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

Metabolically-Healthy Obesity and Coronary Artery Calcification

ObjectivesThe purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women.BackgroundThe risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial.MethodsWe conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5.ResultsMHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups.ConclusionsMHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health

Diffusely Increased ¹⁸F-FDG Uptake in the Thyroid Gland and Risk of Thyroid Dysfunction: A Cohort Study

The impact of incidentally identified diffuse thyroid FDG uptake on 18F-FDG PET/CT scan on the incidence of thyroid dysfunction remains unclear. We examined the association of diffuse thyroid FDG uptake with the development of thyroid dysfunction. This cohort study involved 39,098 Korean adults who were free of malignancy and thyroid disease at baseline and underwent regular health checkup examinations including an 18F-FDG whole body PET/CT scan, thyroid-stimulating hormone and free thyroxine. The participants were annually or biennially followed for up to 5 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Diffuse thyroid uptake was positively associated with increased risk of thyroid dysfunction in both the cross-sectional and cohort studies. During 104,261.4 person-years of follow-up, 102 incident hypothyroidism cases and 172 hyperthyroidism cases were identified. Multivariable-adjusted HR (95% CI) for incident hypothyroidism or hyperthyroidism comparing diffuse thyroid uptake to no uptake were 15.72 (9.23&#8211;26.77) and 7.38 (4.23&#8211;12.87), respectively. In this large cohort, incidentally, identified diffuse thyroid uptake on 18F-FDG PET/CT was associated with increased risk of both prevalent and incident thyroid dysfunction. Therefore, baseline and follow-up evaluations in individuals with diffuse thyroid uptake may help identify individuals with thyroid dysfunction

Menopausal Transition, Body Mass Index, and Prevalence of Mammographic Dense Breasts in Middle-Aged Women

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35&ndash;65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend &lt; 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96&ndash;1.00) in early transition, 0.89 (0.86&ndash;0.92) in late transition, and 0.55 (0.52&ndash;0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87&ndash;0.98), 0.83 (0.77&ndash;0.90) and 0.36 (0.31&ndash;0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women

Alcoholic and nonalcoholic fatty liver disease and incident hospitalization for liver and cardiovascular diseases

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

Nonalcoholic Fatty Liver Disease and Risk of Early-Onset Vasomotor Symptoms in Lean and Overweight Premenopausal Women

The role of nonalcoholic fatty liver disease (NAFLD) in vasomotor symptom (VMS) risk in premenopausal women is unknown. We examined the prevalence of early-onset VMSs according to NAFLD status in lean and overweight premenopausal women. This cross-sectional study included 4242 premenopausal Korean women (mean age 45.4 years). VMSs (hot flashes and night sweats) were assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. Hepatic steatosis was determined using liver ultrasound; lean was defined as a body mass index of &lt;23 kg/m(2). Participants were categorized into four groups: NAFLD-free lean (reference), NAFLD-free overweight, lean NAFLD, and overweight NAFLD. Compared with the reference, the multivariable-adjusted prevalence ratios (PRs) (95% confidence intervals (CIs)) for VMSs in NAFLD-free overweight, lean NAFLD, and overweight NAFLD were 1.22 (1.06-1.41), 1.38 (1.06-1.79), and 1.49 (1.28-1.73), respectively. For moderate-to-severe VMSs, the multivariable-adjusted PRs (95% CIs) comparing NAFLD-free overweight, lean NAFLD, and overweight NAFLD to the reference were 1.38 (1.10-1.74), 1.73 (1.16-2.57), and 1.74 (1.37-2.21), respectively. NAFLD, even lean NAFLD, was significantly associated with an increased risk of prevalent early-onset VMSs and their severe forms among premenopausal women. Further studies are needed to determine the longitudinal association between NAFLD and VMS risk.N

Low levels of alcohol consumption, obesity and development of fatty liver with and without evidence of advanced fibrosis

The effects of low level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations between 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). A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption &lt;30g/day (men) and &lt;20g/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 (aHR) and 95% confidence intervals (CI). 43,466 participants developed HS. 2,983 participants developed HS with an increase in FIB‐4 index (to intermediate or high scores). Comparing light‐drinkers and moderate‐drinkers with non‐drinkers, aHR (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 non‐drinkers, aHR (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 non‐obese and obese individuals although the association was stronger in non‐obese individuals (p for interaction by obesity=0.017). Conclusion 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

Automated comprehensive CT assessment of the risk of diabetes and associated cardiometabolic conditions

Background: CT, performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored.Purpose: to evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities.Materials and Methods: this retrospective study included Korean adults (age ≥25 years) who underwent health screening with 18F-fluorodeoxyglucose (18F-FDG) PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral/subcutaneous fat, muscle, bone density, liver fat, all normalized to height (m2) and aortic calcification. Predictive performance was assessed using area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively.Results: the cross-sectional and cohort analyses included 32166 (mean age, 44.6 years ±5.7 [SD], 28833 men) and 27298 adults (mean age, 43.8 years ±4.8 [SD], 24820 men), respectively. Diabetes prevalence and incidence were 6% at baseline and 9% during the 7.3-year median follow-up, respectively. The visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUCs of 0.70 (95%CI: 0.68, 0.71) in men and 0.82 (95%CI: 0.78, 0.85) in women, and Harrell C-indices of 0.68 (95%CI: 0.67, 0.69) in men and 0.82 (95%CI: 0.77, 0.86) in women, respectively. Combining the visceral fat, muscle area indices, liver fat fraction, and aortic calcification improved the predictive performance, yielding Harrell C-indices of 0.69 (95%CI: 0.68, 0.71) in men and 0.83 (95%CI: 0.78, 0.87) in women. Visceral fat index AUCs for identifying metabolic syndrome were 0.81 (95%CI: 3 0.80, 0.81) in men and 0.90 (95%CI: 0.88, 0.91) in women. Automated CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores &gt;100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95.Conclusion: automated comprehensive multiorgan CT analysis identified individuals at current and future high risk of diabetes and other cardiometabolic comorbidities<br/