Oxidative balance score as a useful predictive marker for new-onset type 2 diabetes mellitus in Korean adults aged 60 years or older: The Korean Genome and Epidemiologic Study-Health Examination (KoGES-HEXA) cohort.

BACKGROUND: The oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. METHODS: We assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. RESULTS: A total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47-1.07]) but was significant in T3 at (0.47 [0.30-0.75]) (p for trend = 0.002). CONCLUSIONS: The study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.

Optimizing Embryo Collection for Application of CRISPR/Cas9 System and Generation of Fukutin Knockout Rat Using This Method.

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

METS-IR and all-cause mortality in Korean over 60 years old: Korean genome and epidemiology study-health examinees (KoGES-HEXA) cohorts.

Background: The metabolic score for insulin resistance index (METS-IR) is a novel non insulin-based marker that indicates the risk for metabolic syndrome and type 2 diabetes mellitus (T2DM). However, METS-IR has not been investigated in relation to all-cause mortality. We investigated the longitudinal effect of METS-IR on all-cause mortality in a significantly large cohort of Korean adults over 60 years old. Methods: Data were assessed from 30,164 Korean participants over 60 years of age from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort data, linked with the death certificate database of the National Statistical Office. The participants were grouped into three according to METS-IR tertiles. We used multivariate Cox proportional-hazard regression models to prospectively assess hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) over an 11-year postbaseline period. Results: During the mean 11.7 years of follow-up, 2,821 individuals expired. The HRs of mortality for METS-IR tertiles were 1.16 (95% CI, 1.01-1.34) in T3 after adjustment for metabolic parameters, but the T2 did not show statistical significance towards increases for incident mortality respectively. In subgroup analysis depending on the cause of mortality, higher METS-IR was associated with cancer mortality (HR, 1.23, 95% CI, 1.01-1.51) but not with cardiovascular mortality (HR, 1.14, 95% CI, 0.83-1.57) after adjustment for the same confounding variables. Conclusion: The METS-IR may be a useful predictive marker for all-cause mortality and cancer mortality, but not for cardiovascular mortality in subjects over 60 years of age. This implies that early detection and intervention strategies for metabolic syndrome could potentially benefit this identified group.

Oxidative Balance Score and New-Onset Type 2 Diabetes Mellitus in Korean Adults without Non-Alcoholic Fatty Liver Disease: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) Cohort.

The oxidative balance score (OBS) is a novel composite of pro- and anti-oxidative markers for assessing the risk of cardiometabolic diseases and non-alcoholic fatty liver disease (NAFLD). However, it has not yet been established whether the OBS is related to type 2 diabetes mellitus (T2DM), especially in a population without NALFD. Therefore, we aimed to investigate the longitudinal effect of the OBS on T2DM in a large cohort of Korean adults without NALFD. Data were assessed from 9798 participants without NALFD from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort. The participants were divided into three groups according to OBS tertiles, identified as T1-T3. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional hazard regression models over 6 years following the baseline survey. During the mean 3.5 years of follow-up, 145 individuals (1.48%; 56 men and 89 women) developed T2DM. The HRs of T2DM for the OBS tertiles were 0.79 (95% CI, 0.53-1.18) and 0.60 (95% CI, 0.39-0.93) in the T2 and T3 groups after adjusting for metabolic parameters in subjects without NALFD, respectively; however, the T2 group did not show statistical significance toward a decrease in incident T2DM. A low OBS may be a useful predictive marker in new-onset T2DM for middle-aged and older subjects without NALFD. This implies that the OBS could be an additional valuable tool for assessing the incidence of T2DM among individuals without NAFLD.

The effects of Korean Red Ginseng on stress-related neurotransmitters and gene expression: A randomized, double-blind, placebo-controlled trial.

Background: Korean Red Ginseng (KRG) is an effective anti-stress treatment. In this study, we investigated the therapeutic potential effects of KRG on relieving stress in a general population using transcriptome analysis. Methods: We conducted an 8-week clinical pilot study on 90 healthy men who reported stress. The study was completed by 43 participants in the KRG group and 44 participants in the placebo group. Participants were randomized 1:1 to the KRG and placebo groups. We evaluated the stress by stress response inventory (SRI) at baseline and 8 weeks. The main outcomes were changes in the levels of neurotransmitters (NTs) and NT-related gene expression. NTs were analyzed using automated (GC) content, and levels of gene expression were measured by reads per kilobase of transcript per million mapped reads (RPKM). Results: The KRG group showed significantly preserved epinephrine decrease compared with placebo group at 8 weeks (changes in epinephrine, KRG vs. placebo; -1623.2 ± 46101.5 vs. -35116.3 ± 86288.2, p = 0012). Among subjects who higher SRI score, meaning stress increased compared to baseline, the KRG group showed a smaller decrease in serotonin than the placebo group (changes in serotonin, KRG vs. placebo; -2627.5 ± 5859.1 vs, -8087.4 ± 7162.4, p = 0.005) and a smaller increase in cortisol than the placebo group (changes in cortisol, KRG vs. placebo; 1912.7 ± 10097.75 vs. 8046.2 ± 8050.6 , p = 0.019) in subgroup analysis. Transcriptome findings indicated that KRG intake affects gene expression related with metabolism of choline, adrenalin, and monoamine. Conclusion: These findings suggest that KRG has beneficial effects on the amelioration of stress response in NTs, and this effect is more prominent in stressful situations. Further clinical studies are required to confirm the anti-stress effect of KRG.

Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES).

PURPOSE: Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults. METHODS: We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders. RESULTS: Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84). CONCLUSION: Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

Combined effect of serum carcinoembryonic antigen and hepatic steatosis on new-onset ischemic heart disease among middle-aged and older Korean adults: a cohort study.

Background: Carcinoembryonic antigen (CEA) is a commonly used tumor marker in cancer screening. However, it has also been associated with metabolic alterations. Hepatic steatosis, the accumulation of fat in liver cells, is associated with various cardiovascular risk factors. This study investigated the risk of ischemic heart disease (IHD) in individuals with elevated CEA levels, hepatic steatosis, and their co-occurrence. Methods: The study cohort comprised 5,580 Korean adults who underwent health examinations between November 2006 and June 2010. Data regarding baseline CEA levels, hepatic steatosis status, and development of IHD were collected. Hepatic steatosis was defined as more than two findings: deep attenuation, vascular blurring, and increased liver echogenicity on abdominal ultrasound. Participants were divided into four groups based on their CEA and hepatic steatosis status: no hepatic steatosis and low CEA (group 1), no hepatic steatosis and elevated CEA (group 2), low CEA and hepatic steatosis (group 3), and elevated CEA and hepatic steatosis (group 4). Results: A total of 226 (4.1%) participants developed IHD during the follow-up period. Participants with elevated CEA levels and hepatic steatosis (group 4) had the highest cumulative incidence of IHD in comparison to other groups (p < 0.001). The combined effect of elevated CEA levels and hepatic steatosis showed significantly greater area under the receiver operating characteristic curve than hepatic steatosis alone (p < 0.001). Furthermore, participants with elevated CEA and hepatic steatosis (group 4) had higher risk of developing IHD compared to those with low CEA and no hepatic steatosis (group 1) (hazard ratio: 1.63, 95% confidence interval: 1.04-2.55, p = 0.034). Conclusion: Co-occurrence of elevated CEA levels and hepatic steatosis increases the risk of IHD. Comprehensive risk assessment is crucial to guide interventions and improve cardiovascular health in individuals with both the conditions.

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes.

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86-1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55-1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03-2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03-2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease.

Sex-specific associations of γ-glutamyltransferase to HDL-cholesterol ratio and the incident risk of cardiovascular disease: three Korean longitudinal cohorts from different regions.

Background: The combination of gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) (GGT/HDL-C) is a novel noninsulin-based marker for assessing the risk of nonalcoholic fatty liver disease and type 2 diabetes mellitus. However, whether the GGT/HDL-C ratio is related to the risk of incident cardiovascular disease (CVD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of GGT/HDL-C ratio on incident CVD risk in three large cohorts of Korean men and women. Methods: Data were assessed from 27,643 participants without CVD from the Korean Genome and Epidemiology Study (KoGES), Health Risk Assessment Study (HERAS), and Korea Health Insurance Review and Assessment (HIRA) (HERAS-HIRA) datasets. The participants were divided into four groups according to the GGT/HDL-C quartiles. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD using multivariate Cox proportional-hazard regression models over a 50-month period following the baseline survey. Results: During the follow-up period, 949 patients (3.4%; 529 men and 420 women) developed CVD. The HRs of CVD for GGT/HDL-C quartiles 2-4 were 1.36 (95% CI, 0.91-2.02), 1.54 (95% CI, 1.05-2.26), and 1.66 (95% CI, 1.12-2.47) after adjusting for metabolic parameters in women, but GGT/HDL-C did not show a trend toward increases in incident CVD in men. Regional discrepancies were evident in the results; the increase in HR in the metropolitan hospital cohort was more pronounced than that in the urban cohort, and the risk was not increased in the rural cohort. Conclusion: GGT/HDL-C ratio may be a useful predictive marker for CVD in women. Furthermore, the prevalence of CVD was strongly correlated with the GGT/HDL-C ratio in metropolitan areas, and this correlation was more significant than that observed with GGT or HDL-C in isolation.

Korean Red Ginseng Potentially Improves Maintaining Antibodies after COVID-19 Vaccination: A 24-Week Longitudinal Study.

Despite the effectiveness and safety of COVID-19 vaccines, vaccine-induced responses decline over time; thus, booster vaccines have been approved globally. In addition, interest in natural compounds capable of improving host immunity has increased. This study aimed to examine the effect of Korean Red Ginseng (KRG) on virus-specific antibodies after COVID-19 vaccination. We conducted a 24 week clinical pilot study of 350 healthy subjects who received two doses of the COVID-19 vaccine and a booster vaccination (third dose). These subjects were randomized 1:2 to the KRG and control groups. We evaluated antibody response five times: just before the second dose (baseline), 2 weeks, 4 weeks, 12 weeks after the second dose, and 4 weeks after the third dose. The primary endpoints were changes in COVID-19 spike antibody titers and neutralizing antibody titers. The antibody formation rate of the KRG group was sustained higher than that of the control group for 12 weeks after the second dose. This trend was prominently observed in those above 50 years old. We found that KRG can help to increase and maintain vaccine response, highlighting that KRG could potentially be used as an immunomodulator with COVID-19 vaccines.

The Combination of Uric Acid and Hemoglobin Levels Predicts the Incident Risk of Ischemic Heart Disease More Than Uric Acid Alone in Non-Diabetic Koreans: A Longitudinal Study Using National Health Insurance Data.

Uric acid has been related to cardiovascular disease (CVD). Recently, slightly elevated hemoglobin (Hb) was also shown to be associated with CVD. We retrospectively investigated the joint effect of uric acid and elevated Hb by comparing normal-range uric acid alone on incident ischemic heart disease (IHD) risk in a large cohort of non-diabetic Korean adults using National Health Insurance data. We assessed 16,786 participants without diabetes (8595 men and 8191 women) using extensive cohort data. High Hb was defined as ≥16.4 g/dL in men and 13.8 g/dL in women (>75th percentile). We analyzed the data using two different methods. First, the participants were divided into quartiles according to uric acid levels. Second, subjects were also divided into quartiles: reference (group 1), high uric acid and normal Hb (group 2), normal uric acid and high Hb (group 3), and normal uric acid and high Hb (group 4). We evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox regression analysis over a 50-month follow-up. During the follow-up, 345 (1.9%) participants developed IHD. In the analysis using both uric acid and Hb, compared with the reference group, the HRs for IHD were 1.37 (95% CI, 1.01-1.86) in the second group, 1.63 (95% CI, 1.21-2.21) in the third group, and 1.86 (95% CI, 1.30-2.67) in the fourth group after adjusting for IHD risk factors. Subsequently, patients with high uric acid are more likely to develop incident IHD than control patients. Moreover, we confirmed the joint effects of high uric acid and high hemoglobin on incident IHD. Awareness of these interactions is essential for clinicians. Risk factor management and screening for IHD are part of the routine management of patients with high uric acid and Hb.

Lipid Accumulation Product Index Predicts New-Onset Type 2 Diabetes Among Non-Obese Koreans: A 12-Year Longitudinal Study.

Purpose: The lipid accumulation product (LAP) has been a potential indicator of central lipid accumulation status. This study aimed to assess the longitudinal association between LAP index and incident type 2 diabetes among non-obese Korean adults using a large, community-based Korean cohort observed over 12 years. Patients and Methods: This study included 4281 non-diabetic adults without generalized obesity and abdominal obesity and aged 40-69 years from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to LAP index quartiles, calculated as (waist circumference [cm] - 65) x (triglycerides [mmol/L]) in men and (waist circumference [cm] - 58) x (triglycerides [mmol/L]) in women. We prospectively assessed hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes using multivariate Cox proportional hazard regression models. Results: Overall, 608 (14.2%) participants developed type 2 diabetes during the follow-up period. HRs for incident type 2 diabetes in the second, third, and fourth LAP quartile were 1.32 (95% CI: 0.97-1.79), 1.51 (95% CI: 1.11-2.06), and 2.14 (95% CI: 1.56-2.94), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance. Conclusion: A high LAP index can be an additional indicator for new-onset T2DM among middle-aged and elderly non-obese Koreans.

Potential Association of Isolated γ-Glutamyltransferase Elevation with Incident Ischemic Heart Disease in Lean Koreans.

Isolated elevation of γ-glutamyltransferase (GGT), a microsomal membrane-bound protein, is commonly observed in non-obese Koreans without diabetes, and its clinical implications are not well-known. Therefore, we aimed to investigate the longitudinal effect of isolated GGT on the incidence of ischemic heart disease (IHD) risk in a large cohort of lean non-diabetic Koreans. Data were obtained from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) datasets. The participants were divided into four groups according to the GGT quartile after the exclusion of those participants with diabetes, a body mass index (BMI) ≥ 25 kg/m2, alanine aminotransferase (ALT) ≥ 40 IU/L, and aspartate aminotransferase (AST)/ALT > 1.5, as well as those positive for hepatitis B surface antigen or hepatitis C antibody. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazard regression models over a 50-month period. During the follow-up period, 183 individuals (1.85%) developed IHD. After setting the lowest GGT quartile as a reference group, the HRs of IHD for GGT quartiles 2−4 were 1.66 (95% CI 0.95−2.89), 1.82 (95% CI 1.05−3.16), and 1.98 (95% CI 1.12−3.50), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol consumption, physical activity, mean arterial blood pressure, fasting plasma glucose, and dyslipidemia. An isolated high GGT may be an additional measure for assessing and managing future IHD risks among lean Koreans without diabetes.

Dyslipidaemia-Genotype Interactions with Nutrient Intake and Cerebro-Cardiovascular Disease.

A comprehensive understanding of gene-diet interactions is necessary to establish proper dietary guidelines to prevent and manage cardio-cerebrovascular disease (CCD). We investigated the role of genetic variants associated with dyslipidaemia (DL) and their interactions with macro-nutrients for cardiovascular disease using a large-scale genome-wide association study of Korean adults. A total of 58,701 participants from a Korean genome and epidemiology study were included. Their dietary intake was assessed using a food frequency questionnaire. Dyslipidaemia was defined as total cholesterol (TCHL) ≥ 240 mg/dL, high-density lipoprotein (HDL) < 40 mg/dL, low-density lipoprotein (LDL) ≥ 160 mg/dL, triglycerides (TG) ≥ 200 mg/dL, or dyslipidaemia history. Their nutrient intake was classified as follows: protein intake: high ≥ 30%, 30% > moderate ≥ 20%, and 20% > low in daily total energy intake (TEI); carbohydrate intake: high ≥ 60%, 60% > moderate ≥ 50%, and 50% > low; fat intake: high ≥ 40%, 40% > moderate ≥ 30%, and 30% > low. Odds ratios and 95% confidence intervals were calculated after adjusting for age; sex; body mass index (BMI); exercise status; smoking status; alcohol intake; principal component 1 (PC1); principal component 2 (PC2); and intake of carbohydrates, fats, and proteins. This analysis included 20,596 patients with dyslipidaemia and 1027 CCD patients. We found that rs2070895 related to LIPC was associated with HDL-cholesterol. Patients with the minor allele (A) in rs2070895 had a lower risk of CCD than those carrying the reference allele (G) (odds ratio [OR] = 0.8956, p-value = 1.78 × 10−2). Furthermore, individuals consuming protein below 20% TEI with the LIPC reference allele had a higher risk of CCD than those with the minor allele (interaction p-value 6.12 × 10−3). Our findings suggest that the interactions of specific polymorphisms associated with dyslipidaemia and nutrients intake can influence CCD.

Predictive Value of Serum Uric Acid to HDL Cholesterol Ratio for Incident Ischemic Heart Disease in Non-Diabetic Koreans.

HDL cholesterol, besides its function in lipid metabolism, plays a role in suppressing blood oxidation reactions and protecting vascular endothelial cells. The uric acid/HDL cholesterol ratio (UHR) has recently attracted attention as a new biomarker for evaluating interactions between inflammatory and anti-inflammatory substances in the blood. This study aimed to investigate the longitudinal association between UHR and incident ischemic heart disease (IHD). Data from 16,455 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korean Health Insurance Review and Assessment (HIRA) were assessed. Over 50 months after baseline enrolment, 321 (2.0%) participants developed IHD. The HRs of incident IHD were 0.85 (95% CI, 0.55-1.29), 1.42 (95% CI, 0.94-2.13), and 1.57 (95% CI, 1.01-2.45) in the second, third, and fourth UHR quartiles, respectively, after adjusting for potential confounding variables. In the subgroup analysis by sex-specific quartile, women tended to have higher HRs in the highest UHR quartile. We found that high UHR values were positively associated with incident IHD in Koreans without diabetes. An increased UHR may be a useful measure by which to assess cardiovascular risk in the preclinical stage.

Genome-Wide Association of New-Onset Hypertension According to Renin Concentration: The Korean Genome and Epidemiology Cohort Study.

The renin-angiotensin system (RAS) is a crucial regulator of vascular resistance and blood volume in the body. This study aimed to examine the genetic predisposition of the plasma renin concentration influencing future hypertension incidence. Based on the Korean Genome and Epidemiology Cohort dataset, 5211 normotensive individuals at enrollment were observed over 12 years, categorized into the low-renin and high-renin groups. We conducted genome-wide association studies for the total, low-renin, and high-renin groups. Among the significant SNPs, the lead SNPs of each locus were focused on for further interpretation. The effect of genotypes was determined by logistic regression analysis between controls and new-onset hypertension, after adjusting for potential confounding variables. During a mean follow-up period of 7.6 years, 1704 participants (32.7%) developed hypertension. The low-renin group showed more incidence rates of new-onset hypertension (35.3%) than the high-renin group (26.5%). Among 153 SNPs in renin-related gene regions, two SNPs (rs11726091 and rs8137145) showed an association in the high-renin group, four SNPs (rs17038966, rs145286444, rs2118663, and rs12336898) in the low-renin group, and three SNPs (rs1938859, rs7968218, and rs117246401) in the total population. Most significantly, the low-renin SNP rs12336898 in the SPTAN1 gene, closely related to vascular wall remodeling, was associated with the development of hypertension (p-value = 1.3 × 10-6). We found the candidate genetic polymorphisms according to blood renin concentration. Our results might be a valuable indicator for hypertension risk prediction and preventive measure, considering renin concentration with genetic susceptibility.

Longitudinal Effects of Serum Calcium and Phosphate Levels and Their Ratio on Incident Ischemic Heart Disease among Korean Adults.

Serum calcium and phosphate levels are controlled by a regulatory system, but their individual concentration tendencies and interactions may affect long-term vascular health. This study aimed to assess the effects of serum calcium and phosphate levels on incident ischemic heart disease (IHD) in a large-scale community-dwelling Korean cohort. We evaluated 15,259 non-diabetic individuals (median age, 45 years; range, 30-85) without previous IHD or ischemic stroke using the Korean National Health Insurance data. The study population was classified based on the calcium, phosphate, and calcium/phosphate ratios. Using Cox proportional hazards regression models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD over 50 months after baseline enrolment. The age- and sex-adjusted incidence of IHD gradually increased with serum calcium and phosphate quartiles and decreased with calcium/phosphate ratio quartiles, with an overall crude rate of 2.1% (315/15,259). After setting the lowest calcium, phosphate, and calcium/phosphate ratio quartiles as a reference group, the HRs (95% CIs) of the highest calcium, phosphate, and calcium/phosphate ratio quartiles for IHD were 1.77 (1.15-2.72), 1.73 (1.18-2.55), and 0.58 (0.39-0.87), respectively, after adjusting for potential confounding variables. Serum calcium and phosphate levels were positively associated with IHD incidence, while the serum calcium/phosphate ratio exhibited an inverse relationship. Serum calcium and phosphate homeostasis may merit serious consideration to understand the pathogenesis of coronary atherosclerosis as a risk modifier for IHD.

Relationship of the Triglyceride-Glucose Index with Subclinical White Matter Hypersensitivities of Presumed Vascular Origin Among Community-Dwelling Koreans.

PURPOSE: The triglyceride-glucose (TyG) index, a widely accessible measure, has been a surrogate indicator of peripheral insulin resistance, and its clinical importance continues to grow in East Asia. We hypothesized that the TyG index is relevant to subclinical white matter hypersensitivities (WMHs) of presumed vascular origin among community-dwelling Koreans. METHODS: We investigated the relationship between the TyG index and WMHs on brain magnetic resonance imaging scans in 2417 Koreans over 45 years of age without a history of cancer, stroke, or ischemic heart disease. The study population was divided into four groups according to the TyG index quartiles. Using multiple logistic regression analysis, we assessed the odds ratios (ORs) and 95% confidence intervals (95% CIs) for WMHs across the TyG index quartiles. RESULTS: The prevalence of WMHs was significantly higher in the fourth TyG index quartile, with an overall rate of 9.3%. After adjusting for potential confounding variables, the ORs of WMHs for the TyG index quartiles were 1.00, 1.47 (95% CI, 0.91-2.40), 1.76 (95% CI, 1.05-2.97), and 6.79 (95% CI, 3.85-1.54), respectively. CONCLUSION: We found that higher TyG index values were associated with the brain's WMHs of presumed vascular origin. Our findings suggest that the serum TyG index could be an additional valuable biomarker for assessing the risk of cerebral small vessel disease in the preclinical stage.

Clinical Practice Guidelines for Managing Frailty in Community-Dwelling Korean Elderly Adults in Primary Care Settings.

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and "healthy aging" become more and more important, these guidelines are also expected to increase in clinical usefulness.

Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans.

Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72-2.19), 1.19 (95% CI 0.90-1.57) and 1.76 (95% CI 1.04-2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.