Correlation between Gut Microbiota and Six Facets of Neuroticism in Korean Adults.

A person high in neuroticism is more likely to experience anxiety, stress, worry, fear, anger, and depression. Previous studies have shown that the gut microbiota can influence personality and mental disorders, including stress, anxiety, and depression, through the gut-brain axis. Here, we investigated the correlations between the sub-facet of neuroticism and gut microbiota using the Revised NEO Personality Inventory and the 16S rRNA gene sequencing data 784 adults. We found that the high anxiety and vulnerability group showed significantly lower richness in microbial diversity than a group with low anxiety and vulnerability. In beta diversity, there was a significant difference between the low and high groups of anxiety, self-consciousness, impulsiveness, and vulnerability. In taxonomic compositions, Haemophilus belonging to Gammaproteobacteria was correlated with the Neuroticism domain as well as N1 anxiety and N6 vulnerability facets. The high N1 anxiety and N6 vulnerability group was correlated with a low abundance of Christensenellaceae belonging to Firmicutes Clostridia. High N4 self-consciousness was correlated with a low abundance of Alistipes and Sudoligranulum. N5 impulsiveness was correlated with a low abundance of Oscillospirales. Our findings will contribute to uncovering the potential link between the gut microbiota and neuroticism, and the elucidation of the correlations of the microbiome-gut-brain axis with behavioral changes and psychiatric cases in the general population.

Gut microbiota and metabolic health among overweight and obese individuals.

Although obesity is associated with numerous diseases, the risks of disease may depend on metabolic health. Associations between the gut microbiota, obesity, and metabolic syndrome have been reported, but differences in microbiomes according to metabolic health in the obese population have not been explored in previous studies. Here, we investigated the composition of gut microbiota according to metabolic health status in obese and overweight subjects. A total of 747 overweight or obese adults were categorized by metabolic health status, and their fecal microbiota were profiled using 16S ribosomal RNA gene sequencing. We classified these adults into a metabolically healthy group (MH, N = 317) without any components of metabolic syndrome or a metabolically unhealthy group (MU, N = 430) defined as having at least one metabolic abnormality. The phylogenetic and non-phylogenetic alpha diversity for gut microbiota were lower in the MU group than the MH group, and there were significant differences in gut microbiota bacterial composition between the two groups. We found that the genus Oscillospira and the family Coriobacteriaceae were associated with good metabolic health in the overweight and obese populations. This is the first report to describe gut microbial diversity and composition in metabolically healthy and unhealthy overweight and obese individuals. Modulation of the gut microbiome may help prevent metabolic abnormalities in the obese population.

Major Lipids, Apolipoproteins, and Alterations of Gut Microbiota.

The gut microbiota has been linked to blood lipids. However, the relationship between the gut microbiome and other lipid markers like apolipoproteins A1 (apoA1) and B (apoB) as well as classical lipid markers in Asians remain unclear. Here, we examined the associations between gut microbial diversity and taxonomic compositions with both apolipoproteins and lipid markers in a large number of Korean patients. The fecal 16S rRNA gene sequencing data from 1141 subjects were analyzed and subjects were categorized into control group (G0) or abnormal group (G1) according to blood lipid measurements. The microbial diversity and several taxa of the gut microbiota were significantly associated with triglyceride, apoA1, and apoB levels, but not with total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. The alpha diversity of the gut microbiota was inversely associated with high triglyceride level. Interestingly, G1 of apoA1 showed increased microbial richness and distinct microbial community compared with G0 of apoA1. A high abundance of Fusobacteria and low abundance of Oscillospira were found in the hypertriglyceridemia group. In this large-scale study, we identified associations of gut microbiota with apolipoproteins and classical lipid markers, indicating that the gut microbiota may be an important target for regulating blood lipids.

Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis.

BACKGROUND AND AIMS: The effects of low-level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low-level alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category). APPROACH AND RESULTS: A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1-9.9, and 10-29.9 g/day (10-19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB-4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for incident HS were 0.93 (0.90-0.95) and 0.90 (0.87-0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for developing HS plus intermediate/high FIB-4 were 1.15 (1.04-1.27) and 1.49 (1.33-1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB-4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017). CONCLUSIONS: Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.

Solitary kidney and risk of chronic kidney disease.

The renal outcome of solitary kidney remains controversial. We examined the longitudinal association of congenital or acquired solitary kidney with the development of chronic kidney disease (CKD). A cohort study was performed involving 271,171 Korean men and women free of CKD at baseline who underwent a health screening program and who were followed annually or biennially for an average of 5.4 years. Solitary kidney was determined based on ultrasonographic findings. CKD was defined as an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 and/or the presence of proteinuria in two or more consecutive visits. During 1,472,519.6 person-years of follow-up, 2989 participants developed CKD (incidence rate: 2.0 per 1000 person-years). After adjustment for potential confounders, the aHR (95% CIs) for incident CKD comparing solitary kidney to the control was 3.26 (1.63-6.54). In analyses of cause-specific solitary kidney, aHR (95% CIs) for CKD comparing unilateral nephrectomy and congenital solitary kidney to the control were 6.18 (2.31-16.49) and 2.22 (0.83-5.92), respectively. The association between solitary kidney and CKD was stronger in men. Having a solitary kidney was independently associated with an increased risk of CKD development. Therefore, preventive strategies for reducing the risk of CKD are required in individuals with a solitary kidney.

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.

Alcoholic and Nonalcoholic Fatty Liver Disease and Liver-Related Mortality: A Cohort Study.

OBJECTIVES: We compared liver-related mortality by fibrosis severity between 2 types of fatty liver disease (FLD), nonalcoholic FLD (NAFLD) and alcoholic FLD (AFLD), in a large cohort of nonobese and obese individuals. METHODS: A cohort study was performed with 437,828 Korean adults who were followed up for up to 14 years. Steatosis was diagnosed based on ultrasonography; fibrosis severity was determined by the fibrosis 4 (FIB-4) score. Vital status and liver-related deaths were ascertained through linkage to national death records. RESULTS: The prevalence of NAFLD and AFLD was 20.9% and 4.0%, respectively. During 3,145,541.1 person-years of follow-up, 109 liver-related deaths were identified (incidence rate of 3.5 per 10 person-years). When changes in fatty liver status, FIB-4 scores, and confounders during follow-up were updated as time-varying covariates, compared with the reference (absence of both excessive alcohol use and FLD), the multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality among those with low, intermediate, and high FIB-4 scores were 0.43 (0.19-0.94), 2.74 (1.23-6.06), and 84.66 (39.05-183.54), respectively, among patients with NAFLD, whereas among patients with AFLD, the corresponding hazard ratios (95% confidence intervals) were 0.67 (0.20-2.25), 5.44 (2.19-13.49), and 59.73 (27.99-127.46), respectively. The associations were more evident in nonobese individuals than in obese individuals (P for interaction = 0.004). DISCUSSION: In this large cohort of young and middle-aged individuals, NAFLD and AFLD with intermediate to high fibrosis scores were associated with an increased risk of liver-related mortality in a dose-dependent manner, especially among nonobese individuals.

Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study.

OBJECTIVE: Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). DESIGN: A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. RESULTS: Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. CONCLUSION: In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.

Smoking and the Risk of Non-Alcoholic Fatty Liver Disease: A Cohort Study.

OBJECTIVES: The role of smoking in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. We assessed the risk of incident NAFLD according to smoking status and urinary cotinine levels. METHODS: We performed a cohort study of 199,468 Korean adults without NAFLD at baseline who were followed annually or biennially for a median of 4.1 years. The presence of fatty liver was determined using ultrasound. NAFLD severity was assessed using NAFLD fibrosis score (NFS), a non-invasive fibrosis marker. RESULTS: During 1,070,991 person-years of follow-up, 45,409 participants developed NAFLD. Self-reported current smoking, pack-years, and urinary cotinine level were significantly associated with increased risk for NAFLD. For men, the multivariable-adjusted hazard ratios (aHR) (95% confidence intervals (CI)) for incident NAFLD comparing 10-19.9, and ≥20 pack-years to 0 pack-years were 1.25 (1.21- 1.29), and 1.36 (1.30-1.42), respectively; for women, aHR (95% CI) for NAFLD comparing 5-9.9, and ≥10 pack-years to 0 pack-years were 1.25 (1.04-1.50), and 1.46 (1.17-1.81), respectively. Smoking pack-years were also associated with increased risk for NAFLD plus intermediate or high fibrosis score. For men, the aHR (95% CI) for NAFLD plus intermediate or high NFS comparing ≥20 pack-years to 0 pack-years was 1.29 (1.18-1.42); for women, the aHR (95% CI) comparing ≥10 pack-years to 0 pack-years was 1.75 (1.12-2.73). CONCLUSIONS: In a large cohort of young and middle-aged men and women, current smoking, pack-years, and urinary cotinine levels were positively associated with the risk of incident NAFLD, suggesting that smoking contributes to the development of NAFLD.

Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease: A Cohort Study.

The effect of modest alcohol consumption on fibrosis progression in the general population with nonalcoholic fatty liver disease (NAFLD) remains unclear. We examined the association of nonheavy alcohol consumption with worsening of noninvasive fibrosis indices in a large-scale, low-risk population with NAFLD. A cohort study was performed in 58,927 Korean adults with NAFLD and low fibrosis scores who were followed for a median of 4.9 years. Non-, light, and moderate drinkers were defined as 0 g/day, 1-9.9 g/day, and 10-29.9 g/day (10-19.9 g/day for women), respectively. Progression from low to intermediate or high probability of advanced fibrosis was assessed using noninvasive indices including NAFLD fibrosis score (NFS) and Fibrosis-4 Index (FIB-4). A parametric proportional hazards model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During 347,925.4 person-years of follow-up, 5,630 subjects with low FIB-4 progressed to intermediate or high FIB-4. The multivariable-adjusted HRs (95% CI) for worsening of FIB-4 comparing light and moderate drinkers with nondrinkers were 1.06 (0.98-1.16) and 1.29 (1.18-1.40), respectively. Similarly, using NFS, corresponding HRs (95% CI) comparing light and moderate drinkers with nondrinkers were 1.09 (1.02-1.16) and 1.31 (1.23-1.40), respectively. Furthermore, the association of moderate drinkers with worsening of either FIB-4 or NFS remained significant after introducing alcohol use and confounders treated as time-varying covariates. Conclusion: In this large-scale cohort of young and middle-aged individuals with NAFLD, nonheavy alcohol consumption, especially moderate alcohol consumption, was significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.

Metabolically healthy and unhealthy obesity phenotypes and risk of renal stone: a cohort study.

BACKGROUND/OBJECTIVES: Although obesity is considered an independent risk factor of nephrolithiasis, little is known about the effect of obesity on nephrolithiasis according to metabolic health status. We investigated the association between body mass index (BMI) category and the incidence of nephrolithiasis in metabolically healthy and unhealthy individuals. SUBJECTS/METHODS: The cohort consisted of 270,190 Korean adults free of nephrolithiasis at baseline, who were followed-up annually or biennially for a median of 4.1 years. Nephrolithiasis were determined based on ultrasonographic findings. Being metabolically healthy was defined as not having any metabolic syndrome component. A parametric Cox model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During 1,415,523.0 person-years of follow-up, 13,450 participants developed nephrolithiasis (incidence rate, 9.5 per 1000 person-years). Obesity was positively associated with an increased risk of incident nephrolithiasis in dose-response manner, but the association was stronger in metabolically healthy individuals. Among metabolically healthy individuals, the multivariable-adjusted HRs (95% CIs) for incident nephrolithiasis comparing BMIs 23-24.9, 25-29.9, and ≥30 with a BMI of 18.5-22.9 kg/m2 as the reference were 1.02 (0.95-1.10), 1.12 (1.03-1.22), and 1.72 (1.21-2.44), respectively, whereas corresponding HRs (95% CIs) in metabolically unhealthy individuals were 1.10 (1.04-1.17), 1.27 (1.20-1.34), and 1.36 (1.22-1.51), respectively. The association between obesity and incident nephrolithiasis was stronger in men and current smokers. CONCLUSIONS: Obesity was associated with a higher incidence of nephrolithiasis in both metabolically healthy and unhealthy individuals, indicating obesity per se as an independent risk factor for nephrolithiasis.

Bidirectional Association between Nonalcoholic Fatty Liver Disease and Gallstone Disease: A Cohort Study.

Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are often found to coexist but the sequential relationship of NAFLD and GD to each other remains controversial. We prospectively evaluated the bidirectional relationship of NAFLD with GD. A cohort study was performed on Korean adults who underwent a health checkup and were followed annually or biennially for a mean of 6.0 years. Fatty liver and gallstones were diagnosed by ultrasound. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NAFLD severity was determined by non-invasive fibrosis markers. Among 283,446 participants without either gallstones or cholecystectomy at baseline, 6440 participants developed gallstones. Among 219,641 participants without NAFLD at baseline, 49,301 participants developed NAFLD. The multivariable-adjusted hazard ratio (95% confidence interval) for incident gallstone comparing the NAFLD group vs. the non-NAFLD group was 1.26 (1.17⁻1.35). Increased non-invasive fibrosis markers of NAFLD were positively associated with an increased incidence of gallstones in a graded and dose-responsive manner (p-trend < 0.01). The multivariable-adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing gallstone and cholecystectomy to no GD were 1.14 (1.07⁻1.22) and 1.17 (1.03⁻1.33), respectively. This large-scale cohort study of young and middle-aged individuals demonstrated a bidirectional association between NAFLD and GD. NAFLD and its severity were independently associated with an increased incidence of gallstones, while GD and cholecystectomy were also associated with incident NAFLD. Our findings indicate that the conditions may affect each other, requiring further studies to elucidate the potential mechanisms underlying this association.

Physical activity and impaired left ventricular relaxation in middle aged adults.

The aim of this study was to examine the relationship between physical activity level and impaired left ventricular (LV) relaxation in a large sample of apparently healthy men and women. We conducted a cross-sectional study in 57,449 adults who underwent echocardiography as part of a comprehensive health examination between March 2011 and December 2014. Physical activity level was assessed using the Korean version of the International Physical Activity Questionnaire Short Form. The presence of impaired LV relaxation was determined based on echocardiographic findings. Physical activity levels were inversely associated with the prevalence of impaired LV relaxation. The multivariable-adjusted odds ratios (95% confidence interval) for impaired LV relaxation comparing minimally active and health-enhancing physically active groups to the inactive group were 0.84 (0.77-0.91) and 0.64 (0.58-0.72), respectively (P for trend < 0.001). These associations were modified by sex (p for interaction <0.001), with the inverse association observed in men, but not in women. This study demonstrated an inverse linear association between physical activity level and impaired LV relaxation in a large sample of middle-aged Koreans independent of potential confounders. Our findings suggest that increasing physical activity may be independently important in reducing the risk of impaired LV relaxation.

Low relative muscle mass and left ventricular diastolic dysfunction in middle-aged adults.

OBJECTIVES: The association between low skeletal muscle mass and left ventricular diastolic dysfunction (LVDD), a predictor of future heart failure, is largely unexplored. We investigated the relationship between relative muscle mass and LVDD. METHODS: We conducted a cross-sectional study in 67,106 Koreans who underwent an echocardiography as part of a comprehensive health examination between January 2012 and December 2014. Skeletal muscle mass index (SMI) [SMI (%)=total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. The presence of LVDD was determined using echocardiographic findings. RESULTS: In 67,106 participants, 19,232 subjects (28.7%) and 1553 subjects (2.3%) had LVDD and left ventricular (LV) hypertrophy, respectively. SMI was positively associated with E/A ratio and septal E', whereas E/E' ratio and LV mass index were negatively associated with SMI. Lower SMI was associated with increased presence of LVDD. In a multivariable-adjusted model controlling for potential confounders including physical activity, insulin resistance, and LV mass, the odds ratios for LVDD in SMI quartiles 1, 2, and 3 compared with quartile 4 were 2.11 (1.97-2.25), 1.79 (1.68-1.90), and 1.45 (1.36-1.55), respectively (P for trend<0.001). CONCLUSIONS: In a large sample of young and middle-aged Korean adults, low relative muscle mass was independently associated with increased risk of LVDD, indicating an independent role of skeletal muscle mass in the pathogenesis of LVDD.

Coexistence of Colorectal Adenomas and Coronary Calcification in Asymptomatic Men and Women.

GOALS: Because of shared risk factors between clinically manifest cardiovascular disease and colorectal cancer, we hypothesized the coexistence of subclinical atherosclerosis measured by coronary artery calcium (CAC) and colorectal adenoma (CRA) and that these 2 processes would also share common risk factors. BACKGROUND: No study has directly compared the risk factors associated with subclinical coronary atherosclerosis and CRA. STUDY: This was a cross-sectional study using multinomial logistic regression analysis of 4859 adults who participated in a health screening examination (2010 to 2011; analysis 2014 to 2015). CAC scores were categorized as 0, 1 to 100, or >100. Colonoscopy results were categorized as absent, low-risk, or high-risk CRA. RESULTS: The prevalence of CAC>0, CAC 1 to 100 and >100 was 13.0%, 11.0%, and 2.0%, respectively. The prevalence of any CRA, low-risk CRA, and high-risk CRA was 15.1%, 13.0%, and 2.1%, respectively. The adjusted odds ratios (95% confidence interval) for CAC>0 comparing participants with low-risk and high-risk CRA with those without any CRA were 1.35 (1.06-1.71) and 2.09 (1.29-3.39), respectively. Similarly, the adjusted odds ratios (95% confidence interval) for any CRA comparing participants with CAC 1 to 100 and CAC>100 with those with no CAC were 1.26 (1.00-1.6) and 2.07 (1.31-3.26), respectively. Age, smoking, diabetes, and family history of CRC were significantly associated with both conditions. CONCLUSIONS: We observed a graded association between CAC and CRA in apparently healthy individuals. The coexistence of both conditions further emphasizes the need for more evidence of comprehensive approaches to screening and the need to consider the impact of the high risk of coexisting disease in individuals with CAC or CRA, instead of piecemeal approaches restricted to the detection of each disease independently.

Association Between Sonographically Diagnosed Nephrolithiasis and Subclinical Coronary Artery Calcification in Adults.

BACKGROUND: Although recent studies suggest an association between nephrolithiasis and clinical cardiovascular events, this association has been underexplored. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 62,091 asymptomatic adults without known coronary heart disease who underwent a screening health examination that included cardiac tomography. PREDICTOR: Nephrolithiasis. OUTCOME: Coronary artery calcification (CAC). MEASUREMENTS: Nephrolithiasis assessed using ultrasonography of the abdomen. CAC scoring assessed using cardiac computed tomography. RESULTS: The prevalence of CAC scores > 0 was 13.1% overall. Participants with nephrolithiasis had a higher prevalence of coronary calcification than those without (19.1% vs 12.8%). In Tobit models adjusted for age and sex, the CAC score ratio comparing participants with nephrolithiasis with those without nephrolithiasis was 1.56 (95% CI, 1.19-2.05). After further adjustment for screening center, year of screening examination, physical activity, alcohol intake, smoking status, education level, body mass index, family history of cardiovascular disease, total energy intake, glucose concentration, systolic blood pressure, triglyceride concentration, high-density lipoprotein cholesterol concentration, uric acid concentration, and estimated glomerular filtration rate, the CAC score ratio was attenuated, but remained significant (CAC score ratio, 1.31; 95% CI, 1.00-1.71). LIMITATIONS: Computed tomographic diagnosis of nephrolithiasis was unavailable. CONCLUSIONS: Nephrolithiasis was associated with the presence of CAC in adults without known coronary heart disease, supporting the hypothesis that these 2 health conditions share a common pathophysiology.

Association of Age at Menarche With Left Ventricular Diastolic Dysfunction in Middle-Aged Women.

BACKGROUND: There is sparse research on whether if early menarche is related to left ventricular (LV) diastolic dysfunction. The present study examined this relationship in Korean women.Methods and Results:In a cross-sectional study we analyzed the records of 18,910 Korean women (≥30 years) who underwent echocardiography as part of a comprehensive health examination. Age at menarche was assessed using standardized, self-administered questionnaires. Presence of LV diastolic dysfunction was determined from the echocardiographic findings. Of the 18,910 women, 3,449 had LV diastolic dysfunction. Age at menarche was inversely associated with prevalence of LV diastolic dysfunction. In a multivariable-adjusted model, odds ratios (95% confidence interval) for LV diastolic dysfunction comparing menarche age to menarche at 15-18 years were 1.77 (1.38-2.27) for <12 years, 1.31 (1.11-1.54) for 12 years, 1.26 (1.11-1.43) for 13 years, and 1.03 (0.91-1.15) for 14 years (P for trend <0.001). Adjusting for body mass index or percent fat mass partially reduced these associations. CONCLUSIONS: This large study found an inverse relationship between menarche age and LV diastolic dysfunction. Future prospective studies are needed to investigate potential causal relationships.

Relative muscle mass and the risk of incident type 2 diabetes: A cohort study.

AIMS: The association between relative muscle mass (RMM) and incidence of type 2 diabetes (T2DM) is largely unknown. We examined whether RMM predicted development of T2DM in an apparently young healthy population. METHODS: This cohort study was comprised of 113,913 men and 89,854 women, free of T2DM at baseline, who underwent a health checkup examination and were followed-up annually or biennially for an average of 2.9 years. We used skeletal muscle mass index (SMI) as an indicator of RMM. SMI (%) [total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. The study outcome was incident T2DM, defined as fasting serum glucose ≥126 mg/dL, HbA1C ≥6.5%, or use of medication for T2DM. RESULTS: During 589,098.8 person-years of follow-up, 4,264 individuals developed T2DM (incidence rate, 7.2 per 1000 person-years). Median age (range) at baseline was 39.1 years (18.1-87.1). RMM was negatively associated with incidence of T2DM in a dose-response manner. The multivariate-adjusted hazard ratios (95% CIs) for incident T2DM comparing quartiles 3, 2 and 1 of RMM to the highest quartile were 1.32 (1.14-1.52), 1.63 (1.42-1.86), and 2.21 (1.94-2.51), respectively, for males and 1.18 (0.88-1.58), 1.46 (1.11-1.91), and 1.96 (01.51-2.53) for females (P for trend <0.001; 0.011). This association was stronger in younger or premenopausal subjects. CONCLUSIONS: RMM was negatively associated with development of T2DM in a large sample of young and middle-aged Korean adults. Further research is required to determine whether preservation of muscle mass through intervention affects the risk of T2DM.

Non-alcoholic fatty liver disease and the development of nephrolithiasis: A cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation or precursor of metabolic syndrome, may increase nephrolithiasis, a renal manifestation of insulin resistance, but the prospective association between NAFLD and incident nephrolithiasis has not been evaluated. We examined the association of NAFLD with the development of nephrolithiasis in a large cohort of Korean men and women. METHODS: We performed a cohort study of 208,578 Korean adults who underwent a health checkup examination between January 2002 and December 2014 and were followed-up annually or biennially through December 2014. NAFLD was defined as the presence of fatty liver in the absence of excessive alcohol use or other identifiable causes. Fatty liver and nephrolithiasis were determined based on ultrasonographic findings. We used a parametric Cox model to estimate the adjusted hazard ratios (HRs) of nephrolithiasis according to the presence of NAFLD. RESULTS: During 1,054,887.6 person-year of follow-up, 16,442 participants developed nephrolithiasis. After adjusting for age, center, year of screening exam, smoking status, alcohol intake, physical activity, education level, body mass index, history of hypertension and diabetes, HOMA-IR, uric acid and C-reactive protein, male participants with NAFLD had a significantly increased risk of nephrolithiasis than those without NAFLD (adjusted HR 1.17, 95% CI 1.06-1.30). However, no association between NAFLD and nephrolithiasis was observed in women (adjusted HR 0.97, 95% CI 0.81-1.16). CONCLUSIONS: In this large cohort study of young and middle-aged Koreans, NAFLD was significantly associated with an increased incidence of nephrolithiasis in men but not in women.

Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism.

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. SUBJECTS/METHODS: We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 85 mmHg) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. RESULTS: Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of α-tocopherol increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of ß-carotene increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). CONCLUSIONS: These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.