Effect of RANKL on Lower Depressive Symptoms In Hemodialysis Patients.

Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (ß - 4.527, 95% CI - 8.310 to - 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (ß - 5.603, 95% CI - 9.715 to -1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19-0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12-0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients.Trial registration WHO registry, No. KCT0003281, date: January 12, 2017.

Decreased estimated glomerular filtration rate increase the risk of pancreatic cancer: A nationwide retrospective cohort study.

BACKGROUND AND AIM: Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories. METHODS: In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m2 ) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups. RESULTS: During the 3 493 589.05 person-years of follow-up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24-1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47-2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62-2.60) for group 1 (eGFR < 45) in the multivariate adjusted model. CONCLUSIONS: Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups.

The possible association of dietary fiber intake with the incidence of depressive symptoms in the Korean population.

OBJECTIVES: This study investigates the effect of dietary fiber on the prevention of depressive symptoms. METHODS: In a cohort of 88,826 Korean adults (57,284 men and 31,542 women), we longitudinally evaluated the risk of depressive symptoms according to quartiles of dietary fiber intake for 5.8 years of follow-up. A food frequency questionnaire was used in evaluating dietary fiber intake. Depressive symptoms were assessed by the Center for Epidemiological Studies-Depression (CES-D) scale, in which CES-D ≥ 16 was defined as depressive symptoms. The Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptoms (adjusted HR [95% CI]). Subgroup analysis was performed for gender and BMI (≥25 or <25). RESULT: In men, the risk of depressive symptoms significantly decreased with the increase of dietary fiber (quartile 1: reference, quartile 2: 0.93 [0.87-0.99], quartile 3: 0.91 [0.85-0.98] and quartile 4: 0.84 [0.77-0.92]). This association was more prominently observed in men with BMI ≥ 25 (quartile 1: reference, quartile 2: 0.95 [0.86-1.06], quartile 3: 0.88 [0.79-0.99] and quartile 4: 0.84 [0.73-0.97]). Women did not show a significant association between quartile groups of dietary fiber intake and the risk of depressive symptoms across subgroup analysis for BMI. CONCLUSION: High intake of dietary fiber is potentially effective in reducing depressive symptoms in Korean men. The protective effect of dietary fiber on depressive symptoms may vary by gender and obesity.

Chinese visceral adiposity index and its relation to abnormal left ventricular remodeling assessed by relative wall thickness and left ventricular mass index.

BACKGROUND AND AIMS: The Chinese visceral adipose index (CVAI) is more significantly associated with cardiometabolic risk factors than other obesity indices. This study investigated the relationship between CVAI and left ventricular (LV) remodeling. METHODS AND RESULTS: This study included 75,132 Koreans who underwent echocardiography during a health checkup. They were grouped according to quartile levels of the CVAI, body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). LV remodeling was defined as the presence of abnormal relative wall thickness (ARWT) and left ventricular hypertrophy (LVH). Multivariate adjusted logistic regression analysis (adjusted OR [95% confidence interval]) was used to analyze the association between ARWT and LVH according to the quartile levels of each index. Receiver operating characteristic (ROC) graphs and areas under the curve (AUC) were calculated to identify the predictive ability of the indices for ARWT and LVH. ARWT was associated proportionally with CVAI quartiles in both men (second quartile: 1.42 [1.29-1.56], third quartile: 1.61 [1.46-1.77], fourth quartile: 2.01 [1.84-2.21]), and women (second quartile: 1.06 [0.78-1.45], third quartile: 1.15 [0.86-1.55], and fourth quartile: 2.09 [1.56-2.80]). LVH was significantly associated with third (1.74 [1.07-2.83]) and fourth quartile (1.94 [1.18-3.20]) groups of CVAI in women. ROC and AUC analyses indicated that CVAI was superior to other indices in predicting ARWT in men and LVH and ARWT in women. CONCLUSION: The CVAI is an effective surrogate marker of LV remodeling, particularly in women.

The longitudinal analysis for the association between smoking and the risk of depressive symptoms.

BACKGROUND: Despite high smoking rate in people with depressive symptoms, there is ongoing debate about relationship between smoking and depressive symptoms. METHODS: Study participants were 57,441 Korean men. We collected their baseline data between 2011 and 2012, and conducted follow-up from 2013 to 2019. They were categorized by smoking status (never: < 100 cigarettes smoking in life time, former: currently quitting smoking, and current smoker: currently smoking), smoking amount (pack/day and pack-year) and urine cotinine excretion. The development of depressive symptoms was determined in CES-D score ≥ 16. Cox proportional hazards model was used to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptoms in relation to smoking status, smoking amount, and urine cotinine excretion. RESULTS: During 6.7 years of median follow-up, the risk of depressive symptoms increased in order of never (reference), former (HR = 1.08, 95% CI: 1.01-1.15) and current smoker (HR = 1.24, 95% CI: 1.16-1.32). Among current smoker, the risk of depressive symptoms increased proportionally to daily smoking amount (< 1 pack; HR = 1.21, 95% CI: 1.13-1.29, and ≥ 1 pack; HR = 1.34, 95% CI: 1.23 - 1.45). This pattern of relationship was consistently observed for pack-year in former smoker and current smoker. Additionally, urine cotinine excretion was proportionally associated with the risk of depressive symptoms. CONCLUSION: Exposure to smoking was associated with the increased risk of depressive symptoms. Dose dependent relationship was observed between smoking amount and the risk of depressive symptoms.

Changes in smoking status, amount of smoking and their relation to the risk of microvascular complications in men with diabetes mellitus.

BACKGROUND: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive. METHOD: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount. RESULTS: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy. CONCLUSIONS: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients.

Environment-wide association study to identify exposure pathways of bisphenol A in Korean children and adolescents: Korean National Environmental Health Survey (KoNEHS) 2018-2020.

Bisphenol A (BPA) is an endocrine-disrupting chemical commonly used in manufacturing plastic products. Despite ongoing efforts and regulatory measures, BPA exposure among children persists. This study aimed to identify the modifiable factors associated with urinary BPA levels in Korean children and adolescents. We conducted an environment-wide association study (EWAS) using data from the Korean National Environmental Health Survey (KoNEHS) Cycle 4. This study included 578 preschoolers, 736 school-aged children, and 828 adolescents. A total of 117, 103, and 102 modifiable factors were selected from KoNEHS Cycle 4. Each modifiable factor associated with urinary BPA levels was tested using a multivariable linear regression model. Subsequently, multiple testing corrections were performed using false discovery rate (FDR) estimation. For the validation phase, we used the iteration of the least absolute shrinkage and selection operator (LASSO), a machine learning-based regression analysis. After the validation phase of the LASSO regression, two modifiable factors were identified as being significantly related to urinary BPA levels in preschoolers. Urinary cotinine levels and the use of slime or clay toys were positively associated with urinary BPA levels in preschoolers. However, no significant associations were observed between school-aged children and adolescents. Our results suggest novel exposure pathways to BPA in recent lifestyles and contribute to the development of effective prevention strategies. These modifiable factors provide valuable targets for interventions aimed at reducing BPA exposure in children. Further research is needed to explore additional modifiable factors and confirm our results in larger and more diverse populations.

Change in smoking status and its relation to the risk of gastroduodenal ulcer in Korean men.

BACKGROUND AND AIM: Smoking is associated with the increased risk of gastroduodenal ulcer. However, although smoking status can vary over time, most of studies have analyzed this association with smoking status at a single point of time. We analyzed the risk of gastroduodenal ulcer according to change in smoking status for more than 5 years. METHODS: Study participants were 43 380 Korean adults free of gastroduodenal ulcer who received health check-up between 2002 and 2013. Through evaluating their smoking status (never, quitter, and current) at 2003-2004 and 2009, they were categorized them into seven groups (never-never, never-quitter, never-current, quitter-quitter, quitter-current, current-quitter, and current-current) and monitored until 2013 to identify incident gastroduodenal ulcer. Cox-proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident gastroduodenal ulcer according to changes in smoking status and smoking amount. RESULTS: Compared with never-never group (reference), other groups had the significantly increased adjusted HRs and 95% CI for gastroduodenal ulcer. In particular, participants with current smoking (never-current, quitter-current, and current-current) had the relatively higher HRs than other groups (never-quitter: 1.200 [1.070-1.346], never-current: 1.375 [1.156-1.636], quitter-quitter: 1.149 [1.010-1.306], quitter-current: 1.325 [1.058-1.660], current-quitter: 1.344 [1.188-1.519], and current-current: 1.379 [1.256-1.513]). Heavy smoker had the highest risk for gastroduodenal ulcer, followed by moderate and light smoker. CONCLUSION: People who ever experienced smoking had increased risk of gastroduodenal ulcer. Out of smoking status, current smoking is more associated with the increased risk of gastroduodenal ulcer than past smoking.

Association of metabolites of benzene and toluene with lipid profiles in Korean adults: Korean National Environmental Health Survey (2015-2017).

BACKGROUND: Environmental exposure to benzene and toluene is a suspected risk factor for metabolic disorders among the general adult population. However, the effects of benzene and toluene on blood lipid profiles remain unclear. In this study, we investigated the association between urinary blood lipid profiles and metabolites of benzene and toluene in Korean adults. METHODS: We analyzed the data of 3,423 adults from the Korean National Environmental Health Survey Cycle 3 (2015-2017). We used urinary trans,trans-muconic acid (ttMA) as a biomarker of benzene exposure, and urinary benzylmercapturic acid (BMA) as an indicator of toluene exposure. Multivariate logistic regression analyses were performed to explore the association between blood lipid profiles and urinary metabolites of benzene and toluene. Additionally, we examined the linear relationship and urinary metabolites of benzene and toluene between lipoprotein ratios using multivariate regression analyses. RESULTS: After adjusting for covariates, the fourth quartile (Q4) of ttMA [odds ratio (OR) (95% confidence interval, CI = 1.599 (1.231, 2.077)] and Q3 of BMA [OR (95% CI) = 1.579 (1.129, 2.208)] were associated with an increased risk of hypertriglyceridemia. However, the Q4 of urinary ttMA [OR (95% CI) = 0.654 (0.446, 0.961)] and Q3 of urinary BMA [OR (95% CI) = 0.619 (0.430, 0.889)] decreased the risk of a high level of low-density lipoprotein cholesterol (LDL-C). Higher urinary ttMA levels were positively associated with the ratio of triglycerides to high-density lipoproteins [Q4 compared to Q1: ß = 0.11, 95% CI: (0.02, 0.20)]. Higher urinary metabolite levels were negatively associated with the ratio of low-density lipoprotein to high-density lipoprotein [Q4 of ttMA compared to reference: ß = -0.06, 95% CI: (-0.11, -0.01); Q4 of BMA compared to reference: ß = -0.13, 95% CI: (-0.19, -0.08)]. CONCLUSION: Benzene and toluene metabolites were significantly and positively associated with hypertriglyceridemia. However, urinary ttMA and BMA levels were negatively associated with high LDL-C levels. These findings suggest that environmental exposure to benzene and toluene disrupts lipid metabolism in humans.

Smoking Status, Intensity of Smoking, and Their Relation to Left Ventricular Hypertrophy in Working Aged Korean Men.

INTRODUCTION: Smoking is an established risk factor for atherosclerotic cardiovascular disease. However, the effect of smoking on left ventricular (LV) structure has been less studied. This study was designed to assess the association of smoking status and smoking intensity with left ventricular hypertrophy (LVH). METHODS: Study subjects were 53,666 working aged Korean men who received echocardiography as an item of health check up. They were grouped by smoking status (never, former, and current smokers), pack-year of smoking (never, <10, 10-19.9, and ≥20 pack-year), and urine cotinine excretion (<100, 100-999, ≥1000 ng/mL). Multivariate logistic regression analysis was used in calculating adjusted odds ratios (ORs) and 95% confidence interval for LVH (adjusted odds ratios [95% confidence interval]). The proportions of abnormal LV geometry patterns were compared among groups. RESULTS: Former and current smokers had the higher levels in LV mass index, relative wall thickness, and the prevalence of LVH than never smoker. The association with LVH increased in order of never (reference), former (1.44 [1.01-2.04]), and current smokers (2.10 [1.44-3.05]). LVH showed the proportional relationship with pack-year of smoking (never smoker: reference, <10: 1.45 [1.01-2.08], 10-19.9: 1.73 [1.17-2.57], ≥20: 2.43 [1.58-3.74]) and urine cotinine excretion (never smoker: reference, 100-999: 1.70 [1.21-2.37], >1000: 1.97 [1.43-2.72]). The proportions of abnormal LV geometry patterns were higher in smoking groups than never smoking group. CONCLUSION: Exposure to tobacco use and intensity of smoking was associated with LVH in working aged population. IMPLICATIONS: In working aged Koreans with mean age of 39.9 ± 7.0 years, former and current smokers are more likely to have LVH than never smoker. Dose-dependent relationship was found between the smoking status (never, former, and current smokers), pack-year of smoking, urine cotinine excretion, and LVH. These findings indicate that smoking has an adverse influence on LV structure even in relatively young age group.