Vitamin D Status and Reference Intervals Measured by Liquid Chromatography-Tandem Mass Spectrometry for the Early Adulthood to Geriatric Ages in a South Korean Population during 2017-2022.

This study aimed to describe the latest 25-hydroxyvitamin D (25(OH)D) status of the South Korean population aged ≥ 20 years using 25(OH)D concentrations measured by liquid chromatography-tandem mass spectrometry and to determine the factors associated with total 25(OH)D concentrations. This cross-sectional, retrospective study consecutively selected 119,335 subjects with a median age of 57 (20-101) years who underwent health checkups among 13 Korean cities during 2017-2022. The total 25(OH)D concentration was 54.5 ± 24.0 nmol/L (mean ± SD). The 7.6%, 47.5%, and 82.9% of participants had 25(OH)D less than 25, 50, and 75 nmol/L, respectively. The prevalence of 25(OH)D deficiency (<25 nmol/L) was higher in females than in males (8.9% vs. 6.1%) and varied between age groups, decreasing in older subjects. Those aged 20-29 years had the highest prevalence of 25(OH)D deficiency (23.0% in females and 20.1% in males), which also varied between cities. In the adjusted model, female sex, older age, summer and autumn seasons, lower body mass index (<25 kg/m2), and lower high-sensitivity C-reactive protein concentration (<1 mg/L) were associated with higher total 25(OH)D concentrations. This study could provide an exact understanding of the status of vitamin D and help devise strategies to prevent vitamin D deficiency among the Korean population.

Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare.

BACKGROUND: A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission. METHODS: This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi. RESULTS: The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67-1.00, P = 0.05) and HDL-C (OR = 1.17, 95% CI = 1.03-1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis. CONCLUSION: The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD. TRIAL REGISTRATION: ICTRP, cris.nih.go.kr (KCT0006380).

Reference intervals of cell population data parameters in Sysmex XN-Series and its patterns of changes from early adulthood to geriatric ages in South Korea.

INTRODUCTION: Cell population data (CPD) parameters may be putative biomarkers for the screening of various diseases including some infections and myelodysplastic syndrome. This study aimed to establish the age- and sex-specific reference intervals (RIs) for the CPD parameters in the Korean population. METHODS: The reference population for the RIs of CPD parameters comprised 124 856 subjects aged 20-99 years. CPD parameters were obtained from Sysmex XN-2000 (Kobe, Japan) datasets from 17 health promotion centers in 13 South Korean cities. We determined significant partitions for age and sex, and calculated RIs according to Clinical and Laboratory Standards Institute C28-A3 guidelines. RESULTS: The side scattered light intensity in the neutrophil area and the lymphocyte area did not require sex-related partitioning except in those over the age of 50, among whom the lower limit (LL) and upper limit (UL) were lower in females. However, the side scattered light distribution width in the lymphocyte area required age- and sex-related partitioning, in which LL and UL were higher in females. The LL and UL of the fluorescent light distribution width were higher in males in the neutrophil area and higher in females in the lymphocyte area, but age-related partitioning was not required. The forward scattered light intensity in the neutrophil area, lymphocyte area, and monocyte area did not require age-related partitioning in males. CONCLUSION: This study has determined comprehensive age- and sex-specific RIs for CPD parameters, which could help to prove the clinical significance of these parameters in the Sysmex XN-2000.

SARS-CoV-2 Antibody Response and Sustainability after a Third Dose of BNT162b2 in Healthcare Workers at Health Promotion Centers.

The aim of this study was to determine the antibody response and the sustainability of immunogenicity after a third dose of BNT162b2 (BNT) in homologous [ChAdOx1 (ChAd)/ChAd, BNT/BNT, and mRNA-1273 (Moderna)/Moderna] and heterologous (ChAd/BNT) vaccinations of two primary doses with different schemes. This prospective observational study recruited consenting healthcare workers from 16 health checkup centers in 13 Korean cities. Three-point blood tests were analyzed as the antibody response after the third vaccination: T3-1 (1 month after the third dose), T3-3 (3 months after the third dose), and T3-4-10 (4-10 months after the third dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). The antibody levels were significantly higher in the Moderna /Moderna and BNT/BNT groups than in the ChAd/ ChAd and ChAd/BNT groups (p < 0.05) at T3-1. At T3-3, antibody levels had decreased by 29.1% in the BNT/BNT group and by 45.3% in the ChAd/ChAd group compared with the antibody levels at T3-1. The anti-SARS-CoV-2 S-RBD IgG levels at T3-1 were significantly associated with having received mRNA vaccines as the two primary doses (p < 0.001). The third dose of BNT induced an increased humoral immune response in various vaccination schemes, which was more prominent for the two primary doses of homologous mRNA vaccines. However, this immunogenicity decreased within 3-10 months after the third dose. These results suggest that another booster dose (a fourth dose), which would be able to counteract SARS-CoV-2 variants, is needed.

Establishment and validation of reference intervals for tumor markers (AFP, CEA, CA19-9, CA15-3, CA125, PSA, HE4, Cyfra 21-1, and ProGRP) in primary care centers in Korea: A cross-sectional retrospective study.

Background and Aims: The reference interval (RI) for a tumor marker may vary between populations, detection systems, and the methods used to obtain their values. The aims of this study were to establish age- and sex-specific RIs for the following nine common tumor markers and to validate the established RIs in Korean adults: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA15-3, CA125, Human epididymis protein 4 (HE4), total prostate specific antigen, cytokeratin fragment (Cyfra) 21-1, and progastrin-releasing peptide (ProGRP). Methods: This cross-sectional study consecutively selected 214,159 individuals (aged 18-98 years) who underwent health checkups at 16 health-promotion centers in 13 Korean cities. Finally, 62,752 examinees were used to establish the RIs after removing outliers. RIs were established using an indirect method according to the CLSI EP28-A3C guideline. The established RIs were validated by calculating the proportion of individuals outside each RI. Results: Sex-related differences were observed for AFP, CEA, CA19-9, Cyfra 21-1, and ProGRP (p < 0.05): AFP, CEA and Cyfra 21-1 were higher in males, and CA19-9 and proGRP were higher in females. Most of the tumor markers except CA15-3 and CA125 increased with age: CA125 decreased at ≥50 years of age (p < 0.05), while CA15-3 did not vary with age. Less than 5% of subjects were outside all RIs (the 2.5th and 97.5th percentiles) established in the present study. Meanwhile, less than 3% of the healthy reference subjects fell outside the current and manufacturers' RIs of all tumor markers except Cyfra 21-1. Conclusion: This study has determined age- and sex-specific RIs for nine common tumor markers in the healthy Korean population, which could be useful for clinicians making clinical decisions and assessments.

Chronic kidney disease in nonalcoholic fatty liver disease at primary healthcare centers in Korea.

BACKGROUND: The prevalence rates of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are expected to increase with the rising trends in diabetes and obesity associated with aging populations. Considering the impacts of coexistent NAFLD and CKD on morbidity and mortality rates, screening strategies for groups at high-risk of CKD are needed in community-dwelling individuals with NAFLD. The aims of this study were to determine the prevalence and distribution of CKD in NAFLD, as well as the risk factors for CKD and the correlation with liver fibrosis in asymptomatic individuals with NAFLD at primary healthcare centers in Korea. METHODS: This retrospective cross-sectional study used data from 13 health-promotion centers in 10 Korean cities. Liver steatosis and stiffness were assessed using ultrasonography and magnetic resonance elastography (MRE), respectively. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2, and urine albumin-to-creatinine ratio or proteinuria. CKD was categorized into four stages: no CKD, mild, moderate, and severe. Comparisons according to the CKD stages in NAFLD were performed using Student's t-test or the chi-square test. Multivariable logistic regression analyses were performed to identify the risk factors for CKD and the correlation with liver fibrosis in NAFLD. RESULTS: The prevalence of CKD was 12.4% in NAFLD. Albuminuria (16.2%) and proteinuria (8.0%) were more prevalent in NAFLD. NAFLD (odd ratio = 1.27, 95% CI = 1.09-1.48, P = 0.003) was independently associated with CKD of at least mild stage. However, there was no significant association between CKD of at least moderate stage and NAFLD after adjusting for age and a metabolically unhealthy status. CKD was associated with significant liver fibrosis as measured by MRE in NAFLD. CONCLUSION: The presence of NAFLD and liver fibrosis were independent risk factors for CKD, but NAFLD was not an independent risk factor for the later stages of CKD.

The usefulness of the estimated average glucose/fasting blood glucose ratio for pancreatic ß-cell function assessment in hyperglycemia during health checkups.

BACKGROUND: Type 2 diabetes (T2DM) is a disease marked by inadequate insulin secretion by pancreatic beta-cell function (BCF) failure and insulin resistance (IR). Assessing and managing the BCF and IR should be started early to prevent or delay the progression of the disease. The aim of this study was to determine the usefulness of the estimated average glucose (eAG)/fasting blood glucose (FBG) ratio for pancreatic BCF in hyperglycemia. METHODS: This cross-sectional study consecutively selected 10,594 subjects who underwent a health checkup at 16 health checkup centers in 13 Korean cities between 2019 and 2021. The subjects consisted of 3003 patients with normoglycemia, 3413 with impaired fasting glucose and 4178 with T2DM. The eAG was calculated using Nathan's regression equation. BCF and IR were estimated by the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Multivariate (adjusted) regression analysis was performed to evaluate the association between the eAG/FBG ratio and HOMA. RESULTS: The median values among FBG groups for the eAG/FBG ratio, HOMA-ß, -IR and insulin differed significantly (p < 0.001). The second-, third- and fourth-quartile groups of the eAG/FBG ratio had positive higher correlation coefficients [9.533, 10.080 and 12.021, respectively (all p < 0.001)] for HOMA-ß than the first quartile group, and higher negative coefficients for HOMA-IR [-0.696, -0.727 and -0.598, respectively (all p = 0.001)]. CONCLUSION: The eAG/FBG ratio was significantly correlated with both HOMA-ß and -IR, which suggests that eAG/FBG ratio reveals BCF and IR in hyperglycemia. Measurement of this ratio could be useful for monitoring BCF and IR in prediabetes and T2DM.

Antibody response after two doses of homologous or heterologous SARS-CoV-2 vaccines in healthcare workers at health promotion centers: A prospective observational study.

Assaying of anti-spike-protein receptor-binding domain (S-RBD) antibodies are used to aid evaluations of the immune statuses of individuals. The aim of this study was to determine the antibody response after two doses of homologous or heterologous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and to identify the factors affecting this response among healthcare workers (HCWs) at health promotion centers. In this prospective observational study, 1095 consenting HCWs were recruited from 16 health checkup centers and were tested at T0 (day of first dose), T1-1 (1 month after first dose), T2-0 (day of second dose), T2-1 (1 month after second dose), and T2-3 (3 months after second dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). At T1-1, anti-SARS-CoV-2 S-RBD IgG levels were significantly higher in participants who received messenger RNA (mRNA) vaccines than in those who received viral vector vaccines (p < 0.001). At T2-1, anti-SARS-CoV-2 S-RBD IgG levels were about 10 times higher than at T1-1 in participants who received homologous mRNA vaccines, which decreased to a third of those at T2-3. Anti-SARS-CoV-2 S-RBD IgG levels were highest among those who received homologous mRNA vaccines, followed by heterologous mRNA viral vector vaccines and homologous viral vector vaccines at T2-3 (p < 0.001). In a multivariable linear regression analysis, being female, taking at least one mRNA vaccine, and having a history of recovery from coronavirus disease 2019 (COVID-19) were significantly associated with anti-S-RBD levels. Anti-SARS-CoV-2 S-RBD IgG levels were decreased at 3 months after two-dose vaccinations and were associated with sex, vaccine type, and COVID-19 history.

Associations of complete blood count parameters with pancreatic beta-cell function and insulin resistance in prediabetes and type 2 diabetes mellitus.

INTRODUCTION: Previous studies found controversial associations of CBC parameters with pancreatic beta-cell function (BCF) and insulin resistance (IR). The aim of this was to determine the independent associations of CBC parameters with BCF and IR in prediabetes and type 2 diabetes mellitus (T2DM). METHODS: This study selected subjects who underwent health checkups at 16 health-promotion centers in 13 Korean cities during 2021. The subjects comprised 1470 patients with normoglycemia, 1124 with prediabetes, and 396 with T2DM. BCF and IR were assessed using the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Correlation and multiple linear regression analyses were used to determine the correlation between CBC parameters and HOMA. RESULTS: While HOMA-IR gradually increased according to red blood cell count quartiles (1.22, 1.40, 1.47, and 1.91, in the first, second, third, and fourth quartiles, respectively; p < 0.001), there was no correlation after adjusting for waist circumference (WC) and HbA1c. The red blood cell distribution width (RDW) was associated with HOMA-ß [coefficient (ß) = 15.527, p = 0.002], but not with HOMA-IR. White blood cells (WBCs) were associated with HOMA-IR and HOMA-ß, which was stronger in HOMA-ß (ß = 0.505 vs 15.171, p = 0.002) after adjusting for WC and HbA1c. The platelet count was correlated with HOMA-IR and HOMA-ß, which only remained in HOMA-ß (ß = 15.581, p = 0.002) after adjusting for WC and HbA1c. CONCLUSION: RDW, WBC, and platelet counts were independently associated with only HOMA-ß in prediabetes and T2DM. This suggests that these CBC parameters could represent BCF in prediabetes and T2DM.

The Reproducibility and Usefulness of Estimated Average Glucose for Hyperglycemia Management during Health Checkups: A Retrospective Cross-Sectional Study.

HbA1c reflects average glucose levels over 3 months, but it does not measure glycemic variability. This study aimed to determine the reproducibility and usefulness of HbA1c-derived estimated average glucose (eAG) and to analyze the factors associated with eAG during health checkups. This cross-sectional retrospective study consecutively selected subjects who had undergone health checkups at 16 health-promotion centers in 13 Korean cities in 2020. The subjects comprised 182,848 healthy subjects with normoglycemia, 109,555 with impaired fasting glucose (IFG), and 35,632 with diabetes. eAG was calculated using Nathan's regression equation. In all subjects, fasting plasma glucose (FPG) was found to be fairly strongly correlated with eAG (r = 0.811). When the subjects were divided into FPG subgroups, the strength of the correlation decreased among those with normoglycemia and IFG (p < 0.001). Higher eAG levels were associated with older age, females, higher FPG, and lower HDL-C and triglycerides (p < 0.05). The proportion of subjects with a higher value of FPG than eAG was 46.3% in poorly controlled diabetic patients, compared with only 1.5% in normoglycemic subjects. This suggests eAG could help patients to understand their glycemic variability intuitively and healthcare providers to identify patients who might worsen in hyperglycemia control through measuring the difference between eAG and FPG.

Subclinical steatohepatitis and advanced liver fibrosis in health examinees with nonalcoholic fatty liver disease (NAFLD) in 10 South Korean cities: A retrospective cross-sectional study.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) has a risk of progressing to cirrhosis. The prevalence of NASH and its associated risk factors in community populations are relatively unknown. This study aimed to determine the prevalence of NASH and advanced liver fibrosis using magnetic resonance elastography (MRE), and determine those risk factors in health examinees with asymptomatic fatty liver. METHODS: This study consecutively selected subjects who underwent health checkups at 13 health-promotion centers in 10 Korean cities between 2018 and 2020. Hepatic steatosis and stiffness were assessed using ultrasonography and MRE, respectively. Stages of liver stiffness were estimated using MRE with cutoff values for NASH and advanced liver fibrosis of 2.91 and 3.60 kPa, respectively. RESULTS: The overall prevalence of NASH and advanced liver fibrosis in the subjects with fatty liver were 8.35% and 2.04%, respectively. Multivariate logistic regression analysis indicated that central obesity (OR = 5.12, 95% CI = 2.70-9.71), increased triglyceride (OR = 3.29, 95% CI = 1.72-6.29), abnormal liver function test (OR = 3.09, 95% CI = 1.66-5.76) (all P<0.001), and decreased high-density lipoprotein cholesterol (OR = 5.18, 95% CI = 1.78-15.05) (P = 0.003) were associated with NASH. The main risk factor for advanced liver fibrosis was diabetes (OR = 4.46, 95% CI = 1.14-17.48) (P = 0.032). CONCLUSION: NASH or advanced liver fibrosis is found in one-tenth of health examinees with asymptomatic fatty liver. This suggests that early detection of NASH should be considered to allow early interventions such as lifestyle changes to prevent the adverse effects of NASH and its progression in health examinees with asymptomatic fatty liver.

Reference interval and the role of plasma oligomeric beta amyloid in screening of risk groups for cognitive dysfunction at health checkups.

BACKGROUND: Alzheimer's disease (AD) has a prolonged preclinical stage characterized by cognitive dysfunction. Simple, reliable, and noninvasive biomarkers reflecting the pathogenesis of AD are needed for screening cognitive dysfunction in primary health care. The aims of this study were to determine (1) the potential utility of the Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) value in cognitive assessments and (2) the reference interval (RI) of plasma MDS-OAß values in the general population. METHODS: This prospective study consecutively recruited 1,594 participants who underwent health checkups including cognitive function examination at 16 health-promotion centers in Korea between December 2020 and January 2021. The inBloodTM OAß test (PeopleBio, Gyeonggi-do, Republic of Korea) was utilized to quantify MDS-OAß values in plasma. The reference subjects were obtained among those with normal general cognition on cognitive screening tools. RIs were established according to the CLSI C28-A3 guidelines. RESULTS: The median MDS-OAß value was higher in subjects with Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) scores ≥8 than in those with KDSQ-C scores of 6-7 (P = 0.013). The median MDS-OAß value was higher in subjects with Mini-Mental State Examination for Dementia Screening (MMSE-DS) scores of 21-26 than in those with MMSE-DS scores ≥27 (P = 0.011). The RI (one-side upper 95th percentile) of the MDS-OAß value was 0.80 ng/mL (95% confidence interval = 0.78-0.82) in those aged ≥50 years. CONCLUSIONS: The plasma MDS-OAß value reflects cognitive function as assessed using the KDSQ-C and MMSE-DS. RIs obtained from a large and cognitively healthy community-based sample are presented.

Nationwide seroprevalence of antibodies to SARS-CoV-2 in asymptomatic population in South Korea: a cross-sectional study.

OBJECTIVE: Asymptomatic active infection might be an important contributor to the COVID-19 outbreak. Serological tests can assess the extent of exposure and herd immunity to COVID-19 in general populations. This study aimed to estimate the nationwide seroprevalence of SARS-CoV-2 antibodies according to age, sex and clinical status in South Korea. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study randomly selected health examinees who underwent health check-up at 16 health promotion centres in 13 Korean cities across the country between late September and early December 2020. Residual serum samples were obtained from 4085 subjects (2014 men and 2071 women). Antibodies to SARS-CoV-2 were measured by electrochemiluminescence immunoassay using Elecsys Anti-SARS-CoV-2 (Roche Elecsys, Mannheim, Germany). PRIMARY AND SECONDARY OUTCOME MEASURES: Fisher's exact test was used to compare the seroprevalence according to sex, age group and region. The relative risks of being seropositive according to the characteristics of the study subjects were analysed using logistic regression analysis. RESULTS: The overall seroprevalence of anti-SARS-CoV-2 was 0.39% (95% CI=0.20% to 0.58%): 0.30% (95% CI=0.06% to 0.54%) for men and 0.48% (95% CI=0.18% to 0.78%) for women. The rate of anti-SARS-CoV-2 positivity varied significantly between different regions of Korea (p=0.003), but not with age group, sex, or the statuses of obesity, diabetes, hypertension or smoking. CONCLUSIONS: Most of the Korean population is still immunologically vulnerable to SARS-CoV-2, but the seroprevalence has increased relative to that found in studies performed prior to September 2020 in Korea.

Prevalence of liver fibrosis and associated risk factors in the Korean general population: a retrospective cross-sectional study.

OBJECTIVES: The health burden of chronic liver disease is increasing worldwide. Its main histological consequence is liver fibrosis, and eventually cirrhosis. This process is rarely diagnosed at the pre-cirrhotic stage due to it being asymptomatic. Little is known about the prevalence of liver fibrosis and associated risk factors in the general population. The aims of this study were to determine the prevalence and distribution of liver fibrosis using magnetic resonance elastography (MRE), as well as the risk factors associated with liver fibrosis in the asymptomatic general population. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional retrospective study consecutively selected subjects who underwent health check-ups including MRE at 13 health promotion centres in Korea between 2018 and 2020. Liver fibrosis was estimated using MRE with cut-off values for significant and advanced liver fibrosis of 2.90 and 3.60 kPa, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The Χ2 test was used to compare the prevalence of liver fibrosis according to sex and age groups. Multivariable logistic regression analyses were performed to identify the factors for significant and advanced liver fibrosis. RESULTS: Among the 8183 subjects, 778 (9.5%) had ≥significant fibrosis (≥2.9 kPa), which included 214 (2.6%) subjects with ≥advanced fibrosis (≥3.6 kPa). Multivariable analysis revealed that liver fibrosis was associated with age (OR=1.34, 95% CI=1.18 to 1.51), male sex (OR=3.18, 95% CI=1.97 to 5.13), diabetes (OR=2.43, 95% CI=1.8 to 3.28), HBsAg positivity (OR=3.49, 95% CI=2.55 to 4.79), abnormal liver function test (OR=1.9, 95% CI=1.49 to 2.42) and obesity (OR=1.77, 95% CI=1.35 to 2.32) (all p<0.001), as well as metabolic syndrome (OR=1.4, 95% CI=1.05 to 1.87) (p=0.024). CONCLUSIONS: The prevalence of significant or more liver fibrosis was high in the Korean general population and much higher among individuals with risk factors. This suggests that screening of liver fibrosis should be considered in general population, especially among high-risk groups.

Reference interval and the role of soluble suppression of tumorigenicity 2 (sST2) in subclinical cardiac dysfunction at health checkups.

BACKGROUND: Soluble ST2 (sST2) is known to predict adverse outcomes and death in individuals with established heart failure. However, the role of sST2 testing in the general population has not been established. The aims of this study were to determine the reference interval (RI) and the clinical utility of sST2 in subclinical cardiac dysfunction in general population. METHODS: This cross-sectional study consecutively selected 41,806 general subjects at health checkups who underwent echocardiography and sST2 testing at 16 health promotion centers in 13 Korean cities. The reference subjects were obtained among those with normal findings in echocardiography. Sex-specific RIs were established according to the CLSI C28-A3 guidelines. sST2 was measured using immunoassay with the Presage ST2 assay (Critical Diagnostics). RESULTS: In the general subjects, age, sex, BMI, systolic blood pressure, blood glucose, creatinine, liver function, and triglycerides were associated with the sST2 levels. The RI for sST2 was higher in males (≤49.6 ng/mL, 95% CI = 48.5-51.5) than in females (≤44.5 ng/mL, 95% CI = 43.5-45.6) and higher in subjects aged < 40 years than ≥ 40 years in both sexes. The sST2 levels were 29.1 ± 10.7 (mean ± SD) and 29.1 ± 14.4 ng/mL in the groups with normal cardiac function and subclinical cardiac dysfunction, respectively. The sST2 level was not associated with subclinical cardiac dysfunction (odd ratio = 1.002, P = .13). CONCLUSIONS: RIs obtained from a large and echocardiography-proven healthy community-based sample are presented. Subclinical cardiac dysfunction was associated with older age, male sex, and metabolic factors but not with the sST2 level.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BACKGROUND: Mild-to-moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase-to-platelet ratio (APRI) and the Fibrosis-4 index (FIB-4) in health checkups. METHODS: This cross-sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results. RESULTS: The median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34-0.61), 0.48 (0.38-0.68), 0.64 (0.43-1.03), and 1.01 (0.75-1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB-4 and APRI. CONCLUSION: Serum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

Distribution of hemoglobin levels and prevalence of anemia according to sex, age group, and region in 13 Korean cities.

INTRODUCTION: The distribution of hemoglobin (Hb) levels and the prevalence of anemia are significant public health indicators. The aims of this study were to determine the distribution of Hb levels and the prevalence of anemia according to sex, age group, and region throughout Korea. METHODS: The study analyzed data on 1 159 298 subjects who received health checkups at 16 health-promotion centers in 13 Korean cities during 2018. Anemia and its severity were defined according to the World Health Organization classification for Hb levels as follows: mild anemia (11-12.9 g/dL in males and 11-11.9 g/dL in females), moderate anemia (10-10.9 g/dL in both sexes), and severe anemia (<10.0 g/dL in both sexes). RESULTS: The Hb level in the general sample was lower in females (13.25 ± 1.13 g/dL, mean ± SD) than in males (15.29 ± 1.22 g/dL). The overall prevalence of anemia was 6.0% (2.98% in males and 8.56% in females), and the prevalence of severe anemia was 0.92% (0.23% in males and 1.51% in females). While the prevalence of anemia increased monotonically with age in males, it was bimodal in females with two peaks at 40-49 years and ≥80 years. The highest prevalence of anemia in females aged 40-49 years was attributed to microcytic anemia, while increases in anemia prevalence in males aged ≥50 years and females aged ≥70 years were attributed to macrocytic anemia. CONCLUSION: The distribution of Hb levels and the prevalence of anemia overall and by severity differ according to sex, age group, and region throughout Korea.

Subclinical Iron Deficiency in Non-Anemic Individuals: A Retrospective Analysis of Korean Health Examinees.

OBJECTIVES: Non-anemic individuals may have undetected subclinical iron deficiency (SID). The aims of this study were to determine the prevalence of SID and identify the associated factors for SID. In addition, the screening performance of red blood cell (RBC) indices for SID in health check-ups was assessed. METHODS: This study was conducted with 16,485 non-anemic health examinees (3,567 males and 12,918 females) who underwent tests for iron variables (serum iron, total iron-binding capacity, ferritin, and iron saturation) at 16 health-promotion centers in 13 cities in Korea between January 2017 and June 2018. SID was defined as a decreased ferritin level (<24 µg/L in males and <15 µg/L in females) and either a decreased serum iron level (<44 µg/dL in males and <29 µg/dL in females) or a transferrin saturation of <20%. RESULTS: The prevalence rates of SID were 0.6 and 3.3% in males and females, respectively. In terms of age and sex, SID was most prevalent in males aged ≥70 years (7.8%) and females aged 15-49 years (7.6%). There were significant differences in the hemoglobin (Hb) level, white blood cell count, platelet count, mean corpuscular volume, mean corpuscular Hb (MCH), and RBC distribution width (RDW) between the SID and non-SID groups (p < 0.001). The factors associated with SID in males were older age (odds ratio, OR, 1.069, 95% confidence interval, CI, 1.03-1.109, p = 0.004), lower Hb (OR 0.58, 95% CI 0.345-0.976, p = 0.04), lower MCH (OR 0.433, 95% CI 0.298-0.629, p < 0.001), and higher RDW (OR 1.374, 95% CI 1.001-1.887, p = 0.049), while in females they were lower body mass index (BMI; OR 0.929, 95% CI 0.895-0.963, p < 0.001) and younger age (OR 0.954, 95% CI 0.945-0.963, p < 0.001), as well as lower Hb, lower MCH, and higher RDW. The AUC for the MCH (0.877, 95% CI 0.793-0.960 in males; 0.872, 95% CI 0.853-0.890 in females) indicates that the MCH at cut-offs of 29.2 and 29.3 pg are the best discriminators of SID in males and females, respectively (p < 0.001). CONCLUSIONS: Reproductive-age females with a lower BMI and elderly males are high-risk groups for SID. MCH is a reliable RBC index for the screening of SID. For the population with defined risk factors, including females with lower BMI and elderly males, screening for SID is needed to prevent the development of anemia.

Plasma NT-proBNP levels associated with cardiac structural abnormalities in asymptomatic health examinees with preserved ejection fraction: a retrospective cross-sectional study.

OBJECTIVES: Stage B heart failure (HF) is defined as an asymptomatic abnormality of the heart structure or function. The circulating level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in symptomatic patients with left ventricular (LV) dysfunction caused by a structural or functional abnormality. This study investigated the association of the NT-proBNP level with echocardiography-detected cardiac structural or diastolic abnormalities in asymptomatic subjects with preserved LV systolic function (ejection fraction >50%). METHODS: We retrospectively studied 652 health examinees who underwent echocardiography and an NT-proBNP test at a health-promotion centre in Seoul, between January 2016 and September 2018. The left ventricular mass index (LVMI) and the left atrial dimension (LAD) were used as markers for structural abnormalities, and the mean e' velocity and mitral early flow velocity/early diastolic tissue velocity (E/e') ratio were used as markers for diastolic dysfunction. The plasma NT-proBNP level was measured using electrochemiluminescence immunoassay (DPC Immulite 2000 XPi, Siemens Healthcare Diagnostics, Tarrytown, New York, USA). RESULTS: Subjects with preclinical structural abnormalities were older and had a higher body mass index (BMI), higher blood pressure, lower high-density lipoprotein cholesterol level, higher NT-proBNP level, and higher E/e' (p<0.05). Multivariate regression analysis indicated that the factors associated with a higher NT-proBNP level were older age, female sex, lower BMI, higher creatinine level, higher LVMI and higher LAD (p<0.01). CONCLUSION: Diastolic dysfunction is not associated with higher NT-proBNP levels, whereas preclinical cardiac structural abnormalities, as well as older age, female sex, lower BMI, and higher creatinine level, are associated with higher NT-proBNP levels.

Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea.

BACKGROUND: Sampling a healthy reference population to generate reference intervals (RIs) for complete blood count (CBC) parameters is not common for pediatric and geriatric ages. We established age- and sex-specific RIs for CBC parameters across pediatric, adult, and geriatric ages using secondary data, evaluating patterns of changes in CBC parameters. METHODS: The reference population comprised 804,623 health examinees (66,611 aged 3-17 years; 564,280 aged 18-59 years; 173,732 aged 60-99 years), and, we excluded 22,766 examinees after outlier testing. The CBC parameters (red blood cell [RBC], white blood cell [WBC], and platelet parameters) from 781,857 examinees were studied. We determined statistically significant partitions of age and sex, and calculated RIs according to the CLSI C28-A3 guidelines. RESULTS: RBC parameters increased with age until adulthood and decreased with age in males, but increased before puberty and then decreased with age in females. WBC and platelet counts were the highest in early childhood and decreased with age. Sex differences in each age group were noted: WBC count was higher in males than in females during adulthood, but platelet count was higher in females than in males from puberty onwards (P<0.001). Neutrophil count was the lowest in early childhood and increased with age. Lymphocyte count decreased with age after peaking in early childhood. Eosinophil count was the highest in childhood and higher in males than in females. Monocyte count was higher in males than in females (P<0.001). CONCLUSIONS: We provide comprehensive age- and sex-specific RIs for CBC parameters, which show dynamic changes with both age and sex.