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Abstract Carbohydrate antigen 19–9 (CA19-9) levels are associated with glycemic control, insulin resistance, and chronic complications in patients with type 2 diabetes (T2D). Women generally show higher CA19-9 levels despite a greater T2D prevalence in men. We evaluated the sex-specific longitudinal associations between CA19-9 levels and T2D incidence. Korean adults (n = 329,380) without previous cancer or T2D were categorized into four groups based on their CA19-9 levels. The study end point was the development of incident T2D during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) according to CA19-9 levels. During a median follow-up of 6.1 years (3.3–9.3 years), the incidence rates of T2D were 9.9 per 1,000 person-years in men and 3.6 per 1,000 person-years in women. In the time-dependent analysis, adjusted HRs (95% confidence intervals) for incident T2D comparing CA19-9 levels of 10.0–19.9, 20.0–29.9, and ≥ 30 U/mL to the reference (

Abstract Background Increasing evidence supports the association between body mass index (BMI), Alzheimer’s disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer’s and vascular markers in relation to metabolic health status. Methods We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aβ positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aβ positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores. Results Being underweight increased the risk of Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13–4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50–0.80). Especially, obesity decreased the risk of Aβ positivity (OR = 0.38, 95% CI 0.26–0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16–2.47). Decreased Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 1.423, p = 0.037) compared to being normal weight, especially in the MH group. Conclusions Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer’s markers, which, in turn, lead to better clinical outcomes.

Abstract Background The effects of glycemic status and insulin resistance on lung cancer remain unclear. We investigated the associations between both glycemic status and insulin resistance, and lung cancer mortality, in a young and middle-aged population with and without diabetes. Methods This cohort study involved individuals who participated in routine health examinations. Lung cancer mortality was identified using national death records. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% CIs for lung cancer mortality risk. Results Among 666,888 individuals (mean age 39.9 ± 10.9 years) followed for 8.3 years (interquartile range, 4.6–12.7), 602 lung cancer deaths occurred. Among individuals without diabetes, the multivariable-adjusted HRs (95% CI) for lung cancer mortality comparing hemoglobin A1c categories (5.7–5.9, 6.0–6.4, and ≥ 6.5% or 39–41, 42–46, and ≥ 48 mmol/mol, respectively) with the reference (

Abstract Background Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. Methods We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI’s performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A–D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. Results Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7–77.3] vs. 67.1% [95% CI, 58.8–74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9–93.2] vs. 77.6% [95% CI, 61.7–77.9]), PPV (1.5% [95% CI, 1.2–1.9] vs. 0.5% [95% CI, 0.4–0.6]), recall rate (7.1% [95% CI, 6.9–7.2] vs. 22.5% [95% CI, 22.2–22.7]), and AUC values (0.8 [95% CI, 0.76–0.84] vs. 0.74 [95% CI, 0.7–0.78]) (all P

Objective Optimal metabolically healthy status is important to prevent various chronic diseases. This study investigated the association between lifelog-derived physical activity and metabolically healthy status. Methods This cross-sectional study included 51 Korean adults aged 30–40 years with no history of chronic diseases. Physical activity data were obtained by the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Lifelog-derived physical activity was defined by step counts and walking speed for 1 week, as recorded by the Samsung Health application on both the Samsung Galaxy Fit2 and mobile phones. Participants without metabolic syndrome components were categorized as the metabolically healthy group ( n = 31) and the remaining participants as the metabolically unhealthy group ( n = 20). Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models. The predictive ability of each physical activity measure was evaluated according to the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) values. Results Among the physical activity measures, lifelog-derived walking speed was significantly inversely associated with prevalent metabolically unhealthy status. The lifelog component model including walking speed, age, and sex had the highest AUC value for metabolically unhealthy status. Adding lifelog-derived step counts to the IPAQ-SF-derived metabolic equivalent (MET) model (including age, sex, and IPAQ-SF-METs) yielded 37% and 13% increases in the NRI and IDI values, respectively. Incorporating walking speed into the IPAQ-SF-derived MET model improved metabolically unhealthy status prediction by 42% and 21% in the NRI and IDI analyses, respectively. Conclusions Slow walking speed derived from the lifelog was associated with a higher prevalence of metabolically unhealthy status. Lifelog-derived physical activity information may aid in identifying individuals with metabolic abnormalities.

Objective To investigate the association between the use of limaprost and the risk of bleeding. Methods A self-controlled case series analysis was conducted using the National Health Insurance Service-National Sample Cohort database in South Korea. We identified patients aged 18 years or older who had at least one prescription of limaprost and were diagnosed with at least one case of bleeding between 2003 and 2019. The incidence rate ratio (IRR) of bleeding was calculated by dividing the incidence rate in the exposed period to limaprost by that in the unexposed period and adjusted for age using conditional Poisson regression model. Results Among 72,860 patients with limaprost prescriptions and bleeding diagnoses, there were 184,732 events of bleeding. After adjusting for age, the IRR was 1.47 (95% confidence interval [CI], 1.43–1.50), wherein the IRR was the highest during the 0–7 days after limaprost initiation (IRR, 2.11; 95% CI, 2.03–2.18). Risk of bleeding was higher when limaprost was concomitantly used with antithrombotics or other drugs for spinal stenosis treatment, and when higher daily doses of limaprost were administered. Conclusion Our findings suggest that the risk of bleeding increased by 1.5-fold in periods of limaprost exposure compared to unexposed periods, with particularly higher risks observed during the first week after limaprost initiation, with concomitant drugs related to bleeding, and with a higher daily dose. A careful risk-benefit assessment is warranted when initiating limaprost, especially when administered with other medications or in higher daily doses.

Abstract Studies have presented that high intake of sugar-sweetened carbonated beverage (SSCB) was more associated with the prevalence of depression. However, longitudinal evidence is still insufficient to identify whether the effect of SSCB on incident depression is independent of metabolic factors. Therefore, to evaluate the effect of SSCB consumption on the risk of depression, we analyzed the risk of depression according to the consumption of SSCB in 87,115 working aged Koreans who responded to Center for Epidemiologic Studies Depression (CES-D) scale. They were categorized into 5 groups by SSCB consumption based on one serving dose (200 ml) with never/almost never,

Abstract Despite the increasing prevalence of lean nonalcoholic fatty liver disease (NAFLD), its risk factors are not well established. We examined the association between long working hours and incident NAFLD in lean Korean workers with emphasis on sex-based effect modification. This cohort study involved 46,113 non-overweight (BMI

The purposes of this study were to develop an artificial intelligence (AI) model for future breast cancer risk prediction based on mammographic images, investigate the feasibility of the AI model, and compare the AI model, clinical statistical risk models, and Mirai, a state of-the art deep learning algorithm based on screening mammograms for 1–5-year breast cancer risk prediction. We trained and developed a deep learning model using a total of 36,995 serial mammographic examinations from 21,438 women (cancer-enriched mammograms, 17.5%). To determine the feasibility of the AI prediction model, mammograms and detailed clinical information were collected. C-indices and area under the receiver operating characteristic curves (AUCs) for 1–5-year outcomes were obtained. We compared the AUCs of our AI prediction model, Mirai, and clinical statistical risk models, including the Tyrer–Cuzick (TC) model and Gail model, using DeLong’s test. A total of 16,894 mammograms were independently collected for external validation, of which 4002 were followed by a cancer diagnosis within 5 years. Our AI prediction model obtained a C-index of 0.76, with AUCs of 0.90, 0.84, 0.81, 0.78, and 0.81, to predict the 1–5-year risks. Our AI prediction model showed significantly higher AUCs than those of the TC model (AUC: 0.57; p < 0.001) and Gail model (AUC: 0.52; p < 0.001), and achieved similar performance to Mirai. The deep learning AI model using mammograms and AI-powered imaging biomarkers has substantial potential to advance accurate breast cancer risk prediction.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is known to be associated with a high risk of clinically diagnosed Alzheimer’s disease (AD). Additionally, the prevalence of NAFLD and AD is higher in elderly females than in males. However, a sex-specific association between NAFLD and amyloid-beta (Aβ) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and Aβ deposition in a large-sized cohort of cognitively unimpaired (CU) individuals.MethodsWe enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged ≥45 years who underwent Aβ positron emission tomography (PET). The presence of NAFLD, assessed using the hepatic steatosis index, and the severity of NAFLD, assessed using the Fibrosis-4 index, were considered predictors. Aβ deposition on PET was considered as an outcome.ResultsFemales had a higher frequency of NAFLD than males (48 and 23.2%, p

Abstract We investigated the association of metabolically healthy (MH) and unhealthy (MU) obesity with incident lung dysfunction. This cohort study included 253,698 Korean lung disease-free adults (mean age, 37.4 years) at baseline. Spirometry-defined lung dysfunction was classified as a restrictive pattern (RP) or obstructive pattern (OP). We defined obesity as BMI ≥ 25 kg/m2 and MH as the absence of any metabolic syndrome components with a homeostasis model assessment of insulin resistance

Abstract This nationwide population-based cohort study searched for demographic, comorbid, behavioral, and reproductive risk factors for idiopathic macular hole (MH) development using data provided by the Korean National Health Insurance Service. A total of 4,496,867 individuals aged 50–79 years who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Participants were followed up until December 2018, and incident cases of idiopathic MH were identified. Prospective associations between incident idiopathic MH and various covariates were investigated using multivariable-adjusted Cox proportional hazard models. During an average follow-up period of 4.91 years, 3054 patients were newly diagnosed with idiopathic MHs. Women showed greater risk (hazard ratio of 1.71) and earlier presentation of idiopathic MH than men. Compared to the normal body mass index group, the obese group (≥ 25 kg/m2) showed a significantly lower risk of idiopathic MH. Among postmenopausal women, those with two or more children showed a greater risk of idiopathic MH than those who had not been pregnant, with a hazard ratio of 1.80. In conclusion, idiopathic MH occurred earlier and greater in women. Childbirth were associated with an increased risk of MH development, and obesity was associated with a lower risk of MH.

Abstract Background The relationship of specific body composition in the thighs and brain amyloid-beta (Aβ) deposition remained unclear, although there were growing evidence that higher muscle and fat mass in thighs had a protective effect against cardiometabolic syndromes. To determine whether muscle mass and fat mass in the thighs affected amyloid-beta (Aβ) positivity differently in relation to gender, we investigated the association of muscle mass and fat mass with Aβ positivity using positron emission tomography (PET) in individuals without dementia. Methods We recruited 240 participants (134 [55.8%] males, 106 [44.2%] females) without dementia ≥45 years of age who underwent Aβ PET, bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) scans of the hip in the health promotion center at Samsung Medical Center in Seoul, Korea. Lower extremity skeletal muscle mass index (LASMI) was measured using BIA, and gluteofemoral fat percentage (GFFP) was estimated using DEXA scans of the hip. We investigated the associations of LASMI and GFFP with Aβ positivity using logistic regression analyses after controlling for age, APOE4 genotype, and cognitive stage. Results Higher muscle mass in the thighs, measured as LASMI (odds ratio [OR]=0.27, 95% confidence interval [CI] 0.08 to 0.84, p=0.031) was associated with a lesser risk of Aβ positivity in only females. Higher fat mass in the thighs, measured as GFFP (OR=0.84, 95% CI 0.73 to 0.95, p=0.008) was associated with a lesser risk of Aβ positivity in only males. However, the association between LAMSI (p for interaction= 0.810), GFFP (p for interaction= 0.075) and Aβ positivity did not significantly differ by gender. Furthermore, LAMSI only negatively correlated with centiloid (CL) values in females (r=−0.205, p=0.037), and GFFP only negatively correlated with CL values only in males (r=−0.253, p=0.004). Conclusions Our findings highlight the importance of recognizing that gender differences exist with respect to the specific body composition to potentially protect against Aβ deposition. Therefore, our results may help in designing gender-specific strategies for controlling body composition to prevent Aβ deposition.

Abstract The effect of sarcopenic visceral obesity on the risk of nonalcoholic fatty liver disease (NAFLD) is uncertain. We investigated (a) whether the skeletal muscle mass to visceral fat area ratio (SV ratio), as a measure of sarcopenic visceral obesity, is a risk factor for NAFLD; and (b) whether the SV ratio adds to conventional adiposity measures to improve prediction of incident NAFLD. Adults without NAFLD (n = 151,017) were followed up for a median of 3.7 years. Hepatic steatosis was measured using ultrasonography, and liver fibrosis scores were estimated using the Fibrosis‐4 index (FIB‐4) and the NAFLD Fibrosis Score (NFS). Cox proportional hazards models were used to determine sex‐specific adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]). The incremental predictive performance was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Multivariable aHRs (95% CIs) for incident NAFLD comparing the lowest versus the highest quintile of SV ratio were 3.77 (3.56–3.99) for men and 11.69 (10.46–13.06) for women (p–interaction by sex

Abstract We investigated the associations between serum lipid profiles and risk of early-onset vasomotor symptoms (VMSs) in premenopausal women. This cohort study comprised 2,540 premenopausal women aged 42–52 years without VMSs at baseline (median follow-up: 4.4 years). VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire (Korean version). Early-onset VMSs were defined as VMSs that occurred premenopause; moderate/severe VMSs were defined as a score of ≥ 3 points (range: 0 to 6, 6 being most bothersome). Cox proportional hazard regression models were used to estimate hazard ratios with 95% confidence intervals (CI) for the development of VMSs across the lipid levels. Higher low-density lipoprotein (LDL) cholesterol levels were positively associated with increased risk of early-onset VMSs. Compared to the

Abstract The role of anti-Müllerian hormone (AMH) levels in incident vasomotor symptoms (VMS) is largely unknown. This study aimed to investigate the relationship between AMH levels and the development of early-onset VMS among premenopausal women. Our cohort study comprised 2041 premenopausal women aged 42–52 years free of VMS at baseline whose AMH levels were measured. VMS, including hot flushes and night sweats, were assessed using the Korean version of the Menopause-specific Quality of Life questionnaire. Early-onset VMS was defined as the occurrence of VMS prior to menopause. Parametric proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CI. During a median follow-up of 4.4 years, 708 premenopausal women developed early-onset VMS (incidence rate, 8.0 per 100 person-years). Lower AMH levels were statistically significantly associated with an increased risk of early-onset VMS. After adjusting for age and other confounders, multivariable-adjusted HRs (95% CI) for incident VMS comparing AMH quintiles 4–1 to the highest quintile were 1.02 (0.78–1.33), 1.37 (1.06–1.76), 1.36 (1.04–1.76), and 2.38 (1.84–3.08), respectively (P for trend

Background 2018 American Heart Association/American College of Cardiology cholesterol guideline recommends statin in patients with chronic and/or stable liver disease for secondary prevention of atherosclerotic cardiovascular disease yet remains equivocal on the adequate intensity of statin for patients with chronic liver disease (CLD). We aimed to assess the association between statin intensity and mortality among patients with CLD with atherosclerotic cardiovascular disease. Methods and Results We conducted a population‐based cohort study in South Korea. We assessed the risk of survival and clinical outcomes using inverse probability of treatment‐weighted Cox proportional hazards regression. We also estimated the absolute risk difference between treatment groups based on the Poisson distribution. During an average of 2.35 person‐years, 10 442 patients with CLD with atherosclerotic cardiovascular disease were identified. Among those patients, 5515 (52.8%) received high‐intensity statin, and 4927 (47.2%) received low/moderate‐intensity statin. High‐intensity statin was associated with lower risk for all‐cause mortality (hazard ratio [HR], 0.83 [95% CI, 0.75–0.92]), cardiovascular‐cause mortality (HR, 0.85 [0.71–1.01]), liver‐cause mortality (HR, 0.72 [0.54–0.97]) compared with low/moderate‐intensity statin. Although both hospitalizations for recurrent myocardial infarction and stroke were shown to be increased among high‐intensity statin users, effect estimate was homogeneous in the absolute scale (myocardial infarction: HR, 1.12 [1.04–1.19], risk difference, 7.57 [−0.69 to 15.84] per 1000 person‐years; stroke: HR, 1.11 [0.97 to 1.27]; risk difference, −1.70 [−5.19 to 1.78]). Conclusions Among patients with CLD with atherosclerotic cardiovascular disease, high‐intensity statin was significantly associated with a lower risk of mortality. These findings herein support the guidelines for statin use in patients with CLD while demonstrating potential benefit of optimal intensity use.

Abstract The role of the gut microbiome in the development of renal stone diseases has not been well characterized. This study focused on the taxonomic and functional profiles of gut microbiomes according to the prevalence and incidence of nephrolithiasis. Stool samples from 915 Korean adults were collected at baseline. Participants were followed for a median of 4.0 years. We evaluated the biodiversity of the gut microbiota and taxonomic profiles associated with nephrolithiasis status, using 16S rRNA gene sequencing. Nephrolithiasis status was categorized into three groups: control (no-stone at both baseline and follow-up visits), incidental nephrolithiasis, and prevalent nephrolithiasis. Compared to the control and incidental nephrolithiasis, the prevalent nephrolithiasis showed a reduced evenness in alpha diversity. Nephrolithiasis was associated with a reduced abundance of some key taxa involved in short-chain fatty acid production. Moreover, the abundance of Bifidobacterium, which possess oxalate-degrading ability, was higher in the control. Conversely, there was no significant difference in the bacterial composition between the incidental and prevalent nephrolithiasis. In our study with repeated nephrolithiasis measurements, prevalent renal stones were associated with an altered gut microbiota composition compared to the control. Besides the known oxalate degradation pathway, other functional pathways inferred in this study require further investigation.

Abstract Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011–2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P

Abstract Reduced heart rate variability (HRV) is reflective of autonomic imbalance. However, its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. We investigated the association between 10-s HRV and incident NAFLD. A cohort of 154,286 Korean adults with no NAFLD at baseline were followed up. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). A total of 27,279 incident HS (median follow up of 4.2 years) and 1250 incident HS plus high FIB-4 (median follow up of 4.2 years) cases were identified at follow-up. The multivariable adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) in a model with time-dependent variables for incident HS, comparing the lowest quintile to the highest and reference quintile of the RMSSD, was 1.43 (1.37–1.49), and the corresponding HR for incident HS plus intermediate/high FIB-4 was 1.70 (1.35–2.15). Similarly, SDNN was inversely associated with incident HS and HS plus intermediate/high FIB-4. The results were similar using the NAFLD fibrosis score. Autonomic imbalance assessed by HRV may help to identify individuals at a high risk of HS and its progression and warrant further studies.

ObjectivesThe relationship of body mass index (BMI) changes and variability with amyloid-β (Aβ) deposition remained unclear, although there were growing evidence that BMI is associated with the risk of developing cognitive impairment or AD dementia. To determine whether BMI changes and BMI variability affected Aβ positivity, we investigated the association of BMI changes and BMI variability with Aβ positivity, as assessed by PET in a non-demented population.MethodsWe retrospectively recruited 1,035 non-demented participants ≥50 years of age who underwent Aβ PET and had at least three BMI measurements in the memory clinic at Samsung Medical Center. To investigate the association between BMI change and variability with Aβ deposition, we performed multivariable logistic regression. Further distinctive underlying features of BMI subgroups were examined by employing a cluster analysis model.ResultsDecreased (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.16–2.42) or increased BMI (OR = 1.60, 95% CI 1.11–2.32) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI variability. A greater BMI variability (OR = 1.73, 95% CI 1.07–2.80) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI change. We also identified BMI subgroups showing a greater risk of Aβ positivity.ConclusionOur findings suggest that participants with BMI change, especially those with greater BMI variability, are more vulnerable to Aβ deposition regardless of baseline BMI. Furthermore, our results may contribute to the design of strategies to prevent Aβ deposition with respect to weight control.

Abstract We examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004–1.30) and 1.40 (1.21–1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.

Abstract The effect of light-to-moderate alcohol consumption on cancer risk remains controversial. We examined the association between low-level alcohol consumption and cancer mortality. A cohort study included 331,984 Korean adults free of cancer at baseline who underwent a comprehensive health checkup examination. Participants were categorized into never drinkers, former drinkers, and current drinkers who were further divided into light, moderate, heavy, and very heavy drinkers. Vital status and cancer-related deaths were ascertained through links to national death records. During 1,633,906 person-years of follow-up (median 5.3 years interquartile range 3.8–6.2), 374 cancer-related deaths were identified (cancer-cause mortality rate of 23 per 105 person-years). When former and never drinkers were classified as non-drinkers, the light drinkers had a lowest risk of cancer mortality compared with non-drinkers and other current drinkers (J-shaped); however, with consideration of lifetime abstinence history, current drinking was positively associated with cancer mortality in a dose-dependent manner. When changes in alcohol drinking status and confounders during follow-up were updated as time-varying covariates and never drinkers were used as the reference, the multivariable-adjusted hazard ratios (HRs) (95% confidence intervals, CIs) for cancer mortality among current light, moderate, heavy, and very heavy drinkers were 1.58 (1.03–2.43), 2.28 (1.41–3.70), 2.34 (1.42–3.85), and 2.97 (1.80–4.90), respectively, and the highest risk of cancer mortality was observed in former drinkers, who had an HR (95% CI) of 3.86 (2.38–6.28). Alcohol consumption was significantly and positively associated with an increased risk of cancer mortality in a dose-dependent manner, beginning with light drinkers.

Abstract The longitudinal relationship between smoking status and risk of developing visual impairment (VI) remains unclear. We examined the relationship of smoking status and urinary cotinine level, an objective measure of smoking, with incidence of VI. This cohort study included 279,069 individuals free of VI who were followed for up to 8.8 years (median 4.8 years). VI was defined as when bilateral visual acuity was worse than 0.5 (cutoffs of 0.3 Logarithm of the Minimum Angle of Resolution). During 1,324,429.8 person-years of follow-up, 7852 participants developed new-onset bilateral VI. Self-reported current smoking status was associated with increased risk of developing VI in both men and women, with a stronger association in women (P for interaction = 0.01). Multivariable adjusted hazard ratios (95% confidence intervals) for incident VI comparing current smokers to never-smokers were 1.14 (1.04–1.25) in men and 1.52 (1.28–1.80) in women. Urinary cotinine levels of ≥ 100 ng/ml were significantly associated with increased risk of incident VI, and these associations remained when introducing changes in urinary cotinine and other confounders during follow-up as time-varying covariates. Cigarette smoking assessed based on self-report and urinary cotinine level was associated with increased incidence of VI. Our findings identify smoking as an independent risk factor for VI.

BackgroundWe evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.MethodsThis is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.ResultsThe multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.ConclusionHigh VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.

The aim of this study was to assess the risk of liver fibrosis in those with no glucose intolerance, prediabetes, or diabetes. A cross-sectional study was conducted based on a cohort from a health examination program which included a magnetic resonance elastography (MRE). Participants were classified into three groups according to glucose tolerance: no glucose intolerance, prediabetes, and diabetes mellitus. Liver fibrosis was evaluated by liver stiffness measurement (LSM) value using two-dimensional real-time MRE. The risk of significant liver fibrosis was compared among three groups. A total of 2,090 subjects were included: no glucose intolerance (n = 889); prediabetes (n = 985); and diabetes (n = 216). Mean values of LSM in those with no glucose intolerance, prediabetes, and diabetes were 2.37 ± 0.43 kPa, 2.41 ± 0.34 kPa, and 2.65 ± 0.70 kPa, respectively (p

Background Studies have shown that short‐term exposure to air pollution is associated with cardiac arrhythmia hospitalization and mortality. However, the relationship between long‐term particulate matter air pollution and arrhythmias is still unclear. We evaluate the prospective association between particulate matter (PM) air pollution and the risk of incident arrhythmia and its subtypes. Methods and Results Participants were drawn from a prospective cohort study of 178 780 men and women who attended regular health screening exams in Seoul and Suwon, South Korea, from 2002 to 2016. Exposure to PM with an aerodynamic diameter of ≤10 and ≤2.5 μm (PM10 and PM2.5, respectively) was estimated using a land‐use regression model. The associations between long‐term PM air pollution and arrhythmia were examined using pooled logistic regression models with time‐varying exposure and covariables. In the fully adjusted model, the odds ratios (ORs) for any arrhythmia associated with a 10 μg/m3 increase in 12‐, 36‐, and 60‐month PM10 exposure were 1.15 (1.09, 1.21), 1.12 (1.06, 1.18), and 1.14 (1.08, 1.20), respectively. The ORs with a 10 μg/m3 increase in 12‐ and 36‐month PM2.5 exposure were 1.27 (1.15, 1.40) and 1.10 (0.99, 1.23). PM10 was associated with increased risk of incident bradycardia and premature atrial contraction. PM2.5 was associated with increased risk of incident bradycardia and right bundle‐branch block. Conclusions In this large cohort study, long‐term exposure to outdoor PM air pollution was associated with increased risk of arrhythmia. Our findings indicate that PM air pollution may be a contributor to cardiac arrhythmia in the general population.

Abstract Background The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women. Methods Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR)

Abstract This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m2. The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (−0.79% per year, 95% CI −1.31%, −0.27%) compared to those without it (0.30%, 95% CI −0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was −1.06% (−1.73%, −0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline (

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Abstract Background We investigated the association between physiologic bowel FDG uptake and gut microbiota. FDG uptake in the normal large and small intestine is widely variable both in distribution and intensity. The etiology of physiologic bowel 18F-FDG activity remains unknown. Results We included 63 healthy male subjects. After overnight fasting, blood samples and 18F-FDG PET/CT scans were taken. Fecal samples were collected, and gut microbiota were analyzed by 16S rRNA gene-pyrosequencing. The physiologic bowel FDG uptake was classified into three groups by visual assessment and measured using the maximum and mean standardized uptake value. We used the total bowel to liver uptake ratio (TBRmax and TBRmean). There was no significant difference in age, BMI, or lipid profiles between groups. To identify specific microbial taxa associated with the bowel FDG uptake while accounting for age and BMI, we performed a generalized linear model. At the genus level, the group with focal or intense FDG uptake in the intestine was associated with low abundance of unclassified Clostridiales. The group with intestinal FDG uptake lower than the liver was associated with high abundance of Klebsiella. TBRmax and TBRmean were negatively associated with abundance of unclassified Enterobacteriaceae. Conclusion We cautiously speculate that physiologic bowel FDG activity might be caused by an increase in intestinal permeability and may reflect an impaired barrier function in the intestine.

Abstract The role of hepatitis virus infection in glucose homeostasis is uncertain. We examined the associations between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the development of diabetes in a cohort (N = 439,708) of asymptomatic participants in health screening examinations. In cross-sectional analyses, the multivariable-adjusted odds ratio for prevalent diabetes comparing hepatitis B surface antigen (HBsAg) (+) to HBsAg (−) participants was 1.17 (95% CI 1.06–1.31; P = 0.003). The corresponding odds ratio comparing hepatitis C antibodies (HCV Ab) (+) to HCV Ab (−) participants was 1.43 (95% CI 1.01–2.02, P = 0.043). In prospective analyses, the multivariable-adjusted hazard ratio for incident diabetes comparing HBsAg (+) to HbsAg (−) participants was 1.23 (95% CI 1.08–1.41; P = 0.007). The number of incident cases of diabetes among HCV Ab (+) participants (10 cases) was too small to reliably estimate the prospective association between HCV infection and diabetes. In this large population at low risk of diabetes, HBV and HCV infections were associated with diabetes prevalence and HBV infection with the risk of incident diabetes. Our studies add evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

Abstract Background Gut microbiota plays an important role in the harvesting, storage, and expenditure of energy obtained from one’s diet. Our cross-sectional study aimed to identify differences in gut microbiota according to body mass index (BMI) in a Korean population. 16S rRNA gene sequence data from 1463 subjects were categorized by BMI into normal, overweight, and obese groups. Fecal microbiotas were compared to determine differences in diversity and functional inference analysis related with BMI. The correlation between genus-level microbiota and BMI was tested using zero-inflated Gaussian mixture models, with or without covariate adjustment of nutrient intake. Results We confirmed differences between 16Sr RNA gene sequencing data of each BMI group, with decreasing diversity in the obese compared with the normal group. According to analysis of inferred metagenomic functional content using PICRUSt algorithm, a highly significant discrepancy in metabolism and immune functions (P

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Background There are limited outcome studies of hypertension among young adults, especially using the new blood pressure (BP) categories from the American College of Cardiology and the American Heart Association. We examined associations between the new BP categories and the risk of incident cardiovascular disease (CVD) in low‐risk and young adults. Methods and Results A cohort study was performed in 244 837 Korean adults (mean age, 39.0 years; SD, 8.9 years) who underwent a comprehensive health examination at Kangbuk Samsung Hospital from January 1, 2011, to December 31, 2016; they were followed up for incident CVD via linkage to the Health Insurance and Review Agency database until the end of 2016, with a median follow‐up of 4.3 years. BP was categorized according to the new American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines. During 924 420.7 person‐years, 1435 participants developed new‐onset CVD (incidence rate of 16.0 per 104 person‐years). The multivariable‐adjusted hazard ratios (95% CIs ) for CVD comparing elevated BP, stage 1 hypertension, stage 2 hypertension, treated and strictly controlled (systolic BP/diastolic BP

Pathophysiological background in different phenotypes of nonalcoholic fatty liver disease (NAFLD) remains to be elucidated. The aim was to investigate the association between fecal and blood microbiota profiles and the presence of NAFLD in obese versus lean subjects. Demographic and clinical data were reviewed in 268 health checkup examinees, whose fecal and blood samples were available for microbiota analysis. NAFLD was diagnosed with ultrasonography, and subjects with NAFLD were further categorized as obese (body mass index (BMI) ≥25) or lean (BMI

ObjectiveAnemia of chronic disease (ACD) refers to hypoproliferative anemia in the context of acute or chronic activation of the immune system. There is a paucity of prospective data addressing the risk factors for ACD development. An association between common chronic diseases and ACD was examined cross-sectionally and longitudinally.MethodA cohort of 265,459 healthy participants without ACD at baseline were prospectively followed annually or biennially.ResultsDuring average follow-up period of 62 months, 4,906 participants developed ACD (incidence rate 3.58 per 1000 person-years). Multivariable-adjusted hazard ratio (HR) [95% confidence interval (CI)] for incident ACD comparing estimated glomerular filtration rate 30-60 and < 30 vs. ≥ 60 ml/min/1.73 m2 were 3.93 [3.18-4.85] and 39.11 [18.50-82.69]; HRs [95% CI] for ACD comparing prediabetes and diabetes vs. normal were 1.19 [1.12-1.27] and 2.46 [2.14-2.84], respectively. HRs [95% CI] for incident ACD comparing body-mass-index (BMI) of < 18.5, 23-24.9 and ≥ 25 vs. 18.5-22.9 kg/m2 were 0.89 [0.78-1.00], 0.89 [0.80-0.99] and 0.78 [0.66-0.91], respectively. HRs [95% CI] for incident ACD comparing prehypertension and hypertension vs. normal were 0.79 [0.73-0.86] and 1.10 [0.99-1.23], respectively. Metabolic syndrome, hypertension, chronic liver disease, and chronic obstructive pulmonary disease were not associated with incident ACD.ConclusionsThe severity of chronic kidney disease and diabetic status were independently associated with an increased incidence of ACD, whereas prehypertension and an increasing BMI were significantly associated with decreased risk of ACD.