

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness, which represents sub-clinical atherosclerosis. Pulsatile stress and high-sensitivity C-reactive protein (hs-CRP) are associated with arteriosclerosis. However, there is no prospective data confirming whether changes in pulsatile stress and inflammatory markers affect the progression of arterial stiffness. The aim of this study was to investigate the relationships over time between the effects of changes in pulsatile stress and hs-CRP, and arterial stiffness progression during a 2-year follow-up. METHODS: We performed a longitudinal study involving 3978 participants. All participants underwent a physical examination in 2010-2011 and 2012-2013, during which we measured participants' hs-CRP levels, brachial-ankle pulse wave velocity (baPWV), and pulsatile stress. RESULTS: Baseline hs-CRP was correlated with baPWV (r = 0.18, P = 0.000); however the correlation was weaker than that with systolic blood pressure (r = 0.65), pulsatile stress (r = 0.57), and rate-pressure product (r = 0.58). Multiple linear regression analysis demonstrated that changes in pulsatile stress, mean arterial pressure, and low-density lipoprotein-C (LDL-C) were positively correlated with changes in baPWV, with correlation coefficients of 0.27, 0.25, and 0.07, respectively, but not with changes in hs-CRP. Moreover, each 100-aU increase in pulsatile stress, 1 mmHg increase in mean blood pressure, and 1 mmol/L increase in LDL-C was associated with a 3 cm/s, 4.78 cm/s, and 17.37 cm/s increase in baPWV, respectively. CONCLUSIONS: Pulsatile stress increases are associated with arterial stiffness progression, but that changes in hs-CRP had no effect on arterial stiffness progression. Hs-CRP may simply be a marker of inflammation in arterial stiffness and has no association with arterial stiffness progression.

Neck circumference is associated with hyperuricemia: a cross-sectional study.

BACKGROUND/OBJECTIVE: Neck circumference (NC) is associated with metabolic abnormalities, independent of other obesity indices. However, data are limited regarding the potential relation between NC and serum uric acid (UA) concentrations. Therefore, we evaluated the cross-sectional association between NC and UA concentration, and odds of having hyperuricemia in a community-based cohort. SUBJECTS AND METHODS: The current study included 87,782 participants (16,317 women and 71,465 men, 52.2 ± 14.1 y) of the Kailuan Study. NC and UA concentration were measured in 2014. We used generalized linear model to investigate the association between NC and serum UA concentration and logistic regression model to investigate the association between NC and likelihood of having hyperuricemia (≥ 7 mg/dl in men and ≥ 6 mg/dl in women), adjusting for demographic factor, anthropometric indices, plasma lipid profiles, blood glucose, blood pressure, physical exercise, snoring, smoking, diet quality, and alcohol consumption. RESULTS: Higher NC was associated with higher serum UA concentration, and higher odds of hyperuricemia in both men and women after adjusting for potential confounders (both p < 0.001). Each additional 5-cm increase in NC was associated with 6% higher likelihood of having hyperuricemia (adjusted OR = 1.06; 95% CI 1.02, 1.1) in men and 17% in women (adjusted OR = 1.17; 95% CI 1.06, 1.28) (p interaction = 0.01). Similar pattern was observed after excluding participants who reported use of anti-hypertensive drugs, participants with obesity or higher waist circumference, and participants with history of gout and chronic kidney diseases. CONCLUSIONS: Higher NC was associated with higher serum UA concentration and higher risk of hyperuricemia in Chinese adult population. CLINICAL TRIAL NUMBER: Kailuan Study (ChiCTR-TNRC-11001489).