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Background: Recent studies have suggested that increased brachial-ankle pulse wave velocity (baPWV) is a risk factor for diabetes. Exploring its relationship with insulin resistance is of interest, necessitating further studies across different sexes and age groups., Methods and Results: This cohort study involved 119 170 Korean adults with an average age of 39.8 years, none of whom had diabetes at baseline. As part of a health screening, baPWV measurements were taken. Over a median follow-up period of 5.6 years, fasting blood glucose, glycated hemoglobin, insulin levels, and questionnaire responses were collected. The risk of developing diabetes was evaluated using a flexible parametric proportional hazards model with data stratified by sex and age group (<40 versus ≥40 years). During the follow-up period, diabetes was diagnosed in 5966 participants (5.0%). A fully adjusted model found that the hazard ratios for diabetes onset associated with baPWV quartiles Q2 (1171.0-1270.5 cm/s), Q3 (1271.0-1376.0 cm/s), and Q4 (≥1376.5 cm/s) compared with Q1 (<1171.0 cm/s) were 1.06 (95% CI, 0.96-1.17), 1.25 (1.14-1.38), and 1.48 (1.34-1.62), respectively ( P for trend <0.001). A significant sex-based interaction was noted in this association, with women showing a higher risk of diabetes development. Furthermore, higher baPWV quartiles were associated with an increased risk of developing insulin resistance, defined as the homeostatic model assessment of insulin resistance., Conclusions: These findings highlight the importance of arterial stiffness, as measured by elevated baPWV, in the development of diabetes and insulin resistance. Notably, this study highlighted a strong association, particularly among women.

Aims: There is a lack of evidence regarding the sex-specific impact of arterial stiffness on the incidence of chronic kidney disease (CKD). This study assessed the relationship between arterial stiffness based on brachial-ankle pulse wave velocity (baPWV) and incident CKD in men and women., Methods: Individuals who participated in health checkups and underwent concomitant baPWV measurement between 2006 and 2019 were included. They were free of CKD at baseline. The participants were categorized into 4 groups based on their baPWV values (cm/s) as follows: ＜1,200 cm/s for normal, ≥ 1,200 and ＜1,400 for high normal, ≥ 1,400 and ＜1,800 for borderline, and ≥ 1,800 cm/s. The primary outcome was CKD development (estimated glomerular filtration rate ＜60 mL/min/1.73 m 2 )., Results: A total of 130,100 participants were enrolled, with a mean age of 40.5±8.2 years old. During the mean of 5.6 years of follow-up, 906 (0.7%) participants developed incident CKD. The cumulative incidence of CKD was 0.3%, 0.5%, 1.4%, and 6.2% in the normal, high normal, borderline, and abnormal groups, respectively. In the multivariable-adjusted model including systolic blood pressure, compared with the normal baPWV group, abnormal baPWV group demonstrated a significantly increased risk of incident CKD in women. However, among men, any other baPWV groups were not associated with a significantly elevated risk of incident CKD., Conclusions: Increased arterial stiffness, as measured by baPWV, was associated with an increased risk of incident CKD, with notable sex-specific differences. These findings underscore the utility of baPWV for identifying CKD risk in women and offer valuable insights into sex-specific differences in arterial stiffness and CKD development.

Background: Metabolic risk factors are a significant cause of global burden among adolescents and young adults, but there is a lack of attention to the burden attributable to these metabolic risk factors globally., Aims: This study aims to provide comprehensive estimates of five important metabolic risk factors and the attributable disease burden in people aged 15-39 years from 1990 to 2021, based on the Global Burden of Disease Study (GBD) database., Methods: Global total deaths and disability-adjusted life years (DALYs) were used to describe the burden attributable to five common metabolic risk factors, including high fasting plasma glucose (FPG), high low-density lipoprotein cholesterol (LDL-C), high systolic blood pressure (SBP), high body mass index (BMI), and kidney dysfunction, in adolescents and young adults. The estimated annual percentage changes (EAPC) of DALYs were utilized to depict the trends from 1990 to 2021., Results: From 1990 to 2021, the DALY rates attributable to all metabolic risk factors showed a globally significant upward trend, with EAPC reaching 33.0 % (27.4-38.7). Compared to females, males had a heavier burden and a more significant increase in deaths and DALYs attributable to metabolic risk factors. High BMI and high FPG have become the top two metabolic risk factors in 2021, with summary exposure variables (SEV) rising by 84.2 % and 53.6 %, respectively. Low-middle socio-demographic index (SDI), middle SDI, and high SDI regions experienced upward regional trends in DALY rates, while low SDI regions remained stable. Among 204 countries and territories, 101 (49.5 %) showed a significant increase in DALY rates, as indicated by the EAPC., Conclusions: There is a substantial global burden attributable to metabolic risk factors in adolescents and young adults in 2021, especially high BMI and high FPG. This calls for further investigation and intervention to address this emerging trend., Competing Interests: Conflict of interest Christopher D. Byrne has received grant support from Echosens. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. Anoop Misra has received honoraria from Novo Nordisk, Astra Zeneca, Janssen, Lupin, Eli Lilly, US Vitamins, and Boehringer Ingelheim. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Alice P.S. Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Sander Lefere has received research grant from Inventiva. Mohit Kehar is a consultant for Mirum. Nicholas Beng Hui Ng has received honoraria from Novo Nordisk and Abbott. No other disclosures were reported., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aims: Arterial stiffness, a known cardiovascular risk factor, is associated with increasing age and arteriosclerosis. This study examines age-related annual changes in arterial stiffness in a large cohort of healthy individuals without cardiovascular disease, hypertension, or diabetes mellitus., Methods: The study included 195,405 Korean adults aged 30-79 years who attended a health check-up between 2006 and 2019. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), and the final cohort for the baPWV annual change analysis comprised 147,313 participants., Results: The study found that baPWV values increase progressively with age in both sexes, with the most notable changes occurring in the 70-79 age group. The spread in baPWV measurements, as indicated by the interquartile ranges, generally increases with age but was particularly pronounced in women in the 50s and 60s age groups, with men showing a greater spread in the 70-79 age group. The average annual change in baPWV (ΔbaPWV) values increased from 1.48 cm/s (95 % CI: 0.80-2.16) in the 30-39 age group to 23.72 cm/s (95 % CI: 16.25-31.19) in the 70-79 age group in men. Similarly, for women, the average ΔbaPWV values increased from 1.80 cm/s (95 % CI: 0.93-2.68) to 18.51 cm/s (95 % CI: 7.18-29.85) in the 30-39 and 70-79 age groups, respectively. The study observed that arterial stiffness in men consistently increases across all age groups, whereas in women, it does not significantly increase annually before age 50 but shows a steeper rise after this age., Conclusions: This study emphasizes the progressive nature of arterial stiffness with aging in a healthy population. It highlights notable differences in the rate of progression and the distribution of baPWV between men and women, with men exhibiting a greater spread in the oldest age group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex., Methods: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI)., Results: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17])., Conclusion: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide., Competing Interests: Declaration of competing interest John D. Ryan received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. Luca Valenti reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie, Resalis, grants from Gilead. Alice Pik-Shan Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Gregory Y. H. Lip serves as consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation programme. Anoop Misra has received honorarium from Abbott, Roche, Jannsen, Boehringer Ingelheim, Lupin, Cipla, US Vitamins, and Novo Nordisk. Christopher D. Byrne has received grant support from Echosens. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Christos S. Mantzoros reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. No other disclosures were reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The introduction of CT scans and the subsequent Agatston score in the 1990s drastically improved our ability to detect coronary artery calcification (CAC). This led to its incorporation into cardiovascular risk assessment guidelines set forth by organizations such as the American Heart Association (AHA) and the American College of Cardiology (ACC). Over time, these guidelines have evolved significantly, reflecting an increasing understanding of CAC. Physical activity has become a key factor in the management of cardiovascular disease. However, the relationship between physical activity and CAC remains complex. Although physical activity is generally beneficial for cardiovascular health, paradoxically, high levels of physical activity have been associated with elevated CAC scores. However, these higher CAC levels may indicate the presence of more stable, calcified plaques that provide protection against plaque rupture. These contradictory findings call for balanced interpretations that acknowledge the cardiovascular benefits of physical activity. This review examines the historical development of clinical guidelines for CAC, the paradoxical relationship between physical activity and CAC, and potential underlying mechanisms. It emphasizes the need for future research to utilize objective measures and consistent methodologies to better understand the relationship between physical activity and CAC.

Background: We examined the comparative associations between non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) definitions with risk of developing chronic kidney disease (CKD) and abnormal albuminuria., Methods: We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver ultrasonography. Participants were further subdivided into no steatotic liver disease (no-SLD), NAFLD-only, MASLD-only, both NAFLD and MASLD, and SLD not categorized as NAFLD or MASLD groups. Cox proportional hazards models were used to analyze the risk of incident CKD and albuminuria., Results: Compared with either the no-NAFLD or no-MASLD groups, the NAFLD and MASLD groups were associated with a higher risk of incident CKD (NAFLD: adjusted hazard ratio (HR), 1.18 [95% CI, 1.01-1.38]; MASLD: adjusted HR, 1.21 [95% CI, 1.04-1.39]). Among the five subgroups, both NAFLD and MASLD group had the strongest association with risk of incident CKD (adjusted HR, 1.21 [95% CI, 1.04-1.42]). The MASLD-only group had the strongest association with incident abnormal albuminuria, with an adjusted HR comparable to that of the both NAFLD and MASLD group (adjusted HR 1.96 [95% CI, 1.44-2.67] for the MASLD-only, and adjusted HR 1.98 [95% CI, 1.58-2.49] for the both NAFLD and MASLD group versus the no-SLD group). The NAFLD-only group was not independently associated with risk of CKD or abnormal albuminuria., Conclusions: These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-558/coif). M.H.Z. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. G.T. is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. C.D.B. was supported in part by the Southampton National Institute for Health and Care Research Biomedical Research Centre (NIHR203319), UK. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Dendritic spine dysfunction is a key feature of Alzheimer's disease (AD) pathogenesis. Human T-cell lymphoma invasion and metastasis 2 (TIAM2) is expressed in two isoforms, the full length (TIAM2L) and a short transcript (TIAM2S). Compared to TIAM2L protein, which is undetectable, TIAM2S protein is abundant in human brain tissue, especially the hippocampus, and can promote neurite outgrowth in our previous findings. However, whether enhanced hippocampal TIAM2S expression can alleviate cognitive deficits in Alzheimer's disease model mice remains unclear., Methods: We crossbred 3xTg-AD with TIAM2S mice to generate an AD mouse model that carries the human TIAM2S gene (3xTg-AD/TIAM2S mice). The Morris water maze and object location tests assessed hippocampus-dependent spatial memory. Lentiviral-driven shRNA or cDNA approaches were used to manipulate hippocampal TIAM2S expression. Golgi staining and Sholl analysis were utilized to measure neuronal dendrites and dendritic spines in the mouse hippocampi., Results: Compared to 3xTg-AD mice, 3xTg-AD/TIAM2S mice displayed improved cognitive functions. According to the hippocampus is one of the earliest affected brain regions by AD, we further injected TIAM2S shRNA or TIAM2S cDNA into mouse hippocampi to confirm whether manipulating hippocampal TIAM2S expression could affect AD-related cognitive functions. The results showed that the reduced hippocampal TIAM2S expression in 3xTg-AD/TIAM2S mice abolished the memory improvement effect, whereas increased hippocampal TIAM2S levels alleviated cognitive deficits in 3xTg-AD mice. Furthermore, we found that TIAM2S-mediated memory improvement was achieved by regulating dendritic plasticity., Conclusions: These results will provide new insights into connecting TIAM2S with AD and support the notion that TIAM2S should be investigated as potential AD therapeutic targets., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background and Objectives: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy., Methods: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years., Results: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups., Conclusions: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Aim: We compared the association between the baseline and average lipid parameters over time and the coronary artery calcification (CAC) risk., Methods: Participants who underwent annual (biannual) health examinations and coronary artery computed tomography to measure CAC at least twice between March 2010 and December 2019, with a baseline CAC of 0, were included. The levels of apolipoprotein B (ApoB), Apolipoprotein A-I (ApoA1), ApoB/ApoA1, non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), TG/HDL-C, and TC/HDL-C were measured or calculated. The remnant cholesterol (RC) levels were calculated. The average lipid parameters before study entry were calculated using data from 2002 to 2010. The participants were divided into quartiles (Q) according to the parameter values. Cox proportional hazard modeling, adjusted for confounding factors, compared the CAC risk of the highest quartile to the lowest quartile., Results: Among 29,278 participants (mean age, 39.19±5.21; men, 88.27%), 2,779 developed CAC ＞0. The highest quartile of ApoB showed a numerically strong association with CAC risk, compared with the lowest quartile of ApoB (Q1: reference; Q2: HR,1.41, 95% CI,1.25-1.59; Q3: HR,1.97, 95% CI,1.75-2.21; Q4: HR,2.72, 95% CI,2.41-3.07). RC showed a modest association with CAC risk (Q1: reference; Q2: HR,1.13, 95% CI,0.99-1.28; Q3: HR,1.3, 95% CI,1.15-1.47; Q4: HR,1.7, 95% CI,1.51-1.91). The strength of the association was comparable between the parameters at baseline and the average lipid parameters over time., Conclusions: A high ApoB level showed a strong association with CAC risk compared with the lowest ApoB quartile. The baseline lipid parameters can predict CAC development as effectively as the average of multiple measurements can.

Background/Objectives : Smoking cessation is acknowledged for its health benefits. However, it paradoxically increases diabetes mellitus (DM) risk shortly after quitting due to weight gain. This research aimed to investigate how smoking status could affect the development of DM, focusing on how the risk of acquiring diabetes changed over time after quitting smoking, independent of variables such as weight gain. Methods : The data of 386,558 participants of the Kangbuk Samsung Health Study, excluding those with pre-existing DM, were examined. Smoking status and its long-term effects on DM risk were assessed using multivariate Cox proportional hazards models. Lifestyle factors, including weight change, physical activity levels, and alcohol intake, were adjusted as time-varying covariates throughout the follow-up period. Results : Modified hazard ratios (HRs) indicated no notable disparity in DM risk between individuals who previously smoked and those who had never smoked (HR: 1.04, 95% CI: 0.999-1.08, p -value < 0.001). In contrast, current smokers exhibited a significantly increased DM risk (HR: 1.29, 95% CI: 1.24-1.35, p -value < 0.001). Within the first six years post-cessation, former smokers initially faced a higher DM risk than never smokers (0-2 years, HR: 1.22, 95% CI: 1.15-1.31, p -value < 0.001; 3-5 years, HR: 1.11, 95% CI: 1.04-1.20, p -value < 0.001). After 12 years, they realigned with never smokers (12-46 years, HR: 0.92, 95% CI: 0.86-0.98, p -value = 0.002). Current smokers consistently showed a higher DM risk (0-9 years, HR: 1.29, 95% CI: 1.14-1.46, p -value < 0.001). Adjusting for covariates such as weight change and physical activity did not alter these findings. Conclusions : Our results indicated that former smokers initially experienced an elevated risk of DM relative to never smokers. This increased risk aligned with the risk of never smokers after six years, and the risk continued to improve after 12 years compared to never smokers. This contrasted with current smokers, who maintained a heightened risk of DM, even when adjustments were made for weight change, physical activity, and alcohol intake as time-varying covariates.

Background and Aims: This cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV)., Methods and Results: Participants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29-1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31-1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43-1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08-2.46]; Men, aHR 1.45 [95% CI, 1.35-1.56])., Conclusions: Both NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier B.V.)

Acanthamoeba , a widely distributed free-living amoeba found in various environments, is an opportunistic pathogen responsible for causing Acanthamoeba keratitis, a condition that may lead to blindness. However, identifying the pathogenicity of Acanthamoeba is challenging due to its complex life cycle, ability to adapt to different environments, variable virulence factors, and intricate interactions with the host immune system. Additionally, the development of an effective model for studying Acanthamoeba pathogenicity is limited, hindering a comprehensive understanding of the mechanisms underlying its virulence and host interactions. The aim of this study was to develop an ex vivo model for Acanthamoeba infection using porcine eyeballs and to evaluate the pathogenicity of the Acanthamoeba isolates. Based on slit lamp and biopsy analysis, the developed ex vivo model is capable of successfully infecting Acanthamoeba within 3 days. Histopathological staining revealed that clinical isolates of Acanthamoeba exhibited greater corneal stroma destruction and invasion in this model than environmental isolates. Our results highlight the importance of an ex vivo porcine eye model in elucidating the pathogenesis of Acanthamoeba infection and its potential implications for understanding and managing Acanthamoeba -related ocular diseases.

This study evaluated an oscillometric device (OD), Microlife WatchBP Office AFIB, and a hybrid manual auscultatory device (AD), Greenlight 300TM, to determine a suitable blood pressure (BP) measurement device for the Korea National Health and Nutrition Examination Survey in a mercury-free context. Adhering to the 2018 Universal Standard's suggested consensus, the study involved 800 subjects (mean age 51.2 ± 17.5 years; 44.3% male), who underwent triplicate BP measurements following 5 min of rest in a randomized order (OD-first: 398 participants; AD-first: 402 participants). BP difference was calculated as OD value minus AD value, with results stratified by measurement sequence. The overall BP difference and tolerable error probability were -1.1 ± 6.5/-2.6 ± 4.9 mmHg and 89.2%/92.5% for systolic/diastolic BP (SBP/DBP), respectively. Lin's concordance correlation coefficient was 0.907/0.844 for SBP/DBP (OD-first/AD-first: 0.925/0.892 for SBP, 0.842/0.845 for DBP). The overall agreement for hypertension (BP ≥ 140 and/or 90 mmHg) was 0.71 (p < 0.0001), and the OD underestimated the overall hypertension prevalence by 5.1%. Analysis of the AD-first data revealed a lower level of agreement compared to the OD-first data; however, the observed blood pressure difference adhered to Criterion 1 of the 2018 Universal Standard. Microlife met the Criterion 1 of 2018 Universal Standard but underestimated the prevalence of hypertension. The BP discrepancy increased with higher BP levels, male sex, and smaller AC. With increasing age, the discrepancy decreased for SBP and increased for DBP., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low-risk populations. To address this, we evaluated the association between ECG abnormality and mortality., Methods and Results: We retrospectively assessed baseline ECG and all-cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check-ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All-cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow-up period of 8.8 years. Major ECG abnormalities were associated with all-cause mortality (hazard ratio [HR], 1.11 [95%, 1.03-1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63-2.27]) compared with no ECG abnormalities. All-cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1-4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1-2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15-2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05-4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26-1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02-1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15-9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33-4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35-2.19]), major Q-wave abnormality (HR, 1.6 [95% CI, 1.08-2.39]), and major ST-T abnormality (HR, 1.76 [95% CI, 1.01-3.04])., Conclusions: ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q-wave and ST-T abnormalities, were associated with cardiovascular mortality in a low-risk population.

Background: Left ventricular diastolic dysfunction (LVDD) is often associated with elevated blood pressure (BP). It is prevalent among hypertensive patients. Additionally, increased BP variability has been linked to LVDD. However, the precise connection between LVDD and BP variability within the general population remains unclear. Thus, this study aimed to evaluate this association in a general population., Methods: A total of 2,578 participants(1,311 females) with a mean age of 47.8 ± 6.7 years who had echocardiographic data from the Korean Genome and Epidemiology study with 16 years of follow-up were analyzed. LVDD was identified through the last echocardiography during the follow-up period. BP variability was assessed using mean, standard deviation (SD), and coefficient of variance (CV)., Results: LVDD was detected in 249 individuals. The cohort was divided into an LVDD group and a normal LV diastolic function group. The LVDD group had a higher percentage of females, more advanced age, higher body mass index (BMI), higher BP and BUN levels, lower heart rate, lower hemoglobin, and lower serum creatinine than the normal LV diastolic function group. Remarkably, LVDD was associated with higher BP variability. In the multivariate analysis, LVDD was associated with increased age, female sex, increased BMI, hypertension, and increased BUN. Elevated mean systolic and diastolic BPs, SD of systolic BP, mean pulse pressure (PP), SD of PP, and CV of PP were significantly linked to LVDD even after adjusting for other significant variables in the multivariate analysis., Conclusions: LVDD was identified in 249 (9.7%) participants. Increased long-term BP variability was significantly associated with LVDD in this population-based cohort., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction., Methods and Results: The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25])., Conclusions: There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

Diabetes may induce multiple organ damage; therefore, early detection of individuals at high-risk of incident diabetes is important for timely risk assessment and intervention. Arterial stiffness (AS) occurs as a result of functional and structural changes in the arterial wall. Growing body of evidence suggests that AS is a risk factor for incident diabetes. Although each study could use different indicators for AS (ex cf-PWV, baPWV, etc.), they came to similar conclusion that AS was associated with higher risk of incident diabetes. The underlying mechanisms for the relationship of AS with risk of diabetes remain to be elucidated, but there could be several potential mechanisms. Diabetes and AS are expected to share common risk factors and influence each other, but recent research showed some evidence that AS can directly increase the risk of diabetes. The link between AS and incident diabetes has important clinical implications. First, it suggests that AS might be a useful marker for identifying people at high risk for developing diabetes. Second, it suggests that reducing AS may prevent or delay the onset of diabetes. Early detection and possible slowing of the vascular stiffening process with pharmacological agents and lifestyle interventions may reduce associated risks for diabetes., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Accurate blood pressure (BP) measurement is crucial for hypertension detection and management. The Korea National Health and Nutrition Examination Survey (KNHANES) assesses the health of Koreans using representative cross-sectional data. BP measurements were historically done with mercury sphygmomanometers for participants aged ≥10 years. However, KNHANES transitioned to Greenlight 300 TM (mercury-free auscultatory device) in 2020 for participants aged ≥6 years and used dual devices (Microlife WatchBP Office AFIB and Greenlight) in 2021-2022. To ensure consistency, KNHANES will adopt Microlife as the unified BP device with Greenlight for device validation from 2023. Under the new protocol, participants aged ≥6 years will have their BP measured three times at 30-second intervals after a 5-minute rest under ambient temperature (20-25℃) and noise ≤65 dB. The average of the 2nd and 3rd readings will be used as the representative BP value. The quality control (QC) program involves four trained examiners passing the "quality control and assurance of BP measurement program" three times annually, and undergoing "video monitoring of weekly calibration process" once a year. Additionally, the QC team will conduct "on-site evaluations of BP measurement" at mobile examination centers three times a year. A Five-Step QC process for BP devices was also developed. This document outlines the standardized BP measurement protocol and rigorous QC program in KNHANES, aiming to ensure accurate and reliable BP data for epidemiological research and public health policymaking in South Korea., (© 2023. The Korean Society of Hypertension.)

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes., (© 2023. The Korean Society of Hypertension.)

Background: Acanthamoeba and Klebsiella pneumoniae are both environmental commensals. Recently, clinical harm caused by hypermucoviscous K. pneumoniae has been observed. However, the interaction between these microbes and the origin of hypermucoviscous K. pneumoniae have not been reported., Methodology/principal Findings: Here, we report that the bacterial capsule is enlarged when co-cultured with Acanthamoeba using India ink staining, and this effect depends on the number of parasites present. This interaction results in an enhancement of capsular polysaccharide production in the subsequent generations of K. pneumoniae, even without co-culturing with Acanthamoeba. The hypermucoviscosity of the capsule was examined using the sedimentation assay and string test. We also screened other K. pneumoniae serotypes, including K1, K2, K5, and K20, for interaction with Acanthamoeba using India ink staining, and found the same interaction effect., Conclusions/significance: These findings suggest that the interaction between Acanthamoeba and K. pneumoniae could lead to harmful consequences in public health and nosocomial disease control, particularly hypermucoviscous K. pneumoniae infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists., Methods and Results: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management., Conculsions: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research., (© 2023. Asian Pacific Association for the Study of the Liver.)

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background and Aims: A new diagnostic criterion of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. However, only few studies have shown that MAFLD predicts cardiovascular disease (CVD) mortality better than non-alcoholic fatty liver disease (NAFLD). Therefore, a cohort study was conducted to assess this relationship., Methods and Results: Health examination data from health care centers in South Korea were assessed after excluding participants with missing covariates and cancer history (n = 701,664). Liver ultrasonography reports, laboratory and anthropometric data were extracted. Diagnoses of NAFLD and MAFLD were performed according to standard definitions. Participants were categorized based on the presence of NAFLD and MAFLD. In addition, participants were classified into five categories: no fatty liver disease (no FLD), NAFLD-only, MAFLD-only, both FLDs, and alcoholic FLD (AFLD) and non-MAFLD. Multivariable regression modeling was performed. The median follow-up duration was 8.77 years, and 52.56% of participants were men. After stratifying the cohort into no-MAFLD and MAFLD groups, MAFLD was associated with increased CVD mortality (adjusted HR 1.14, 95% CI 1.02-1.28). When participants were divided into no-NAFLD and NAFLD groups, there was a non-significant trend towards an increase in CVD mortality in NAFLD group (adjusted HR 1.07, 95% CI 0.95-1.21). When participants were divided into five categories, MAFLD-only group showed increased CVD mortality (adjusted HR 1.35, 95% CI 1.07-1.70) while NAFLD-only group showed no significant association with CVD mortality (adjusted HR 0.67, 95% CI 0.38-1.19)., Conclusions: In conclusion, MAFLD is associated with increased CVD mortality in a relatively young Korean population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: We conducted a cohort study to determine the screening intervals of metabolic disorders., Method: Participants without diabetes mellitus (DM), hypertension (HTN), dyslipidemia, and abdominal obesity who underwent health examinations (2005-2019) in Korea were included. Participants were grouped according to baseline fasting glucose, LDL-C level, blood pressure (BP), and waist circumference (WC). The time to develop metabolic disorders and the percentile of survival time was assessed in each group., Result: The median follow-up duration was 4.94 years (n=222,413; mean age 37.13 ± 7.49 years). After 8.32(95 %CI 8.22-8.41), 3.01(2.89-3.31), and 1.11(1.03-1.25) years, 10 % of participants developed DM in fasting glucose levels of 100-110, 110-120, and 120-125 mg/dL, respectively. After 8.40(8.33-8.45), 6.33(6.20-6.47), and 1.99(1.97-2.00) years, 10 % developed HTN in BP 120/70, 120/70-130/80, and 130/80-140/90 mmHg, respectively. After 5.99(5.94-6.04), 2.84(2.77-2.90), and 1.36(1.30-1.44) years, 10 % developed dyslipidemia in LDL-C 100-120, 120-140, and 140-160 mg/dL, respectively. After 4.62(4.41-4.80) and 1.67(1.64-1.69) years, 10 % developed abdominal obesity in baseline WC < 80(Women;W)/85(Men;M) and < 85(W)/90(M) cm, respectively., Conclusion: In adults aged 30-40, the screening interval of metabolic disorders should be individualized based on the baseline metabolic derangement. An individual with borderline values may need an annual screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Patients with hypertension are at higher risk for dementia than the general population. We sought to understand the relative importance of various risk factors in the development of dementia among patients with hypertension. This population-based cohort study used data from the Korean National Insurance Service database. Using the Cox proportional hazard model, R2 values for each potential risk factor were calculated to test the relative importance of risk factors for the development of dementia. Eligible individuals were adults 40 to 79 years of age with hypertension and without a history of stroke and dementia between 2007 and 2009. A total of 650,476 individuals (mean age, 60 ± 11 years) with hypertension were included in the analyses. During a mean follow-up of 9.5 years (±2.8 years), 57,112 cases of dementia were observed. The three strongest predictors of dementia were age, comorbidity burden (assessed using the Charlson Comorbidity Index), and female sex (R2 values, 0.0504, 0.0023, and 0.0022, respectively). The next strongest risk factors were physical inactivity, smoking, alcohol consumption, and obesity (R2 values, 0.00070, 0.00024, 0.00021, and 0.00020, respectively). Across all age groups, physical inactivity was an important risk factor for dementia occurrence. In summary, controlling and preventing comorbidities are of utmost importance to prevent dementia in patients with hypertension. More efforts should be taken to encourage physical activity among patients with hypertension across all age groups. Furthermore, smoking cessation, avoiding and limiting alcohol consumption, and maintaining an appropriate body weight are urged to prevent dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background : Increased coronary artery calcification (CAC) has been reported in individuals with high levels of physical activity (PA). However, the association between increased CAC in a physically active population and cardiovascular mortality has not yet been well-established. This study aimed to investigate the association between PA levels and the presence or absence of CAC and cardiovascular mortality. Methods : A cohort study was conducted from 1 January 2011 to 30 December 2019. Mortality data were updated until 30 December 2020. The study population comprised 56,469 individuals who had completed the International Physical Activity Short Form Questionnaire and had undergone CAC score evaluation using a CT scan. We divided the participants into four groups: physically inactive individuals without CAC, physically inactive individuals with CAC, moderately active and health-enhancing physically active (HEPA) individuals without CAC, and moderately active and HEPA individuals with CAC. The primary outcome was cardiovascular mortality. The Cox proportional hazard model with confounding factor adjustment was conducted. Inverse probability of treatment weighting-based marginal-structural modelling was conducted. Results : The median follow-up duration was 6.60 years. The mean (SD) age of the study participants was 41.67 (±10.91) years, with 76.78% ( n = 43,359) men. Compared with individuals without CAC, individuals with CAC demonstrated higher cardiovascular disease mortality regardless of PA level (Inactive and CAC > 0, HR 2.81, 95% CI: 1.76-19.19; moderately active and HEPA HR 3.27, 95% CI: 1.14-9.38). Conclusions : The presence of CAC might be associated with cardiovascular mortality regardless of PA level.

Background: In cross-sectional and retrospective cohort studies, we examined comparative associations between nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) and risk of having or developing coronary artery calcification (CAC)., Methods: Participants who had health examinations between 2010 and 2019 were analyzed. Liver ultrasonography and coronary artery computed tomography were used to diagnose fatty liver and CAC. Participants were divided into a MAFLD and no-MAFLD group and then NAFLD and no-NAFLD groups. Participants were further divided into no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD groups. Logistic regression modeling was performed. Cox proportional hazard model was used to examine the risk of incident CAC in participants without CAC at baseline and who had at least two CAC measurements., Results: In cross-sectional analyses, 162 180 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of prevalent CAC (NAFLD: adjusted odds ratio [OR], 1.34 [95% CI, 1.29-1.39]; MAFLD: adjusted OR, 1.44 [95% CI, 1.39-1.48]). Among the 4 groups, the MAFLD-only group had the strongest association with risk of prevalent CAC (adjusted OR, 1.60 [95% CI, 1.52-1.69]). Conversely, the NAFLD-only group was associated with a lower risk of prevalent CAC (adjusted OR, 0.76 [95% CI, 0.66-0.87]). In longitudinal analyses, 34 233 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of incident CAC (NAFLD: adjusted hazard ratio, 1.68 [95% CI, 1.43-1.99]; MAFLD: adjusted hazard ratio, 1.82 [95% CI, 1.56-2.13]). Among these 4 groups, the MAFLD-only group had the strongest associations with risk of incident CAC (adjusted hazard ratio, 2.03,[95% CI, 1.62-2.55]). The NAFLD-only group was not independently associated with risk of incident CAC (adjusted hazard ratio, 0.88 [95% CI, 0.44-1.78]) Conclusions: Both NAFLD and MAFLD are significantly associated with an increased prevalence and incidence of CAC. These associations tended to be stronger for MAFLD.

Mercury-free sphygmomanometers are gradually replacing the traditional sphygmomanometers in clinical settings and epidemiological surveys for measuring blood pressure (BP) due to mercury toxicity. No direct comparative studies have evaluated BP differences and statistical errors of automated oscillometric devices (ODs) against electronic auscultatory devices (ADs) for epidemiologic surveys. Herein, we evaluated the validity of ODs for the Korea National Health and Nutrition Examination Survey (KNHANES) using the Universal Standard for BP device validation through a direct comparison with ADs as the reference standard. Four trained observers performed validation on 278 volunteers aged ≥ 19 years with a standardized BP measurement protocol. Agreement between the BP measurements recorded with an OD against those recorded with an AD was assessed by Lin's concordance correlation coefficient (CCC) and Bland-Altman's limits of agreement. To evaluate the agreement for BP classification, weighted kappa values were estimated. To explore the factors associated with BP measurement differences between the 2 devices, multiple linear regression analysis was performed. The average BP differences (OD-AD) were 2.6 ± 6.2 mm Hg for systolic BP (SBP) and -5.1 ± 5.6 mm Hg for diastolic BP (DBP). Lin's CCCs were 0.927 and 0.768 for the overall SBP and DBP, respectively. The cumulative percentage of absolute errors ≤10 mm Hg was 88.1% for SBP and 81.3% for DBP. The weighted kappa value for the Joint National Committee 7 BP classification was 0.75 (95% confidence interval: 0.68-0.81). An OD overestimated the prevalence of SBP (0.3%, P = .0222) and underestimated the prevalence of DBP (1.8%, P < .0001). Multivariate analysis to identify the risk factors for BP difference revealed the arm circumference (AC) to be negatively associated with BP difference. Male sex was positively associated, while age was negatively associated with SBP difference. OD-DBP was positively associated with DBP difference and negatively associated for DBP absolute error. ODs met the accuracy requirements of the Universal Standard criteria against ADs for SBP but not for DBP. Thus, the DBP values may be underestimated by ODs in the KNHANES., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The newly proposed term "metabolic dysfunction-associated fatty liver disease" (MAFLD) is replacing the old term "non-alcoholic fatty liver disease" (NAFLD) in many global regions, because it better reflects the pathophysiology and cardiometabolic implications of this common liver disease. The proposed change in terminology from NAFLD to MAFLD is not simply a single-letter change in an acronym, since MAFLD is defined by a set of specific and positive diagnostic criteria. In particular, the MAFLD definition specifically incorporates within the classification recognized cardiovascular risk factors. Although convincing evidence supports a significant association between both NAFLD and MAFLD, with increased risk of CVD morbidity and mortality, neither NAFLD nor MAFLD have received sufficient attention from the Cardiology community. In fact, there is a paucity of scientific guidelines focusing on this common and burdensome liver disease from cardiovascular professional societies. This Perspective article discusses the rationale and clinical relevance for Cardiologists of the newly proposed MAFLD definition., (© 2022. The Author(s).)

Background: It is unclear what thresholds and targets of office blood pressure (BP) for treatment are appropriate in younger (<50 years old) hypertensive patients. Thus, the aim of this study was to evaluate associations of office BP levels with major cardiovascular events (MACEs) in these patients., Methods: Using the Korean National Health Insurance Service database, data of 98 192 younger (<50 years old) hypertensive patients having BP measurements available without any history of cardiovascular events from 2002 to 2011 were extracted. This cohort study evaluated associations of BP levels (<120/<70, 120-129/70-79, 130-139/80-89, 140-149/90-99, and ≥150/≥100 mmHg) with MACEs. The study outcome was MACE, a composite of cardiovascular death, myocardial infarction, stroke, and heart failure., Results: In all patients, those treated with antihypertensive medication accounted for 34.7% and those who achieved BP less than 130/80 mmHg accounted for 35.5%. During a mean follow-up of 9.5 ± 2.8 years, 4918 (5%) MACEs were documented in our cohort. The risk of MACE was the lowest [adjusted hazard ratio: 0.77, 95% confidence interval (CI) 0.66-0.89] for those with BP level of less than 120/less than 70 mmHg. It was the highest (hazard ratio 2.0, 95% CI 1.83-2.19) for those with BP level of at least 150/at least 100 mmHg in comparison with those with BP level of 130-139/80-89 mmHg. These results were consistent for all age groups (20-29, 30-39, and 40-49 years) and both sexes., Conclusion: Elevated BP level from less than 120 mmHg/less than 70 mmHg is significantly correlated with an increased risk of MACE in younger (<50 years old) Korean hypertensive patients. Lowering BP to less than 120 mmHg/less than 70 mmHg is needed for these patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy., Methods: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study., Results: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions., Conclusions: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy., Trial Registration: NCT03156842, Registered 17 May 2017., (© 2022. The Author(s).)

Objective: The aim of this study was to develop, compare, and validate models for predicting cardiovascular disease (CVD) mortality and hospitalization with hypertension using a conventional statistical model and a deep learning model., Methods: Using the database of Korean National Health Insurance Service, 2,037,027 participants with hypertension were identified. Among them, CVD (myocardial infarction or stroke) death and/or hospitalization that occurred within one year after the last visit were analyzed. Oversampling was performed using the synthetic minority oversampling algorithm to resolve imbalances in the number of samples between case and control groups. The logistic regression method and deep neural network (DNN) method were used to train models for assessing the risk of mortality and hospitalization., Findings: Deep learning-based prediction model showed a higher performance in all datasets than the logistic regression model in predicting CVD hospitalization (accuracy, 0.863 vs. 0.655; F 1 -score, 0.854 vs. 0.656; AUC, 0.932 vs. 0.655) and CVD death (accuracy, 0.925 vs. 0.780; F 1 -score, 0.924 vs. 0.783; AUC, 0.979 vs. 0.780)., Interpretation: The deep learning model could accurately predict CVD hospitalization and death within a year in patients with hypertension. The findings of this study could allow for prevention and monitoring by allocating resources to high-risk patients.

Data on the association between height and cardiovascular risk are still conflicting. Moreover, no reports are showing this issue in hypertensive patients. This study was performed to investigate whether height affects cardiovascular prognosis in hypertensive patients using nation-wide real-world data. Using the Korean National Health Insurance Service database, we analyzed 461,492 Korean hypertensive patients without any prior history of cardiovascular disease between January 2002 and December 2017. The incidence of a composite of cardiovascular death, myocardial infarction, and stroke was assessed according to height quintiles. In univariable comparisons, the taller the patients, the younger the age and the higher the proportion of men. In multivariable cox regression analyses, height was not associated with the occurrence of cardiovascular events. Although the risk of clinical events increased in some height quintiles compared to the first height quintile, there was no tendency to increase the risk according to the increase in the height quintile. These results were similar even when men and women were analyzed separately. In the same quintile group of height, there were no significant differences in clinical outcomes between sexes. In Korean hypertensive patients, there was no association between height and the occurrence of cardiovascular events. This result did not differ by sex. The clinical use of height for CVD prediction seems to be still tricky in hypertensive patients., (© 2022. The Author(s).)

Grafts used for corneal donation should be sterile to avoid transplantation failure and secondary infection. However, there are no clear and globally accepted specifications from eye banks on microbial sampling sites. The objective of this study was to analyze microbial contamination of corneal grafts collected from different sampling sites. We found that the contamination rates and strain compositions significantly differed at different sampling sites. To clarify the effect of the microbial sampling site on corneal graft contamination, microbial sampling was conducted using 30 corneal grafts at the extraocular and intraocular sides of the graft in 2020 from the National Eye Bank of Taiwan. Microbial contamination significantly differed (p < 0.05) between the different sampling sites on the graft according to McNemar’s test. Although the two sampling sites showed the same specificity (33.33%), the sensitivity of sampling on the extraocular side (82.35%) was higher than that on the intraocular side (17.65%) of the graft. Donor-associated factors, including the cause of death, operating place, and cold compression, were analyzed using chi-square statistics, which revealed no significant differences in microbial contamination. Thus, our data provide evidence for the microbial sampling site of donated grafts and clear specifications for maintaining the quality of corneal grafts.

Background: Previous studies have reported that abnormal glucose metabolism is associated with poor cancer outcomes. Glycated hemoglobin A1c (HbA1c) is an important indicator of glucose metabolism. This study aimed to investigate the relationship between nondiabetic HbA1c levels and cancer-related mortality., Methods: This was a retrospective cohort study of Koreans who attended an annual or biennial health checkup program. The study group was categorized based on the quintile of HbA1c level (Q1, 3.0-5.1%; Q2, 5.2-5.3%; Q3, 5.4%; Q4, 5.5-5.6%, Q5, 5.7-6.4%). Cancer-related mortality was determined using the mortality data from the Korea National Statistical Office. Participants with an established diagnosis of diabetes or cancer were excluded. Cancer-related mortality was assessed depending on each HbA1c level with adjustment for factors that could influence mortality., Results: A total of 589,457 participants were included in this study. During a median follow-up duration of 6.99 years, 1712 cancer-related deaths were reported. The risk of cancer-related mortality was significantly higher in the Q5 group (hazard ratio (HR) 1.23, range 1.02-1.47 in model 1; HR 1.25, range 1.04-1.50 in model 2). HbA1c levels were linearly associated with cancer-related deaths (Ptrend = 0.021 in model 1; 0.013 in model 2). HbA1c level and colorectal, stomach, and lung cancer mortality exhibited a positive relationship, whereas liver cancer-related mortality showed an inverse relationship with HbA1c level (Ptrend = 0.001)., Conclusions: Our study showed that abnormal glucose metabolism is significantly associated with cancer-related mortality, and its relationship varies with each type of cancer.

Background Apart from nondippers' impact on cardiovascular events, the prevalence of isolated nocturnal hypertension (INH) and its consequences on both the heart and brain were not clearly investigated in the general population. Methods and Results The participants underwent ambulatory blood pressure monitoring evaluations for arterial stiffness, echocardiography, and brain magnetic resonance imaging. They were grouped into normotension, INH, and overt diurnal hypertension, based on ambulatory blood pressure monitoring and history of antihypertensive treatment. White matter hyperintensity, arterial stiffness, and echocardiographic parameters were compared. Of the 1734 participants, there were 475 (27.4%) subjects with normotension, 314 with INH (18.1%), and 945 with overt diurnal hypertension (54.5%). Prevalence of INH was not different between sex or age. Of INH, 71.3% (n=224) was caused by elevated diastolic blood pressure. After multivariable adjustment, INH showed higher pulse wave velocity ( P <0.001) and central systolic blood pressure ( P <0.001), left ventricular mass index ( P =0.026), and worse left ventricular diastolic function (early diastolic mitral annular velocity) ( P <0.001) than normotension. Mean white matter hyperintensity scores of INH were not different from normotension ( P =0.321), but the odds for white matter hyperintensity presence were higher in INH than normotension (odds ratio, 1.504 [95% CI, 1.097-2.062]; P =0.011). Conclusions INH was common in the general population and associated with increased arterial stiffness, left ventricular hypertrophy, and diastolic dysfunction. White matter hyperintensity was more likely to be present in the INH group than in the normotension group. The use of ambulatory blood pressure monitoring should be encouraged to identify masked INH and prevent the occurrence of cardiovascular events.

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Hypertension and diabetes mellitus are major chronic diseases that are important factors in the management of cardiovascular disease. In order to prevent the occurrence of chronic diseases, proper health management through periodic health check-ups is necessary. The purpose of this study is to determine the incidence of hypertension and diabetes mellitus according to the health check-up, and to develop a predictive model for hypertension and diabetes according to the health check-up. We used the National Health Insurance Corporation database of Korea and checked whether hypertension or diabetes occurred from that date according to the number of health check-ups over the past 10 years. Compared to those who underwent five health check-ups, those who participated in the first screening had hypertension (OR = 2.18, 95% CI = 2.14-2.22), diabetes mellitus (OR = 1.33, 95% CI = 1.30-1.35) and both diseases (OR = 2.46, 95% CI = 2.39-2.53); individuals who underwent 10 screenings had hypertension (OR = 0.86, 95% CI = 0.83-0.88), diabetes mellitus (OR = 0.83, 95% CI = 0.81-0.85) and both diseases (OR = 0.83, 95% CI = 0.79-0.87). Individuals who attended fewer than five screenings compared with individuals who attended five or more screenings had hypertension (OR = 1.61, 95% CI = 1.59-1.62; AUC = 0.66), diabetes mellitus (OR = 1.21, 95% CI = 1.20-1.22; AUC = 0.59) and both diseases (OR = 1.75, 95% CI = 1.72-1.78, AUC = 0.63). The machine learning-based prediction model using XGBoost showed higher performance in all datasets than the conventional logistic regression model in predicting hypertension (accuracy, 0.828 vs. 0.628; F1-score, 0.800 vs. 0.633; AUC, 828 vs. 0.630), diabetes mellitus (accuracy, 0.707 vs. 0.575; F1-score, 0.663 vs. 0.576; AUC, 0.710 vs. 0.575) and both diseases (accuracy, 0.950 vs. 0.612; F1-score, 0.950 vs. 0.614; AUC, 0.952 vs. 0.612). It was found that health check-up had a great influence on the occurrence of hypertension and diabetes, and screening frequency was more important than other factors in the variable importances.

Aims: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH., Methods: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified., Results: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease., Conclusions: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Background: We investigated the association between individual components of metabolic syndrome (MetS) and left ventricular (LV) geometric changes, including diastolic dysfunction, in a large cohort of healthy individuals., Methods: Overall, 148 461 adults who underwent echocardiography during a health-screening program were enrolled. Geographic characteristics on echocardiography and several markers of LV relaxation function were identified according to individual MetS components. Univariate linear regression analysis and a multivariate regression model adjusted for factors known to influence LV relaxation function were conducted., Results: The prevalence of LV diastolic dysfunction (LVDD) was higher in the MetS group than in the non-MetS group (0.56% vs. 0.27%, p < .001). In univariate and multivariate analyses, E/A ratio, e' velocity, and left atrial volume index were significantly associated with each component of MetS and covariates (all p ≤ .001). In the age- and sex-adjusted model, MetS was significantly associated with LVDD (odds ratio [95% confidence interval], 1.350 [1.103, 1.652]). However, subjects with more MetS components did not have a significantly higher risk of LVDD. As the analysis was stratified by sex, the multivariate regression model showed that MetS was significantly associated with LVDD only in men (1.3 [1.00, 1.68]) with higher risk in more MetS component (p for trend < .001). In particular, triglyceride (TG) and waist circumference (WC) among MetS components were significantly associated with LVDD in men., Conclusions: MetS was associated with the risk of LVDD, especially in men, with a dose-dependent association between an increasing number of components of MetS and LVDD. TG and WC were independent risk factors for LVDD in men., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Objectives: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP)., Methods: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg)., Results: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05-1.24) but not in those by the 2017 ACC/AHA definition. Elevated on-treatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18-1.70) and stroke (aHR, 1.19; 95% CI, 1.08-1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10; 95% CI, 1.04-1.16). Similar results were seen in the propensity-score-matched cohort., Conclusion: Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022. The Korean Society of Cardiology.)

Although several large trials that included African American patients with hypertension have demonstrated the superiority of diuretics as an initial monotherapy, its applicability to other ethnicities remains questionable. The purpose of this study was to investigate whether diuretics as first-line antihypertensive medications are superior to other classes of drugs in the Korean population. Using the Korean National Health Insurance Service database, we analyzed 95,201 Korean hypertensive patients without prior history of cardiovascular disease who started a single antihypertensive drug between January 2002 and December 2017. The primary endpoint was a composite of cardiovascular death, myocardial infarction and stroke. Each endpoint was compared among five classes of antihypertensive drugs [diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and beta-blockers (BBs)]. In multivariable Cox analysis, diuretics were superior to ACEIs (hazard ratio [HR], 1.58-2.01), inferior to ARBs (HR, 0.37-0.43) and similar to CCBs and BBs for the primary endpoint. Similar findings were obtained for all-cause and cardiovascular mortality and stroke. This result was consistently observed in the longer treatment group and in the propensity score-matched pairs. In Korean hypertensive patients without cardiovascular disease, initiation with diuretics could not be superior to other medications, but rather inferior to ARBs in preventing adverse cardiovascular outcomes. Randomized studies are needed to confirm our results., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The objective of this research is to investigate the spatial and temporal patterns of bacteriological quality in raw oysters sampled from different aquacultural farms located in Aberdeen Typhoon Shelter, Carp Gates, Lau Fau Shan, Ma Wan, and Mui Wo in Hong Kong. Magallana hongkongensis and Crassostrea rhizophorae were collected and analyzed for fecal coliforms. Throughout the 13-month monitoring period, all samples had generally high bacterial loads, ranging from 1.4 × 10 7  cfu/g to 8.9 × 10 7  cfu/g and exceeded the guideline suggested by the HKSAR government (i.e. 700 MPN/100 g). Besides, a linear regression analysis showed that the amount of fecal coliforms in raw oysters had strong correlations (p < 0.05) to the monthly rainfall records throughout the monitoring period. Such findings illustrate the high loading of pathogenic microorganisms in the tissue of oysters which represent a potential threat of people contracting foodborne diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Only a few studies have evaluated the relationship between physical activity (PA) and Homeostatic model assessment for insulin resistance (HOMA-IR). Therefore, we aimed to analyze the association between HOMA-IR and PA. We included 280,194 Korean without diabetes who underwent health examinations. The short form of the International Physical Activity Questionnaire was completed. PA level was divided into sedentary, mild PA, and health-enhancing PA (HEPA). The HOMA-IR levels were calculated. Confounding factors including waist circumference were adjusted. The median follow-up duration was 4.13 years. A significant inverse relationship was observed between PA level and HOMA-IR (p < 0.001). Compared with the sedentary group, HOMA-IR was lower in the HEPA group (p < 0.001), even when HEPA group decreased PA level over time (p < 0.001). Mild PA (p < 0.001) or HEPA showed a lower risk of HOMA-IR progression (p < 0.001). Increasing PA or maintaining HEPA was significantly associated with a lower HOMA-IR (p < 0.001), HOMA-IR improvement (p < 0.001), and a lower risk of HOMA-IR progression (p < 0.001). Our findings support the inverse relationship between PA and HOMA-IR in a population without diabetes. PA might improve IR and prevent its progression among populations without diabetes, independent of the waist circumference., (© 2022. The Author(s).)

Background: Data on whether physical activity (PA) levels are related to nonalcoholic fatty liver disease (NAFLD) when considering body mass index (BMI) are scarce. We assessed whether PA affects the development or resolution of NAFLD in conjunction with BMI changes., Methods: Overall, 130,144 participants who underwent health screening during 2011-2016 were enrolled. According to the PA level in the Korean version of the validated International PA Questionnaire Short Form, participants were classified into the inactive, active, and health-enhancing PA (HEPA) groups., Results: In participants with increased BMI, the hazard ratio (HR) and 95% confidence interval after multivariable Cox hazard model for incident NAFLD was 0.97 (0.94-1.01) in the active group and 0.94 (0.89-0.99) in the HEPA group, whereas that for NAFLD resolution was 1.03 (0.92-1.16) and 1.04 (0.88-1.23) (reference: inactive group). With increased BMI, high PA affected only new incident NAFLD. PA enhancement or maintenance of sufficient PA prevented new incident NAFLD. In participants with decreased BMI, the HRs were 0.98 (0.90-1.07) and 0.88 (0.78-0.99) for incident NAFLD and 1.07 (0.98-1.17) and 1.33 (1.18-1.49) for NAFLD resolution in the active and HEPA groups, respectively. With decreased BMI, high PA reduced incident NAFLD and increased NAFLD resolution. Maintenance of sufficient PA led to a considerable resolution of NAFLD., Conclusion: In this large longitudinal study, PA prevented incident NAFLD regardless of BMI changes. For NAFLD resolution, sufficient PA was essential along with BMI decrease. Maintaining sufficient PA or increasing the PA level is crucial for NAFLD prevention or resolution., (© 2022. The Author(s).)

Background and Aims: Inter-arm blood pressure differences (IADs) are known to be associated with adverse cardiovascular outcomes. We evaluated the distribution of IADs in a large cohort of apparently healthy people and the association of IADs with brachial-ankle pulse wave velocity (baPWV) and coronary artery calcium (CAC)., Methods: Blood pressure was measured in both arms of 117,407 people who participated in the Kangbuk Samsung Health Study. IAD was defined as the absolute difference in systolic blood pressure in both arms and was confirmed by measuring the baPWV using an automatic oscillometric device. Arterial stiffness was measured by the baPWV, and CAC was assessed using multi-detector computed tomography., Results: The mean IAD in the overall subjects was 3.09 ± 2.83 mmHg, 6 mmHg in the 90th percentile, 8 mmHg in the 95th percentile, and 10 mmHg in the 97th percentile. In the multivariable-adjusted analysis of 92,949 subjects excluding those with a history of HTN, DM, and cardiovascular disease (CVD), increasing IAD did not statistically increase the risk of developing a CAC >0. However, IAD was associated with a baPWV >1400 cm/s (odds ratio [95% confidence interval], 1.23 [1.13-1.35] in the total cohort, 1.19 [1.08-1.31] in males, and 1.39 [1.11-1.73] in females)., Conclusions: More than 97% of all participants had an IAD of 10 mmHg or less. IAD was significantly associated with arterial stiffness, reflecting arteriosclerosis, but not with the presence of CAC, reflecting atherosclerosis. IAD may be a valuable tool for the early detection of asymptomatic, low-risk individuals with subclinical arterial disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coronary artery calcium score (CACS) is associated with increased risk of atrial fibrillation (AF). However, the relationship between the burden of CACS and extra-coronary calcium and the AF is unclear. This cross-sectional study retrospectively analyzed the data of 143,529 participants (74.9% men; mean age, 41.7 ± 8.6 years) who underwent health examination including non-contrast cardiac CT and electrocardiography, from 2010 to 2018 to evaluate the association between cardiac calcium and AF. AF was diagnosed in 679 participants. The prevalence of AF was significantly increased as the CACS increased ( p < 0.01). Multivariable analysis adjusted for age, sex, body mass index, hypertension, diabetes, hyperlipidemia, smoking, alcohol, and history of coronary artery disease showed a significant association between a high CACS ≥1000 and AF (OR 2.26, 95% CI 1.07-4.77, p = 0.032). In a subgroup analysis of participants with a CACS ≥100, aortic valve and thoracic aorta calcium were significantly associated with AF (OR 3.49, 95% CI 1.57-7.77, p = 0.002 and OR 2.19, 95% CI 1.14-4.21, p = 0.01, respectively). High CACS was associated with AF, and extra-coronary atherosclerosis was associated with AF in participants with a moderate to very high CACS.