Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease.

OBJECTIVE: To examine the associations between the allergic triad (asthma, allergic rhinitis, atopic dermatitis) and risk of dementia. METHODS: Participants comprised 6,785,948 adults aged ≥40 years who participated in a national health examination in 2009 without any history of dementia before baseline. From 2009 to 2017, we prospectively investigated the associations between physician-diagnosed allergic diseases and risk of incident dementia (all-cause, Alzheimer's disease [AD], vascular dementia [VaD]) ascertained using national health insurance claims data. RESULTS: During 8.1 years of follow-up, 260,705 dementia cases (195,739 AD, 32,789 VaD) were identified. Allergic diseases were positively associated with dementia risk. Compared with individuals without allergic diseases, multivariable hazard ratios (HRs) of all-cause dementia were 1.20 (95% confidence interval [CI] 1.19-1.22) in those with asthma, 1.10 (95% CI 1.09-1.12) with allergic rhinitis, 1.16 (95% CI 1.11-1.21) with atopic dermatitis, and 1.13 (95% CI 1.12-1.14) with any of these allergies. Similarly, individuals with any of the allergic triad had a higher risk of AD (HR 1.16, 95% CI 1.14-1.17) and VaD (HR 1.04; 95% CI 1.01-1.06) than those without any allergic disease. As the number of comorbid allergic diseases increased, the risk of dementia increased linearly (Ptrend ≤ 0.002). Compared with individuals without allergies, those with all three allergic diseases had substantially increased risk of all-cause dementia (HR 1.54, 95% CI 1.35-1.75), AD (HR 1.46; 95% CI 1.25-1.70), and VaD (HR 1.99, 95% CI 1.44-2.75). INTERPRETATION: Asthma, allergic rhinitis, and atopic dermatitis were significantly associated with increased risk of all-cause dementia and subtypes, with dose-effect relationships with the severity of allergic diseases. ANN NEUROL 2023;93:384-397.

Interaction between visceral adiposity and ambient air pollution on LDL cholesterol level in Korean adults.

BACKGROUND: Although previous reports have found that obesity intensifies the negative impact of long-term air pollution exposure on the low-density lipoprotein-cholesterol (LDL-C) level, few studies have examined whether the type of abdominal adiposity, such as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and the visceral-to-subcutaneous fat ratio (VSR) affects this relationship. We investigated the association between ambient air pollution and LDL-C in Korean adults and identified whether this association is different by the type of abdominal adiposity. METHODS: A total of 2737 adults were included. Abdominal fat areas were quantified by computed tomography, and the annual average concentration of air pollutants was included in this analysis. RESULTS: In the total sample, none of the air pollutants was associated with LDL-C level in either the crude or adjusted model (all p > 0.05). The association was not significant even in subgroups stratified according to the obesity status defined by body mass index, and no interaction on the LDL-C level was also found (all pint > 0.05). In the subgroup analysis stratified according to adiposity level, particulate matter with an aerodynamic diameter of ≤10 µm (PM10) [ß (SE) = 3.58 (1.59); p = 0.0245] and sulfur dioxide (SO2) exposures [ß (SE) = 2.71 (1.27); p = 0.0330] in the high-VAT group were associated with the increased LDL-C level. Interactions on LDL-C level were also found between VAT level and ambient air pollutants such as PM10 and SO2 (both pint < 0.05). In the analysis of the VSR, PM10 exposure showed a significant interaction on LDL level (pint = 0.0032). However, the strength of these associations was not significant across all SAT subgroup (all pint > 0.05). CONCLUSIONS: In conclusion, we found that association between air pollution exposure and LDL-C level is different by abdominal fat distribution.

Explaining the Rationale of Deep Learning Glaucoma Decisions with Adversarial Examples.

PURPOSE: To illustrate what is inside the so-called black box of deep learning models (DLMs) so that clinicians can have greater confidence in the conclusions of artificial intelligence by evaluating adversarial explanation on its ability to explain the rationale of DLM decisions for glaucoma and glaucoma-related findings. Adversarial explanation generates adversarial examples (AEs), or images that have been changed to gain or lose pathologic characteristic-specific traits, to explain the DLM's rationale. DESIGN: Evaluation of explanation methods for DLMs. PARTICIPANTS: Health screening participants (n = 1653) at the Seoul National University Hospital Health Promotion Center, Seoul, Republic of Korea. METHODS: We trained DLMs for referable glaucoma (RG), increased cup-to-disc ratio (ICDR), disc rim narrowing (DRN), and retinal nerve fiber layer defect (RNFLD) using 6430 retinal fundus images. Surveys consisting of explanations using AE and gradient-weighted class activation mapping (GradCAM), a conventional heatmap-based explanation method, were generated for 400 pathologic and healthy patient eyes. For each method, board-trained glaucoma specialists rated location explainability, the ability to pinpoint decision-relevant areas in the image, and rationale explainability, the ability to inform the user on the model's reasoning for the decision based on pathologic features. Scores were compared by paired Wilcoxon signed-rank test. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivities, and specificities of DLMs; visualization of clinical pathologic changes of AEs; and survey scores for locational and rationale explainability. RESULTS: The AUCs were 0.90, 0.99, 0.95, and 0.79 and sensitivities were 0.79, 1.00, 0.82, and 0.55 at 0.90 specificity for RG, ICDR, DRN, and RNFLD DLMs, respectively. Generated AEs showed valid clinical feature changes, and survey results for location explainability were 3.94 ± 1.33 and 2.55 ± 1.24 using AEs and GradCAMs, respectively, of a possible maximum score of 5 points. The scores for rationale explainability were 3.97 ± 1.31 and 2.10 ± 1.25 for AEs and GradCAM, respectively. Adversarial example provided significantly better explainability than GradCAM. CONCLUSIONS: Adversarial explanation increased the explainability over GradCAM, a conventional heatmap-based explanation method. Adversarial explanation may help medical professionals understand more clearly the rationale of DLMs when using them for clinical decisions.

Association of early-onset diabetes, prediabetes and early glycaemic recovery with the risk of all-cause and cardiovascular mortality.

AIMS/HYPOTHESIS: The increasing incidence of diabetes among young adults is a disease burden; however, the effects of early-onset diabetes, prediabetes and glycaemic recovery on CVD or mortality remain unclear. We aimed to investigate the association of these factors with 10 year all-cause mortality, CVD mortality and CVD incidence in Korean young adults. METHODS: This large and longitudinal cohort study included data from the Korean National Health Insurance Service-National Health Information Database; 2,502,375 young adults aged 20-39 years without diabetes mellitus and CVD at baseline were included. Glycaemic status was measured twice, first in 2002-2003 and second in 2004-2005. Changes in fasting glucose levels were evaluated according to fasting glucose status: normal fasting glucose (NFG; <5.5 mmol/l), impaired fasting glucose (IFG; 5.5-6.9 mmol/l), and diabetic fasting glucose (DFG; ≥7.0 mmol/l). Primary outcomes were all-cause and CVD mortality risk. The secondary outcome was incidence of CVD, including acute myocardial infarction and stroke. All outcomes arose from the 10 year follow-up period 1 Jan 2006 to 31 December 2015. RESULTS: Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had increased all-cause mortality (HR [95% CI] 1.60 [1.44, 1.78] and 1.13 [1.09, 1.18], respectively) and CVD incidence (1.13 [1.05, 1.23] and 1.04 [1.01, 1.07], respectively). In those with DFG at baseline, early recovery to NFG and IFG was associated with decreased all-cause mortality (0.57 [0.46, 0.70] and 0.65 [0.53, 0.81], respectively) and CVD incidence (0.70 [0.60, 0.81] and 0.78 [0.66, 0.91], respectively). Among patients with IFG at baseline, early recovery to NFG was associated with decreased CVD mortality (0.74 [0.59, 0.93]). CONCLUSIONS/INTERPRETATION: Early-onset diabetes or prediabetes increased CVD risks and all-cause mortality after the 10 year follow-up. Furthermore, recovery of hyperglycaemia could reduce the subsequent 10 year risk for CVD incidence and all-cause mortality. Graphical abstract.

Long-term Mortality Risks Among Living Kidney Donors in Korea.

RATIONALE & OBJECTIVE: Living kidney donors may have a higher risk for death and kidney failure. This study aimed to investigate the long-term mortality experience of living kidney donors compared with members of the general public in Korea who underwent voluntary health examinations. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We first calculated standardized mortality ratios for 1,292 Korean living kidney donors who underwent donor nephrectomy between 1982 and 2016 and 72,286 individuals who underwent voluntary health examinations between 1995 and 2016. Next we compared survival between the 1,292 living kidney donors and a subgroup of the health examination population (n=33,805) who had no evident contraindications to living kidney donation at the time of their examinations. Last, a matched comparator group was created from the health examination population without apparent contraindication to donation by matching 4,387 of them to donors (n=1,237) on age, sex, body mass index, estimated glomerular filtration rate, urine dipstick albumin excretion, previously diagnosed hypertension and diabetes, and era. EXPOSURES: Donor nephrectomy. OUTCOMES: All-cause mortality and other clinical outcomes after kidney donation. ANALYTICAL APPROACH: First, standardized mortality ratios were calculated separately for living kidney donors and the health examination population standardized to the general population. Second, we used Cox regression analysis to compare mortality between living kidney donors versus the subgroup of the health examination population without evident donation contraindications. Third, we used Cox regression analysis to compare mortality between living kidney donors and matched comparators from the health examination population without apparent contraindication to donation. RESULTS: The living kidney donors and health examination population had excellent survival rates compared with the general population. 52 (4.0%) of 1,292 kidney donors died during a mean follow-up of 12.3±8.1 years and 1,072 (3.2%) of 33,805 in the health examiner subgroup without donation contraindications died during a mean follow-up of 11.4±6.1 years. Donor nephrectomy did not elevate the hazard for mortality after multivariable adjustment in kidney donors and the 33,805 comparators (adjusted HR, 1.01; 95% CI, 0.71-1.44; P=0.9). Moreover, living donors showed a similar mortality rate compared with the group of matched healthy comparators. LIMITATIONS: Donors from a single transplantation center. Residual confounding owing to the observational study design. CONCLUSIONS: Kidney donors experienced long-term rates of death comparable to nondonor comparators with similar health status.

Association of anemia with mobility capacity in older adults: a Korean nationwide population-based cross-sectional study.

BACKGROUND: Over 10% of adults aged ≥65 years have anemia, as defined by the World Health Organization (WHO). As the timed up and go (TUG) test is one of the most widely used tests of mobility, this study investigated whether anemia was associated with mobility capacity assessed using the TUG test in older adults. METHODS: Subjects belonging to the Korean National Health Insurance Service-National Health Screening Cohort of the National Health Information Database were reviewed. Subjects were included if they had completed the TUG test as part of the National Screening Program for Transitional Ages in Korea. An abnormal TUG test result was defined as a time of ≥10 s and anemia was defined according to the WHO criteria as a hemoglobin (Hb) concentration of < 13.0 g/dL in men and < 12.0 g/dL in women. The association between anemia and TUG test results was evaluated using four multiple logistic regression models with different levels of adjustment. Stratified analysis according to risk factors was performed. RESULTS: The 81,473 subjects included 41,063 (50.4%) women and 40,410 (49.6%) men. Mean TUG time was 8.44 ± 3.08 s, and abnormal TUG test results were observed in 22,138 (27.2%) subjects. Mean Hb concentration was 13.72 ± 1.41 g/dL, and 10,237 (12.6%) subjects had anemia. U-shaped associations between Hb concentration and TUG test results were observed in both sexes. Subjects with anemia were 19% more likely to have abnormal TUG test results, according to the fully adjusted model (adjusted odds ratio: 1.192, 95% confidence interval: 1.137-1.247). Similar results were observed for both sexes. Stratified analysis showed that subjects with anemia were more likely to have abnormal TUG test results regardless of risk factors. CONCLUSIONS: Individuals with anemia are more likely to have abnormal TUG test results, regardless of risk factors, than individuals without anemia. U-shaped relationships between Hb concentrations and TUG test results were observed in both sexes, although the optimal Hb concentration differed between men and women.

Association of timed up and go test outcomes with future incidence of cardiovascular disease and mortality in adults aged 66 years: Korean national representative longitudinal study over 5.7 years.

BACKGROUND: The timed up and go test (TUG) is one of the most widely used tests of mobility. We aimed to examine whether the TUG is associated with cardiovascular (CV) events, CV mortality, and all-cause mortality. METHODS: Subjects in the senior cohort database of the Korean National Health Insurance Service (2002-2013) who completed the TUG as part of the National Screening Program for Transitional Ages (NSPTA) during 2007-2008 were identified. An abnormal TUG result was defined as a time ≥ 10 s. Cox proportional hazard models were used to assess the associations between TUG results and CV events, CV mortality, and all-cause mortality. RESULTS: The mean follow-up period was 5.7 years. Incidence rates of CV events in the normal and abnormal TUG groups were 7.93 and 8.98 per 1000 person-years, while CV mortality rates were 0.96 and 1.51 per 1000 person-years, respectively. In a fully adjusted model, we found that abnormal TUG results were not associated with the incidences of CV events and CV mortality. However, abnormal TUG results (≥10 s) resulted in a 2.9-fold increase in CV mortality in women (adjusted hazard ratio 2.90, 95% confidence interval 1.15-7.30). Further, participants lacking certain CV risk factors, such as current cigarette smoking, obesity, or diabetes, had a higher CV mortality rate when TUG results were abnormal. CONCLUSIONS: Abnormal TUG results in subjects aged 66 years were associated with future CV mortality in women and in subjects without obesity, diabetes, or cigarette smoking. In patient with mobility impairment, physicians should consider CV disease risk, especially in women.

Increased Risk of Osteoporotic Fracture in Postgastrectomy Gastric Cancer Survivors Compared With Matched Controls: A Nationwide Cohort Study in Korea.

OBJECTIVES: Gastrectomy can lead to bone loss. Previous studies have suggested that there is an increased risk of fracture in gastric cancer survivors. However, these studies were performed without proper control groups. Therefore, we used Korean national health insurance data to compare the fracture risk in gastric cancer survivors who received gastrectomy to that of the general population. METHODS: A total of 133,179 gastric cancer survivors were included and matched to noncancer controls using 1:1 propensity score matching. Cox proportional hazards regression analysis was used to determine the relative risk of fracture between the gastric cancer survivors and matched controls. We also examined the factors associated with fracture in gastric cancer survivors. RESULTS: Compared with the matched controls, gastric cancer survivors had an elevated risk of osteoporotic fracture (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.53-1.70), which was most prominent in patients who underwent total gastrectomy (HR 2.18, 95% CI 1.96-2.44) and adjuvant chemotherapy (HR 2.01, 95% CI 1.81-2.23). In multivariate analysis, anemia was significantly associated with increased fracture risk (aHR 1.34, 95% CI 1.13-1.59), while decrease in weight >5% was not (aHR 1.06, 95% CI 0.89-1.25). DISCUSSION: Gastric cancer survivors who underwent gastrectomy had an increased osteoporotic fracture risk than did matched controls. Total gastrectomy, adjuvant chemotherapy, and anemia were associated with an even higher risk in these patients. Additional studies are needed to establish optimal strategies, such as screening for osteoporosis and preventive interventions, that will reduce fracture risk in this population.

Risk of Coronary Heart Disease and Ischemic Stroke Incidence in Gastric Cancer Survivors: A Nationwide Study in Korea.

BACKGROUND: Small studies suggest improvement of cardiovascular risk profiles and reduced cardiovascular mortality after gastrectomy for gastric cancer. In our study using national health insurance data, we investigated coronary heart disease (CHD) and ischemic stroke incidence among gastric cancer patients who received gastrectomy compared with general population controls. METHODS: A total of 98,936 gastric cancer patients were included in the study and matched to non-cancer controls via 1:1 propensity score matching. Competing risk regression analysis was used to determine the relative risk of CHD and ischemic stroke, with cancer mortality as the competing risk. Changes in cardiovascular risk profile before and after gastrectomy were tested, and factors associated with CHD or ischemic stroke incidence among gastric cancer patients were analyzed. RESULTS: Compared with the matched controls, gastric cancer patients who received gastrectomy were shown to have a decreased risk for both CHD (subdistribution hazard ratio [SHR] 0.60, 95% confidence interval [CI] 0.57-0.63) and ischemic stroke (SHR 0.72, 95% CI 0.69-0.75). Decreases in body mass index (BMI), blood pressure, blood sugar, and lipid and hemoglobin levels were marked after gastrectomy. Among gastric cancer patients, those who lost > 5% of their body weight were at lower risk of developing CHD (SHR 0.82, 95% CI 0.71-0.96) and ischemic stroke (SHR 0.85, 95% CI 0.75-0.98). CONCLUSIONS: CHD and ischemic stroke risk decreased after gastrectomy. The amount of weight loss and accompanying metabolic changes seemed to mediate the reduction of such risk. Reassessment of cardiovascular risk factors after gastrectomy and consideration of cardiovascular risk in the selection of treatment modality are suggested.

The effect of change in fasting glucose on the risk of myocardial infarction, stroke, and all-cause mortality: a nationwide cohort study.

BACKGROUND: The effect of change in blood glucose levels on the risk of cardiovascular disease among individuals without diabetes is currently unclear. We aimed to examine the association of change in fasting serum glucose with incident cardiovascular disease and all-cause mortality among representative large population. METHODS: We analyzed the data from retrospective cohort of Korean National Health Insurance Service. In total, 260,487 Korean adults aged over 40 years, without diabetes mellitus and cardiovascular disease at baseline measured change in fasting serum glucose according to the criteria of impaired and diabetic fasting glucose status: normal fasting glucose (NFG, fasting glucose: < 100 mg/dL), impaired fasting glucose (IFG, fasting glucose: 100.0-125.9 mg/dL), and diabetic fasting glucose (DFG, fasting glucose: ≥ 126.0 mg/dL). Compared to the persistently unchanged group (i.e. NFG to NFG or IFG to IFG), Cox proportional hazards regression analyses were performed in the changed group to obtain the hazards ratio (HR) with 95% confidence interval (CI) for the subsequent median 8-year myocardial infarction, stroke, and all-cause mortality. RESULTS: Compared to individuals with persistent NFG (i.e., NFG to NFG), individuals who shifted from NFG to DFG had an increased risk of stroke (HR [95% CI]: 1.19 [1.02-1.38]) and individuals who shifted from NFG to IFG or DFG had increased risks of all-cause mortality (HR [95% CI]: 1.08 [1.02-1.14] for NFG to IFG and 1.56 [1.39-1.75] for NFG to DFG). Compared to individuals with persistent IFG, individuals who shifted from IFG to DFG had an increased risk of MI and all-cause mortality (HR [95% CI]: 1.65 [1.20-2.27] and 1.16 [1.02-1.33], respectively). CONCLUSIONS: Increasing fasting glucose in non-diabetic population is associated with risks of the MI, stroke, and all-cause mortality, which is more rapid, more severe.

Trends and Cut-Point Changes in Obesity Parameters by Age Groups Considering Metabolic Syndrome.

BACKGROUND: Non-communicable diseases (NCDs) are an important issue worldwide. Obesity has a close relationship with NCDs. Various age-related changes should be considered when evaluating obesity. METHODS: National representative cohort data from the National Health Insurance Service National Sample Cohort from 2012 to 2013 were used. Sex-specific and age group-specific (10-year intervals) means for body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR) were calculated. Optimal cut-points for obesity parameters were defined as the value predicting two or more components of metabolic syndrome (except WC). RESULTS: The mean value and optimal cut-point for BMI decreased with age for men. The mean BMI value for women increased with age, but optimal cut-points showed no remarkable difference. The mean WC of men increased with age, but the optimal cut-points were similar for age groups. For women, the mean value and optimal cut-point for WC increased with age. Regarding WtHR, the mean value and optimal cut-point increased with age for men and women. Differences across age groups were larger for women. CONCLUSION: The mean values of the obesity indices and the optimal cut-points were changed according to age groups. This study supports the necessity of applying age group-specific cut-points for the various obesity parameters.

Association of Blood Pressure Classification in Korean Young Adults According to the 2017 American College of Cardiology/American Heart Association Guidelines With Subsequent Cardiovascular Disease Events.

Importance: Among young adults, the association of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) High Blood Pressure Clinical Practice Guidelines with risk of cardiovascular disease (CVD) later in life is uncertain. Objective: To determine the association of blood pressure categories before age 40 years with risk of CVD later in life. Design, Setting, and Participants: This population-based cohort study from the Korean National Health Insurance Service consisted of 2 488 101 adults aged 20 through 39 years with blood pressure measurements taken twice from 2002 through 2005. Starting from January 1, 2006, participants were followed up until the date of CVD diagnosis, death, or December 31, 2015. Exposures: Participants were categorized by blood pressure readings: normal (systolic, <120 mm Hg; diastolic, <80 mm Hg), elevated (sytolic, 120-129 mm Hg; diastolic, <80 mm Hg), stage 1 hypertension (systolic, 130-139 mm Hg; diastolic, 80-89 mm Hg), and stage 2 hypertension (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg). Main Outcomes and Measures: The primary outcome was CVD defined as 2 or more days of hospitalization due to CVD or death due to CVD. The secondary outcomes were coronary heart disease (CHD) and stroke. Results: The study population consisted of 2 488 101 participants (median age, 31 years [interquartile range, 27-36 years], 789 870 women [31.7%]). A total of 44 813 CVD events were observed during a median follow-up duration of 10 years. Men with baseline stage 1 hypertension compared with those with normal blood pressure had higher risk of CVD (incidence, 215 vs 164 per 100 000 person-years; difference, 51 per 100 000 person-years [95% CI, 48-55]; adjusted hazard ratio [HR], 1.25 [95% CI, 1.21-1.28]), CHD (incidence, 134 vs 103 per 100 000 person-years; difference, 31 per 100 000 person-years [95% CI, 28-33]; adjusted HR, 1.23 [95% CI, 1.19-1.27]), and stroke (incidence, 90 vs 67 per 100 000 person-years; difference, 23 per 100 000 person-years [95% CI, 21-26]; adjusted HR, 1.30 [95% CI, 1.25-1.36]). Women with baseline stage 1 hypertension compared with those with normal blood pressure had increased risk of CVD (incidence, 131 vs 91 per 100 000 person-years; difference, 40 per 100 000 person-years [95% CI, 35-45]; adjusted HR, 1.27 [95% CI, 1.21-1.34]), CHD (incidence, 56 vs 42 per 100 000 person-years; difference, 14 per 100 000 person-years [95% CI, 11-18]; adjusted HR, 1.16 [95% CI, 1.08-1.25]), and stroke (incidence, 79 vs 51 per 100 000 person-years; difference, 28 per 100 000 person-years [95% CI, 24-32]; adjusted HR [1.37, 95% CI, 1.29-1.46]). Results for state 2 hypertension were consistent. Conclusions and Relevance: Among Korean young adults, stage 1 and stage 2 hypertension, compared with normal blood pressure, were associated with increased risk of subsequent cardiovascular disease events. Young adults with hypertension, defined by the 2017 ACC/AHA criteria, may be at increased risk of cardiovascular disease.

Is Vitamin D an Independent Risk Factor of Nonalcoholic Fatty Liver Disease?: a Cross-Sectional Study of the Healthy Population.

The association between vitamin D levels and nonalcoholic fatty liver disease (NAFLD) has been recognized. However, few studies showed independent associations between vitamin D deficiency and NAFLD after a sex-related adjustment for metabolic factors. We aimed to study whether vitamin D deficiency is an independent risk factor of NAFLD even after controlling for metabolic syndrome and visceral fat in both sexes. In this cross-sectional study, 7,514 Korean adults (5,278 men, 2,236 women) participated in a health check-up program. They underwent blood tests, abdominal computed tomography (CT) of the visceral fat area, and ultrasonography for NAFLD screening. Multiple logistic regression analysis was used to investigate the association of vitamin D deficiency with NAFLD according to the sex differences. Vitamin D deficiency is associated with NAFLD. The adjusted odds ratio (aOR) for NAFLD increased sequentially with decreasing vitamin D level, even after adjusting for metabolic syndrome and visceral fat. The subjects in the vitamin D sufficiency group (20-30 ng/mL) had an aOR for NAFLD of 1.18 (95% CI, 1.00-1.39), whereas the deficiency group (< 20 ng/mL) had an aOR of 1.29 (95% CI, 1.10-1.52). However, we have detected a significant sex-related interaction when analyzing the results. A significant relationship between vitamin D deficiency and NAFLD was found in men (aOR, 1.33; 95% CI, 1.11-1.60) but not in women.

Insulin Resistance Is a Risk Factor for Silent Lacunar Infarction.

BACKGROUND AND PURPOSE: This study aims to investigate the association between insulin resistance (IR) and silent lacunar infarction (SLI) in healthy adults. METHODS: We recruited 2326 healthy Korean adults who took health checkups, including a brain magnetic resonance imaging. SLI was defined as an infarction measuring 0.3 to 1.5 cm in diameter that was localized in the territory of perforating branches of cerebral arteries, as seen in the brain magnetic resonance imaging. The homeostasis model assessment-estimated insulin resistance index was used for IR estimation, and the cutoff value for its diagnosis for Koreans was 2.56. RESULTS: The mean age of the study population was 56.2 years (range, 40-79 years), and 1279 subjects (55.0%) were male. The prevalence of SLI and IR was 8.1% and 18.1%, respectively. In multivariate logistic analysis, after adjusting for traditional SLI-associated risk factors, IR was positively associated with the prevalence of SLI (adjusted odds ratio, 1.69; 95% confidence interval, 1.16-2.46). The proportion of subjects with multiple SLI lesions (≥2) was also higher in the IR (+) group than that in the IR (-) group (4.3% versus 1.7%; P<0.001). In ordered logistic regression, IR was positively associated with an increase in SLI severity (adjusted odds ratio, 1.76; 95% confidence interval, 1.21-2.56). CONCLUSIONS: IR is an independent risk factor of SLI presence and its severity in Koreans. Whether improvement of IR might prevent SLI occurrence needs to be addressed by clinical trials.

High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers.

UNLABELLED: Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7≤ FIB-4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50-13.92) and subjects with FIB-4 ≥2.4 showed an aHR of 21.34 (95% CI: 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index: 0.701 vs. 0.831; P = 0.001). FIB-4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C-index: 0.775 vs. 0.701; P = 0.040). CONCLUSION: High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB-4 may play a valuable role in HCC screening among HBsAg carriers.

Visceral Fat Is an Independent Predictor of Cerebral Microbleeds in Neurologically Healthy People.

BACKGROUND: Obesity has a significant contribution to the risk of intracerebral hemorrhage (ICH). However, little is known about the association between central obesity and the presence of cerebral microbleeds (CMBs), a precursor of ICH. We sought to assess whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are associated with the presence of CMB. METHODS: We conducted a cross-sectional study of 1,737 neurologically healthy people (mean age 55.9 ± 9.1; 790 men), who underwent brain MRI and abdominal CT. Risk factors, anthropometric parameters and clinical information were obtained. CMBs were evaluated through T2*-weighted gradient-recalled echo MRI. The cross-sectional surface areas of the abdominal fat compartments were calculated. Study subjects were stratified into quartiles according to the distribution of VAT/SAT ratio. RESULTS: A total of 75 (4.3%) subjects were found to have CMBs. Subjects with a greater quartile of VAT/SAT ratio were more likely to have higher numbers of CMBs (0 to ≥2; p = 0.001). In multivariable analysis, age and history of hypertension were associated with the presence of CMB (OR 1.09, 95% CI 1.06-1.13, p < 0.001; OR 1.70, 95% CI 1.01-2.84, p = 0.046, respectively). A dose-response relationship was observed between the extent of VAT/SAT quartile and CMB: compared to the lowest VAT/SAT quartile, OR 2.14 (95% CI 0.86-5.35) for second VAT/SAT quartile; OR 2.26 (95% CI 0.86-5.92) for third VAT/SAT quartile; and OR 2.91 (95% CI 1.04-8.12) for the highest VAT/SAT quartile (p for trend 0.03). CONCLUSION: In our study, higher VAT/SAT ratios were found to be independent predictors of CMBs in neurologically healthy people. This finding strengthens previous data, suggesting that visceral fat distribution is an important contributor to cerebral small vessel disease.

Mean corpuscular volume levels and all-cause and liver cancer mortality.

BACKGROUND: An elevated mean corpuscular volume (MCV) is associated with aging, nutrition, alcohol abuse and more, and it is known as a survival predictor in chronically ill patients. The aim of this study was to investigate the association between MCV levels and mortality from all-causes, cancer and site-specific cancer in a non-anemic healthy population. METHODS: A total of 36,260 participants aged 40 years or older who underwent routine check-ups at Seoul National University Hospital Health Promotion Center between 1995 and 2008 were followed-up for mortality until December 31, 2008, retrospectively. RESULTS: During an average follow-up of 8.0 years, 1107 deaths including 547 cancer deaths were observed. The adjusted hazard ratios (aHRs) of the subjects with the highest quartile of MCV ≥95.8 fL in men and MCV ≥94.2 fL in women for all-cause and cancer mortality were 1.44 [95% confidence interval (CI), 1.15-1.80] and 1.51 (95% CI, 1.10-2.07) for men and 1.55 (95% CI, 1.08-2.22) and 1.25 (95% CI, 0.74-2.11) for women, respectively, compared with those in the reference group (90.5 fL≤MC <93.0 fL in men and 89.2 fL≤MCV<91.6 fL in women). Elevated MCV level was related to an increased risk of liver cancer mortality in men (aHR, 3.55; 95% CI, 1.75-7.21). CONCLUSIONS: This study suggests that the elevated MCV level in non-anemic cancer-free individuals was associated with increased all-cause mortality in both men and women, and with cancer mortality, in particular liver cancer mortality in men. Future prospective studies are required to consolidate our findings.

Network analysis of human diseases using Korean nationwide claims data.

OBJECTIVE: To investigate disease-disease associations by conducting a network analysis using Korean nationwide claims data. METHODS: We used the claims data from the Health Insurance Review and Assessment Service-National Patient Sample for the year 2011. Among the 2049 disease codes in the claims data, 1154 specific disease codes were used and combined into 795 representative disease codes. We analyzed for 381 representative codes, which had a prevalence of >0.1%. For disease code pairs of a combination of 381 representative disease codes, P values were calculated by using the χ(2) test and the degrees of associations were expressed as odds ratios (ORs). RESULTS: For 5515 (7.62%) statistically significant disease-disease associations with a large effect size (OR>5), we constructed a human disease network consisting of 369 nodes and 5515 edges. The human disease network shows the distribution of diseases in the disease network and the relationships between diseases or disease groups, demonstrating that diseases are associated with each other, forming a complex disease network. We reviewed 5515 disease-disease associations and classified them according to underlying mechanisms. Several disease-disease associations were identified, but the evidence of these associations is not sufficient and the mechanisms underlying these associations have not been clarified yet. Further research studies are needed to investigate these associations and their underlying mechanisms. CONCLUSION: Human disease network analysis using claims data enriches the understanding of human diseases and provides new insights into disease-disease associations that can be useful in future research.

Prediction of future hepatocellular carcinoma incidence in moderate to heavy alcohol drinkers with the FIB-4 liver fibrosis index.

BACKGROUND: Although heavy alcoholics are at heightened risk for hepatocellular carcinoma (HCC), there are no guidelines that recommend HCC screening for heavy alcoholics. This study investigated FIB-4, a noninvasive and easily applicable liver fibrosis index, as a risk factor for HCC incidence among alcohol drinkers without viral hepatitis. METHODS: This retrospective cohort study included 6661 generally healthy adults who were 30 years old or older, did not have chronic viral hepatitis, and visited Seoul National University Hospital for a general, routine health evaluation. The future HCC incidence was determined from National Health Insurance medical service claims data (median follow-up, 6.2 years). RESULTS: With adjustments for age, sex, body mass index, smoking, and alcohol, compared with subjects with FIB-4 values less 1.00, subjects with FIB-4 values greater than or equal to 1.75 and less than 2.10 and subjects with FIB-4 values greater than or equal to 2.10 had adjusted hazard ratios (aHRs) of 5.18 (95% confidence interval [CI], 1.12-24.00) and 13.63 (95% CI, 3.77-49.33), respectively, for HCC incidence. This was heightened in subjects who drank more 30 g of alcohol per day: the aHRs were 8.39 (95% CI, 1.28-54.87) and 16.58 (95% CI, 3.87-71.04), respectively. FIB-4 was shown to have a higher predictive value for HCC incidence than ultrasonographically detected liver cirrhosis (C-index, 0.665 vs 0.527; P = .044). CONCLUSIONS: High FIB-4 is a risk factor with a high predictive value for HCC incidence, especially among moderate to heavy alcoholics (>30 g/d). FIB-4 is a readily available and probably cost-effective clinical tool with potential value for identifying subpopulations of alcoholics at particularly high risk who would benefit from regular HCC screening. Further investigations are warranted to validate our results; nonetheless, our study suggests that FIB-4 may be useful in HCC screening among alcoholics.