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Epigallocatechin gallate (EGCG) is a polyphenolic component of green tea that has anti-oxidative and anti-inflammatory effects in neurons. Ischemic stroke is a major neurological disease that causes irreversible brain disorders. It increases the intracellular calcium concentration and induces apoptosis. The regulation of intracellular calcium concentration is important to maintain the function of the nervous system. Hippocalcin is a neuronal calcium sensor protein that controls intracellular calcium concentration. We investigated whether EGCG treatment regulates the expression of hippocalcin in stroke animal model and glutamate-induced neuronal damage. We performed middle cerebral artery occlusion (MCAO) to induce cerebral ischemia. EGCG (50 mg/kg) or phosphate buffered saline was injected into the abdominal cavity just before MCAO surgery. The neurobehavioral tests were performed 24 h after MCAO surgery and cerebral cortex tissue was collected. MCAO damage induced severe neurobehavioral disorders, increased infarct volume, and decreased the expression of hippocalcin in the cerebral cortex. However, EGCG treatment improved these deficits and alleviated the decrease in hippocalcin expression in cerebral cortex. In addition, EGCG dose-dependently alleviated neuronal cell death and intracellular calcium overload in glutamate-exposed neurons. Glutamate exposure reduced hippocalcin expression, decreased Bcl-2 expression, and increased Bax expression. However, EGCG treatment mitigated these changes caused by glutamate toxicity. EGCG also attenuated the increase in caspase-3 and cleaved caspase-3 expressions caused by glutamate exposure. The effect of EGCG was more pronounced in non-transfected cells than in hippocalcin siRNA-transfected cells. These findings demonstrate that EGCG protects neurons against glutamate toxicity through the regulation of Bcl-2 family proteins and caspase-3. It is known that hippocalcin exerts anti-apoptotic effect through the modulation of apoptotic pathway. Thus, we can suggest evidence that EGCG has a neuroprotective effect by regulating hippocalcin expression in ischemic brain damage and glutamate-exposed cells.

BackgroundThe interaction between smoking and the use of antiplatelet agents on the prognosis of vasospastic angina (VA) is rarely investigated.MethodsVA-Korea is a nation-wide multi-center registry with prospective design (n = 1812). The primary endpoint was the composite occurrence of acute coronary syndrome (ACS), symptomatic arrhythmia, and cardiac death. Log-rank test and Cox proportional hazard model were for statistical analysis. Also, we conducted interaction analysis in both additive and multiplicative scales between smoking and antiplatelet agents among VA patients. For additive scale interaction, relative excess risk due to interaction (RERI) was calculated and for multiplicative scale interaction, the ratio of hazard ratio (HR) was calculated. All statistical analysis conducted by Stata Ver 16.1.ResultsPatients who were smoking and using antiplatelet agents had the highest incidence rate in the primary composite outcome. The incidence rate was 3.49 per 1,000 person-month (95% CI: 2.30-5.30, log-rank test for primary outcome p = 0.017) and HR of smoking and using antiplatelet agents was 1.66 (95%CI: 0.98-2.81). The adjusted RERI of smoking and using antiplatelet agents was 1.10 (p = 0.009), and the adjusted ratio of HR of smoking and using antiplatelet agents was 3.32 (p = 0.019). The current study observed the interaction between smoking and using antiplatelet agents in both additive and multiplicative scales.ConclusionsSmoking was associated with higher rates of unfavorable clinical outcomes among VA patients taking antiplatelet agents. This suggested that VA patients, especially those using antiplatelet agents should quit smoking.

BACKGROUND:For a better heart failure outcome, it is fundamental to improve the awareness of heart failure at the general population level. We conducted this study to identify the current status of awareness of heart failure in the Korean general population. METHODS:This cross-sectional nationwide survey recruited a total of 1,032 participants aged 30 years or older, based on a stratification systematic sampling method. A 23-item questionnaire was surveyed through telephone interviews. RESULTS:Although 80% of the participants had heard of heart failure, 47% exactly defined what heart failure is. A minority of participants correctly recognized the lifetime risk of developing heart failure (21%) as well as the mortality (16%) and readmission risk (18%) of heart failure and the cost burden of heart failure admission (28%). Regarding preferred treatment options, 71% of the participants chose a treatment option that could improve the quality of life. Approximately two-thirds of the participants agreed that current medical treatment could reduce mortality and improve the quality of life. More than half of the participants (59%) thought that heart failure patients should live quietly and reduce all physical activities. Across survey items, we found a lower awareness state in the elderly groups and people at lower income and educational levels. CONCLUSIONS:The current awareness status of heart failure in the Korean general population is still low. Proactive educational efforts should be made to improve public awareness with special attention to individuals with lower disease awareness.

AimsThis study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF).Methods and results12,654 dataset from 2165 patients with AHF in two hospitals were used as train data for DAHF development, and 4759 dataset from 4759 patients with AHF in 10 hospitals enrolled to the Korean AHF registry were used as performance test data. The endpoints were in-hospital, 12-month, and 36-month mortality. We compared the DAHF performance with the Get with the Guidelines-Heart Failure (GWTG-HF) score, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score, and other machine-learning models by using the test data. Area under the receiver operating characteristic curve of the DAHF were 0.880 (95% confidence interval, 0.876-0.884) for predicting in-hospital mortality; these results significantly outperformed those of the GWTG-HF (0.728 [0.720-0.737]) and other machine-learning models. For predicting 12- and 36-month endpoints, DAHF (0.782 and 0.813) significantly outperformed MAGGIC score (0.718 and 0.729). During the 36-month follow-up, the high-risk group, defined by the DAHF, had a significantly higher mortality rate than the low-risk group(pConclusionDAHF predicted the in-hospital and long-term mortality of patients with AHF more accurately than the existing risk scores and other machine-learning models.

BACKGROUND:We investigated the role of nutritional risk index (NRI) in predicting 1-year mortality in patients with acute decompensated heart failure (ADHF). METHODS:Among 5,625 cohort patients enrolled in Korean Acute Heart Failure (KorAHF) Registry, a total of 5,265 patients who were possible to calculate NRI [NRI = (1.519 x serum albumin [g/dl]) + (41.7 x weight [kg]/ideal body weight [kg])] were enrolled. The patients were divided into 4 groups according to the NRI quartile; Q1 100 (n = 1711, 65.6 ± 14.5 years, 779 males). Primary end-point was all-cause mortality at 1-year clinical follow-up. RESULTS:The 1-year mortality was significantly increased as the NRI quartile decreased, and the lowest NRI quartile was associated with the highest 1-year mortality (Q1: 27.5% vs. Q2: 20.9% vs. Q3: 12.9% vs. Q4: 8.7%, linear p

BackgroundIn clinical practice, a risk prediction model is an effective solitary program to predict prognosis in particular patient groups. B-type natriuretic peptide (BNP)and N-terminal pro-b-type natriuretic peptide (NT-proBNP) are widely recognized outcome-predicting factors for patients with heart failure (HF).This study derived external validation of a risk score to predict 1-year mortality after discharge in hospitalized patients with HF using the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)program data. We also assessed the effect of adding BNP or NT-proBNP to this risk score model in a Korean HF registry population.Method and resultsWe included 5625 patients from the Korean acute heart failure registry (KorAHF) and excluded those who died in hospital. The MAGGIC constructed a risk score to predict mortality in patients with HF by using 13 routinely available patient characteristics (age, gender, diabetes, chronic obstructive pulmonary disorder (COPD), HF diagnosed within the last 18 months, current smoker, NYHA class, use of beta blocker, ACEI or ARB, body mass index, systolic blood pressure, creatinine, and EF). We added BNP or NT-proBNP, which are the most important biomarkers, to the MAGGIC risk scoring system in patients with HF. The outcome measure was 1-year mortality. In multivariable analysis, BNP or NT-proBNP independently predicted death. The risk score was significantly varied between alive and dead groups (30.61 ± 6.32 vs. 24.80 ± 6.81, p < 0.001). After the conjoint use of BNP or NT-proBNP and MAGGIC risk score in patients with HF, a significant difference in risk score was noted (31.23 ± 6.46 vs. 25.25 ± 6.96, p < 0.001).The discrimination abilities of the risk score model with and without biomarker showed minimal improvement (C index of 0.734 for MAGGIC risk score and 0.736 for MAGGIC risk score plus BNP or NT-proBNP, p = 0.0502) and the calibration was found good. However, we achieved a significant improvement in net reclassification and integrated discrimination for mortality (NRI of 33.4%,p < 0.0001 and IDI of 0.002, p < 0.0001).ConclusionIn the KorAHF, the MAGGIC project HF risk score performed well in a large nationwide contemporary external validation cohort. Furthermore, the addition of BNP or NT-proBNPto the MAGGIC risk score was beneficial in predicting more death in hospitalized patients with HF.

The prognostic values of the left ventricular ejection fraction (LVEF) and end-diastolic dimension (LVEDD) have primarily been shown among patients with chronic heart failure (HF), with little representation of patients with acute HF (AHF). Therefore, we investigated the value of these echocardiographic parameters in predicting clinical outcomes among patients in the Korean Heart Failure (KorHF) Registry.The KorHF Registry consists of 3,200 patients who were hospitalized with AHF from 2005 to 2009. The Kaplan-Meier method was used to estimate survival and readmission, and differences were assessed using the log-rank test. Predictors of survival were identified using univariate and multivariate Cox proportional hazards regression analyses.Echocardiograms from 2,910 of the 3,200 patients (90.9%) were evaluated. The median LVEF and LVEDD (37% and 56 mm, respectively) were used as cut-offs for the binary transformation of each parameter. The cumulative death-free survival rates for all patients did not significantly differ based on LVEF or LVEDD quartiles; however, an LVEF greater than the median was associated with a better prognosis in ischemic HF patients (log-rank test; p = 0.039). Among ischemic HF patients, LVEF (dichotomized) was a significant predictor of death in a Cox model after adjusting for a history of HF, age, systolic blood pressure (SBP), serum sodium, sex, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), acute myocardial infarction (AMI), atrial fibrillation (Af) and anemia (hazard ratio (HR) 1.475, 95% confidence interval (CI) 1.099-1.979, p = 0.010). The cumulative readmission-free survival rates significantly differed among ischemic HF patients only when based on LVEDD quartiles (log-rank test; p = 0.001). In multivariate Cox proportional hazards regression analyses, LVEDD (dichotomized) remained a significant variable only among patients with ischemic HF after adjusting for sex, age, AMI, DM, COPD, serum sodium, SBP, blood urea nitrogen (BUN) and anemia (HR 1.401, 95% CI 1.067-1.841, p = 0.015).Among ischemic AHF patients in the KorHF Registry, LVEF is associated with mortality, whereas LVEDD is only associated with readmission in a binary transformed form.

Gestational hypertensive diseases (GHD) and gestational diabetes mellitus (GDM) increase the risk of cardiovascular disease (CVD) later in life. However, the association between gestational medical diseases and familial history of CVD has not been investigated to date. In the present study, we examined the association between familial history of CVD and GHD or GDM via reliable questionnaires in a large cohort of registered nurses.The Korean Nurses' Survey was conducted through a web-based computer-assisted self-interview, which was developed through consultation with cardiologists, gynecologists, and statisticians. We enrolled a total of 9,989 female registered nurses who reliably answered the questionnaires including family history of premature CVD (FHpCVD), hypertension (FHH), and diabetes mellitus (FHDM) based on their medical knowledge. Either multivariable logistic regression analysis or generalized estimation equation was used to clarify the effect of positive family histories on GHD and GDM in subjects or at each repeated pregnancy in an individual.In this survey, 3,695 subjects had at least 1 pregnancy and 8,783 cumulative pregnancies. Among them, 247 interviewees (6.3%) experienced GHD and 120 (3.1%) experienced GDM. In a multivariable analysis adjusted for age, obstetric, and gynecologic variables, age at the first pregnancy over 35 years (adjusted OR 1.61, 95% CI 1.02-2.43) and FHpCVD (adjusted OR 1.60, 95% CI 1.16-2.22) were risk factors for GHD in individuals, whereas FHH was not. FHDM and history of infertility therapy were risk factors for GDM in individuals (adjusted OR 2.68, 95% CI 1.86-3.86; 1.84, 95% CI 1.05-3.23, respectively). In any repeated pregnancies in an individual, age at the current pregnancy and at the first pregnancy, and FHpCVD were risk factors for GHD, while age at the current pregnancy, history of infertility therapy, and FHDM were risk factors for GDM.The FHpCVD and FHDM are significantly associated with GHD and GDM, respectively. Meticulous family histories should be obtained, and women with family histories of these conditions should be carefully monitored during pregnancy.

Microtubule stabilizing agents (MTSA) are known to inhibit vascular smooth muscle cell (VSMC) proliferation and migration, and effectively reduce neointimal hyperplasia and restenosis. Epothilones (EPOs), non-taxane MTSA, have been found to be effective in the inhibition of VSMC proliferation and neointimal formation by cell cycle arrest. However, effect of EPOs on apoptosis in hyper-proliferated VSMCs as a possible way to reduce neointimal formation and its action mechanism related to VSMC viability has not been suited yet. Thus, the purposes of the present study was to investigate whether EPOs are able to inhibit neointimal formation by inducing apoptosis within the region of neointimal hyperplasia in balloon-injured rat carotid artery, as well as underlying action mechanism. Treatment of EPO-B and EPO-D significantly induced apoptotic cell death and mitotic catastrophe in hyper-proliferated VSMCs, resulting in cell growth inhibition. Further, EPOs significantly suppressed VSMC proliferation and induced apoptosis by activation of p53-dependent apoptotic signaling pathway, Bax/cytochrome c/caspase-3. We further demonstrated that the local treatment of carotid arteries with EPOs potently inhibited neointimal lesion formation by induction of apoptosis in rat carotid injury model. Our findings demonstrate a potent anti-neointimal hyperplasia property of EPOs by inducing p53-depedent apoptosis in hyper-proliferated VSMCs.

Despite the benefits of successful percutaneous coronary interventions (PCIs) for chronic total occlusion (CTO) lesions, PCIs of CTO lesions still carry a high rate of adverse events, including in-stent restenosis (ISR). Because previous reports have not specifically investigated the intravascular ultrasound (IVUS) predictors of ISR in CTO lesions, we focused on these predictors. We included 126 patients who underwent successful PCIs, using drug-eluting stents, and post-PCI IVUS of CTO lesions. Patient and lesion characteristics were analyzed to elucidate the ISR predictors. In each lesion, an average of 1.7 ± 0.7 (mean length, 46.4 ± 20.3 mm) stents were used. At 9 months follow-up, 14 (11%) patients demonstrated ISR, and 8 (6.3%) underwent target lesion revascularization. Multivariate logistic regression analysis showed that the independent predictors of ISR were the post-PCI minimal luminal diameter (MLD) and the stent expansion ratio (SER; minimal stent cross-sectional area (CSA) over the nominal CSA of the implanted stent), measured using quantitative coronary angiography (QCA) and IVUS, respectively. A receiver operating characteristic analysis indicated that the best post-PCI MLD and SER cut-off values for predicting ISR were 2.4 mm (area under the curve [AUC], 0.762; 95% confidence interval (CI), 0.639-0.885) and 70% (AUC, 0.714; 95% CI, 0.577-0.852), respectively. Lesions with post-PCI MLD and SER values less than these threshold values were at a higher risk of ISR, with an odds ratio of 23.3 (95% CI, 2.74-198.08), compared with lesions having larger MLD and SER values. Thus, the potential predictors of ISR, after PCI of CTO lesions, are the post-PCI MLD and SER values. The ISR rate was highest in lesions with a post-PCI MLD ≤2.4 mm and an SER ≤70%.

Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea.The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction

Oxidative stress occurs with disturbed blood flow, inflammation and cardiovascular disease (CVD), yet free-radical scavenging antioxidants have shown limited benefit in human CVD. Thioredoxin-1 (Trx1) is a thiol antioxidant protecting against non-radical oxidants by controlling protein thiol/disulfide status; Trx1 translocates from cytoplasm to cell nuclei due to stress signaling, facilitates DNA binding of transcription factors, e.g., NF-κB, and potentiates inflammatory signaling. Whether increased nuclear Trx1 contributes to proatherogenic signaling is unknown.In vitro and in vivo atherogenic models were used to test for nuclear translocation of Trx1 and associated proinflammatory signaling. Disturbed flow by oscillatory shear stress stimulated Trx1 nuclear translocation in endothelial cells. Elevation of nuclear Trx1 in endothelial cells and transgenic (Tg) mice potentiated disturbed flow-stimulated proinflammatory signaling including NF-κB activation and increased expression of cell adhesion molecules and cytokines. Tg mice with increased nuclear Trx1 had increased carotid wall thickening due to disturbed flow but no significant differences in serum lipids or weight gain compared to wild type mice. Redox proteomics data of carotid arteries showed that disturbed flow stimulated protein thiol oxidation, and oxidation was higher in Tg mice than wild type mice.Translocation of Trx1 from cytoplasm to cell nuclei plays an important role in disturbed flow-stimulated proatherogenesis with greater cytoplasmic protein oxidation and an enhanced nuclear transcription factor activity. The results suggest that pharmacologic interventions to inhibit nuclear translocation of Trx1 may provide a new approach to prevent inflammatory diseases or progression.

Previous studies have reported a considerable association between the VerifyNow (Accumetrics, San Diego, CA, USA) P2Y12 assay results and hematocrit. No reports, however, have described an association between the multiple electrode platelet aggregometry (MEA; Dynabyte, Munich, Germany) adenosine diphosphate (ADP) assay results and hematocrit. This study was conducted to evaluate the influence of hematocrit on the results of 2 different point-of-care platelet function tests.A total of 462 consecutive patients who were undergoing percutaneous coronary intervention were enrolled. Platelet function was evaluated with both the VerifyNow P2Y12 and MEA ADP assays.Anemic patients (n = 152, 32.9%) demonstrated a significantly higher rate of cardiac death, myocardial infarction, and stroke (5.3% vs. 2.3%, p = 0.046) during the follow-up (median: 18.8 months). Although the VerifyNow P2Y12 assay results demonstrated a significant inverse correlation with hematocrit (r = -0.409, p

Proteases regulate a large number of biological processes in plants, such as metabolism, physiology, growth, and defense. In this study, we carried out virus-induced gene silencing assays with pepper cDNA clones to elucidate the biological roles of protease superfamilies. A total of 153 representative protease genes from pepper cDNA were selected and cloned into a Tobacco rattle virus-ligation independent cloning vector in a loss-of-function study. Silencing of 61 proteases resulted in altered phenotypes, such as the inhibition of shoot growth, abnormal leaf shape, leaf color change, and lethality. Furthermore, the silencing experiments revealed that multiple proteases play a role in cell death and immune response against avirulent and virulent pathogens. Among these 153 proteases, 34 modulated the hypersensitive cell death response caused by infection with an avirulent pathogen, and 16 proteases affected disease symptom development caused by a virulent pathogen. Specifically, we provide experimental evidence for the roles of multiple protease genes in plant development and immune defense following pathogen infection. With these results, we created a broad sketch of each protease function. This information will provide basic information for further understanding the roles of the protease superfamily in plant growth, development, and defense.

Background: Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea., Method and Results: The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction <45%) admitted to 23 university hospitals. The guideline adherence indicator (GAI) was defined as a performance measure on the basis of 3 pharmacological classes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone antagonist (AA). Based on the overall adherence percentage, subjects were divided into 2 groups: those with good guideline adherence (GAI ≥50%) and poor guideline adherence (GAI <50%). We included 1319 regional participants as representatives of the standard population from the Korean national census in 2008. Adherence to drugs at discharge was as follows: ACEI or ARB, 89.7%; BB, 69.2%; and AA, 65.9%. Overall, 82.7% of the patients had good guideline adherence. Overall mortality and re-hospitalization rates at 1 year were 6.2% and 37.4%, respectively. Survival analysis by log-rank test showed a significant difference in event-free survival rate of mortality (94.7% vs. 89.8%, p = 0.003) and re-hospitalization (62.3% vs. 56.4%, p = 0.041) between the good and poor guideline-adherence groups., Conclusions: Among patients with systolic HF in Korea, adherence to pharmacologic treatment guidelines as determined by performance measures, including prescription of ACEI/ARB and BB at discharge, was associated with improved clinical outcomes.