Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey.

PURPOSE: We aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population. METHODS: We categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM). RESULTS: The TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone. CONCLUSION: TE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.

Comparison of Metabolic Risk Factors Based on the Type of Physical Activity in Korean Adolescents: Results from a Nationwide Population-Based Survey.

BACKGROUND: Physical activity (PA) is associated with a favorable metabolic risk profile in adults. However, its role in adolescents remains unclear. In this study, using data (2019-2021) from the 8th Korea National Health and Nutrition Examination Survey, we investigated the optimal exercise type for preventing metabolic complications in adolescents. METHODS: A total of 1,222 eligible adolescent participants (12-18-year-old) were divided into four groups as follows: aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (CE), and no exercise (NE). Daily PA was assessed using the international PA questionnaire. Blood samples were collected to measure lipid, glucose, and insulin levels. Additionally, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) indices were measured. Multivariate regression analysis was used to compare the metabolic risk factors across the PA groups before and after propensity score matching (PSM) adjustment for confounding variables. RESULTS: The CE group exhibited improved fasting glucose levels, lower TyG index, reduced white blood cell count, and higher high-density lipoprotein (HDL) cholesterol levels than the NE group. The RE group exhibited lower mean blood pressure, triglyceride, fasting insulin, HOMA-IR, TyG index and a reduced risk of metabolic syndrome than the NE group. The AE group had higher total and HDL cholesterol levels. In detailed comparison of the AE and RE groups, the RE group consistently exhibited favorable metabolic parameters, including lower blood pressure and total and low-density cholesterol levels, which persisted after PSM. CONCLUSION: These findings highlight the positive effects of PA on cardiovascular risk factors in adolescents. Thus, RE may have a more favorable metabolic effect than AE. Further studies are needed to validate the benefits of exercise according to the exercise type.

Association between triglyceride-glucose index and low-density lipoprotein particle size in korean obese adults.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) is the lipoprotein marker among the various lipoproteins that is most strongly related to atherosclerosis. Insulin resistance (IR) can alter lipid metabolism, and sdLDL-C is characteristic of diabetic dyslipidemia. Therefore, this study sought to inspect the relationship between the triglyceride-glucose (TyG) index and mean low-density lipoprotein (LDL) particle size. METHODS: In this study, a total of 128 adults participated. The correlation coefficients between various lipoproteins and the TyG index were compared using Steiger's Z test and the Spearman correlation. The independent link between the TyG index and mean LDL particle size was demonstrated by multiple linear regression analysis. To identify the TyG index cutoff value for the predominance of sdLDL particles, receiver operating characteristic curves were plotted. RESULTS: Mean LDL particle size correlated more strongly with the TyG index than did very low-density lipoprotein, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Regression analysis demonstrated that mean LDL particle size had a strong association with the TyG index (ß coefficient = -0.038, P-value < 0.001). The TyG index optimal cutoff value for sdLDL particle predominance and the corresponding area under the curve (standard error: 0.028, 95% confidence interval: 0.842-0.952) were 8.72 and 0.897, respectively, which were close to the cutoff value of diabetes risk in Koreans. CONCLUSIONS: Mean LDL particle size is more strongly correlated with the TyG index than do other lipid parameters. After correcting for confounding variables, mean LDL particle size is independently linked with the TyG index. The study indicates that the TyG index is strongly related to atherogenic sdLDL particles predominance.

Genome-wide association and replication studies for handedness in a Korean community-based cohort.

INTRODUCTION: Handedness is a conspicuous characteristic in human behavior, with a worldwide proportion of approximately 90% of people preferring to use the right hand for many tasks. In the Korean population, the proportion of left-handedness is relatively low at approximately 7%-10%, similar to that in other East-Asian cultures in which the use of the left hand for writing and other public activities has historically been oppressed. METHODS: In this study, we conducted two genome-wide association studies (GWASs) between right-handedness and left-handedness, and between right-handedness and ambidexterity using logistic regression analyses using a Korean community-based cohort. We also performed association analyses with previously reported variants and our findings. RESULTS: A total of 8806 participants were included for analysis, and the results identified 28 left-handedness-associated and 15 ambidexterity-associated loci; of these, two left-handedness loci (NEIL3 [rs11726465] and SVOPL [rs117495448]) and one ambidexterity locus (PDE8B/WDR41 [rs118077080]) showed near genome-wide significance. Association analyses with previously reported variants replicated ANKS1B (rs7132513) in left-handedness and ANKIB1 (rs2040498) in ambidexterity. CONCLUSION: The variants and positional candidate genes identified and replicated in this study were largely associated with brain development, cerebral asymmetry, neurological processes, and neuropsychiatric diseases in line with previous findings. As the first East-Asian GWAS related to handedness, these results may provide an intriguing reference for further human neurologic research in the future.

Dyslipidemia Risk in Thyroid Cancer Patients: A Nationwide Population-Based Cohort Study.

Objective: Thyroid cancer (TC) prevalence has been rapidly increasing. While the relationship between thyroid hormones and lipids has been widely investigated, studies regarding dyslipidemia in patients with TC have been scarce and controversial. We aimed to investigate dyslipidemia risk after TC diagnosis compared to the general population without TC. Method: A population-based prospective study was conducted using data from the Korean National Health Insurance Service-National Sample Cohort Database 2.0 (NHIS-NSC DB 2.0), with health insurance claim data of 1,108,369 subjects between 2002 and 2015. The final study sample comprised 466,735 adult subjects without TC or dyslipidemia diagnoses before the index year, 2009. Bidirectional analyses were performed using prospective and retrospective concepts. In the prospective analysis, Kaplan-Meier estimates were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between TC and dyslipidemia. The retrospective analysis involved 1:5 nested case-control matching based on dyslipidemia status and conditional logistic regression analysis. Results: No significant difference in dyslipidemia incidence was observed between TC patients and the control group, in either the prospective matched (log-rank P = 0.483) or non-matched (log-rank P = 0.424) analyses, or the retrospective analysis (P = 0.3724). In the prospective analysis, 193 patients after TC diagnosis showed similar risk of developing dyslipidemia with the 466,542 controls during the median 7 years of follow-up (unadjusted hazard ratio [HR], 1.102; 95% confidence interval [CI], 0.878-1.383; adjusted HR, 0.932; 95% CI, 0.707-1.230). Multiple propensity score-adjusted models showed similar results, and 114 patients and 570 matched controls showed an HR of 0.818 (95% CI, 0.598-1.120). In the retrospective comparison of dyslipidemia risk in 170 patients and 277,864 controls, the odds ratio was 0.822 (95% CI, 0.534-1.266). Conclusions: Dyslipidemia risk was not significantly different between patients with TC and the general population, in both prospective and retrospective analyses.

Association of Longitudinal Trajectories of Insulin Resistance With Adverse Renal Outcomes.

OBJECTIVE: To analyze the relationship between time-serial changes in insulin resistance and renal outcomes. RESEARCH DESIGN AND METHODS: A prospective cohort of subjects from the general population without chronic kidney disease (CKD) underwent a biennial checkup for 12 years (n = 5,347). The 12-year duration was divided into a 6-year exposure period, where distinct HOMA for insulin resistance (HOMA-IR) trajectories were identified using latent variable mixture modeling, followed by a 6-year event accrual period, from which the renal outcome data were analyzed. The primary end point was adverse renal outcomes, defined as a composite of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in two or more consecutive checkups or albumin ≥1+ on urine strip. RESULTS: Two distinct groups of HOMA-IR trajectories were identified during the exposure period: stable (n = 4,770) and increasing (n = 577). During the event accrual period, 449 patients (8.4%) developed adverse renal outcomes, and the risk was higher in the increasing HOMA-IR trajectory group than in the stable group (hazard ratio 2.06, 95% CI 1.62-2.60, P < 0.001). The results were similar after adjustment for baseline clinical characteristics, comorbidities, anthropometric and laboratory findings, eGFR, and HOMA-IR. The clinical significance of increasing HOMA-IR trajectory was similar in three or four HOMA-IR trajectories. The increasing tendency of HOMA-IR was persistently associated with a higher incidence of adverse renal outcomes, irrespective of the prevalence of diabetes. CONCLUSIONS: An increasing tendency of insulin resistance was associated with a higher risk of adverse renal outcomes. Time-serial tracking of insulin resistance may help identify patients at high risk for CKD.

Defining Essential Topics and Procedures for Korean Family Medicine Residency Training.

BACKGROUND: This study aims to create a comprehensive list of essential topics and procedural skills for family medicine residency training in Korea. METHODS: Three e-mailed surveys were conducted. The first and second surveys were sent to all board-certified family physicians in the Korean Academy of Family Medicine (KAFM) database via e-mail. Participants were asked to rate each of the topics (117 in survey 1, 36 in survey 2) and procedures (65 in survey 1, 19 in survey 2) based on how necessary it was to teach it and personal experience of utilizing it in clinical practice. Agreement rates of the responses were calculated and then sent to the 32 KAFM board members in survey 3. Opinions on potential cut-off points to divide the items into three categories and the minimum achievement requirements needed to graduate for each category were solicited. RESULTS: Of 6,588 physicians, 256 responded to the first survey (3.89% response rate), 209 out of 6,669 to the second survey (3.13%), and 100% responded to the third survey. The final list included 153 topics and 81 procedures, which were organized into three categories: mandatory, recommended, and optional (112/38/3, 27/33/21). For each category of topics and procedures, the minimum requirement for 3-year residency training was set at 90%/60%/30% and 80%/60%/30%, respectively. CONCLUSION: This national survey was the first investigation to define essential topics and procedures for residency training in Korean family medicine. The lists obtained represent the opinions of Korean family physicians and are expected to aid in the improvement of family medicine training programs in the new competency-based curriculum.

Comparison of the effectiveness of Martin's equation, Friedewald's equation, and a Novel equation in low-density lipoprotein cholesterol estimation.

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R2, RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R2 = 0.88/0.91; vs FLDL: RMSE = 13.66/10.42 mg/dL; R2 = 0.82/0.89; vs SLDL: RMSE = 12.36/9.39 mg/dL; R2 = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500-600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin's equation may be optimal for LDL-C and ASCVD risk estimation.

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia.

BACKGROUND: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients. METHODS: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci. RESULTS: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10-9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10-8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10-8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10-9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10-8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10-8]). CONCLUSIONS: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population.

Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes-metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.

A Patient with Neutropenia and Splenomegaly: A Case Report from Department of Family Medicine in Tertiary Hospital Center.

Pancytopenia represents a unique challenge for primary care doctors and its etiological causes encompass various specialties, including hematology and rheumatology. Despite the existence of effective tests such as bone marrow biopsy and immunoassays to rule out the potential causes of pancytopenia, it is often difficult to pinpoint the exact diagnosis. In this case report, we have described such a 'gray zone' patient, who presented with pancytopenia, neutropenia, and splenomegaly, and was being treated for fungal pneumonia before being transferred to Severance Hospital (department of family medicine). As the patient had a 10-year history of multiple, long-term hospital admissions that were having a severely debilitating impact on the quality of life, we performed a partial splenic embolization as a potential cure for the symptoms. Although this induced acute blood count recovery, it failed to prevent eventual mortality from septic shock.

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk.

The role of sodium in hypertension remains unresolved. Although genetic factors have a significant impact on high blood pressure, studies comparing genetic susceptibility between people with low and high sodium diets are lacking. We aimed to investigate the genetic variations related to hypertension according to sodium intake habits in a large Korean population-based study. Data for a total of 57,363 participants in the Korean Genome and Epidemiology Study Health Examination were analyzed. Sodium intake was measured by a semi-quantitative food frequency questionnaire. We classified participants according to sodium intake being less than or greater than 2 g/day. We used logistic regression to test single-marker variants for genetic association with a diagnosis of hypertension, adjusting for age, sex, body mass index, exercise, alcohol, smoking, potassium intake, principal components 1, and principal components 2. Significant associations were defined as p < 5 × 10-8. In participants whose sodium intake was greater than 2 g/day, chromosome 6 open reading frame 10 (C6orf10)-human leukocyte antigen (HLA)-DQB1 rs6913309, ring finger protein (RNF)213 rs112735431, glycosylphosphatidylinositol anchored molecule-like (GML)- cytochrome P450 family 11 subfamily B member 1(CYP11B1) rs3819496, myosin light chain 2 (MYL2)-cut like homeobox 2 (CUX2) rs12229654, and jagged1 (JAG1) rs1887320 were significantly associated with hypertension. In participants whose intake was less than 2 g/day, echinoderm microtubule-associated protein-like 6(EML6) rs67617923 was significantly associated with hypertension. Genetic susceptibility associated with hypertension differed according to sodium intake. Identifying gene variants that contribute to the dependence of hypertension on sodium intake status could make possible more individualized nutritional recommendations for preventing cardiovascular diseases.

Clinical Practice Guideline for Care in the Last Days of Life.

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients' physical and mental symptoms, psychological support, appropriate decision-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world. This guideline should be applied in a way that takes into account specific health care environments, including the resources of medical staff and differences in the available resources of each institution. This guideline can be used by all medical institutions in South Korea.

Association between C-Reactive Protein and Metabolic Syndrome in Korean Adults.

BACKGROUND: The prevalence of metabolic syndrome (MetS) is increasing, and obesity, insulin resistance, and inflammation are the known risk factors. However, results of previous studies regarding the relationship between MetS and inflammation have not been consistent. This study aimed to identify the associations between C-reactive protein (CRP) and MetS and its components in obese and non-obese men and women. METHODS: This was a cross-sectional study based on the 6th Korea National Health and Nutrition Examination Survey (2015), and a nationally representative sample of 3,013 Korean adults aged 40-78 years were included. Those with cardiovascular disease, cancer, CRP level >10 mg/L, white blood cell count >10,000/mm3 , chronic kidney disease, and lung/liver disease were excluded. RESULTS: Approximately 11.0%, 50.0%, 8.4%, and 48.8% of non-obese men, obese men, non-obese women, and obese women presented with MetS (P<0.001), respectively. In all four groups, those who presented with MetS or its components showed a higher high-sensitivity (hs-CRP) average than those without. Multivariate regression analysis showed the increased risk of developing MetS with higher quartiles of hs-CRP level in obese (3rd and 4th quartiles: odds ratios [ORs], 3.87 and 2.57, respectively) and non-obese women (4th quartile: OR, 2.63). The different components also showed increased ORs in the four groups. However, no statistically significant trend in the relationship was found in men. CONCLUSION: Low-grade inflammation may increase the risk of MetS in Korean women independent of adiposity. However, due to the cross-sectional design of the present study, further studies must be conducted to identify the causal relationship between inflammation and metabolic disorders.

Caspase cleavage product lacking amino-terminus of IkappaBalpha sensitizes resistant cells to TNF-alpha and TRAIL-induced apoptosis.

In response to a diverse array of signals, IkappaBalpha is targeted for phosphorylation-dependent degradation by the proteasome, thereby activating NF-kappaB. Here we demonstrate a role of the cleavage product of IkappaBalpha in various death signals. During apoptosis of NIH3T3, Jurkat, Rat-1, and L929 cells exposed to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas, serum deprivation, or TNF-alpha, respectively, IkappaBalpha was cleaved in a caspase-dependent manner. In vitro and in vivo cleavage assays and site-directed mutagenesis showed that caspase-3 cleaved IkappaBalpha between Asp31 and Ser32. Expression of the cleavage product lacking amino-terminus (1-31), DeltaIkappaBalpha, sensitized otherwise resistant NIH3T3 fibroblast cells to apoptosis induced by TNF-alpha or TRAIL, and HeLa tumor cells to TNF-alpha. DeltaIkappaBalpha was more pro-apoptotic compared to wild type or cleavage-resistant (D31E)IkappaBalpha mutant and the sensitization elicited by DeltaIkappaBalpha was as effective as that by the dominant negative mutant, (S32,36A)IkappaBalpha, in NIH3T3 cells. DeltaIkappaBalpha suppressed the transactivation of NF-kappaB induced by TNF-alpha or TRAIL, as reflected by luciferase-reporter activity. Conversely, expression of the p65 subunit of NF-kappaB suppressed TNF-alpha-, TRAIL-, and serum deprivation-induced cell death. On the contrary, DeltaIkappaBalpha was less effective at increasing the death rate of HeLa cells that were already sensitive to death signals including TRAIL, etoposide, or taxol. These results suggest that DeltaIkappaBalpha generated by various death signals sensitizes cells to apoptosis by suppressing NF-kappaB activity.