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Background A deep learning (DL) model to identify lung cancer screening candidates based on their chest radiographs requires external validation with a recent real-world non-U.S. sample. Purpose To validate the DL model and identify added benefits to the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations in a health check-up sample. Materials and Methods This single-center retrospective study included consecutive current and former smokers aged 50-80 years who underwent chest radiography during a health check-up between January 2004 and June 2018. Discrimination performance, including receiver operating characteristic curve analysis and area under the receiver operating characteristic curve (AUC) calculation, of the model for incident lung cancers was evaluated. The added value of the model to the 2021 USPSTF recommendations was investigated for lung cancer inclusion rate, proportion of selected CT screening candidates, and positive predictive value (PPV). Results For model validation, a total of 19 488 individuals (mean age, 58 years ± 6 [SD]; 18 467 [95%] men) and the subset of USPSTF-eligible individuals (

Objectives: We introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies.Methods: We mainly focused on the characteristics of individual cohort studies from the KCC. We developed “PROFAN”, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated.Results: The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917-72 102.Conclusions: We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.

BackgroundIdentifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.ObjectiveTo assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.MethodsUsing data from the Parkinson’s Progression Markers Initiative (PPMI)de novoPD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.ResultsHalf of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at thenextannual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (ppp=0.0341), lower dopamine transporter binding (p=0.0043), and lower CSF total α-synuclein levels (p=0.0033). Symptomatic treatment was not significantly associated with reaching a milestone (p=0.1639).ConclusionsClinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear.This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as "slow" and "accelerated" and compared among four different sonographic changes in steatosis status: "normal," "improved," "worsened," and "persistent." A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function.Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEVRegression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.

Supplementary Figure Legends - PDF file 151K, Legend for Supplementary Figures S1-S6

Supplementary Figure S2 PDF - PDF file 414K, Activation of autophagy in AMC-HN-9 cells

Supplementary Methods - PDF file 168K, Additional experimental procedures, including western blot, RT-PCR, cell cycle analysis, etc. Also includes supplementary references

SummaryBackgroundRecent research demonstrates that α-synuclein seed amplification assays (αSyn-SAA) accurately differentiate Parkinson’s disease (PD) patients from healthy controls (HC). We used the well-characterized, multicenter Parkinson’s Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of αSyn-SAA and to examine whether the assay identifies heterogeneity among patients and enables early identification in at-risk groups.MethodsαSyn-SAA analysis of cerebrospinal fluid (CSF) was performed using previously described methods. We assessed sensitivity and specificity in PD and HC, including subgroups based on genetic and clinical features. We determined the frequency of positive αSyn-SAA results in prodromal participants (REM sleep behavior disorder and hyposmia) and non-manifesting carriers (NMCs) of genetic variants associated with PD and compared αSyn-SAA to clinical measures and other biomarkers.Findings1,123 participants were included: 545 PD, 163 HCs, 54 participants with scans without evidence of dopaminergic deficit (SWEDDs), 51 prodromal participants, and 310 NMCs. Sensitivity and specificity for PD versus HC were 88% and 96%, respectively. Sensitivity in sporadic PD with the typical olfactory deficit was 99%. The proportion of positive αSyn-SAA was lower in subgroups including LRRK2 PD (68%) and sporadic PD patients without olfactory deficit (78%). Participants with LRRK2 variant and normal olfaction had an even lower αSyn-SAA positivity rate (35%). Among prodromal and at-risk groups, 86% of RBD and hyposmic cases had positive αSyn-SAA. 8% of NMC (either LRRK2 or GBA) were positive.InterpretationThis study represents the largest analysis of αSyn-SAA for biochemical diagnosis of PD. Our results demonstrate that the assay classifies PD patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis. These findings suggest a crucial role for αSyn-SAA in therapeutic development, both to identify pathologically defined subgroups of PD patients and to establish biomarker-defined at-risk cohorts.FundingPPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including: PPMI is supported by a consortium of private and philanthropic parnters: Abbvie, AcureX, Aligning Science Across Parkinson’s, Amathus Therapeutics, Avid Radiopharmaceuticals, Bial Biotech, Biohaven, Biogen, BioLegend, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel, Coave, DaCapo Brainscience, 4D Pharma, Denali, Edmond J. Safra Foundation, Eli Lilly, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, VanquaBio, Verily, Voyager Therapeutics, and Yumanity.Research in ContextEvidence before the studyWe searched PubMed with the terms Parkinson’s disease (PD), prodromal, Non-manifest carriers, GBA, LRRK2 and real-me quaking-induced conversion (RT-QuIC), protein misfolding cyclic amplification (PMCA), and seed amplification assay (SAA) for articles published in English on or before Oct 25, 2022, in any field. This is a large and rapidly growing literature, and a number of studies were identified, including case-series of PD patients with and without genetic variants, individuals with isolated REM sleep behavior disorder (RBD), and a small number of studies of non-manifesting carriers of genetic variants (4) associated with PD.Added value of the studyTo our knowledge, this is the largest report of comparative data from a cohort of PD patients, healthy controls, individuals with clinical syndromes prodromal to PD (hyposmia and RBD), and non-manifest carriers ofLRRK2 G2019SandGBA N370Smutations. The strengths of our data include a large sample size, robust clinical data set, a high percentage of DAT scans completed, and the ability to compare non-manifest carriers to similar aged healthy controls, which allows for inter-group comparisons and sub-group analysis. The key novel findings in this study include: 1) marked variability in rates of positive αSyn-SAA results particularly among LRRK2 variant carriers depending on olfactory performance and sex; 2) αSyn-SAA positivity in prodromal and NMCs without dopaminergic imaging abnormalities in a substantial number of cases, while the converse is less common, indicating that αSyn-SAA may be a very early indicator of synucleinopathy. We also confirmed the high diagnostic accuracy of αSyn-SAA for sporadic PD vs. HC and that αSyn-SAA is negative in the vast majority of NMC, suggesting that the presence of synuclein aggregates in CSF is not a life-long trait but rather acquired at some point relatively close to disease onset.Implications of all available evidenceOur results demonstrate that the assay classifies PD patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis. These findings suggest a crucial role for αSyn-SAA in therapeutic development, both to identify pathologically defined subgroups of PD patients and to establish biomarker-defined at-risk cohorts.

Injection laryngoplasty (IL) is performed to reduce the gap between vocal folds induced by unilateral vocal fold paralysis (UVFP). Voice quality after IL may be different due to other factors that influence voice quality. Voice therapy has been reported to improve voice quality after IL in patients with UVFP. This study evaluated the efficacy of voice therapy combined with IL.Patients with UVFP who underwent IL as primary therapy from March 2017 to June 2019 were evaluated. The enrolled patients were divided into two groups, those who did and did not receive voice therapy after IL. Voice quality was evaluated using perceptual, acoustic, and aerodynamic parameters, and voice handicap index-30 scores one month after IL and after completing each treatment.Of 261 patients who underwent IL during the study period, 40 were enrolled, including 21 who did and 19 who did not receive voice therapy. Voice parameters one month after IL did not differ between these two groups. Jitter, shimmer, noise-to-harmonic ratio, and mean flow rate decreased, while maximum phonation time increased after voice therapy (both P0.05). In the absence of voice therapy, improved voice parameters were maintained for six months after IL. Total voice handicap index-30 scores decreased, from 35.6 to 19.1 (P0.05), in patients who received voice therapy.Voice therapy following IL is beneficial to patients with UVFP. Combined treatment can help to maintain improved voice quality more than six months after IL.

Moyamoya disease, a rare chronic cerebrovascular disease with a fragile vascular network at the base of the brain, can cause ischemic or hemorrhagic strokes or seizures. Precise blood pressure control and adequate analgesia are important for patients with moyamoya disease to prevent neurological events such as ischemia and hemorrhage. This study aimed to compare the intraoperative mean arterial pressure of pregnant women with moyamoya disease according to the mode of anesthesia (general anesthesia versus spinal anesthesia) used during cesarean delivery.We retrospectively reviewed the medical records of 87 cesarean deliveries in 74 patients who had been diagnosed with moyamoya disease before cesarean delivery. The primary outcome, intraoperative maximum mean arterial pressure during anesthesia, was compared according to the type of anesthesia administered (general versus spinal anesthesia). Other perioperative hemodynamic data (lowest mean arterial pressure, incidence of hypotension, vasopressor use, and antihypertensive agent use), maternal neurologic symptoms, neonatal outcomes (Apgar scores7, ventilatory support, and intensive care unit admission), maternal and neonatal length of stay, postoperative pain scores, and rescue analgesic use were assessed as secondary outcomes.While the lowest blood pressure during anesthesia and incidence of hypotension did not differ between the 2 groups, the maximum mean arterial pressure during anesthesia was lower in the spinal anesthesia group than that in the general anesthesia group (104.8 ± 2.5 vs 122.0 ± 4.6; P = .002). Study data did not support the claim that maternal neurologic symptoms differ according to the type of anesthesia used (5.6% vs 9.3%; P = .628); all patients recovered without any sequelae. The postoperative pain scores were lower, and fewer rescue analgesics were used in the spinal anesthesia group than in the general anesthesia group. Other maternal and neonatal outcomes were not different between the 2 groups.Compared with general anesthesia, spinal anesthesia mitigated the maximum arterial blood pressure during cesarean delivery and improved postoperative pain in patients with moyamoya disease.

Background/Objectives: Shoulder function is an important aspect of health related quality of life (QOL). Neck dissection impairment index (NDII) is a simple shoulder-specific questionnaire. This study aimed to evaluate the association between QOL and NDII in patients who underwent neck dissection to validate the Korean version of NDII.Materials & Methods: This study enrolled 74 patients with head and neck cancer who underwent neck dissection from December 2013 to April 2014. Patients completed questionnaires on QOL including the European Organization of Research and Treatment of Cancer 30-item Core QOL questionnaire (EORTC QLQ-C30) and NDII which was translated into Korean. Validity was evaluated by calculating the Pearson correlation coefficient between NDII and EORTC QLQ-C30.Results: We compared preoperative, postoperative within a week, 1st and 3rd months NDII scores. The total NDII scores were 14.7, 47.4, 33.7 and 34.3 each. Clinical variables including gender, site of primary tumor, performing revision neck dissection, radiotherapy and flap reconstruction were not significantly associated with NDII. However NDII mean score of patients who underwent unilateral neck dissection over 3 levels is most increased after operation. During all periods NDII scores were significantly associated with functioning score. Although other scores are lower correlation than function scores, global health status scores and symptom scores are also correlation with NDII.Conclusion: NDII was valid instrument and can be used not only in the clinical practice to assess shoulder dysfunction but also in the simple instrument to evaluate global QOL in Korea patients with having neck dissection.

The prevalence and intensity of Opisthorchis viverrini metacercariae (OvMc) were investigated in fish from 3 southern administrative regions along the Mekong River in Cambodia, i.e., Phnom Penh, Takeo, and Kandal Provinces from 2017 to 2020. A total of 295 freshwater fish (24 species) were transported to our laboratory with ice and examined using the artificial digestion method. In Phnom Penh, among 4 fish species positive for OvMc, 9 (23.7%) of 38 specimens examined were infected, and their intensity of infection averaged 4.3 metacercariae per infected fish. In Takeo Province, among 10 fish species positive for OvMc, 24 (38.1%) out of 63 fish examined were infected, and their intensity of infection was av. 14.4 metacercariae per infected fish. In particular, all of 3 Osteochilus schlegelii fish examined were infected, and their infection intensity was high, 34.7 metacercariae per fish. In Kandal Province, among 6 fish species positive for OvMc, 46 (90.2%) out of 51 specimens examined were infected, and their infection intensity was 24.0 metacercaraie per infected fish. All fish of Systomus orphoides (n=17), Barbonymus altus (n=14), and Rasbora aurotaenia (n=2) were infected, and their intensity of infection averaged 37.7, 21.6, and 18.5 metacercariae per fish, respectively. Metacercariae of Haplochis yokogawai, Haplorchis taichui, and Centrocestus formosanus were detected in fish from Takeo and Kandal Provinces. From these results, it has been confirmed that a variety of fish species from Phnom Penh, Takeo, and Kandal Provinces are commonly infected with OvMc, and preventive measures to avoid human O. viverrini infection should be performed in Cambodia.

In this study, experiments were carried out to evaluate the seismic performance of a hybrid prestressed precast concrete (HPPC) system devised to ensure the integrity of precast concrete (PC) beam-column joints by introducing the post-tensioning method. A total of four full-scale HPPC beam-column joints were fabricated, and the presence of a topping slab, a post-tensioned length, and a type of tendon were set as the main variables. The quasi-static cyclic loading tests were performed to analyze the load-story drift ratio response, failure mode, ductility, residual deformation, and energy dissipation capacity of each specimen. The seismic performance of the specimen was then quantitatively evaluated based on the acceptance criteria of the ACI 374 report. The shear strength estimation model for the HPPC beam-column joints was also proposed and the proposed model was verified in detail using the test results.

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6 474 (1 484 cases and 4 990 controls) and 1 654 (557 cases and 1 097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10− 8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15–1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1 757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (15 771 cases and 178 777 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.

Background and Objectives Scalp angiosarcoma is a rare but aggressive vascular malignancy. It is often found in the advanced state and tends to cause distant metastasis at an early stage. There is no consensus on a treatment modality, although wide excision followed by adjuvant therapy is currently used. The purpose of this study was to analyze the treatment results and disease progress pattern of scalp angiosarcoma in a single institution.Subjects and Method We enrolled patients who diagnosed with scalp angiosarcoma at Asan Medical Center from March 2011 to September 2019. Disease course and prognostic factors were analyzed by estimating overall survival rate and disease free survival.Results A total 12 patients were enrolled in this study. The median overall survival was 16.0 months. The 3-year-survival rate was 10.6%, and the median disease free survival was 5.0 months. On the average, it took 11.4 months till death after recurrence.Conclusion Although wide surgical excision and multiple adjuvant therapies are employed, scalp angiosarcoma showed frequent recurrences and metastasis which led to poor outcomes. Further investigations for scalp angiosarcoma are necessary to improve treatment outcomes.

We present theoretical and experimental results to obtain an intuitive understanding of bulk modulus of metamaterials composed of Helmholtz resonators (HR). Using transmission line theory, we introduce an intuitive method to determine the frequency domain in which the negative bulk modulus appears. The results obtained by simulations and experiments are consistent with theoretical results found using transmission line theory. The results suggest that wider negative (BNG) areas of bulk modulus can be obtained using two HRs than one HR of the same total cavity volume.

In this study, three-dimensional K - E turbulence numerical simulations were conducted to analyze the extent of hazardous area for the sonic jet leakage of flammable gas. Incompressible fluid flows were simulated based on an inlet boundary condition estimated using the theory of “equivalent leak diameter” to prevent the direct simulation of sonic flows near the leakage hole. Numerical simulations of 20 methane leakage scenarios providing the lower explosive limit contour showed shapes of the hazardous area with a maximum height of approximately 12-14 times larger than the maximum width, owing to convection. The extents of hazardous area determined using computational fluid dynamics (CFD) were approximately 5%-10% lower than the results obtained with 1 m over based on IEC 60079-10-1. For scenarios in which quantitative data were not calculated using IEC 60079-10-1 due to low release rates, CFD provided quantitative data for the extent of hazardous area, showing nonlinear relationships with the pressure and diameter of leak holes.

All-solid-state batteries (ASSBs) that employ anode-less electrodes have drawn attention from across the battery community because they offer competitive energy densities and a markedly improved cycle life. Nevertheless, the composite matrices of anode-less electrodes impose a substantial barrier for lithium-ion diffusion and inhibit operation at room temperature. To overcome this drawback, here, the conversion reaction of metal fluorides is exploited because metallic nanodomains formed during this reaction induce an alloying reaction with lithium ions for uniform and sustainable lithium (de)plating. Lithium fluoride (LiF), another product of the conversion reaction, prevents the agglomeration of the metallic nanodomains and also protects the electrode from fatal lithium dendrite growth. A systematic analysis identifies silver (I) fluoride (AgF) as the most suitable metal fluoride because the silver nanodomains can accommodate the solid-solution mechanism with a low nucleation overpotential. AgF-based full cells attain reliable cycling at 25 °C even with an exceptionally high areal capacity of 9.7 mAh cm

Suppressor of cytokine signaling (SOCS) proteins are primarily feedback inhibitors of cytokine signaling. The two conserved domains of SOCS proteins have distinct functions. Src homology 2 (SH2) domain inhibits cytokine receptor, while SOCS box acts as an E3 ubiquitin ligase. SOCS2, a cytokine signaling suppressor, has been primarily implicated in regulating inflammatory conditions in neuronal diseases. However, SOCS proteins have been suggested to play diverse roles in healthy and diseased nervous system including neurodegenerative disorders. In this study, SOCS2 was found to be upregulated in Huntington's disease and was substantially induced in extended polyglutamine (polyQ)-expressing striatal cells. The induced level was augmented under aging conditions. In extended polyQ-expressing cells, downregulated SOCS2 improved autophagic dysfunction rather than altered inflammatory conditions. Overall, we suggest that SOCS2 involves in regulating autophagy by functioning as an E3 ligase in extended polyQ conditions, and consequently regulates cell damage and cell death type.

OBJECTIVES/HYPOTHESIS There may be an interobserver variation in the diagnosis of laryngeal disease based on laryngoscopic images according to clinical experience. Therefore, this study is aimed to perform computer-assisted diagnosis for common laryngeal diseases using deep learning-based disease classification models. STUDY DESIGN Experimental study with retrospective data METHODS: A total of 4106 images (cysts, nodules, polyps, leukoplakia, papillomas, Reinke's edema, granulomas, palsies, and normal cases) were analyzed. After equal distribution of diseases into ninefolds, stratified eightfold cross-validation was performed for training, validation process and remaining onefold was used as a test dataset. A trained model was applied to test sets, and model performance was assessed for precision (positive predictive value), recall (sensitivity), accuracy, F1 score, precision-recall (PR) curve, and PR-area under the receiver operating characteristic curve (PR-AUC). Outcomes were compared to those of visual assessments by four trainees. RESULTS The trained deep neural networks (DNNs) outperformed trainees' visual assessments in discriminating cysts, granulomas, nodules, normal cases, palsies, papillomas, and polyps according to the PR-AUC and F1 score. The lowest F1 score and PR-AUC of DNNs were estimated for Reinke's edema (0.720, 0.800) and nodules (0.730, 0.780) but were comparable to the mean of the two trainees' F1 score with the best performances (0.765 and 0.675, respectively). In discriminating papillomas, the F1 score was much higher for DNNs (0.870) than for trainees (0.685). Overall, DNNs outperformed all trainees (micro-average PR-AUC = 0.95; macro-average PR-AUC = 0.91). CONCLUSIONS DNN technology could be applied to laryngoscopy to supplement clinical assessment of examiners by providing additional diagnostic clues and having a role as a reference of diagnosis. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2558-2566, 2021.

In a post-tensioned precast concrete beam–column connection, the precast beams are post-tensioned to ensure the integrity of the connection and to provide recentring characteristics when the connection is subjected to seismic loads. In this study, the post-tensioned precast concrete beam–column connections were tested under reverse-cyclic loading with the test variables of grout strength at the beam–column interface and prestressing stress of stands. The test results showed that the post-tensioned precast concrete beam–column connections have a seismic performance equivalent to that of a conventional reinforced concrete beam–column connection. When high prestress is applied, however, confinement reinforcement is required at the beam ends to secure sufficient deformation capacity without crushing of concrete. An analysis model for post-tensioned precast concrete beam–column connections is also proposed; the model considers the bond properties of prestressing strands, and provides good agreement with the experimental results.

BackgroundClonal hematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of hematopoietic stem cells with age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the pathogenic mechanism of CHIP in atherosclerotic cardiovascular disease (ASCVD) development is not yet fully understood.MethodsIn a cohort comprising 4,300 asymptomatic Korean participants aged 40–79 years, we investigated the risks associated with ASCVD by CHIP and the interplay of CHIP with other traditional risk factors for developing ASCVD. Using coronary computed tomography angiography (CCTA), we noninvasively assessed the changes in coronary arteries to evaluate CHIP-associated atherosclerosis.ResultsCHIP was present in 368 participants (8.6%). The most commonly mutated genes in CHIP included DNMT3A, TET2, and ASXL1. During follow-up (median, 4.7 years), 18 ASCVD cases (4.9%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (pppS-index, 4.61; 95% CI 1.04–20.57, p=0.045). Serial CCTAs supported our findings by displaying de novo measurable coronary atherosclerosis with unstable plaque and in proximal lesions only in CHIP carriers with high LDL cholesterol.ConclusionThe presence of CHIP was significantly associated with the risk of ASCVD through synergy with LDL cholesterol in the general population, which might promote the early stage of coronary atherosclerosis.