Publications by authors named "Weon Kim"

179 Publications

Effects of Fixed-Dose Combination of Low-Intensity Rosuvastatin and Ezetimibe Versus Moderate-Intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized, Double-Blind, Multicenter, Phase III Study.

Clin Ther 2021 Aug 21. Epub 2021 Aug 21.

Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy.

Methods: This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up.

Findings: Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups.

Implications: Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2021.07.016DOI Listing
August 2021

The sGC-cGMP Signaling Pathway as a Potential Therapeutic Target in Doxorubicin-Induced Heart Failure: A Narrative Review.

Am J Cardiovasc Drugs 2021 Jun 21. Epub 2021 Jun 21.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, 23, Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

The anti-cancer agent doxorubicin (DOX) has high cardiotoxicity that is linked to DOX-mediated increase in oxidative stress, mitochondrial iron overload, DNA damage, autophagy, necrosis, and apoptosis, all of which are also associated with secondary tumorigenicity. This limits the clinical application of DOX therapies. Previous studies have attributed DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the production of reactive oxygen species (ROS), which seem to be independent of its anti-tumor DNA damaging effects. Chemo-sensitization of soluble guanylate cyclase (sGC) in the cyclic guanosine monophosphate (cGMP) pathway induces tumor cell death despite the cardiotoxicity associated with DOX treatment. However, sGC-cGMP signaling must be activated during heart failure to facilitate myocardial cell survival. The sGC pathway is dependent on nitric oxide and signal transduction via the nitric oxide-sGC-cGMP pathway and is attenuated in various cardiovascular diseases. Additionally, cGMP signaling is regulated by the action of certain phosphodiesterases (PDEs) that protect the heart by inhibiting PDE, an enzyme that hydrolyses cGMP to GMP activity. In this review, we discuss the studies describing the interactions between cGMP regulation and DOX-mediated cardiotoxicity and their application in improving DOX therapeutic outcomes. The results provide novel avenues for the reduction of DOX-induced secondary tumorigenicity and improve cellular autonomy during DOX-mediated cardiotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40256-021-00487-5DOI Listing
June 2021

2021 Korean Society of Myocardial Infarction Expert Consensus Document on Revascularization for Acute Myocardial Infarction.

Korean Circ J 2021 Apr;51(4):289-307

Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea.

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns, have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2021.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022023PMC
April 2021

Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Oncol 2021 05 18;22(5):620-631. Epub 2021 Mar 18.

Association de Recherche Contre les Cancers dont Gynécologiques-ARCAGY, Paris, France.

Background: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival.

Methods: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients.

Findings: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]).

Interpretation: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients.

Funding: AstraZeneca and Merck.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(21)00073-5DOI Listing
May 2021

Impact of genetic variants on clinical outcome after percutaneous coronary intervention in elderly patients.

Aging (Albany NY) 2021 03 12;13(5):6506-6524. Epub 2021 Mar 12.

Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.

Elderly patients treated with percutaneous coronary intervention (PCI) have a higher risk of both ischemic and bleeding complications than younger patients. However, few studies have reported how genetic information of elderly patients treated with PCI affects clinical outcomes. We investigated the impact of genetic variants on clinical outcomes in elderly patients. Correlations between single-nucleotide polymorphisms (CYP2C19 and P2Y12 receptor gene G52T polymorphism) and clinical outcomes were analyzed in 811 elderly patients (≥75 years of age) from a prospective multicenter registry. The primary endpoint was a composite of myocardial infarction and death. Secondary endpoints were an individual event of death, cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization, stroke, and major bleeding (Bleeding Academic Research Consortium ≥3). Regarding CYP2C19, patients with poor metabolizers had a significantly higher risk for the primary endpoint (hazard ratio [HR] 2.43; 95% confidence interval [95% CI] 1.12-5.24; p=0.024) and secondary endpoints (death and cardiac death). Regarding P2Y12 G52T, the TT group had a significantly higher occurrence of major bleeding than the other groups (HR 3.87; 95% CI 1.41-10.68; p=0.009). In conclusion, poor metabolizers of CYP2C19 and TT groups of P2Y12 G52T may be significant predictors of poor clinical outcomes in elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993709PMC
March 2021

Polygenic risk score validation using Korean genomes of 265 early-onset acute myocardial infarction patients and 636 healthy controls.

PLoS One 2021 4;16(2):e0246538. Epub 2021 Feb 4.

Personal Genomics Institute, Genome Research Foundation, Ulsan, Republic of Korea.

Background: The polygenic risk score (PRS) developed for coronary artery disease (CAD) is known to be effective for classifying patients with CAD and predicting subsequent events. However, the PRS was developed mainly based on the analysis of Caucasian genomes and has not been validated for East Asians. We aimed to evaluate the PRS in the genomes of Korean early-onset AMI patients (n = 265, age ≤50 years) following PCI and controls (n = 636) to examine whether the PRS improves risk prediction beyond conventional risk factors.

Results: The odds ratio of the PRS was 1.83 (95% confidence interval [CI]: 1.69-1.99) for early-onset AMI patients compared with the controls. For the classification of patients, the area under the curve (AUC) for the combined model with the six conventional risk factors (diabetes mellitus, family history of CAD, hypertension, body mass index, hypercholesterolemia, and current smoking) and PRS was 0.92 (95% CI: 0.90-0.94) while that for the six conventional risk factors was 0.91 (95% CI: 0.85-0.93). Although the AUC for PRS alone was 0.65 (95% CI: 0.61-0.69), adding the PRS to the six conventional risk factors significantly improved the accuracy of the prediction model (P = 0.015). Patients with the upper 50% of PRS showed a higher frequency of repeat revascularization (hazard ratio = 2.19, 95% CI: 1.47-3.26) than the others.

Conclusions: The PRS using 265 early-onset AMI genomes showed improvement in the identification of patients in the Korean population and showed potential for genomic screening in early life to complement conventional risk prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246538PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861392PMC
August 2021

ST-Elevation Myocardial Infarction by Nitrate Interruption Immediately after an Ergonovine Provocation Test.

Authors:
Joan Kim Weon Kim

Chonnam Med J 2021 Jan 25;57(1):95-96. Epub 2021 Jan 25.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4068/cmj.2021.57.1.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840348PMC
January 2021

Impact of genetic variants on major bleeding after percutaneous coronary intervention based on a prospective multicenter registry.

Sci Rep 2021 01 19;11(1):1790. Epub 2021 Jan 19.

Division of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University of College of Medicine, Seoul, South Korea.

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08-5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.Trial registration: NCT02707445 ( https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1 ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80319-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815734PMC
January 2021

Low-Dose Triple Antihypertensive Combination Therapy in Patients with Hypertension: A Randomized, Double-Blind, Phase II Study.

Drug Des Devel Ther 2020 31;14:5735-5746. Epub 2020 Dec 31.

Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi, Republic of Korea.

Purpose: We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.

Patients And Methods: After a 1 to 2-week placebo run-in period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.

Results: The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were -17.2, -19.5, -14.9, -18.5, -11.3 and -9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.

Conclusion: Low-dose triple combination therapies could be effective as antihypertensive therapies.

Trial Registration: ClinicalTrials.gov identifier NCT03897868.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S286586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781016PMC
September 2021

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI).

JACC Cardiovasc Interv 2020 10;13(19):2220-2234

Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. Electronic address:

Objectives: The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans.

Background: Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction.

Methods: In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro-B-type natriuretic peptide level at 6 months.

Results: Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro-B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m; p = 0.056) (difference -2.3 ml/m; 95% confidence interval: -4.8 to 0.2 ml/m; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m; p = 0.366) (difference -1.8 ml/m; 95% confidence interval: -3.5 to -0.1 ml/m; p = 0.040).

Conclusions: Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2020.08.007DOI Listing
October 2020

Neointima characteristics as a prognostic marker for drug-coated balloon angioplasty in patients with in-stent restenosis: an optical coherence tomography study.

Coron Artery Dis 2020 12;31(8):694-702

Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine.

Background: Research has shown that the prognosis of in-stent restenosis (ISR) lesions after drug-coated balloon (DCB) angioplasty can differ in relation to in-stent neointimal characteristics. However, changes in neointima characteristics after DCB have not been studied. This study sought to investigate changes in neointima characteristics after DCB for ISR.

Methods: From the Yonsei Optical Coherence Tomography (OCT) registry, data on DCBs performed in patients with ISR were collected. Neointima characteristics were categorized as homogeneous, heterogeneous, layered neointima, and neoatherosclerosis in each OCT procedure. Homogeneous and layered neointima were classified as a favorable neointima, while heterogeneous neointima and neoatherosclerosis were classified as an unfavorable neointima. The data of 67 ISR patients were analyzed.

Results: The median duration between initial and follow-up OCT was 9.6 months. Patients with homogeneous and layered neointima on the initial OCT before DCB mostly appeared as homogeneous (66.7 and 68.2%, respectively) on the follow-up OCT, whereas most of the patients with heterogeneous neointima on the initial OCT remained unaltered (70%). Patients with unfavorable neointima at either the initial (P = 0.023) or the follow-up OCT (P = 0.037) had a worse major adverse cardiovascular event-free survival than the other patients. Patients who showed unfavorable neointima at both the initial and the follow-up OCT had the worst event-free survival (P = 0.038).

Conclusions: The follow-up OCT neointimal characteristics after DCB for ISR was associated with initial OCT characteristics. Sustained unfavorable neointima in serial OCT imaging may reflect poor prognosis in patients with ISR treated with DCB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000946DOI Listing
December 2020

2020 Korean Society of Myocardial Infarction Expert Consensus Document on Pharmacotherapy for Acute Myocardial Infarction.

Korean Circ J 2020 Oct;50(10):845-866

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Clinical practice guidelines published by the European Society of Cardiology and the American College of Cardiology/American Heart Association summarize the available evidence and provide recommendations for health professionals to enable appropriate clinical decisions and improve clinical outcomes for patients with acute myocardial infarction (AMI). However, most current guidelines are based on studies in non-Asian populations in the pre-percutaneous coronary intervention (PCI) era. The Korea Acute Myocardial Infarction Registry is the first nationwide registry to document many aspects of AMI from baseline characteristics to treatment strategies. There are well-organized ongoing and published randomized control trials especially for antiplatelet therapy among Korean patients with AMI. Here, members of the Task Force of the Korean Society of Myocardial Infarction review recent published studies during the current PCI era, and have summarized the expert consensus for the pharmacotherapy of AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2020.0196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515755PMC
October 2020

Troponin Aptamer on an Atomically Flat Au Nanoplate Platform for Detection of Cardiac Troponin I.

Nanomaterials (Basel) 2020 Jul 18;10(7). Epub 2020 Jul 18.

Department of Chemistry, KAIST, Daejeon 34141, Korea.

Well-ordered bioreceptors on atomically flat Au surfaces can be a high-performance biosensor. Cardiac troponin I proteins (cTnIs) have been regarded as a specific biomarker for acute myocardial infarction (AMI). Here, we report the accurate detection of cTnIs using an aptamer-immobilized Au nanoplate platform. The single-crystalline and atomically flat Au nanoplate was characterized by atomic force microscopy. For the precise detection of cTnI, we immobilized an aptamer that can strongly bind to cTnI onto an atomically flat Au nanoplate. Using the aptamer-immobilized Au nanoplate, cTnIs were successfully detected at a concentration of 100 aM (2.4 fg/mL) in buffer solution. Furthermore, cTnIs in serum could be identified at a concentration of 100 fM (2.4 pg/mL). The total assay time was ~7 h. Importantly, the aptamer-immobilized Au nanoplate enabled us to diagnose AMI patients accurately, suggesting the potential of the present method in the diagnosis of AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano10071402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407982PMC
July 2020

BAY60-2770 attenuates doxorubicin-induced cardiotoxicity by decreased oxidative stress and enhanced autophagy.

Chem Biol Interact 2020 Sep 9;328:109190. Epub 2020 Jul 9.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, South Korea. Electronic address:

Background: Doxorubicin (DOX) administration decreases cardiac soluble guanylate cyclase (sGC) activity. We hypothesized that bypassing impaired NO-sGC-cGMP pathway resulting from the activation of oxidized and heme-free soluble guanylate cyclase (sGC) could be a therapeutic target for DOX-mediated cardiomyopathy (DOX-CM). The present study investigated the therapeutic roles and mechanism of BAY60-2770, an activator of oxidized sGC, in alleviating DOX-CM.

Methods: H9c2 cardiomyocytes were pretreated with BAY60-2770 followed by DOX. Cell viability and intracellular reactive oxygen species (ROS) were subsequently measured. To determine the role BAY60-2770 in mitochondrial ROS generation and mitochondrial membrane potential, we examined mitoSOX RED and TMRE fluorescence under DOX exposure. As animal experiments, rats were orally administered with 5 mg/kg of BAY60-2770 at 1 h prior to every DOX treatment and then assessed by echocardiography and apoptotic marker and autophagy.

Results: BAY60-2770 ameliorated cell viability and DOX-induced oxidative stress in H9c2 cells, which was mediated by PKG activation. Mitochondrial ROS and TMRE fluorescence were attenuated by BAY60-2770 in DOX-treated H9c2 cells. DOX-induced caspase-3 activation decreased after pretreatment with BAY60-2770 in vivo and in vitro. Echocardiography showed that BAY60-2770 significantly improved DOX-induced myocardial dysfunction. Autophagosome was increased by BAY60-2770 in vivo.

Conclusions: BAY60-2770 appears to mitigate DOX-induced mitochondrial ROS, membrane potential loss, autophagy, and subsequent apoptosis, leading to protection of myocardial injury and dysfunction. These novel results highlighted the therapeutic potential of BAY60-2770 in preventing DOX-CM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2020.109190DOI Listing
September 2020

Long-Term Clinical Effects of Carotid Intraplaque Neovascularization in Patients with Coronary Artery Disease.

Korean J Radiol 2020 07;21(7):900-907

Cardiovascular Division, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Korea.

Objective: To investigate the predictive value of intraplaque neovascularization (IPN) for cardiovascular outcomes.

Materials And Methods: We evaluated 217 patients with coronary artery disease (CAD) (158 men; mean age, 68 ± 10 years) with a maximal carotid plaque thickness ≥ 1.5 mm for the presence of IPN using contrast-enhanced ultrasonography. We compared patients with (n = 116) and without (n = 101) IPN during the follow-up period and investigated the predictors of major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, coronary artery revascularization, and transient ischemic accident/stroke.

Results: During the mean follow-up period of 995 ± 610 days, the MACE rate was 6% (13/217). Patients with IPN had a higher maximal thickness than those without IPN (2.86 ± 1.01 vs. 2.61 ± 0.84 mm, = 0.046). Common carotid artery-peak systolic velocity, left ventricular mass index (LVMI), and ventricular-vascular coupling index were significantly correlated with MACE. However, on multivariate Cox regression analysis, increased LVMI was independently related to MACE ( < 0.05). The presence of IPN could not predict MACE.

Conclusion: The presence of IPN was related to a higher plaque thickness but could not predict cardiovascular outcomes better than conventional clinical factors in patients with CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289693PMC
July 2020

Substance P enhances the local activation of NKR-expressing c-kit cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

BMC Mol Cell Biol 2020 Jun 9;21(1):41. Epub 2020 Jun 9.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.

Background: Localization of neurokinin 1 receptor (NKR), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NKR signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NKR antagonist) (RP/SP + I/R). The left anterior descending coronary artery was occluded for 40 min followed by 1 day reperfusion with SP or SP + RP or without either. After 1 day, both atria and ventricles as well as the heart apexes were collected.

Results: SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP + I/R rats via NKR activation. In agreement with these observations, NKR-expressing c-Kit Nkx2.5GATA4 cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA approximately 2-fold increase more than RA. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NKR antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit CPCs.

Conclusion: SP/NKR might play a role as a key mediator involved in the cellular response to c-Kit CPC expansion in RA of the heart within 24 h after I/R.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12860-020-00286-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285458PMC
June 2020

Platelet activity with hemoglobin level in patients with hemodialysis: Prospective study.

Medicine (Baltimore) 2020 Mar;99(10):e19336

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.

Background: VerifyNow (VN; Accumetrics, San Diego, CA) P2Y12 reaction unit (PRU) has an inverse relation with hemoglobin level (Hb). Chronic kidney disease (CKD) is associated with low response to clopidogrel and low Hb. Our aim is to investigate the relation between PRU and Hb, and to assess whether Hb directly affects PRU or not in patients with CKD undergoing hemodialysis (HD).

Methods: We analyzed the relation between PRU and Hb in 43 HD patients and compared it with a control group of 127 patients with normal renal function. Both groups underwent percutaneous coronary intervention for stable coronary artery disease. We also compared PRU between the 2 groups considering Hb as a confounding factor.

Results: In the control group, Hb and PRU showed a significant inverse correlation (correlation coefficient r = -0.340; P < .001), but not in the HD group (correlation coefficient r = -0.099; P = .53). PRU was higher in the HD group than the control group after adjusting for the influence of Hb (299.2 [95% confidence interval: 278.4-316.7] vs 248.7 [95% confidence interval: 227.7-269.0]; P < .001), even after propensity score matching (299.2 [95% confidence interval: 278.4-316.7] vs 241.7 [95% confidence interval: 221.8-262.2]; P < .001).

Conclusions: PRU was higher regardless of lower Hb in CKD on HD patients than normal renal function patients. Therefore, Hb was not crucial factor to decide PRU in CKD on HD patients in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000019336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478496PMC
March 2020

Substance P Administered after Myocardial Infarction Upregulates Microphthalmia-Associated Transcription Factor, GATA4, and the Expansion of c-Kit Cells.

Stem Cells Int 2020 10;2020:1835950. Epub 2020 Feb 10.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.

Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper transcription factor, can govern gene expression by binding to E box elements in the promoter region of its target gene. Although high levels of MITF have been observed in cardiomyocytes and the heart, the role of MITF after myocardial infarction (MI) remains unclear. We investigated the association between substance P (SP)/neurokinin-1 receptor (NKR) signaling and MITF expression after MI. Male Sprague-Dawley rats (8 weeks) were randomly divided in two groups: ischemia/reperfusion injury (I/R) and SP injection (5 nmol/kg, SP+I/R). At the end of 7 days, the left ventricle (LV; LV, LV) and infarct-related areas (IA; IA, IA) from the hearts were collected. Immunofluorescence staining demonstrated that the LV had a larger population of c-Kit GATA4 cells, which markedly upregulated MITF, c-Kit, and GATA4. c-Kit cells in the explant-derived cells (EDCs) derived from IA migrated more widely than EDCs IA. Immunofluorescence staining, western blot analysis, and qRT-PCR assay showed that SP-treated c-Kit cells exhibited a high expression of c-Kit, GATA4, and MITF. FTY720 (a MITF inhibitor), RP67580 (NKR inhibitor), or both inhibited the migration and proliferation of c-Kit cells increased by SP and blocked the upregulation of c-Kit, GATA4, and MITF. Overall, we suggest that MITF might be a potential regulator in SP-mediated c-Kit cell expansion post-MI via c-Kit and GATA4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1835950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035579PMC
February 2020

Reassembling Evidence for Treatment in Asymptomatic Carotid Artery Stenosis.

Korean Circ J 2020 Apr 3;50(4):343-345. Epub 2020 Feb 3.

Division of Cardiovascular, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2020.0023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067607PMC
April 2020

Non-Fasting Triglyceride Levels as a Superior Predictor of Cardiovascular Disease.

Circ J 2020 02 14;84(3):386-387. Epub 2020 Feb 14.

Cardiovascular Division, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-20-0068DOI Listing
February 2020

PLF-1 (Proliferin-1) Modulates Smooth Muscle Cell Proliferation and Development of Experimental Intimal Hyperplasia.

J Am Heart Assoc 2019 12 16;8(24):e005886. Epub 2019 Dec 16.

Department of Cardiology/Hypertension and Heart Center Yanbian University Hospital Yanji Jilin China.

Background Although apoptosis and cell proliferation have been extensively investigated in atherosclerosis and restenosis postinjury, the communication between these 2 cellular events has not been evaluated. Here, we report an inextricable communicative link between apoptosis and smooth muscle cell proliferation in the promotion of vascular remodeling postinjury. Methods and Results Cathepsin K-mediated caspase-8 maturation is a key initial step for oxidative stress-induced smooth muscle cell apoptosis. Apoptotic cells generate a potential growth-stimulating signal to facilitate cellular mass changes in response to injury. One downstream mediator that cathepsin K regulates is PLF-1 (proliferin-1), which can potently stimulate growth of surviving neighboring smooth muscle cells through activation of PI3K/Akt/p38MAPK (phosphatidylinositol 3-kinase/protein kinase B/p38 mitogen-activated protein kinase)-dependent and -independent mTOR (mammalian target of rapamycin) signaling cascades. We observed that cathepsin K deficiency substantially mitigated neointimal hyperplasia by reduction of Toll-like receptor-2/caspase-8-mediated PLF-1 expression. Interestingly, PLF-1 blocking, with its neutralizing antibody, suppressed neointima formation and remodeling in response to injury in wild-type mice. Contrarily, administration of recombinant mouse PLF-1 accelerated injury-induced vascular actions. Conclusions This is the first study detailing PLF-1 as a communicator between apoptosis and proliferation during injury-related vascular remodeling and neointimal hyperplasia. These data suggested that apoptosis-driven expression of PLF-1 is thus a novel target for treatment of apoptosis-based hyperproliferative disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.005886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951060PMC
December 2019

Effect of Pre-Procedural Beta-Blocker on Clinical Outcome after Percutaneous Coronary Intervention in Acute Coronary Syndrome.

Int Heart J 2019 Nov 15;60(6):1284-1292. Epub 2019 Nov 15.

Division of Cardiology, Department of Internal Medicine, Konkuk University Medical Center, School of Medicine, Konkuk University.

The efficacy of pre-procedural beta-blocker use in patients with acute coronary syndrome (ACS) is not well established in the current percutaneous coronary intervention (PCI) era. We investigate the effect of pre-procedural beta-blocker use on clinical outcomes in patients with ACS undergoing PCI. Among 44,967 consecutive cases of PCI enrolled in the nationwide, retrospective, multicenter registry (K-PCI registry), 31,040 patients with ACS were selected and analyzed. We classified patients into pre-procedural beta-blocker group (n = 8,678) and pre-procedural no-beta-blocker group (n = 22,362) according to the use of beta-blockers at least for two weeks before index PCI. Propensity score-matching analysis was performed and resulted in 7,445 pairs. The primary outcome was in-hospital cardiac death. In propensity score-matched populations, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death compared with the pre-procedural no-beta-blocker group (1.1% versus 2.0%, unadjusted odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.42-0.73, P < 0.01). In subgroup analysis, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death, compared with the pre-procedural no-beta-blocker group in ST-segment elevation myocardial infarction subpopulation (3.1% versus 6.1%, unadjusted OR: 0.49, 95% CI: 0.34-0.71, P < 0.01) and non-ST-segment elevation myocardial infarction subpopulation (1.5% versus 2.9%, unadjusted OR: 0.51, 95% CI: 0.33-0.79, P < 0.01). However, in unstable angina subpopulation, the in-hospital cardiac death rate was comparable between both groups. In conclusion, the use of pre-procedural beta-blocker was associated with a lower risk of in-hospital cardiac death in patients with ACS undergoing PCI. This result adds to the body of evidence that use of pre-procedural beta-blocker in patients with ACS might be reasonable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1536/ihj.19-175DOI Listing
November 2019

Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy.

Clin Ther 2019 12 11;41(12):2571-2592. Epub 2019 Nov 11.

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy.

Methods: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups.

Findings: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074).

Implications: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2019.10.010DOI Listing
December 2019

An analysis of evidence-based practice courses in Korean nursing education systems.

Heliyon 2019 Oct 12;5(10):e02650. Epub 2019 Oct 12.

Department of Nursing, Gwangju Health University, Gwangju, South Korea.

Objective: This study aims to examine the current status of evidence-based practice (EBP) courses and EBP-related courses in Korean nursing education systems.

Method: Subject institutions were 159 institutions including 99 universities and 60 colleges with a bachelor's degree program accredited by the Korean Accreditation Board of Nursing Education. Two researchers independently collected data from the subject institutions based on the curricula published on the website of each university or college, and the collected datasets were cross-checked to ensure data accuracy.

Results: EBP courses were found in a small portion of institutions (13.2%). Research courses were offered in most institutions (98.7%), but they were usually provided to third- or fourth-year students.

Conclusion: Understanding the concept of EBP and knowledge of nursing research and statistics are both prerequisites to strengthening the EBP competence of nursing students. Therefore, it is imperative to equip them with the required knowledge prior to their clinical practicum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2019.e02650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812239PMC
October 2019

Relative risk of plaque erosion among different age and sex groups in patients with acute coronary syndrome.

J Thromb Thrombolysis 2020 Apr;49(3):352-359

Cardiology Division, Massachusetts General Hospital, Harvard Medical School, GRB 800, 55 Fruit Street, Boston, MA, 02114, USA.

Postmortem studies reported plaque erosion is frequent in young women. Recent in vivo studies failed to show age and sex differences in the plaque erosion prevalence. The aim of this study was to investigate the prevalence of plaque erosion by age and sex among acute coronary syndromes (ACS) patients. From 1699 ACS patients, 1083 with plaque erosion or rupture were analyzed. Patients were categorized as 5 age groups (≤ 50, 51-60, 61-70, 71-80, ≥ 81 years). Overall prevalence of plaque erosion was similar between males and females (p = 0.831). Males age ≤ 50 had higher (p = 0.018) and age 71-80 had lower (p = 0.006) prevalence of plaque erosion. Females age 61-70 had higher (p = 0.021) and age 71-80 had lower (p = 0.045) prevalence of plaque erosion. In advanced age groups (≥ 71 years), rupture was the dominant etiology in both sexes. In multivariate analysis of males, age ≤ 50 demonstrated a trend to increase (OR 1.418, 95% CI 0.961-2.093, p = 0.078) the erosion risk. Females age ≤ 70 independently increased (OR 2.138, 95% CI 1.249-3.661, p = 0.006) the risk for erosion. The prevalence of plaque erosion was similar between males and females. Plaque erosion risk was increased in the males age ≤ 50 and in the females age ≤ 70 among ACS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-019-01969-9DOI Listing
April 2020

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study.

Clin Ther 2019 08 12;41(8):1508-1521. Epub 2019 Jul 12.

Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea. Electronic address:

Purpose: The aim of this study was to evaluate the blood pressure-lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia.

Methods: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non-HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A. Tolerability of combination therapy was compared with other monotherapy groups.

Findings: The percentage changes of LDL-C were -48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and -49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non-HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, -8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group.

Implications: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2019.05.007DOI Listing
August 2019

Rationale and Design of the High Platelet Inhibition with Ticagrelor to Improve Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction (HEALING-AMI) Trial.

Korean Circ J 2019 Jul 22;49(7):586-599. Epub 2019 Mar 22.

Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea.

Background And Objectives: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y₁₂ receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI.

Methods: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol.

Conclusions: HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition.

Trial Registration: ClinicalTrials.gov Identifier: NCT02224534.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2018.0415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597457PMC
July 2019

Substance-P Prevents Cardiac Ischemia-Reperfusion Injury by Modulating Stem Cell Mobilization and Causing Early Suppression of Injury-Mediated Inflammation.

Cell Physiol Biochem 2019 18;52(1):40-56. Epub 2019 Feb 18.

Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Hoegi-Dong, Republic of Korea.

Background/aims: Therapies using stem/progenitor cells have been experimentally and clinically investigated to regenerate damaged hearts. Substance-P (SP) induces bone marrow (BM) stem cell mobilization and suppresses inflammation in ischemic injuries. This study investigated the role of SP in BM stem cell mobilization and immune responses for tissue repair after ischemic-reperfusion injury (IRI), in comparison with that of granulocyte colony-stimulating factor (GCSF).

Methods: SP was intravenously injected into IRI rats and its affect was evaluated by determining colony forming efficiency, immune cell/ cytokine profiles, histological changes, and heart function through echocardiography.

Results: In the rat cardiac IRI model, SP suppressed IRI-mediated tumor necrosis factor-α induction, but increased the levels of interleukin-10, CD206+ monocytes, and regulatory T cells in the blood; reduced myocardial apoptosis at day 1 post-IRI; and markedly stimulated colony forming unit (CFU)-e and (CFU)-f cell mobilization. Efficacy of SP in the recovery of cardiac function after IRI was demonstrated by increased cardiac contractility, accompanied by reduced infarction sizes and fibrosis, and increased revascularization of vessels covered with alpha smooth muscle actin. These effects of SP were confirmed in an acute myocardial infarction (AMI) model. All effects mediated by SP were superior to those mediated by GCSF.

Conclusion: Systemic injection of SP decreased early inflammatory responses and promoted stem cell mobilization, leading to a compact vasculature and improved cardiac function in cardiac IRI and AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.33594/000000004DOI Listing
March 2019

Transcortical photothrombotic pyramidotomy model with persistent motor deficits.

PLoS One 2018 31;13(12):e0204842. Epub 2018 Dec 31.

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.

Traditional pyramidotomy models have a high mortality rate from breathing difficulties and show early recovery from the induced motor deficits. This study establishes a novel pyramidotomy technique in Sprague Dawley rats that generates persistent motor deficits and has a reduced mortality rate. We used viral neural tracing to identify the course and relative distribution of forelimb and hindlimb motor fibers (n = 9). On basis of the neural tracing data, the medullary pyramid was targeted dorsally from the cerebellar cortex for photothrombotic infarct lesioning (n = 18). The photothrombotic technique selectively destroyed the corticospinal fibers in the medullary pyramid with relative preservation of neighboring grey-matter tissue. MicroPET imaging using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG-microPET) showed a decrease in regional cerebral glucose metabolism (rCGM) in the bilateral pyramid and ipsilateral sensory cortex (p < 0.001, FDR q < 0.05). In addition, the trapezoid bodies and superior olivary nuclei showed a decrease in rCGM, compatible with damage caused during the introduction of the optical fiber. Connected structures such as the inferior colliculi and auditory cortices also showed decreases in rCGM in both hemispheres (p < 0.001, FDR q < 0.05). There was a significant and persistent decrease in motor and sensory function in the contralateral limb following pyramidotomy, as demonstrated by performance in the single pellet reaching task and the foot-fault test. There was no operative mortality or loss of respiratory function in this study. These results indicate that photothrombotic pyramidotomy with a dorsal transcortical approach is a safe and reliable technique for generating a pyramidotomy model with persistent motor deficits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204842PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312246PMC
April 2019

Comparison of Resolute zotarolimus-eluting and Xience everolimus-eluting stents in patients with de novo long coronary artery lesions: a randomized LONG-DES VI trial.

Coron Artery Dis 2019 01;30(1):59-66

Asan Medical Center, Heart Institute, University of Ulsan College of Medicine.

Background: Outcomes for stent-based coronary intervention of lesions with long diseased segments remain relatively unfavorable. This study sought to compare the efficacy of Resolute zotarolimus-eluting stents (R-ZES) and Xience everolimus-eluting stents (EES) for very long coronary lesions.

Methods And Results: This randomized, multicenter, prospective trial compared the use of R-ZES with EES for very long (≥50 mm) native coronary lesions. The primary end point was in-segment late luminal loss at 12-month angiographic follow-up. A total of 400 patients were needed to assess the primary end point. However, owing to very slow enrollment of patients, this trial was early terminated (302 patients were enrolled), and thus, this report provides descriptive information on primary and secondary end points. The R-ZES and EES groups had similar baseline characteristics. Lesion length was 49.6±10.2 and 50.6±13.3 mm in the R-ZES and EES groups, respectively (P=0.47). The number of stents used at the target lesion was 2.1±0.3 and 2.2±0.5, respectively. Twelve-month angiographic follow-up was performed in 50% of eligible patients. In-segment late luminal loss did not significantly differ between the R-ZES and EES groups (0.17±0.57 vs. 0.09±0.43 mm, P=0.32). In-segment binary restenosis rates were 8.1 and 5.3% in the R-ZES and EES groups, respectively (P=0.49). There were no significant between-group differences in the rate of adverse events (death, myocardial infarction, stent thrombosis, target lesion revascularization, and composite outcomes).

Conclusion: For patients with very long native coronary artery disease, R-ZES and EES implantation showed comparable angiographic and clinical outcomes through 1 year of follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000680DOI Listing
January 2019
-->