The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

OBJECTIVE: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. BACKGROUND: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. METHODS: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. RESULTS: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). CONCLUSIONS: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome.

BACKGROUND & AIMS: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. METHODS: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. RESULTS: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). CONCLUSION: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

Isolated Hepatitis B Core Antibody Positivity and Long-Term Liver-Related Mortality in Korea: A Cohort Study.

INTRODUCTION: Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults. METHODS: A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records. RESULTS: During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively. DISCUSSION: In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.

Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: A longitudinal cohort study.

BACKGROUND AND AIMS: Whether subjects with NAFLD are at increased risk of sarcopenia is not well established. APPROACH AND RESULTS: This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS. CONCLUSIONS: Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.

Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data.

BACKGROUND: No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user. METHODS: Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed. RESULTS: During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality. CONCLUSIONS: Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.

Modest alcohol intake and mortality in individuals with elevated alanine aminotransferase levels: a nationwide cohort study.

BACKGROUND: Alanine aminotransferase (ALT) levels are widely used to screen liver disease, and many asymptomatic individuals show elevated ALT levels. As elevated ALT level indicates liver injury, even a small amount of alcohol intake may be harmful in subjects with elevated ALT levels, but there is limited evidence of the effect of light to moderate amount of alcohol intake in this subgroup. METHODS: A cohort of 367,612 men and women without established liver diseases (including chronic viral hepatitis, alcohol-associated liver disease, cirrhosis, liver transplantation, or rare forms of liver disease) who underwent at least 1 health screening exam between 2009 and 2015 were assessed for liver-related and all-cause mortality. Elevated ALT levels were defined as ≥ 34 U/L for men and 25 U/L for women. RESULTS: In participants with normal ALT levels, the fully-adjusted hazard ratios (95% CI) for liver-related mortality comparing light and moderate drinkers to non-drinkers were 0.73 (0.51-1.05), and 1.06 (0.73-1.52), respectively. In participants with elevated ALT levels, the corresponding hazard ratios were 1.57 (1.08-2.28), and 2.09 (CI 1.46-2.99), respectively (p value for alcohol intake by ALT interaction < 0.01). For all-cause mortality, the fully-adjusted hazard ratios comparing light and moderate drinkers to non-drinkers in participants with normal ALT levels were 0.72 (0.66-0.77), and 0.89 (0.82-0.97), respectively. In participants with elevated ALT levels, the corresponding hazard ratios were 0.93 (0.81-1.08), and 1.31 (1.14-1.50), respectively (p value for alcohol intake by ALT interaction < 0.01). CONCLUSIONS: Small amounts of alcohol intake were associated with increased liver-related and all-cause mortality among individuals with elevated ALT levels. Subjects with elevated ALT levels should be advised complete abstinence from alcohol.

Liver fibrosis scores and risk of liver-related mortality in young adults with chronic hepatitis B: A cohort study.

The predictive role of noninvasive liver fibrosis scores on liver-related mortality in patients with chronic hepatitis B below 40 years of age remains unclarified. We examined the association of liver fibrosis scores with liver-related mortality in young (<40 years) and older adults with hepatitis B virus (HBV) infection. A cohort study was performed in 21,360 HBsAg-positive Korean adults without liver cirrhosis or liver cancer at baseline who were followed up for up to 18 years. The liver fibrosis scores were determined using the fibrosis-4 score (FIB-4) and aspartate transaminase to platelet ratio index (APRI). Patients' vital status and cause of death were ascertained through the National Death Records. During a median follow-up of 10.2 years, 283 liver-related deaths were identified (liver-related mortality, 127.4/105 person-years). The liver fibrosis scores were significantly associated with increased risks of liver-related mortality; this association did not differ by age group (<40 vs. ≥40 years). The multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality comparing intermediate and high to low FIB-4 scores were 4.23 (1.99-9.00), and 15.16 (5.18-44.38), respectively, among individuals under 40, and 4.46 (3.03-6.56) and 22.47 (15.11-33.41), respectively, among older individuals. These associations were similar in analyses using APRI. In this cohort of HBsAg-positive individuals, the liver fibrosis scores were associated with increased risks of liver-related mortality in young and older adults. The liver fibrosis scores have a role in predicting liver mortality, even in young adults with HBV.

Metabolically healthy and unhealthy obesity and risk of vasomotor symptoms in premenopausal women: cross-sectional and cohort studies.

OBJECTIVE: To examine the relationship between metabolically healthy and unhealthy obesity phenotypes and risk of vasomotor symptoms (VMS) in premenopausal women. DESIGN: Prospective cohort study. SETTING: Middle-aged women in a cohort based on regular health screening examinations. POPULATION: Premenopausal Korean women aged 42-52 years were recruited and were followed up for a median of 4.2 years. The cross-sectional and cohort studies comprised 4672 women and 2590 women without VMS at baseline, respectively. METHODS: Adiposity measures included body mass index (BMI), waist circumference and percentage body fat. Being metabolically healthy was defined as not having any metabolic syndrome components or a homeostasis model assessment of insulin resistance of 2.5 or more. MAIN OUTCOMES MEASURES: VMS (hot flushes and night sweats) assessed using the questionnaire. RESULTS: All adiposity measures were positively associated with an increased risk of VMS in both cross-sectional and longitudinal studies. The multivariable-adjusted prevalence ratio (95% confidence interval [CI]) for VMS comparing percentage body fat of 35% or more with the reference was 1.47 (95% CI 1.14-1.90) in metabolically healthy women, and the corresponding prevalence ratio was 2.32 (95% CI 1.42-3.78) in metabolically unhealthy women (Pinteraction  = 0.334). The multivariable-adjusted hazard ratio for incident VMS comparing percentage body fat of 35% or more with the reference was 1.34 (95% CI 1.00-1.79) in metabolically healthy women, whereas the corresponding hazard ratio was 3.61 (95% CI 1.81-7.20) in metabolically unhealthy women (Pinteraction  = 0.036). The association between BMI, waist circumference and VMS did not significantly differ by metabolic health status. CONCLUSIONS: Maintaining normal weight and being metabolically healthy may help to prevent VMS in premenopausal women. TWEETABLE ABSTRACT: Avoiding obesity and a metabolically unhealthy status may help reduce vasomotor symptoms in premenopausal women.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Alcohol Intake and Mortality in Patients With Chronic Viral Hepatitis: A Nationwide Cohort Study.

INTRODUCTION: We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. METHODS: A total of 364,361 men and women aged 40-84 years who underwent health screening examination between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. RESULTS: In participants without chronic viral hepatitis, the fully adjusted hazard ratios (HRs) for all-cause mortality comparing light, moderate, and heavy drinkers with nondrinkers were 0.92 (95% confidence interval [CI] 0.87-0.98), 1.08 (95% CI 1.01-1.16), and 1.51 (95% CI 1.33-1.72), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.19 (95% CI 1.05-1.36), 1.23 (95% CI 1.06-1.43), and 1.69 (95% CI 1.28-2.24), respectively (P value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared with participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 10.85, 95% CI 9.74-12.09) and extrahepatic cancer mortality (HR 1.37, 95% CI 1.26-1.49). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. DISCUSSION: Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.

Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults.

INTRODUCTION: Dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults. METHODS: A cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status. RESULTS: Within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78-0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69-0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD. DISCUSSION: Ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.

Blood eosinophil counts and the development of obstructive lung disease: the Kangbuk Samsung Health Study.

AIM: The impact of blood eosinophil counts on the development of chronic obstructive lung disease (COPD) is unknown. We investigated whether a higher blood eosinophil count was associated with the risk of developing obstructive lung disease (OLD) in a large cohort of men and women free from lung disease at baseline. METHODS: This was a cohort study of 359 456 Korean adults without a history of asthma and without OLD at baseline who participated in health screening examinations including spirometry. OLD was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1 <80% predicted. RESULTS: After a median (interquartile range) follow-up of 5.6 (2.9-9.2) years, 5008 participants developed incident OLD (incidence rate 2.1 (95% CI 2.1-2.2) per 1000 person-years). In the fully adjusted model, the hazard ratios for incident OLD comparing eosinophil counts of 100- <200, 200- <300, 300- <500 and ≥500 versus <100 cells·µL-1 were 1.07 (95% CI 1.00-1.15), 1.30 (95% CI 1.20-1.42), 1.46 (95% CI 1.33-1.60) and 1.72 (95% CI 1.51-1.95), respectively (ptrend<0.001). These associations were consistent in clinically relevant subgroups, including never-, ex- and current smokers. CONCLUSION: In this large longitudinal cohort study, blood eosinophil counts were positively associated with the risk of developing of OLD. Our findings indicate a potential role of the eosinophil count as an independent risk factor for developing COPD.

Translation and validation of the Korean version of the clinical frailty scale in older patients.

BACKGROUND: Frailty is a multidimensional syndrome that leads to an increase in vulnerability. Previous studies have suggested that frailty is associated with poor health-related outcomes. For frailty screening, the Clinical Frailty Scale (CFS) is a simple tool that is widely used in various translated versions. We aimed to translate the CSF into Korean and evaluated its contents and concurrent validity. METHODS: Translations and back-translations of the CFS were conducted independently. A multidisciplinary team decided the final CFS-K. Between August 2019 and April 2020, a total of 100 outpatient and inpatient participants aged ≥65 years were enrolled prospectively. The clinical characteristics were evaluated using the CFS-K. The CFS-K scores were compared with those of other frailty screening tools using Pearson's correlation coefficient and Spearman's rank correlation. The area under curve (AUC) for identifying the Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 3 or more was calculated for the CFS-K and other screening tools. RESULTS: The mean age of the participants was 76.5 years (standard deviation [SD], 7.0), and 63 (63%) participants were male. The mean CFS-K was 4.8 (SD, 2.5). Low body mass index (p = 0.013) and low score on the Korean version of the Mini-Mental State Examination (p < 0.001) were significantly associated with high CFS-K scores, except for those assigned to scale 9 (terminally ill). The CFS-K showed a significant correlation with other frailty screening tools (R = 0.7742-0.9190; p < 0.01), except in the case of those assigned to scale 9 (terminally ill). In comparison with other scales, the CFS-K identified ECOG PS grade 3 or more with the best performance (AUC = 0.99). Patients assigned to scale 9 on the CFS-K (terminally ill) had similar frailty scores to those assigned to scale 4 (vulnerable) or 5 (mildly frail). CONCLUSIONS: In conclusion, the CFS-K is a valid scale for measuring frailty in older Korean patients. The CFS-K scores were significantly correlated with the scores of other scales. To evaluate the predictive and prognostic value of this scale, further larger-scale studies in various clinical settings are warranted.

Alcoholic and Nonalcoholic Fatty Liver Disease and Incident Hospitalization for Liver and Cardiovascular Diseases.

BACKGROUND & AIMS: We compared the associations of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (AFLD) with risk of incident hospitalization for liver and cardiovascular diseases. METHODS: We collected data from the Kangbuk Samsung Health Study on 218,030 men and women in Korea who underwent a health examination from 2011 through 2016. Fatty liver disease (FLD) was detected by ultrasound during the initial examination. The Fibrosis-4 index was used to identify individuals with liver fibrosis. Participants were followed up for as long as 5.9 years and data on hospitalizations for liver and cardiovascular diseases were collected. RESULTS: The prevalence of NAFLD was 22.0% and the prevalence of AFLD was 6.4%. Over a median follow-up period of 4.2 years, we observed 51 and 1097 incident cases of liver disease- or cardiovascular disease-related hospitalizations, respectively. After adjustment for potential confounders, the multivariable-adjusted hazard ratios for liver disease-related hospitalization, comparing NAFLD and AFLD with the reference category (no excessive alcohol intake and no FLD), were 1.73 (95% CI, 0.76-3.96) and 5.00 (95% CI, 2.12-11.83), respectively. The corresponding hazard ratios for cardiovascular disease hospitalization were 1.20 (95% CI, 1.02-1.40) and 1.08 (95% CI, 0.86-1.34), respectively. Among participants with FLD, the risk of liver disease-related hospitalization increased with high Fibrosis-4 index scores, whereas the risk of incident cardiovascular disease did not. CONCLUSIONS: In a large cohort study, we found an increased risk of liver disease-related hospitalizations for patients with NAFLD or AFLD, especially among those with Fibrosis-4 index scores. An increased risk of cardiovascular disease-associated hospitalization was observed in patients with NAFLD but not AFLD.

Mitochondrial DNA copy number and incident atrial fibrillation.

BACKGROUND: Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. METHODS: We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates. RESULTS: The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups. CONCLUSIONS: Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.

Life's Simple 7 Cardiovascular Health Metrics and Progression of Coronary Artery Calcium in a Low-Risk Population.

Objective- We examined the association of cardiovascular health (CVH) metrics with the development and progression of coronary artery calcium (CAC) among apparently healthy adults. Approach and Results- This cohort study included 65 494 men and women 30 years of age and older free of cardiovascular disease at baseline who underwent a comprehensive exam including CAC scoring. CVH metrics were defined according to the American Heart Association Life's Simple 7 metrics based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. CVH scores range from 0 (all metrics considered unhealthy) to 7 (all metrics considered healthy). Participants were followed-up for a maximum of 6.6 years. Compared with participants with ideal CVH scores 0-1, the multivariable-adjusted difference in the change in geometric means of CAC scores over 5 years of follow-up were -0.40 (-0.62 to -0.19), -0.83 (-1.03 to -0.63), -1.06 (-1.25 to -0.86), -1.22 (-1.42 to -1.03), and -1.05 (-1.42 to -0.69) in participants with ideal CVH scores 2, 3, 4, 5, and 6-7, respectively. The inverse association between CVH scores and progression of CAC was observed both in participants with no CAC and in those with CAC detectable at baseline. Conclusions- A higher ideal CVH metrics score was strongly associated with a lower prevalence of CAC and with lower progression of CAC in males and females in a large cohort of healthy adults. Our findings suggest that maintaining a healthy life habits could help reduce the development and progression of subclinical atherosclerosis and ultimately prevent clinically cardiovascular event.

Hepatitis B virus infection and development of chronic kidney disease: a cohort study.

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) < 60 ml/min/1.73m2 and/or proteinuria. RESULTS: Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03-1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m2 were 1.23 (1.12-1.35; P <  0.001) and 0.89 (0.73-1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline. CONCLUSION: In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD.