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.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

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.

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.

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.

Age-stratified effects of coronary artery calcification on cardiovascular and non-cardiovascular mortality in Korean adults.

AIMS: The role of coronary artery calcium score (CACS) in predicting cardiovascular disease (CVD) and non-CVD mortality in young adults is unclear. We investigated the association of CACS with CVD and non-CVD mortality in young and older individuals. METHODS AND RESULTS: CVD-free Koreans (n = 160 821; mean age, 41.4 years; 73.2% young individuals aged <45 years) who underwent cardiac tomography estimation of CACS (69.7% one-time measurement), were followed-up for a median of 5.6 years. The vital status and cause of death were ascertained from the national death records. Sub-distribution hazard ratios (SHR) and 95% confidence intervals (CIs) for cause-specific mortality were estimated using the Fine and Gray proportional hazards models. Overall, a higher CACS was strongly associated with an increased risk of CVD mortality. Among young individuals, multivariable-adjusted SHR (95% CIs) for CVD mortality comparing a CACS of 1-100, 101-300, and >300 to 0 CACS were 5.67 (2.33-13.78), 22.34 (5.72-87.19), and 74.1 (18.98-239.3), respectively, and among older individuals, corresponding SHR were 1.51 (0.60-3.84), 8.57 (3.05-24.06), and 6.41 (1.98-20.74). The addition of CACS to Framingham risk score significantly but modestly improved risk prediction for CVD mortality in young individuals. Conversely, CACS was significantly associated with non-CVD mortality only in older individuals. CONCLUSIONS: Strong associations of CACS with CVD mortality, but not non-CVD mortality, were observed in young individuals, beginning in the low CACS category. Our findings reaffirm the need for early intervention for young adults even with low CACS to reduce CVD mortality.

Stages of menopause and abnormal lung function: a cross-sectional study of middle-aged women.

OBJECTIVE: Whether hormonal changes during menopausal transition postmenopause stages influence pulmonary function is not clearly understood. We evaluated the association between each stage of menopause and the prevalence of abnormal lung function in healthy middle-aged women. We hypothesized that the prevalence of abnormal lung function would increase from the late menopausal transition stage during menopausal transition postmenopause stages. METHODS: The study population included women 40 to 65 years of age who underwent comprehensive health screening examination at the Kangbuk Samsung Hospital Total Healthcare Centers from January 2015 to December 2017. Stages of menopause (premenopausal, early menopausal transition, late menopausal transition, and postmenopausal) were defined using the 2011 Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Abnormal lung function was defined based on spirometry as forced expiratory volume in 1 second/forced vital capacity less than70% or forced vital capacity less than 80% predicted. Prevalence ratios (PRs) for abnormal lung function by stages of menopause were estimated from logistic regression models adjusted for age, anthropometric measurements, lifestyle factors, medical history, lipid and inflammatory biomarkers, and reproductive factors. RESULTS: Among 43,822 participants, there were 4,615 participants (10.5%) with restrictive ventilatory disorder and 653 participants (1.5%) with obstructive ventilatory disorder. The fully adjusted PRs (95% confidence interval) for abnormal ventilatory disorder comparing early menopausal transition, late menopausal transition, and postmenopausal stage to premenopausal stage were 1.01 (0.94-1.08), 1.13 (1.03-1.22), and 1.10 (0.98-1.22), respectively. The fully adjusted PRs for restrictive ventilatory disorder comparing early menopausal transition, late menopausal transition, and postmenopausal stages to premenopausal stage were 1.02 (0.94-1.11), 1.18 (1.06-1.30), and 1.15 (1.00-1.31), respectively. There was, however, no clear association between stages of menopause and obstructive ventilatory disorder. CONCLUSIONS: In this large study of middle-aged women, the fully adjusted prevalence of abnormal lung function, particularly that of restrictive ventilatory disorder, was higher in women in late menopausal transition and menopausal stages compared to women in premenopausal stage.

Increased burden of coronary artery calcium from elevated blood pressure in low-risk young adults.

BACKGROUND AND AIMS: The relationship between blood pressure (BP) levels given in the new hypertension guidelines by the American College of Cardiology and the American Heart Association (ACC/AHA) and subclinical coronary atherosclerosis in low-risk young adults is unknown. We evaluated the association between the new BP categories and coronary artery calcium (CAC) in low-risk, young and middle-aged adults. METHODS: We performed a cross-sectional study of 96,166 Koreans who underwent a health examination including cardiac tomography estimation of CAC scores in 2012-2017. BP categories were defined according to the 2017 ACC/AHA guidelines. We used Poisson regression models with robust variance to calculate prevalence ratios (PRs) with 95% confidence intervals (CIs) for prevalent CAC >0. RESULTS: Overall, higher BP categories were associated with higher CAC scores in both young (aged 20-39) and middle-aged people (aged 40 years or more). After adjusting for possible confounders, including traditional cardiovascular disease (CVD) risk factors, the multivariable-adjusted PRs (95% CI) for prevalent CAC, comparing elevated BP and stage 1 and 2 hypertension to normal BP, were 1.27 (1.08-1.49), 1.45 (1.28-1.63), and 2.02 (1.67-2.43), respectively, among those aged 20-39 years and 1.25 (1.15-1.36), 1.29 (1.23-1.35), and 1.46 (1.36-1.57), respectively, among those aged ≥40 years. This association was also evident in those with a 10-year CVD risk of <10%. CONCLUSIONS: Higher BP categories were positively associated with prevalent CAC, and that association began in the elevated BP category, even in a young and low-risk population.

Cardiovascular Health Metrics in the Development and Regression of Nonalcoholic Fatty Liver Disease: A Cohort Study.

Cardiovascular Health (CVH) metrics scores are associated with cardiovascular disease but whether CVH scores are associated with nonalcoholic fatty liver disease (NAFLD) is uncertain. Our aim was to investigate associations between CVH scores and development or regression of NAFLD. A cohort study was performed in Korean adults who underwent a comprehensive health examination. The CVH metrics were defined according to the American Heart Association Life's Simple 7 metrics, ranging from 0 (all metrics considered unhealthy) to 7 (all metrics considered healthy). Fatty liver was diagnosed by ultrasound, and liver fibrosis assessed using NAFLD fibrosis score (NFS). Among 93,500 participants without NAFLD or fibrosis at baseline, 15,899 developed NAFLD, and 998 developed NAFLD plus intermediate/high NFS. Healthy CVH metrics were inversely associated with NAFLD and also NAFLD with fibrosis. In time-dependent models after updating the CVH score and confounders as time-varying covariate, the multivariable-adjusted hazard ratio (95% confidence intervals) for incident NAFLD plus intermediate/high NFS participants with CVH metrics score 2, 3, 4, 5, or 6-7 to those with score 0-1 were 0.86 (0.59-1.25), 0.51 (0.36-0.73), 0.44 (0.31-0.62), 0.20 (0.14-0.29) and 0.09 (0.05-0.14), respectively. Regression of NAFLD occurred in 9742/37,517 participants who had NAFLD at baseline with positive association with CVH metrics. Higher CVH scores were significantly associated with both (a) decreased incidence of NAFLD, and (b) regression of existing NAFLD. Promoting adherence to ideal CVH metrics can be expected to reduce the burden of NAFLD as well as cardiovascular disease.

Relationship of the Blood Pressure Categories, as Defined by the ACC/AHA 2017 Blood Pressure Guidelines, and the Risk of Development of Cardiovascular Disease in Low-Risk Young Adults: Insights From a Retrospective Cohort of Young Adults.

Background There are limited outcome studies of hypertension among young adults, especially using the new blood pressure ( BP ) categories from the American College of Cardiology and the American Heart Association. We examined associations between the new BP categories and the risk of incident cardiovascular disease ( CVD ) in low-risk and young adults. Methods and Results A cohort study was performed in 244 837 Korean adults (mean age, 39.0 years; SD , 8.9 years) who underwent a comprehensive health examination at Kangbuk Samsung Hospital from January 1, 2011, to December 31, 2016; they were followed up for incident CVD via linkage to the Health Insurance and Review Agency database until the end of 2016, with a median follow-up of 4.3 years. BP was categorized according to the new American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines. During 924 420.7 person-years, 1435 participants developed new-onset  CVD (incidence rate of 16.0 per 104 person-years). The multivariable-adjusted hazard ratios (95% CI s ) for CVD comparing elevated BP , stage 1 hypertension, stage 2 hypertension, treated and strictly controlled (systolic BP /diastolic BP <130/80 mm Hg with antihypertensive use), treated and controlled (systolic BP 130-139 and diastolic BP 80 to 89 mm Hg with antihypertensive use), treated uncontrolled, and untreated hypertension to normal BP were 1.37 (1.11-1.68), 1.45 (1.26-1.68), 2.12 (1.74-2.58), 1.41 (1.12-1.78), 1.97 (1.52-2.56), 2.29 (1.56-3.37) and 1.93 (1.53-2.45), respectively. Conclusions In this large cohort of low-risk and young adults, all categories of higher BP were independently associated with an increased risk of CVD compared with normal BP , underscoring the importance of BP management even in these low-risk populations.

Delphi Survey for Designing a Intervention Research Study on Childhood Obesity Prevention.

BACKGROUND: The prevalence of childhood obesity in South Korea has increased owing to economic improvement and the prevailing Westernized dietary pattern. As the incidence of chronic diseases caused by obesity is also expected to increase, effective interventions to prevent childhood obesity are needed. Therefore, we conducted a Delphi study to determine the priorities of a potential intervention research on childhood obesity prevention and its adequacy and feasibility. METHODS: The two-round Delphi technique was used with a panel of 10 childhood obesity experts. The panelists were asked to rate "priority populations," "methods of intervention," "measurement of outcomes," "future intervention settings," and "duration of intervention" by using a structured questionnaire. Finally, a portfolio analysis was performed with the adequacy and feasibility indexes as the two axes. RESULTS: For priority populations, the panel favored "elementary," "preschool," and "middle and high school" students in this order. Regarding intervention settings, the panelists assigned high adequacy and feasibility to "childcare centers" and "home" for preschool children, "school" and "home" for elementary school children, and "school" for adolescents in middle and high school. As the age of the target population increased, the panelists scored increasing numbers of anthropometric, clinical, and intermediate outcomes as highly adequate and feasible for assessing the effectiveness of the intervention. CONCLUSION: According to the results of the Delphi survey, the highest-priority population for the research on childhood obesity prevention was that of elementary school students. Various settings, methods, outcome measures, and durations for the different age groups were also suggested.

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.