Dietary iron to total energy intake ratio and type 2 diabetes incidence in a longitudinal 12-year analysis of the Korean Genome and Epidemiology Cohort Study.

PURPOSE: Recent study found iron consumption has been associated with an increased risk of type 2 diabetes (T2DM). Even though, high iron intake is correlated with total caloric intake, most studies have evaluated the individual effect of iron and total caloric intake. The aim of this study was to investigate the effect of iron intake, in conjunction with total energy intake, on developing T2DM. We also investigated the interactions between dietary iron and energy ratios (IERs) and iron-related single nucleotide polymorphisms (SNPs) in the development of T2DM. METHODS: The study was carried out in Ansan and Ansung, Korea, between March 2001 and December 2014. A total of 6413 participants (3073 men and 3340 women), aged 40-69 years, were enrolled in this study. The mean follow-up period was 8.4 years. The study population was divided into quartiles based on IERs with cut-off points at 4.54, 5.41, and 6.29. The odds ratios (ORs) for new-onset T2DM were calculated across each quartile of IERs and a random forest model was constructed using the default settings to predict new-onset T2DM. To confirm the interaction among IERs, SNPs, and the incidence of T2DM, we measured the predictive power of new-onset T2DM using IER and six SNPs in genes related to iron metabolism [rs855791 (TPMRSS6), rs38116479 (TF), rs1799852 (TF), rs2280673, rs1799945 (HFT), rs180562 (HFE)]. RESULTS: The prevalence of T2DM was 762 (11.8%). IERs showed a positive association with T2DM. The ORs were 1.30 (95% CI 1.02-1.67), 1.20 (95% CI 0.94-1.56), and 1.43 (95% CI 1.11-1.86) across the IER quartiles after adjusting for non-dietary and dietary metabolic risk factors. When the IER was 1.89-fold higher than the reference group, the risk of developing T2DM increased by 43% (OR 1.43; 95% CI 1.11-1.86). CONCLUSION: A higher IER was positively associated with developing T2DM independent of dietary or non-dietary risk factors. We also found the possible interactions between the identified SNPs and iron intake in relations to T2DM.

Comparison of bacterial community profiles from large intestine specimens, rectal swabs, and stool samples.

The human gastrointestinal tract contains a complex and dynamic population of microorganisms, known as the gut microbiota. Although interest in the role of the gut microbiota in human health has increased in recent years, there remains no standard sampling protocol for analyzing these organisms. Here, we aimed to characterize the microbial composition of distinct segments of the large intestine and to determine whether rectal swabs are suitable for identifying colon microbiota. A total of 100 participants who underwent screening colonoscopy from October 2019 to October 2020 were included in this study. Large intestinal samples (ascending colon, descending colon, sigmoid colon, and rectum) were aspirated by colonoscopy. Rectal swabs were collected before colonoscopy, and stool samples were collected before patients began colonoscopy preparation. All samples were subjected to 16S ribosomal RNA gene sequencing. We identified differences in the number of phylum-level operational taxonomic units among large intestinal samples, rectal swabs, and stool. Five major phyla were detected in all samples (Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria), although their relative abundances varied. Notably, we found that the microbial compositions of rectal swabs were most similar to those of the sigmoid colon and rectum, whereas the microbiota in stool were relatively different than those from the large intestine and rectal swabs. Our results reveal the existence of microbial heterogeneity within different large intestinal compartments and further suggest that rectal swabs are an acceptable and practical tool for gut microbiota analysis. KEY POINTS: • Our findings highlight local microbiome variations within different regions of the large intestine. • Stool samples do not appear to fully recapitulate the gut microbiome. • Our data from a large population-based cohort indicate that rectal swabs can be used to study the gut microbiome.

The triglyceride-glucose index predicts ischemic heart disease risk in Koreans: a prospective study using National Health Insurance Service data.

BACKGROUND: Ischemic heart disease (IHD) without diabetes is considered an important challenge to human health and is associated with a poor prognosis, as well as a lack of health awareness. We prospectively investigated the relationship between the triglyceride-glucose (TyG) index, a surrogate marker of early insulin resistance, and incident IHD risk in a large cohort of nondiabetic Korean adults using National Health Insurance Service data. METHODS: We assessed 16,455 participants (8426 men and 8029 women) without diabetes using data from a health risk assessment study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. The participants were divided into four groups according to TyG index quartiles, calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazards regression models over a 50-month period that followed the baseline survey. RESULTS: During the follow-up period, 322 (2.0%) participants developed IHD. HRs of IHD for TyG index quartiles 2-4 were 1.61 (95% CI 1.05-2.48), 1.85 (95% CI 1.21-2.81), and 2.29 (95% CI 1.50-3.51), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol intake, and physical activity. CONCLUSIONS: A higher TyG index precedes and significantly predicts future IHD among nondiabetic Koreans. Accordingly, the TyG index may be a useful measure in assessing cardiovascular risk for nondiabetic adults in the preclinical stage.

Anisotropic vacancy-mediated phonon mode softening in Sm and Gd doped ceria.

Ceria doped with Sm and Gd (SDC and GDC) has been suggested as a promising candidate for the electrolyte used in solid oxide fuel cells (SOFCs), since it has relatively high oxygen ion conductivity at intermediate temperature. There have been many previous experimental and computational studies to investigate the properties, structure, and effect of vacancies, etc. for SDC and GDC. However, in these previous studies, it is commonly assumed that the interaction between oxygen vacancies is negligible and many focus only on the mono-vacancy system. In addition, the possibility of anisotropic vibrational motion of the oxygen ions around vacancies is often neglected. In this paper, using both first-principle density-functional theory and classical molecular dynamics calculations, we investigate the structural and vibrational properties of the optimized SDC and GDC structures, such as bonding analysis, phonon density-of-state and mean-square-displacement of the oxygen ions. Also, we report the direction-dependent vibrations at the specific frequency of the oxygen ions near the vacancies, activation energies, and diffusion coefficients of SDC and GDC which can extend our understanding of diffusion dynamics in doped ceria-based electrolytes for SOFC applications.

Genetic Variants Linked to Myocardial Infarction in Individuals with Non-Alcoholic Fatty Liver Disease and Their Potential Interaction with Dietary Patterns.

In recent studies, non-alcoholic fatty liver disease (NAFLD) has been associated with a high risk of ischemic heart disease. This study aimed to investigate a genetic variant within a specific gene associated with myocardial infarction (MI) among patients with NAFLD. We included 57,205 participants from a Korean genome and epidemiology study. The baseline population consisted of 45,400 individuals, with 11,805 identified as patients with NAFLD. Genome-wide association studies were conducted for three groups: the entire sample, the healthy population, and patients with NAFLD. We defined the p-value < 1 × 10-5 as the nominal significance and the p-value < 5 × 10-2 as statistically significant for the gene-by-nutrient interaction. Among the significant single-nucleotide polymorphisms (SNPs), the lead SNP of each locus was further analyzed. In this cross-sectional study, a total of 1529 participants (2.8%) had experienced MI. Multivariable logistic regression was performed to evaluate the association of 102 SNPs across nine loci. Nine SNPs (rs11891202, rs2278549, rs13146480, rs17293047, rs184257317, rs183081683, rs1887427, rs146939423, and rs76662689) demonstrated an association with MI in the group with NAFLD Notably, the MI-associated SNP, rs134146480, located within the SORCS2 gene, known for its role in secreting insulin in islet cells, showed the most significant association with MI (p-value = 2.55 × 10-7). Our study identifies candidate genetic polymorphisms associated with NAFLD-related MI. These findings may serve as valuable indicators for estimating MI risk and for conducting future investigations into the underlying mechanisms of NAFLD-related MI.

The Human Genetic Differences in the Outcomes of mRNA Vaccination against COVID-19: A Prospective Cohort Study.

BACKGROUND: This study aimed to explore how genetic variations in individuals impact neutralization activity post-mRNA vaccination, recognizing the critical role vaccination plays in curbing COVID-19 spread and the necessity of ensuring vaccine efficacy amidst genetic diversity. METHODS: In a 4-week clinical pilot study, 534 healthy subjects received their first COVID vaccine dose, followed by the second dose. Antibody levels were evaluated thrice. From this pool, 120 participants were selected and divided into high- and low-antibody groups based on their levels. Genomic DNA was isolated from peripheral blood mononuclear cells for pilot genome-wide association studies (GWAS) conducted on a single platform. Real-time PCR was used to confirm differences in gene expression identified via GWAS analysis. RESULTS: Three SNPs exceeded the level of p < 1.0 × 10-3. The rs7795433 SNP of the HDAC9 gene (7q21.1) showed the strongest association with COVID-19 vaccination under the additive model (OR = 5.63; p = 3 × 10-5). In the PCR experiments, the AA genotype group showed that the gene expression level of HDAC9 was likely to be decreased in the low-antibody-formation group at the time of vaccination. CONCLUSION: We found that AA genotype holders (rs7795433 SNP of the HDAC9 gene) have a high probability of having a higher antibody count when vaccinated, and GG type holders have a high probability of the opposite. These findings show that the genetic characteristics of vaccinated people may affect antibody production after COVID vaccination.

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.

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.

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.

Metabolic Obesity Phenotypes and Incident Cardiovascular Outcomes in Middle-Aged and Older Korean Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study.

Background: This study investigated the association of four metabolic obesity phenotypes with incident coronary artery disease and stroke in a large-scale, community population-based, prospective Korean cohort observed for over 10 years. Methods: The study participants included 7374 adults aged 40-69 years, drawn from the Korean Genome and Epidemiology Study. Participants with different metabolic obesity phenotypes were categorized according to body weight and metabolic health status into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Combined cardiovascular events were defined as coronary artery disease and stroke. We used multivariate Cox proportional hazards regression models to prospectively assess hazard ratios (HRs) with 95% confidence intervals (CIs) for incident coronary artery disease or stroke over 10 years after the baseline survey. Results: During the follow-up period, newly developed coronary artery disease, stroke, and combined cardiovascular events were diagnosed in 151 (2.0%), 137 (1.9%), and 283 (3.8%) participants, respectively. After adjusting for confounding variables, the HRs (95% CIs) for incident combined cardiovascular events were 1.81 (1.34-2.46) in the MUHO group, 1.29 (0.92-1.81) in the MUHNO group, and 1.21 (0.81-1.79) in the MHO group compared with those in the MHNO group. Conclusions: This study revealed distinct risks associated with four metabolic obesity phenotypes concerning incident coronary artery disease and stroke. After adjusting for potential confounding variables, the results indicated that MUHO, but not MUHNO or MHO, showed a higher risk of developing coronary artery disease and stroke than MHNO.

Single-cell analysis of human PBMCs in healthy and type 2 diabetes populations: dysregulated immune networks in type 2 diabetes unveiled through single-cell profiling.

Abnormalities in glucose metabolism that precede the onset of type 2 diabetes (T2D) activate immune cells, leading to elevated inflammatory factors and chronic inflammation. However, no single-cell RNA sequencing (scRNA-seq) studies have characterized the properties and networks of individual immune cells in T2D. Here, we analyzed peripheral blood mononuclear cells (PBMCs) from non-diabetes and T2D patients by scRNA-seq. We found that CD14 monocytes in T2D patients were in a pro-inflammatory state and intermediate monocytes expressed more MHC class II genes. In T2D patients, cytotoxic CD4 T cells, effector memory CD8 T cells, and γδ T cells have increased cytotoxicity and clonal expansion. B cells were characterized by increased differentiation into intermediate B cells, plasma cells, and isotype class switching with increased expression of soluble antibody genes. These results suggest that monocytes, T cells, and B cells could interact to induce chronic inflammation in T2D patients with pro-inflammatory characteristics.

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.

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.

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.

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.

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.

The relationship between arterial stiffness and nonalcoholic fatty liver disease.

AIM: Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease and some studies have documented its link with cardiovascular risk factors. This study aimed to investigate the association between arterial stiffness and NAFLD. METHODS: Among 1,442 health check-up subjects (955 men, 487 women), we examined the association between brachial-ankle pulse wave velocity (baPWV) as a measurement of arterial stiffness and the presence of NAFLD based on abdominal sonographic findings. Multivariate linear and logistic regression analyses were conducted to examine the independent association between baPWV and the presence of NAFLD in gender-specific manners. RESULTS: In multivariate regression analysis, NAFLD was found to be independently associated with baPWV in both men and women. Moreover, in multivariate logistic regression analysis, a graded independent relation was found between higher levels of baPWV and the prevalence risk of NAFLD. Odds ratios (95% CI) for the highest vs. the lowest quartile of baPWV were 1.85 (range, 1.13-2.62) in men and 3.32 (1.45-7.62) in women after adjusting for age, smoking status, regular exercise, body mass index, blood pressure, fasting plasma glucose, triglyceride, HDL-cholesterol, hypertension and diabetes. CONCLUSION: Arterial stiffness was independently associated with the prevalence risk for NAFLD regardless of classical CVD risk factors.

The relationship of platelet count, mean platelet volume with metabolic syndrome according to the criteria of the American Association of Clinical Endocrinologists: a focus on gender differences.

Metabolic syndrome (MS) is becoming globally prevalent and it is clinically important because of its association with type 2 diabetes and cardiovascular disease, and some cancers. Recently, platelet count has been linked to insulin resistance and MS in addition to being a marker of hemostasis. Also, mean platelet volume (MPV) has been known to represent platelet activity. Platelet counts and MPV are modified by various biosocial and lifestyle factors such as race, age, gender, smoking habit, alcohol consumption, and physical activity. Thus, the direction and magnitude of this association may differ by gender. In this regard, proper interpretion of platelet counts and MPV by gender could be important in the people with MS. We examined the relationship between platelet counts, MPV, and MS through gender-specific analyses for 3827 Korean adults (2169 men and 1658 women) in a health examination program. In women, platelet counts were significantly higher in subjects with MS compared to in those without MS (p < 0.001), whereas MPV was significantly lower (p = 0.001). However, no such trend was observed in men. Multiple regression analyses also showed that MS is positively associated with platelet counts and inversely associated with MPV, independently of confounding variables only in women. The results suggest that platelet counts and MPV might be a surrogate marker associated with clustered MS in women.

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.