Search

In this large-scale nationwide cohort comprising 3 688 787 asymptomatic young adults under 40 years, we showed that the long-term risk of cardiovascular disease (CVD) increased in proportion with cumulative exposure to metabolic risk, as assessed by temporal changes in metabolic syndrome (MetS) status, with blood pressure (BP) demonstrating the greatest impact.The risk of CVD exhibited a gradual increase in accordance with cumulative metabolic risk exposure, with a two-fold increment in the MetS-persistent group.Among the MetS components, persistent exposure to elevated BP had the most profound impact to increase the risk of CVD, and the optimization of BP levels might be helpful to promote long-term cardiovascular health in young adults.Graphical Abstract

In this cohort study of 4300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of LDL cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of ‘early’ stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.Graphical Abstract

Graphical Abstract

Aims We sought to investigate the association of obesity and metabolic health status with the incidence of clinical hypertrophic cardiomyopathy (HCM) diagnosis in the general population. Our goal was to identify modifiable risk factors to attenuate clinical expression of HCM, enabling management evolution from a mostly passive strategy of risk stratification to a proactive strategy of modifying disease expression.Methods Using nationwide population-based data from the Korean National Health Insurance Service, 28,679,891 people who were free of prevalent HCM and who underwent health examinations between 2009 and 2015 were followed until 31 December 2016. The primary outcome was clinical HCM that was defined as incident diagnosis of HCM during the follow-up, after a blanking period of 12 months.Results Over a median follow-up of 5.2 years, 0.027% (n= 7851) of the study participants were diagnosed as incident HCM. The incidence rate per 1000 person-years was 0.059. A significant association was found between body mass index (BMI) and the incidence of clinical HCM after multivariate adjustment, with a hazard ratio per 1 kg/m2increase in BMI of 1.063 (95% confidence interval 1.051–1.075). Metabolically unhealthy participants had a greater incidence of HCM than metabolically healthy participants, regardless of obesity status. The effect of BMI was more pronounced in several subgroups, including participants with no hypertension, those aged less than 65 years and men.Conclusion We found that individuals with obesity and/or metabolic abnormalities had a significantly higher incidence of clinical HCM diagnosis than their counterparts. Efforts to manage obesity and metabolic abnormalities may be important in modifying clinical expression of HCM.

Aims Dyslipidaemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We investigated the risks of death and cardiovascular disease in relation to each lipid component to establish evidence for primary prevention in young adults.Methods In this nationwide population-based cohort study, we analysed 5,688,055 statin-naïve subjects, aged 20–39 years, undergoing general health check-ups between 2009 and 2014. The endpoint was a composite of clinical events including death, myocardial infarction (MI), and stroke. We compared the incidence and risk of clinical events according to each lipid variable.Results During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%): 16,262 deaths (0.29%), 8578 MIs (0.15%), and 5967 strokes (0.10%). The risk of clinical events gradually increased with increasing total cholesterol (TC) and triglycerides and decreasing high-density lipoprotein cholesterol (HDL-C), largely driven by MI. Low-density lipoprotein cholesterol (LDL-C) had a J-shaped association with clinical events, showing the lowest risk for LDL-C of 84–101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted hazard ratio, 1.20; p< 0.001) after adjusting for conventional risk factors.Conclusions For statin-naïve young adults, the risk of clinical events was proportional to lipid levels, positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had an independent and the strongest association with the clinical events. Screening and intervention for abnormal lipid levels, particularly triglycerides, from an early age might be of clinical value.

Autism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8(Chd8+/N2373K) that was first identified in human CHD8(Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice. Autism is ~4 times more common in males. Jung et al. reveal male-preponderant abnormal behaviors in mice lacking CHD8, a chromatin remodeler, accompanying sexually dimorphic changes in neuronal firing, synaptic transmission, and gene expression.

Background:Arterial stiffness has been established as a surrogate marker for the prognosis of cardiovascular disease. Arterial stiffness is also a predictor of future cardiovascular events, and is the earliest detectable manifestation of adverse structural and functional changes to blood vessel walls. Summary and Key Messages:The cardio-ankle vascular index (CAVI) is an index representing the stiffness of the entire arterial segments from the aorta to the ankle independent of the blood pressure at the time of the measurement. This paper provides an overview of the clinical application of arterial stiffness measurement by CAVI in asymptomatic Koreans. It includes the association between cardiometabolic risk factors and CAVI, and the relation between CAVI and asymptomatic coronary artery disease.

Context:Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown.Objective:This study investigated the longitudinal association between NAFLD and CAC score.Design and Setting:This study is a longitudinal cohort study performed in a healthcare center.Participants:Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography.Main Outcome Measures:CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed.Results:More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P< .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01–2.21; P= .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P= .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (Pfor trend = .043).Conclusions:NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

Background Psoriasin is known to be expressed in diverse organs, where it exerts antimicrobial activity. Psoriasin is also involved in the local host defense mechanism against pathogens. We hypothesized that allergy-related T-helper cell type 2 (Th2) cytokines may regulate the expression of psoriasin.Methods We treated normal human nasal epithelial (NHNE) cells with IL-4 or IL-13. Using human nasal tissues, we compared the expression level of psoriasin. We performed real-time polymerase chain reaction and Western blot assays using NHNE cells. Immunohistochemical staining and Western blot assays were performed with human nasal tissues. Furthermore, we studied the antimicrobial activity of nasal secretions from normal and allergic rhinitis patients.Results IL-13 markedly down-regulated psoriasin expression at the gene and protein levels in NHNE cells, and it also decreased the amount of psoriasin protein that was secreted into the extracellular compartment in NHNE cells. IL-4 had no statistically significant effect. Results from immunohistochemical staining and Western blot assays showed that psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. Nasal secretions of allergic rhinitis patients exhibited decreased antimicrobial activity compared with control subjects.Conclusion We found that Th2 cytokines regulated psoriasin expression in NHNE cells, and psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. The decreased expression of psoriasin may be related to the reduction in antimicrobial capacity of nasal secretions under allergic conditions, resulting in an increase in susceptibility to viruses or bacterial infections.

The authors report the effects of heat treatment on the morphological and the crystallization behaviors of a photoresponsive 65CdO-17.5B2O3-17.5SiO2(mol%) bulk glass and its film. The bulk glass exhibited a clear phase-separation morphology when heat treated at 575 °C for 1 h, and started to crystallize preferentially into phases with high CdO contents after heat treatment at 595 °C. Heat treatment of the films at 575 °C for 2 h resulted in simultaneous phase separation and crystallization. The morphology of the film heat treated at 575 °C was found to comprise discontinuous CdO-poor phases formed in the matrix of a CdO-rich phase; however, these discontinuous phases became interconnected upon subsequent heat treatment at temperatures over 575 °C. Various phases were formed concurrently by crystallization, with relatively large crystals of high CdO content preferentially formed in the CdO-rich phase whereas small crystals of low CdO content formed in the CdO-poor phase. The main crystals of the heat-treated films were found to be transformed into crystal phases with higher CdO contents with increasing heat-treatment temperature, and this is likely caused by a change in the composition related to phase separation.

Hierarchically mesoporous TiO2films with a high degree of order and connectivity on the sub-100-nm scale are successfully fabricated by the dual-templating methods sequentially applied. In this approach, the self-assembly of block copolymers combined with sol–gel reaction is first used to generate highly ordered mesoporous films by optimizing their self-assembling behavior. At the next step, 50-nm PS nanoparticles are deposited on the mesoporous films generated in the previous step to produce the colloidal crystals, and their inverse structure with a high degree of order, otherwise, would not form the colloidal crystals but generate a colloidal glassy phase with poor order. In addition to the exceptionally high degree of order, mesoporous films exhibit a high porosity that spans from the top surface to the bottom surface throughout the entire film without clogging. Especially wide pores at the top layer enable functional materials of large size to access the inside the films with small pores, maximizing their performance. As a proof of concept, photocatalytic effects are examined for the mesoporous films with different structures. In terms of the template pattern, the line pattern and bowl structure are also shown to guide the self-assembly of colloidal particles when their characteristic size matches with the particle diameter, in addition to the hexagonal packing.

Background:Dyslipidemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We sought to investigate the risk of death and cardiovascular disease in relation to lipid components to establish evidence for primary prevention in young adults.Methods:In a nationwide cohort using the National Health Insurance claims database, we analyzed 5,688,055 statin-naïve subjects, aged 20-39 years, undergoing health check-up between 2009 and 2014. The study endpoint was a composite of clinical events, including death, myocardial infarction (MI), and stroke. We compared the incidence and the risk of clinical events according to lipid variables, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides.Results:During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%); 16,262 deaths (0.29%), 8,578 MIs (0.15%), and 5,967 strokes (0.10%). The risk of clinical events gradually increased with increasing TC and triglycerides, and decreasing HDL-C, with a great contribution by MI. LDL-C had a J-shaped association with the study endpoint, showing the lowest risk in LDL-C of 84-101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted HR 1.20, p<0.001), after adjusting for conventional risk factors.Conclusions:In ‘statin-naïve’ young adults aged 20-39 years, the risk of clinical events was proportional to lipid levels; positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had the strongest and independent association with clinical events. Screening and intervention of abnormal lipid levels, particularly triglycerides, from an early age might be required.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text