Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population.

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population. METHODS: We enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline. RESULTS: CAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group. CONCLUSION: The TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.

Mildly Abnormal Lipid Levels, but Not High Lipid Variability, Are Associated With Increased Risk of Myocardial Infarction and Stroke in "Statin-Naive" Young Population A Nationwide Cohort Study.

RATIONALE: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. OBJECTIVE: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. METHODS AND RESULTS: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20-1.53) for total cholesterol, 1.41 (1.25-1.60) for LDL-C, 1.28 (1.11-1.47) for triglycerides, and 0.82 (0.72-0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. CONCLUSIONS: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.

Occult Blood in Feces Is Associated with Increased Risk of Psoriasis.

BACKGROUND: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease. METHODS: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017. RESULTS: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results. CONCLUSION: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population.

Melanogenic Properties and Expression Profiles of Melanogenic Paracrine Molecules in Riehl's Melanosis.

Riehl's melanosis is a hyperpigmentary disorder that occurs predominantly on the face and neck. To date, the pathogenesis of Riehl's melanosis with regards to the melanogenic properties and paracrine melanogenic molecules has not well been studied. This study was aimed to provide a novel perspective on the pathogenesis of Riehl's melanosis by identifying the relevant paracrine melanogenic molecules in Riehl's melanosis. Skin biopsies were performed on lesional and normal-appearing perilesional skin of 12 patients with Riehl's melanosis and 12 age- and sex-matched healthy controls. Histopathological and immunohistochemical staining for paracrine melanogenic molecules was analyzed. The major histopathological findings of Riehl's melanosis were basal hyperpigmentation, melanocyte proliferation, interface change, dermal pigmentary incontinence, vascular proliferation, and dermal inflammation. Dermal expression intensities of stem cell factor (SCF) and c-kit were increased in the lesional skin of Riehl's melanosis. In addition, increased expression of epidermal and dermal ET-1 was also observed in the lesional skin of Riehl's melanosis. Increased tissue expressions of SCF, c-kit, and ET-1 in Riehl's melanosis support the role of these paracrine melanogenic molecules in the pathogenesis of Riehl's melanosis. The findings from this study might present useful information on the pathogenetic mechanism of Riehl's melanosis.

Number of remaining teeth and health-related quality of life: the Korean National Health and Nutrition Examination Survey 2010-2012.

OBJECTIVES/AIMS: With the Euro-Qol-5 dimension (EQ-5D) system, we investigated the relationship between the number of remaining teeth and QoL using data from the Korean National Health and Nutrition Examination Survey (KNHANES), 2010-2012. A total of 17,417 participants, more than 19 years old, were finally included in this study (men = 7394 and women = 10,023). Through this study, we have discovered that the remaining teeth affect overall health and that the fewer number of them may indicate a lower quality of life, as well. The quality of life according to the number of remaining teeth was assessed among Koreans using the Euro-Qol-5 dimension (EQ-5D) system. METHOD: The Euro-Qol-5 dimension (EQ-5D) system was used to measure the health-related QoL. Its five dimensions included mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The respondents were asked to choose one of the followings: G 1, no problems; G 2, some problems; and G 3, problematic, to best describe their health status for the five dimensions. Then, we assigned low QoL to G2 + G3 and high QoL to G1. We used age, gender, economic income, educational level, residence, and marital status for the demographic variables and, drinking, smoking, exercise, BMI, and metabolic syndrome for health behaviors. Multiple logistic regression analysis was performed to examine the odds ratios (ORs) and confidence intervals (CIs) for the high QoL (G1) on the five categories of EQ-5D according to the number of remaining teeth. On the basis of the 0-15 remaining teeth group, we drew a comparison of the QoL between the 16-20 and 21-28 remaining teeth groups. RESULTS: Subjects with 21-28 remaining teeth had higher QoL scores and had higher ORs of high QoL, especially for mobility (OR = 1.256, 95% CI = 1.056-1.495), self-care (OR = 1.441, 95% CI = 1.096-1.894), and usual activities (OR = 1.241, 95% CI = 1.022-1.508, respectively), than those with 0-15 remaining teeth after adjusting for age, sex, body mass index, smoking, drinking, exercise, income, education, and metabolic syndrome. ORs from the high QoL had the tendency to increase as the number of remaining teeth increased (all p for trend < 0.05). However, there was no relationship between the number of remaining teeth and QoL in the pain/discomfort and anxiety/depression dimensions. CONCLUSION: The number of remaining teeth was associated with QoL, and subjects who had more teeth obtained higher QoL scores. The subjects in the high QoL group were especially associated with the components of EQ-5D such as mobility, self-care, and daily living.

Arterial stiffness measured by cardio-ankle vascular index in Korean women with polycystic ovary syndrome.

Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. The aim of this study was to evaluate arterial stiffness by CAVI in PCOS patients (n = 26) and in the age-matched controls (n = 59). The CAVI was measured by a single medical professional. The mean age of the women with PCOS was 33.3 (±6.6) years, and that of the matched controls was 33.1 (±5.9) years (p = .861). The mean CAVIs were similar between the patients and controls (6.49 ± 0.41 and 6.39 ± 0.65, respectively, p = .452). The CAVI increased linearly with age in both groups, but in the women with PCOS, CAVI showed relatively strong negative correlations with body mass index (BMI) in both the unadjusted (r = -0.537, p = .005) and adjusted models (r = -0.474, p = .003 after age and BMI adjustment and r = -0.604, p = .033 after age, BMI, sitting auscultatory systolic BP and square root hs-CRP adjustment). In conclusion, relatively young women with PCOS may not have increased arterial stiffness. A negative correlation between CAVI and BMI in women with PCOS requires further study to determine whether vascular adaptation to adiposity occurred in these women. Impact Statement What is already known on this subject? Increased arterial stiffness is one of the earliest adverse structural and functional alterations in blood vessels, potentially leading to later cardiovascular disease. Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. What do the results of this study add? The CAVIs were similar between the women with PCOS and the age-matched controls. The CAVI increased linearly with age in both groups, but in women with PCOS, CAVI showed a relatively strong negative correlation with the body mass index (BMI). What are the implications of these findings for clinical practice and/or further research? Relatively young women with PCOS may not have increased arterial stiffness. However, CAVI showed a negative correlation with BMI only in the women with PCOS, suggesting that adiposity itself is associated with the decreased arterial stiffness in these women. This finding requires a replication, and whether adaptation to the hemodynamic consequences of adiposity occurred in the PCOS patients remains to be established. Further longitudinal studies are needed to verify the relationships among vascular stiffness, adiposity and PCOS.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

BACKGROUND: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. METHODS: We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. RESULTS: In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. CONCLUSIONS: This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Impact of metabolic syndrome on the progression of coronary calcium and of coronary artery disease assessed by repeated cardiac computed tomography scans.

BACKGROUND: It is not clear how severe metabolic syndrome (MS) affects the development of coronary atherosclerosis. METHODS: This was an observational, retrospective cohort study with Koreans who received health check-ups voluntarily. A total of 2426 subjects had baseline and follow-up coronary artery calcium score (CACS) data. Among them, 1079 had coronary computed tomography angiography (CCTA) data. We compared baseline CACS and any progression in subjects with and without MS. A more detailed analysis was conducted for coronary artery disease (CAD), which was defined by coronary artery stenosis (≥50 %), multivessel involvement, and coronary plaques in those patients with CCTA data. RESULTS: At baseline, subjects with MS (34.0 %, n = 825) had higher CACS and more significant coronary artery stenosis, multivessel involvement, and atheromatous plaques than those without MS (P < 0.05 for all). In the follow-up (median 1197 days), subjects with MS showed significant increases in CACS and progression of CAD compared with counterparts without MS, in parallel with the numbers of MS components. Finally, MS was a significant predictor for the progression of CACS (hazard ratio 1.32; 95 % confidence interval 1.06-1.64) and progression of coronary artery stenosis and/or development of vulnerable plaque (hazard ratio 1.47, 95 % confidence interval 1.01-2.15) after adjusting for other cardiovascular risk factors. CONCLUSIONS: Subjects with MS showed progression of CAD as assessed by CACS and CCTA over ~3 years. Therefore, more vigilant screening for coronary vascular health is needed among those with MS.

Systemic Inflammation Is Associated With Coronary Artery Calcification and All-Cause Mortality in Chronic Kidney Disease.

BACKGROUND: Presence of systemic inflammation in chronic kidney disease (CKD) is associated with advanced coronary artery calcification (CAC). The prognostic significance of this association, however, is unknown. We evaluated the associations between CAC, estimated glomerular filtration rate (eGFR) and all-cause mortality, to determine whether the associations differ according to the presence of systemic inflammation. METHODS AND RESULTS: We followed 30,703 consecutive individuals who underwent CAC measurement for a median of 79 months (IQR, 65-96 months). Patients were categorized according to baseline CAC score (0, 1-99, 100-399 and ≥400), eGFR (<45, 45-59, 60-74, 75-89, 90-104, and ≥105 ml/min/1.73 m(2)) and high-sensitivity C-reactive protein (hsCRP; <2.0, and ≥2.0 mg/L). Prevalence and extent of CAC were greater in those with lower eGFR and higher hsCRP accordingly, even after adjustment. Lower eGFR was strongly associated with higher CAC score (≥400), and the association was more significant in patients with higher hsCRP. The greater CAC burden was associated with worse outcome in the CKD patients (eGFR <60 ml/min/1.73 m(2)) only in those with higher hsCRP. CONCLUSIONS: Patients with low eGFR and more extensive CAC had greater risk of mortality, and associations differed according to the presence of systemic inflammation. Among the CKD patients, coronary evaluation may be considered for those with elevated hsCRP. (Circ J 2016; 80: 1644-1652).

Warranty Period of Zero Coronary Artery Calcium Score for Predicting All-Cause Mortality According to Cardiac Risk Burden in Asymptomatic Korean Adults.

BACKGROUND: The aim of this study was to examine whether zero coronary artery calcium (CAC) score is associated with favorable prognosis of all-cause mortality (ACM) according to a panel of conventional risk factors (RF) in asymptomatic Korean adults.Methods and Results:A total of 48,215 individuals were stratified according to presence/absence of CAC, and the following RF were examined: hypertension, diabetes, current smoking, high low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol. The RF were summed on composite score as 0, 1-2, or ≥3 RF present. The warranty period was defined as the time to cumulative mortality rate >1%. Across a median follow-up of 4.4 years (IQR, 2.7-6.6), 415 (0.9%) deaths occurred. Incidence per 1,000 person-years for ACM was consistently higher in subjects with any CAC, irrespective of number of RF. The warranty period was substantially longer (eg, 9 vs. 5 years) for CAC=0 compared with CAC >0. The latter observation did not change materially according to pre-specified RF, but difference in warranty period according to presence/absence of CAC reduced somewhat when RF burden increased. CONCLUSIONS: In asymptomatic Korean adults, the absence of CAC evoked a strong protective effect against ACM as reflected by longer warranty period, when no other RF were present. The usefulness of zero CAC score and its warranty period requires further validation in the presence of multiple RF. (Circ J 2016; 80: 2356-2361).

Association of epicardial fat with left ventricular diastolic function in subjects with metabolic syndrome: assessment using 2-dimensional echocardiography.

BACKGROUND: Metabolic syndrome (MetS) is related with left ventricular diastolic dysfunction (LVDD) and poor cardiovascular outcome. Epicardial adipose tissue (EAT) thickness, measured by echocardiography, is increased in subjects with MetS. However, the association of EAT with LV diastolic function has not been evaluated in subjects with MetS. METHODS: In this retrospective study, EAT thickness was measured in 1,486 consecutive asymptomatic patients with no known heart disease who had transthoracic echocardiography during a self-referred healthcare exam. Subjects with a history of ischemic heart disease, cardiomyopathy or significant valvular heart disease were excluded. LVDD was defined as E/e' ratio ≥ 15. Subjects were grouped into two groups, those with MetS and those without. RESULTS: MetS was present in 346 subjects. There was no difference in LV systolic function between the two groups. However compared to patients without MetS, patients with MetS had larger left atrium (LA) size and higher E/e' ratio (38 ± 5 versus 35 ± 5 mm for LA and 10.0 ± 3.3 versus 8.7 ± 2.7 for E/e' ratio in subjects with versus without MetS both p < 0.001). LVDD was found in 27 (7.8%) subjects with MetS, compared to 30 (2.6%) subjects without MetS (p < 0.001). In subjects with MetS, EAT was significantly correlated with LVDD, even after adjusting for other cardiometabolic risk factors such as age, systolic blood pressure, BMI, blood glucose and LDL cholesterol (OR 1.845, 95% CI 1.153-2.951, p = 0.011). CONCLUSION: Greater EAT is found in subjects with MetS. EAT is significantly associated with LVDD in subjects with MetS, even after adjusting for other risk factors.

Investigating Factors Influencing the National Cancer Screening Program among Older Individuals in Republic of Korea-Data from the Korea National Health and Nutrition Examination Survey VIII.

This study aims to determine the influencing factors of the participation of older individuals aged 65 years and above in South Korea's National Cancer Screening Program (NCSP) using data from the eighth wave (2019-2021) of the Korea National Health and Nutrition Examination Survey (KNHANES VIII), and discuss potential problems and coping strategies. Variables were selected based on Andersen's healthcare utilization model. "Participation in the NSCP" was considered the dependent variable, with independent variables including sociodemographic characteristics (sex, marital status, residence, education level, income level, economic activity, medical coverage type, and private insurance), health conditions (subjective health status, hypertension, and diabetes), and health behaviors (physical activity, monthly alcohol consumption, and current smoking status). The analysis revealed that higher participation rates correlated with being married, having an education level beyond elementary school, being employed, subscribing to private insurance, perceiving oneself as having average or poor health, engaging in physical activity, and not smoking. Sex, residence, income, medical coverage type, hypertension, diabetes, and monthly alcohol consumption were found to be insignificantly correlated. These findings underscore the importance of tailored promotion and health education for older individuals to boost NCSP participation rates, which could ultimately elevate public health standards.

Association between cumulative metabolic risk exposure and cardiovascular disease: a nationwide cohort of over 3.6 million young adults.

AIMS: As lifetime accumulation of cardiovascular risk factors is gaining importance, early identification and management of risk factors are being emphasized. The global prevalence of metabolic syndrome (MetS), a constellation of these risk factors, is increasing, particularly among young adults. In this study, we aim to investigate the association between cumulative exposure to metabolic risk and cardiovascular disease (CVD) in young adults. METHODS AND RESULTS: In this nationwide population-based cohort, we analysed 3 688 787 young adults (<40 years) with 2 biennial National Health Screening examinations from 2009 to 2012. Participants were categorized into MetS-free, MetS-developed, MetS-recovered, or MetS-persistent group, based on MetS presence at each examination. The endpoint was new CVD development, including myocardial infarction (MI) and ischaemic stroke. During follow-up (median, 7.7 years), CVD occurred in 19 219 individuals (0.5%). The incidence rates of CVD were 0.58, 1.17, 1.20, and 1.83 (1000 person-years) in the MetS-free, MetS-developed, MetS-recovered, and MetS-persistent groups, respectively. The CVD risk was proportionally associated with cumulative metabolic risk exposure, with a maximum two-fold increase in the MetS-persistent group [adjusted hazard ratio (aHR) 1.94, 95% confidence interval (CI) 1.84-2.04], followed by the MetS-recovered and the MetS-developed groups with similar risks. Among the MetS components, persistent exposure to elevated blood pressure (BP) had the greatest association with CVD risk (aHR 1.69, 95% CI 1.63-1.76). This tendency was consistent in the separate analyses of the risk of MI and ischaemic stroke. CONCLUSION: The risk of CVD increased in an exposure-dependent manner among young adults. Efforts to optimize the cardiometabolic profile, particularly BP, even after the establishment of MetS, might help promote long-term cardiovascular prognosis.

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

Impact of clonal haematopoiesis on atherosclerotic cardiovascular disease according to low-density lipoprotein cholesterol levels in general population.

AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. METHODS AND RESULTS: Among 4300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2, and ASXL1, in order. During the follow-up (median 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (P < 0.001), indicating an elevated risk of ASCVD associated with CHIP [adjusted hazard ratio (HR) 2.49; 95% confidence interval (CI) 1.45-4.29; P < 0.001]. Notably, with high levels of LDL cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20; 95% CI 3.14-12.23; P < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index 4.94; 95% CI 1.08-22.53; P = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had a significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. CONCLUSION: The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.

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

Noninvasive assessment of myocardial inflammation by cardiovascular magnetic resonance in a rat model of experimental autoimmune myocarditis.

BACKGROUND: Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. METHODS AND RESULTS: The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n=65) and control (n=10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T(2)-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n=10) and control (n=5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T(2)* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08 ± 0.10 versus 0.48 ± 0.20; P<0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (P<0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, P<0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. CONCLUSIONS: Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response.

Statin therapy in patients with atypical chest pain and mild-to-moderate coronary stenosis on 64-slice multidetector coronary computed tomography; a retrospective propensity score matching analysis.

BACKGROUND: The effect of computed tomography (CT)-guided statin therapy on patients with atypical chest pain and mild-to-moderate coronary artery disease has not been elucidated yet. METHODS: A total of 1,952 patients who had 1-69 % stenosis on CT were reviewed retrospectively. After propensity score matching, 643 patients who were prescribed statins after CT (statin users) and 643 patients without statin therapy (statin non-users) were compared. Major cardiovascular events included all-cause death, acute coronary syndrome and stroke. RESULTS: During a median of 42 months' follow-up, all-cause death was reported in 17 patients (1.3 %), of whom 6 (0.9 %) were statin users and 11 (1.7 %) statin nonusers. Major cardiovascular events developed in 6.1 % in the statin user group and 5.6 % in the statin non-users (P = 0.812). When evaluated according to plaque subtypes, statins showed significant benefit in patients who had non-calcified or mixed plaque (HR 0.47, 95 % CI 0.22-1.01, P = 0.047). However, in patients with calcified plaques, statins had no benefit in reducing adverse events (P = 0.620). CONCLUSION: In most patients with mild-to-moderate coronary artery stenosis on CT, statin therapy has no beneficial effect on reducing adverse events. However, in patients with non-calcified or mixed plaques, statin therapy showed a significant benefit. KEY POINTS: • Multidetector CT now identifies numerous subjects with mild-to-moderate coronary stenosis. • Statin therapy has little beneficial effect on patients with calcified plaques. • However, statins reduce adverse events in those with non-calcified or mixed plaques.

Left ventricular dyssynchrony in pre-excitation syndrome: effect of accessory pathway location and reversibility after ablation therapy.

We sought to evaluate the effects and reversibility of different locations of accessory pathways (AP) on left ventricular dyssynchrony (LVdys). The acute and chronic effects of AP were evaluated in a canine model (n = 11) and in patients with pre-excitation syndrome (n = 25). Pre-excitation was simulated in the canine model by applying VDD-type epicardial ventricular pacing near the atrioventricular (AV) groove with 50-ms AV interval after median thoracotomy, at five different sites in each animal. For the simulation of pre-excitation through the septal accessory pathway, right basal septal pacing was performed using a transvenous lead. Left ventricular dyssynchrony was measured by a two-dimensional speckle-tracking technique: before and during pacing in the canine model, and before and within 24 h after the ablation in patients with Wolff-Parkinson-White (WPW) syndrome. In the canine model, the most prominent intraventricular LVdys was observed in left lateral pre-excitation (P < 0.001). In patients with pre-excitation syndrome, LVdys was greatest in patients with left free wall accessory pathways before the ablation (P = 0.013). After catheter ablation, such a difference diminished (P = 0.619). The degree of LVdys was different according to the site of AP in both the acute model and chronic patients, and the most significant LVdys associated with pre-excitation was observed in left lateral AP. Left ventricular dyssynchrony was reversible in patients with WPW syndrome. Left ventricular dyssynchrony observed in patients with pre-excitation syndrome might be a different entity from that observed in patients with heart failure.

Significance of microalbuminuria in relation to subclinical coronary atherosclerosis in asymptomatic nonhypertensive, nondiabetic subjects.

We aimed to investigate the significance of microalbuminuria and its relationship with subclinical atherosclerosis in nonhypertensive and nondiabetic patients, by using coronary artery computed tomography (CT). A total of 1,318 nonhypertensive and nondiabetic subjects who had taken coronary artery CT and measured spot urine albumin to creatinine ratio (UACR) were evaluated. The atherosclerotic changes of coronary arteries were greater in subjects with microalbuminuria, reflected by coronary artery calcium score (CACS) and significant coronary artery stenosis (CACS ≥ 100 in 15.3% vs 7.6% and stenosis ≥ 50% in 11.5% vs 4.9% of patients with vs without microalbuminuria, P = 0.008 and P = 0.011, respectively). Among various parameters that are known as a risk factor or possible biomarkers of coronary artery disease, presence of microalbuminuria, age and Framingham risk score were significantly related to coronary artery stenosis. Among them the presence of microalbuminuria showed stronger correlation than others to the coronary artery stenosis detected by CT, even after adjusting confounding factors (OR 3.397, 95% confidence interval 1.138 to 10.140, P = 0.028). The presence of microalbuminuria by UACR was significantly associated with presence of coronary artery stenosis ≥ 50% in asymptomatic, nonhypertensive and nondiabetic general population. Our study suggests that the presence of microalbuminuria may imply subclinical coronary artery disease, even in asymptomatic population.

Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.

BACKGROUND: We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. METHODS: Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. RESULTS: There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. CONCLUSIONS: Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.

Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity. METHODS: From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions. RESULTS: Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes. CONCLUSIONS: Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.