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.

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.

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 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.

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.

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.

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.

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.

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 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.

Development of Nephrolithiasis in Asymptomatic Hyperuricemia: A Cohort Study.

BACKGROUND: Although the association between gout and nephrolithiasis is well known, the relationship between asymptomatic hyperuricemia and the development of nephrolithiasis is largely unknown. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 239,331 Korean adults who underwent a health checkup examination during January 2002 to December 2014 and were followed up annually or biennially through December 2014. PREDICTOR: Baseline serum uric acid levels of participants. OUTCOME: The development of nephrolithiasis during follow-up. MEASUREMENTS: Nephrolithiasis is determined based on ultrasonographic findings. A parametric Cox model was used to estimate the adjusted HRs of nephrolithiasis according to serum uric acid level. RESULTS: During 1,184,653.8 person-years of follow-up, 18,777 participants developed nephrolithiasis (incidence rate, 1.6/100 person-years). Elevated uric acid level was significantly associated with increased risk for nephrolithiasis in a dose-response manner (P for trend < 0.001) in men. This dose-response association was not observed in women. In male participants, multivariable-adjusted HRs for incident nephrolithiasis comparing uric acid levels of 6.0 to 6.9, 7.0 to 7.9, 8.0 to 8.9, 9.0 to 9.9, and ≥10.0mg/dL with uric acid levels < 6.0mg/dL were 1.06 (95% CI, 1.02-1.11), 1.11 (95% CI, 1.05-1.16), 1.21 (95% CI, 1.13-1.29), 1.31 (95% CI, 1.17-1.46), and 1.72 (95% CI, 1.44-2.06), respectively. This association was observed in all clinically relevant subgroups and persisted even after adjustment for homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein level. LIMITATIONS: Dietary information and computed tomographic diagnosis of nephrolithiasis were unavailable. CONCLUSIONS: In this large cohort study, increased serum uric acid level was modestly and independently associated with increased risk for the development of nephrolithiasis in a dose-response manner in apparently healthy men.

Relationship Between Low Relative Muscle Mass and Coronary Artery Calcification in Healthy Adults.

OBJECTIVE: Sarcopenia or low muscle mass is related to cardiovascular risk factors; however, the association between low muscle mass and subclinical atherosclerosis has been largely unexplored. We investigated whether muscle mass is related to coronary artery calcification (CAC) in a large sample of middle-aged asymptomatic adults. APPROACH AND RESULTS: We performed a cross-sectional study of 31 108 asymptomatic adults without cancer, diabetes mellitus, or known cardiovascular disease who underwent a health checkup examination including cardiac tomography estimation of CAC scores between 2012 and 2013. Skeletal muscle mass index (SMI) [SMI (%)=total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. We assessed the relationship between SMI and CAC scores using both multivariate-adjusted Tobit models and multinomial logistic regression models. Of the 31 108 subjects, 3374 subjects (10.9%) had a CAC score 1 to 100, and 628 subjects (2.0%) had a CAC score >100. SMI was inversely associated with CAC score ratios. Specifically, in a multivariable-adjusted model adjusting for potential confounders, CAC score ratios (95% confidence intervals) of SMI for quartiles 1, 2, and 3 compared with quartile 4 were 2.27 (1.70-3.05), 1.46 (1.15-1.85), and 1.24 (0.98-1.55), respectively (P for trend <0.001). Adjusting for insulin resistance reduced the magnitude of the associations, but they remained statistically significant. CONCLUSIONS: Relative muscle mass was negatively associated with the prevalence of coronary calcification, supporting low muscle mass as an independent risk factor of coronary heart disease.

Relationship Between γ-Glutamyltransferase Levels and Left Ventricular Diastolic Dysfunction.

BACKGROUND: The goal of this study was to examine the association of serum γ-glutamyltransferase (GGT) levels with left ventricular (LV) diastolic dysfunction and LV hypertrophy.Methods and Results:A cross-sectional study of 79,459 Korean men and women who underwent an echocardiography as part of a comprehensive health examination between March 2011 and December 2014. The presence of LV diastolic dysfunction and LV hypertrophy was determined using echocardiography. Of the subjects, 5,447 had LV diastolic dysfunction and 2,070 had LV hypertrophy. Both LV diastolic dysfunction and LV hypertrophy were associated with higher levels of serum GGT. Multivariable-adjusted odds ratios (95% confidence interval) for LV diastolic dysfunction comparing serum GGT quartiles 2-4 with quartile 1 were 1.25 (1.08-1.44), 1.65 (1.43-1.91) and 2.23 (1.92-2.58), respectively (P for trend <0.001). Multivariable-adjusted odds ratios (95% CI) for LV hypertrophy comparing serum GGT quartiles 2-4 with quartile 1 were 1.13 (0.94-1.36), 1.14 (0.93-1.40) and 1.33 (1.07-1.65), respectively (P for trend 0.01). These associations of serum GGT levels with LV diastolic dysfunction and LV hypertrophy were modified by age (P for interaction <0.05). CONCLUSIONS: This study demonstrated a positive association between serum GGT levels and LV diastolic dysfunction and LV hypertrophy in a large cohort of middle-aged men and women independent of potential confounders.

High serum alanine aminotransferase is associated with the risk of colorectal adenoma in Korean men.

BACKGROUND AND AIM: An elevated alanine aminotransferase (ALT) is frequently observed in subjects with metabolic syndrome, which is associated with the risk of colorectal adenoma (CRA). However, the relationship between ALT and CRA remains unclear. Therefore, we aimed to investigate whether high serum ALT is associated with the risk of CRA in a metabolically healthy population. METHODS: We conducted this cross-sectional study in 27,717 asymptomatic Korean adults who underwent a health checkup. Subjects were categorized as adenoma-free, hyperplastic polyp, low-risk adenoma, or high-risk adenoma. High-risk adenoma was defined as three or more adenomas, any adenoma ≥ 10 mm, or adenoma with high-grade dysplasia or villous features. RESULTS: Among all participants, 10.3% and 1.5% of cases were categorized as low-risk and high-risk adenoma, respectively. In multivariate analyses adjusting for age, sex, body mass index, smoking habits, alcohol intake, regular exercise, aspirin and analgesics use, family history of colon cancer, education level, fatty liver, high-sensitivity C reactive protein, homeostasis model assessment of insulin resistance, total cholesterol, and triglyceride, an increase in ALT was positively associated with the prevalence of low-risk and high-risk adenoma (P for trend = 0.029 and 0.027, respectively). The highest quartile group of ALT level showed a significantly increased prevalence in low-risk (odds ratio, 1.17) and high-risk adenoma (odds ratio, 1.48) groups compared with the lowest quartile group. This phenomenon persisted in the subgroup analysis in men, but not in women. CONCLUSIONS: In the asymptomatic healthy population, high serum ALT is significantly associated with the risk of CRA.

Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.

BACKGROUND: The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. OBJECTIVE: To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. DESIGN: Prospective cohort study. SETTING: Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. PARTICIPANTS: 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. MEASUREMENTS: Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. RESULTS: During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were -4.0 (95% CI, -7.8 to -0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. LIMITATION: Chronic kidney disease was identified by a single measurement at each visit. CONCLUSION: Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. PRIMARY FUNDING SOURCE: None.

Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study.

OBJECTIVES: Despite epidemiologic data, definitive evidence for the role of gallstones as a cause for gallbladder cancer is lacking. The goal of this study was to evaluate the association between gallstones, determined by ultrasound, and the risk of gallbladder cancer mortality in a large study of Korean men and women. In addition, the association between gallstones and cholecystectomy, and risk of hepatobiliary cancer mortality was investigated. METHODS: A cohort study was performed for 396,720 South Korean men and women who underwent a health checkup from 2002 to 2012. Hazard ratios for mortality outcomes were estimated using Cox-proportional hazards regression analysis. Vital status and cause of death assignment were based on linkage to the National Death Index of death certificate records. RESULTS: From a total of 2,158,906.2 person-years of follow-up (median follow-up of 5.4 years), we identified 224 deaths from hepatobiliary cancer, comprising 174 cases of liver/intrahepatic bile ducts cancer, 20 cases of gallbladder cancer, and 30 cases of biliary tract cancer. Gallstones were significantly associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic biliary cancer, and gallbladder cancer mortality. The multivariable-adjusted hazard ratios (95% confidence intervals) for hepatobiliary cancer, liver/intrahepatic biliary cancer, and gallbladder cancer mortality comparing subjects having gallstones with those without gallstone disease were 2.74 (1.83-4.10), 2.34 (1.45-3.77), and 7.35 (2.60-20.8), respectively. Cholecystectomy was not significantly associated with hepatobiliary cancer mortality. CONCLUSIONS: In this large cohort study, gallstones were associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic cancer, and gallbladder cancer mortality independent of potential confounders. Future studies with longer follow-up periods that include data on incident cancer cases should provide a more comprehensive view of the role of gallstones in cancer development.

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease.

OBJECTIVES: The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women. METHODS: A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound. RESULTS: During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status. CONCLUSIONS: In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD.

Sleep Duration, Sleep Quality, and Markers of Subclinical Arterial Disease in Healthy Men and Women.

OBJECTIVE: Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial-ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. APPROACH AND RESULTS: We conducted a cross-sectional study of adult men and women who underwent a health checkup examination, including assessment of sleep duration and quality and coupled with either CAC (n=29 203) or brachial-ankle PWV (n=18 106). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing sleep durations of ≤5, 6, 8, and ≥9 hours with 7 hours of sleep were 1.50 (1.17-1.93), 1.34 (1.10-1.63), 1.37 (0.99-1.89), and 1.72 (0.90-3.28), respectively (P for quadratic trend=0.002). The corresponding average differences in brachial-ankle PWV were 6.7 (0.75-12.6), 2.9 (-1.7 to 7.4), 10.5 (4.5-16.5), and 9.6 (-0.7 to 19.8) cm/s, respectively (P for quadratic trend=0.019). Poor subjective sleep quality was associated with CAC in women but not in men, whereas the association between poor subjective sleep quality and brachial-ankle PWV was stronger in men than in women. CONCLUSIONS: In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health.

Associations between amount of smoking and alcohol intake and risk of colorectal neoplasm.

BACKGROUND AND AIM: Although smoking and alcohol has been linked to an increased risk of colorectal neoplasm (CRN), large-scale studies to identify dose-dependent relationship between amount of smoking and alcohol consumption and risk of CRN are rare. We aimed to investigate the risk for CRN according to the amount of smoking and alcohol intake in a large sample of Korean adults. METHODS: A cross-sectional study was performed on 31,714 examinees aged ≥30 years undergoing their first colonoscopy as part of routine preventive health care between 2010 and 2011. Never smokers were compared with six groups of smokers according to smoking amount, and individuals with alcohol intake of ≤ 6.25 g ethanol per day were compared with three groups according to alcohol amount. RESULTS: In adjusted models, the risk of overall CRN increased with increasing amount of smoking (P for trend < 0.001). The adjusted odds ratios for overall CRN comparing never smokers with six smoker groups according to smoking amount (≤2.50, 2.51-5.60, 5.61-9.00, 9.01-13.00, 13.01-19.50, and ≥19.51 pack-years) were 1.02, 1.19, 1.35, 1.53, 1.63, and 2.03, respectively. In addition, the risk of both non-advanced and advanced CRN increased with increasing amount of smoking (both P for trend < 0.001). However, the amount of alcohol consumption was not correlated with the risk of CRN. CONCLUSIONS: The prevalence of CRN was associated with increasing amount of smoking in a dose-response manner, whereas it was not associated with the amount of alcohol consumption. Our study suggests that smoking amount as well as smoking status should be considered for CRN risk stratification.