A multicenter, randomized, and double-blind phase IV clinical trial to compare the efficacy and safety of fixed-dose combinations of amlodipine orotate/valsartan 5/160 mg versus valsartan/hydrochlorothiazide 160/12.5 mg in patients with ess

Ahn, Youngkeun,Kim, Yongcheol,Chang, Kiyuk,Kim, Weon,Rhee, Moo-Yong,Cha, Kwang Soo,Hyon, Min Su,Shim, Chi Young,Lee, Sung Yun,Kim, Doo Il,Kim, Sang Wook,Lim, Sang-Wook,Han, Kyoo-Rok,Jo, Sang-Ho,Lee, N Williams & Wilkins Co 2018 Medicine Vol.97 No.37

<P><B>Abstract</B></P><P><B>Background:</B></P><P>To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy.</P><P><B>Methods:</B></P><P>This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study.</P><P><B>Results:</B></P><P>At 8 weeks after randomization, msDBP was significantly decreased in both groups (−9.44 ± 0.69 mm Hg in the AML/VAL group and −7.47 ± 0.71 mm Hg in the VAL/HCTZ group, both <I>P</I> < .001 vs baseline). Between group difference was −1.96 ± 1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, <I>P</I> = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ± 0.08 mg/dL; <I>P</I> < .001). However, it was slightly decreased from baseline in the AML/VAL group (−0.12 ± 0.08 mg/dL; <I>P</I> = .085). The intergroup difference was significant (<I>P</I> < .001).</P><P><B>Conclusion:</B></P><P>The effectiveness and safety AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in patients with hypertension inadequately controlled by valsartan 160 mg monotherapy.</P>

Effectiveness and Safety of Zotarolimus-Eluting Stent (Resolute™ Integrity) in Patients with Diffuse Long Coronary Artery Disease

Youngkeun Ahn,Keun-Ho Park,Young-Youp Koh,Young-Jae Ki,Sung Soo Kim,Hyun Kuk Kim,Dong-Hyun Choi,Young Joon Hong,Jin-Yong Hwang,Do Hoi Kim,Jay-Young Rhew,Jae Kean Ryu,Jong-Seon Park,Tae Ho Park,Tae-Hyu 대한심장학회 2019 Korean Circulation Journal Vol.49 No.8

Background and Objectives: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. Methods: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. Results: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. Conclusions: Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.

The Need for Re-evaluation of PCI Practice: from Proceduralists to Clinicians

Youngkeun Ahn,Min Chul Kim 대한심장학회 2019 Korean Circulation Journal Vol.49 No.12

Adjuvant role of macrophages in stem cell-induced cardiac repair in rats

Lim, Soo yeon,Cho, Dong Im,Jeong, Hye-yun,Kang, Hye-jin,Kim, Mi Ra,Cho, Meeyoung,Kim, Yong Sook,Ahn, Youngkeun Nature Publishing Group UK 2018 Experimental and molecular medicine Vol.50 No.11

<▼1><P>Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.</P></▼1><▼2><P><B>Heart attacks: mixed cell therapy for heart regeneration</B></P><P>A tailored technique involving stem cells and anti-inflammatory immune cells shows promise for repairing heart tissue damage. Immune cells called anti-inflammatory macrophages are vital for healing of the heart following a heart attack. Youngkeun Ahn, Yong Sook Kim and co-workers at Chonnam National University Hospital in Gwangju, South Korea trialed a novel stem cell therapy on rats to improve cardiac repair. They took bone marrow-derived macrophages and stem cells from each rat and incubated the two cell types together to create individualized treatments. Following induced heart attacks, they injected one group of rats with both cell types, and another group with stem cells only. While heart function improved in both groups, the group treated with both cell types showed significant improvements with a greater reduction in cardiac fibrosis and increased the reparative activity of macrophages.</P></▼2>

Feasibility of Coronary Angiography and Percutaneous Coronary Intervention via Left Snuffbox Approach

김용철,Youngkeun Ahn,Inna Kim,Doo Hwan Lee,Min Chul Kim,Doo Sun Sim,Young Joon Hong,Ju Han Kim,Myung Ho Jeong 대한심장학회 2018 Korean Circulation Journal Vol.48 No.12

Background and Objectives Feasibility of coronary angiography (CAG) and percutaneous coronary intervention (PCI) via left snuffbox approach is still concerned. We aimed to investigate efficacy and safety of the left snuffbox approach for CAG and PCI. Methods Left snuffbox approach was tried in 150 patients who planned to perform CAG or PCI for suspected myocardial ischemia between 1 November 2017 and 31 March 2018. Results Success rate of radial artery (RA) cannulation via snuffbox approach was 88.0% (n=132). Among 132 individuals, 58 (43.9%) acute coronary syndrome (ACS) patients were included. The diameter of snuffbox RA was significantly smaller than conventional RA (2.57 mm vs. 2.72 mm, p<0.001) from quantitative computed angiography of 101 patients. However, CAG via snuffbox approach by 6 French sheath was successfully performed in all 132 patients. In addition, there was significant correlation between the snuffbox and conventional RA diameter (r=0.856, p<0.001). In 42 PCI cases, including 25 patients with acute myocardial infarction (AMI), the success rate of PCI via snuffbox approach was 97.6% (n=41). Intravascular imaging-guided PCI was performed in 8 (19.5%) patients and multi-vessel PCI in 4 (9.8%) cases. Regarding vascular complication, forearm swelling with bruising, not requiring surgery or transfusion, occurred in 2 (4.9%) PCI cases. Conclusions Left snuffbox approach is suitable for CAG and PCI compared with the conventional radial approach.

Image of Statin-Induced Rhabdomyolysis

김민철,Youngkeun Ahn,Kyung Hoon Cho,Doo Sun Sim,Young Joon Hong,Ju Han Kim,Myung Ho Jeong 대한심장학회 2020 Korean Circulation Journal Vol.50 No.8

N

S-306 The effects of statin in AMI patients with high natriuretic peptide level and severe heart failure

( Jiyoung Lee ),( Youngkeun Ahn ),( Myung Ho Jeong ),( Dae Ho Lee ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Background: The benefit of statin therapy in patient with higher grades of heart failure has yet to be determined. The present study was performed to investigate whether statin therapy affects major clinical outcomes in patients with acute myocardial infarction (AMI) and heart failure within 1 year after AMI Methods: A total of 11,592 patients with AMI from a nationwide registry database in Korea were analyzed. The patients who had a natriuretic peptide (NP) measured at admission were categorized into quartiles by plasma level of B-type NP (BNP) or N-terminal pro-B-type NP (NT-proBNP). In a separate analysis, selected patients with left ventricular ejection fraction (LVEF) <40% on initial and/or follow-up echocardiography were evaluated. Major adverse cardiovascular events (MACEs) within 12 months of AMI, including death, nonfatal MI, and revascularization, were assessed, after adjusting for multiple factors. Results: Among 11,592 AMI patients, statin therapy was included in their medication at least from the hospital discharge in 9149 (78.9%) patients, whereas not in the remaining 2443 patients (21.1%), with statin therapy being associated with 24.2% lower risk of MACEs. After adjusting for risk factors, statin therapy was associated with significantly lower the hazard ratios (HRs) for MACEs only in the third and fourth quartiles of plasma NP level. However, statin did not modify the incidence of MACEs in patients with LVEF less than 40%. Conclusions: Our results show that statin therapy decreased the risk of MACEs in AMI patients with higher plasma natriuretic peptide, but not in patients with severe heart failure.

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

Kiyuk Chang,Youngkeun Ahn,Sungmin Lim,Jeong Hoon Yang,Kwan Yong Lee,Eun Ho Choo,Hyun Kuk Kim,Chang-Wook Nam,김원,Jin-Yong Hwang,Seung-Woon Rha,Hyo-Soo Kim,Myeong-Chan Cho,Yangsoo Jang,Myung Ho Jeong 대한심장학회 2021 Korean Circulation Journal Vol.51 No.4

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.

초전도 무기체계 응용

안희성(HeeSung AHN),오영근(YoungKeun OH),이상록(SangLoke LEE) 제어로봇시스템학회 2012 제어로봇시스템학회 합동학술대회 논문집 Vol.2012 No.7

지구온난화, 세계환경변화, 에너지고갈, 방사능 위험, 등으로 세계는 곤경에 처해있으며, 말없는 전쟁 중이고, 이에 대한 해결책 및 대체 에너지로 초전도체를 활용한 녹색화(code green)을 이루고져 하고 있으며, 국방 역시 이의 대처 방안으로 전 세계는 녹색국방을 비젼 및 목표로 하고 있음. 따라서 본고는 초전도 기술을 검토하고 특히 군사 무기체계에 초전도체가 어떻게 응용을 하고 있는지 정리를 하였음.

ANGPTL4 stabilizes atherosclerotic plaques and modulates the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation

Cho Dong Im,Ahn Min Joo,Cho Hyang Hee,Cho Meeyoung,전주희,Kang Bo Gyeong,Lim Soo Yeon,Yoo Soo Ji,Kim Mi Ra,Kim Hyung Seok,Lee Su-Jin,Dat Le Thanh,Lee Changho,Kim Yong Sook,Ahn Youngkeun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Atherosclerosis, the leading cause of death, is a vascular disease of chronic inflammation. We recently showed that angiopoietin-like 4 (ANGPTL4) promotes cardiac repair by suppressing pathological inflammation. Given the fundamental contribution of inflammation to atherosclerosis, we assessed the role of ANGPTL4 in the development of atherosclerosis and determined whether ANGPTL4 regulates atherosclerotic plaque stability. We injected ANGPTL4 protein twice a week into atherosclerotic Apoe−/− mice and analyzed the atherosclerotic lesion size, inflammation, and plaque stability. In atherosclerotic mice, ANGPTL4 reduced atherosclerotic plaque size and vascular inflammation. In the atherosclerotic lesions and fibrous caps, the number of α-SMA(+), SM22α(+), and SM-MHC(+) cells was higher, while the number of CD68(+) and Mac2(+) cells was lower in the ANGPTL4 group. Most importantly, the fibrous cap was significantly thicker in the ANGPTL4 group than in the control group. Smooth muscle cells (SMCs) isolated from atherosclerotic aortas showed significantly increased expression of CD68 and Krüppel-like factor 4 (KLF4), a modulator of the vascular SMC phenotype, along with downregulation of α-SMA, and these changes were attenuated by ANGPTL4 treatment. Furthermore, ANGPTL4 reduced TNFα-induced NADPH oxidase 1 (NOX1), a major source of reactive oxygen species, resulting in the attenuation of KLF4-mediated SMC phenotypic changes. We showed that acute myocardial infarction (AMI) patients with higher levels of ANGPTL4 had fewer vascular events than AMI patients with lower levels of ANGPTL4 (p < 0.05). Our results reveal that ANGPTL4 treatment inhibits atherogenesis and suggest that targeting vascular stability and inflammation may serve as a novel therapeutic strategy to prevent and treat atherosclerosis. Even more importantly, ANGPTL4 treatment inhibited the phenotypic changes of SMCs into macrophage-like cells by downregulating NOX1 activation of KLF4, leading to the formation of more stable plaques.