Ji Yong Jang

Reactive oxygen species play a critical role in collagen-induced platelet activation via SHP-2 oxidation.

AIMSnThe collagen-stimulated generation of reactive oxygen species (ROS) regulates signal transduction in platelets, although the mechanism is unclear. The major targets of ROS include protein tyrosine phosphatases (PTPs). ROS-mediated oxidation of the active cysteine site in PTPs abrogates the PTP catalytic activity. The aim of this study was to elucidate whether collagen-induced ROS generation leads to PTP oxidation, which promotes platelet stimulation.nnnRESULTSnSH2 domain-containing PTP-2 (SHP-2) is oxidized in platelets by ROS produced upon collagen stimulation. The oxidative inactivation of SHP-2 leads to the enhanced tyrosine phosphorylation of spleen tyrosine kinase (Syk), Vav1, and Brutons tyrosine kinase (Btk) in the linker for the activation of T cells signaling complex, which promotes the tyrosine phosphorylation-mediated activation of phospholipase Cγ2 (PLCγ2). Moreover, we found that, relative to wild-type platelets, platelets derived from glutathione peroxidase 1 (GPx1)/catalase double-deficient mice showed enhanced cellular ROS levels, oxidative inactivation of SHP-2, and tyrosine phosphorylation of Syk, Vav1, Btk, and PLCγ2 in response to collagen, which subsequently led to increased intracellular calcium levels, degranulation, and integrin αIIbβ3 activation. Consistent with these findings, GPx1/catalase double-deficiency accelerated the thrombotic response in FeCl3-injured carotid arteries.nnnINNOVATIONnThe present study is the first to demonstrate that SHP-2 is targeted by ROS produced in collagen-stimulated platelets and suggests that a novel mechanism for the regulation of platelet activation by ROS is due to oxidative inactivation of SHP-2.nnnCONCLUSIONnWe conclude that collagen-induced ROS production leads to SHP-2 oxidation, which promotes platelet activation by upregulating tyrosine phosphorylation-based signal transduction.

Gender-Based Differences in the Management and Prognosis of Acute Coronary Syndrome in Korea

Purpose Gender-based differences exist in the characteristics, management, and prognosis of acute coronary syndrome (ACS). However, their impact on prognosis remains unclear. We aimed to identify factors causing these differences in Koreans. Materials and Methods We examined 6,636 ACS patients (66.2% males) visiting 72 Korean hospitals between April-2007 and December-2008. Gender-based differences in clinical demographics, therapy, and outcomes were analyzed over 6 months. Results Women were older than men [mean (standard deviation, SD) age, 67.6 (9.8) vs. 60.6 (11.2) years; p<0.001]; had higher rates of hypertension, diabetes mellitus, and lack of exercise (p<0.001 for all); and lower rates of obesity, familial history of cardiovascular disease (CVD), and smoking (p<0.05 for all). Atypical symptoms were more common in women (20.5% vs. 15.1% in men, p<0.001), whereas myocardial infarction with ST-segment elevation was less common (17.1% vs. 27.8%, p<0.001). Mean (SD) time lapse from symptom onset to arrival at hospital was longer in women [11.44 (18.19) vs. 8.26 (14.89) hours in men, p<0.001], as was the duration of hospitalization [7.58 (7.61) vs. 7.04 (7.72) days, p=0.007]. Fewer women underwent revascularization procedures, including thrombolytic therapy, balloon angioplasty, stent implantation, and coronary artery bypass grafting (79.4% vs. 83.3% men, p<0.001). No significant differences were observed in CVD-related death, recurrent ACS, stroke, refractory angina, or rehospitalization for angina. Conclusion Female ACS patients were older than male subjects and had more atypical presentation. They arrived at the hospital later than men and had longer hospital stays, but less often required revascularization therapy. However, no gender-based differences were noted in ACS-related mortality and morbidity.

Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients.

Background and Objectives We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. Subjects and Methods Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. Results A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. Conclusion Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

Pulmonary Hypertension Associated with Use of Phentermine

Weight-control drugs (known as anorexigens) such as fenfluramine have been linked with pulmonary hypertension in previous reports. In our case, a 29 year old woman was admitted for shortness of breath and was diagnosed with pulmonary hypertension. Three months ago, she had been taking phentermine for five weeks. Other factors that might have contributed to the development of pulmonary hypertension were excluded. With treatment, her symptoms improved. This is the first case that can suggest a possible connection between phenermine single medication with pulmonary hypertension. Phentermine has been considered a relatively safe drug to treat obesity, and further investigation is needed to decide the safety and dosage of phentermine.

Constrictive pericarditis accompanied by swine-origin influenza a (H1N1) infection

Swine-origin influenza A (H1N1) is caused by a new strain of the influenza virus. The disease has spread rapidly and was declared a pandemic in April, 2009. So far, however, there is a scarcity of information regarding the complications of swine influenza. A report of the disease in the winter of 2009 in the Southern Hemisphere found that the most common manifestations of influenza A virus infection are upper respiratory tract infection and pneumonia. Although there may be an association between fulminant myocarditis and Swine influenza, cardiovascular complications resulting from swine Influenza A infection are exceedingly rare. We report a case of acute constrictive pericarditis in a healthy subject infected by the swine-origin influenza A (H1N1) virus.

Study design and rationale of the ‘Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial’: study protocol for a randomized controlled trial

BackgroundThe self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease.Methods/designThe purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12xa0months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound.DiscussionThe SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions.Trial registrationNational Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495), registration date: May 8, 2012

Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI Study

PURPOSEnThis 8-week study in Korea aimed to evaluate the efficacy and tolerability of a telmisartan/amlodipine + hydrochlorothiazide (TAH) combination versus telmisartan/amlodipine (TA) combination in patients with essential hypertension that did not respond appropriately to 4-week treatment with TA.nnnMETHODSnAll patients who met the inclusion criteria received TA (40/5 mg) during a 4-week run-in period (period 1). Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12.5 mg (test group) or TA only (control group). The test and control drugs were administered in each group for 2 weeks (period 2). Patients who completed period 2 underwent 6-week treatment (period 3) with a TAH and TA dose twice that in period 2. The primary end point was the change in MSSBP at week 8 of treatment. Secondary end points were the change in MSSBP at week 2 and MS diastolic BP, BP control rate, and BP response rate at weeks 2 and 8. Treatment tolerability was assessed based on adverse events (AEs), laboratory evaluations (chemistry, hematology, and urinalysis), 12-lead ECG, and physical examination including vital sign measurements.nnnFINDINGSnWe randomized 310 patients to the treatment groups. The mean (SD) ages of the TAH and TA groups were 62.0 (10.8) and 63.4 (10.4) years, respectively. The least squares mean change in MSSBP was significantly greater in the TAH group than in the TA group after 8 weeks (-18.7 vs -12.2 mm Hg; P < 0.001). Similar results were obtained on changes in MSSBP after 2 weeks and changes in sitting diastolic BP, BP control rate, and BP response rate at weeks 2 and 8 compared with the respective baseline values. The prevalences of treatment-emergent AEs (29.0% vs 16.3%; P = 0.008) and adverse drug reactions (20.0% vs 10.5%; P = 0.020) were significantly greater in the TAH group than in the TA group. Most treatment-emergent AEs were mild or moderate; none were severe. The most frequently reported AEs were dizziness and headache.nnnIMPLICATIONnTAH triple therapy was more effective than was TA double therapy in reducing BP in these patients in Korea with essential hypertension that did not adequately respond to TA. ClinicalTrials.gov identifier: NCT02738632.

Effects of Coronary Artery Revascularization with a Polymer-Free Biolimus A9-Coated BioFreedom Stent Versus Bypass Surgery before Noncardiac Surgery.

Purpose The present study aimed to evaluate the efficacy and safety of polymer-free drug-coated BioFreedom stent implantation in comparison to coronary artery bypass graft (CABG) before major noncardiac surgery. Materials and Methods In a multicenter registry, 55 patients required revascularization before major noncardiac surgery that should not be delayed >6 months. Of them, 27 underwent BioFreedom stent implantation and 28 underwent CABG. Primary outcomes included rate of noncardiac surgery, time from revascularization to noncardiac surgery, and occurrence of composite outcomes (all-cause death, myocardial infarction, stent thrombosis, stroke, repeat revascularization, or major bleeding). Results The rate of major noncardiac surgery was significantly higher in the BioFreedom group (92.6%) than in the CABG group (64.3%; p=0.027). Time from revascularization to noncardiac surgery was significantly shorter in the BioFreedom group (38.0 days) than in the CABG group (73.0 days; p=0.042). During the hospitalization for revascularization period, the occurrence of primary outcomes did not differ between the groups. However, the BioFreedom group showed a shorter hospitalization period and lower total treatment cost than the CABG group. During the hospital stay for noncardiac surgery, the occurrence of composite outcome was not significantly different between groups (4% vs. 0%; p>0.999): stroke occurred in only 1 case, and there were no cases of death or stent thrombosis in the BioFreedom group. Conclusion This study demonstrated that BioFreedom stenting as a revascularization strategy before major noncardiac surgery might be feasible and safe in selected patients with less severe coronary artery diseases.

A Newly Formed and Ruptured Atheromatous Plaque within Neointima after Drug-Eluting Stent Implantation: 2-Year Follow-Up Intravascular Ultrasound and Optical Coherence Tomography Studies

Late stent thrombosis (LST) which is a life threatening complication has emerged as a serious problem of drug-eluting stents (DES). Several studies have suggested that incomplete neointimal coverage of stent struts contributes to LST. Progressive atherosclerosis within the neointima is an another possible cause of LST, but this phenomenon has seldom been reported in DES. We present a case of LST following DES implantation after a period of 28 months due to ruptured atheromatous plaque, despite complete neointimal coverage of stent struts proven by optical coherence tomography.