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LDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C-lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician.This multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching.A fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up.In a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed.

Summary Background In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction. Methods In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055. Findings From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority Interpretation In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events. Funding ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

Background Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population. Methods We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250. Findings Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035). Interpretation Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. Funding ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

Prediction models of the formation energies of H, B, C, N, and O atoms in various interstitial sites of hcp-Ti, Zr, and Hf crystals are developed based on machine learning. Parametric models such as linear regression and brute force search (BFS) as well as nonparametric algorithms including the support vector regression (SVR) and the Gaussian process regression (GPR) are employed. Readily accessible chemical and geometrical descriptors allow straightforward implementation of the prediction models without any expensive computational modeling. The models based on BFS, SVR, and GPR show the excellent performance with R2 > 96%.

Existing community detection algorithms may be often unsatisfactory due to low detection accuracy in real-world graphs since the number of edges between the nodes in the same community (i.e., intra-community edges) does not tend to be sufficiently large while the number of edges between the nodes belonging to different communities (i.e., inter-community edges) does not tend to be negligible. In this paper, we present a novel preprocessing method for strengthening the community structure of a given graph by adding non-existent predicted intra-community edges and deleting existing predicted inter-community edges for more accurate community detection. Our preprocessing method does not require any extra information for community reinforcement nor any changes of existing algorithms for community detection. To realize our method, we propose the following three strategies: (1) predicting intra-community and inter-community edges, (2) determining the amount of edges to be added/deleted, and (3) reducing the amount of computations in predicting the type of edges. To validate the effectiveness of our method, we conduct extensive experiments with various existing community detection algorithms on 11 synthetic and 6 real-world graphs. The results demonstrate that (1) our method significantly improves the accuracy up to 91%, regardless of community detection algorithms and graphs and (2) it outperforms two state-of-the-art edge weighting-based preprocessing methods in improving the accuracy up to 105%.

In this paper, we present neighbor-aided rating standardization ( NARS ), a new framework for rating standardization that leverages the ratings of users’ neighbors for more accurate collaborative filtering. Our approach is motivated by the insight that users tend to give ratings to items according to different criteria of their own, which causes the accuracy degradation in item recommendation. Our NARS framework intelligently alleviates the difference in rating criteria among all users through rating standardization in the context of consensus with neighbors. Consensus, referred to as the process of reducing disagreement in rating criteria among users, is facilitated by effectively aggregating the ratings of all users. Consequently, the ratings adjusted with the unified rating criterion among all users (i.e., standardized ratings) can be found via an iterative consensus process and are used as input of CF for top- N recommendation. Experimental results show that our proposed NARS framework consistently improves the accuracy of recommendation in terms of several accuracy metrics compared with various competing CF methods.

This study sought to evaluate the impact of triple antiplatelet therapy on clinical outcomes in patients treated with second-generation drug-eluting stents (DES) for coronary artery disease. There are limited data regarding the impact of triple antiplatelet therapy in patients who underwent implantation of second-generation DES. We planned to randomly assign 2,110 patients treated with second-generation DES to triple (aspirin, clopidogrel, and cilostazol) and dual (aspirin, clopidogrel, and placebo) antiplatelet therapy groups. The primary end point was a composite of death, myocardial infarction, ischemic stroke, or target vessel revascularization (TVR) at 1 year since randomization. The study was stopped early owing to slow enrollment. In total, 404 patients (202 patients each in the triple and dual antiplatelet therapy groups) were finally enrolled. At 1 year, the primary end point had occurred in 3.6% and 9.4% of patients in the triple and dual antiplatelet therapy groups, respectively (hazard ratio [HR] of the triple group 0.396; 95% confidence interval [CI] 0.166 to 0.949; p = 0.038). There was no significant difference between the 2 groups regarding the occurrence of a composite of all-cause death, myocardial infarction, or ischemic stroke (HR 0.583; 95% CI 0.229 to 1.481; p = 0.256). However, the rates of TVR were significantly lower in the triple antiplatelet therapy group than in the dual antiplatelet therapy group (HR 0.118; 95% CI 0.015 to 0.930; p = 0.043). In conclusion, triple antiplatelet therapy with cilostazol after implantation of second-generation DES improved clinical outcomes, mainly by reducing TVR.

It has been insufficiently explored how to perform density-based clustering by exploiting textual attributes on social media. In this paper, we aim at discovering a social point-of-interest (POI) boundary, formed as a convex polygon. More specifically, we present a new approach and algorithm, built upon our earlier work on so cial POI b oundary est imation ( SoBEst ). This SoBEst approach takes into account both relevant and irrelevant records within a geographic area, where relevant records contain a POI name or its variations in their text field. Our study is motivated by the following empirical observation: a fixed representative coordinate of each POI that SoBEst basically assumes may be far away from the centroid of the estimated social POI boundary for certain POIs. Thus, using SoBEst in such cases may possibly result in unsatisfactory performance on the boundary estimation quality (BEQ), which is expressed as a function of the F -measure. To solve this problem, we formulate a joint optimization problem of simultaneously finding the radius of a circle and the POI’s representative coordinate c by allowing to update c . Subsequently, we design an iterative SoBEst ( I-SoBEst ) algorithm, which enables us to achieve a higher degree of BEQ for some POIs. The computational complexity of the proposed I-SoBEst algorithm is shown to scale linearly with the number of records. We demonstrate the superiority of our algorithm over competing clustering methods including the original SoBEst .

In this paper, we introduce a large-scale hierarchical hybrid network (HierHybNET) consisting of both n wireless ad hoc nodes and m base stations (BSs) equipped with l multiple antennas per BS, where the communication takes place from wireless nodes to a remote central processor (RCP) through BSs in a hierarchical way. To understand a relationship between capacity and cost, we deal with a general scenario where m, l, and the backhaul link rate can scale at arbitrary rates relative to n (i.e., we introduce three scaling parameters). In order to provide a cost-effective solution for the deployment of backhaul links connecting BSs and the RCP, we first derive the minimum backhaul link rate required to achieve the same capacity scaling law as in the infinite-capacity backhaul link case. Assuming an arbitrary rate scaling of each backhaul link, a generalized achievable throughput scaling law is then analyzed. Moreover, three-dimensional information-theoretic operating regimes are explicitly identified according to the three scaling parameters. We also characterize an infrastructure-limited regime where the throughput is limited by the backhaul link rate.

Objectives This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions. Background The optimal bifurcation stenting technique needs to be evaluated. Methods The trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis. Results Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84). Conclusions Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.

Few studies have compared the ability of sodium bicarbonate plus N-acetylcysteine (NAC) and sodium chloride plus NAC to prevent contrast-induced nephropathy (CIN) in diabetic patients with impaired renal function undergoing coronary or endovascular angiography or intervention. Diabetic patients (n = 382) with renal disease (serum creatinine ≥1.1 mg/dl and estimated glomerular filtration rate60 ml/min/1.73 m(2)) were randomly assigned to receive prophylactic sodium chloride (saline group, n = 189) or sodium bicarbonate (bicarbonate group, n = 193) before elective coronary or endovascular angiography or intervention. All patients received oral NAC 1,200 mg 2 times/day for 2 days. The primary end point was CIN, defined as an increase in serum creatinine25% or an absolute increase in serum creatinine ≥0.5 mg/dl within 48 hours after contrast exposure. There were no significant between-group differences in baseline characteristics. The primary end point was met in 10 patients (5.3%) in the saline group and 17 (9.0%) in the bicarbonate group (p = 0.17), with 2 (1.1%) and 4 (2.1%), respectively, requiring hemodialysis (p = 0.69). Rates of death, myocardial infarction, and stroke did not differ significantly at 1 month and 6 months after contrast exposure. In conclusion, hydration with sodium bicarbonate is not superior to hydration with sodium chloride in preventing CIN in patients with diabetic nephropathy undergoing coronary or endovascular angiography or intervention.

Objectives The purpose of this study was to determine whether cilostazol reduces intimal hyperplasia in patients undergoing long zotarolimus-eluting stent implantation (stent length: ≥30 mm) for native long coronary lesions (length: ≥25 mm). Background Restenosis after drug-eluting stent implantation remains a significant clinical problem in long coronary lesions. Methods Patients (n = 499) were assigned randomly to triple (aspirin, clopidogrel, and cilostazol, triple group: n = 250) or dual antiplatelet therapy (aspirin and clopidogrel and placebo, dual group: n = 249) for 8 months after long zotarolimus-eluting stent implantation. The primary end point was in-stent late loss at the 8-month angiography according to the intention-to-treat principle. Results The 2 groups had similar baseline characteristics. The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017). Conclusions Patients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927)

Curcumin is a polyphenol responsible for the yellow color of turmeric, a curry spice. A large body of evidence showed that curcumin possessed a variety of beneficial activities. We report a case of transient complete atrioventricular block in a 38-year-old man, after intake of curcumin containing pills for on 1 month. Since all other possible causes of conduction disturbance were excluded and causal relation was achieved by re-intake of the same amount of turmeric containing pills, side-effect of the curcumin containing pills was identified as the most likely diagnosis. After cessation of the pills, no further conduction disturbances and associated symptoms were noticed for the ensuing 6 months since discharge.

Hyperhomocysteinemia is a known risk factor of cardiovascular diseases. Methylenetetrahydrofolate reductase (MTHFR), involved in folate-dependant metabolism, is associated with homocysteine levels. We studied the associations among MTHFR genotypes, coronary artery disease (CAD), and homocysteine levels in 85 patients with CAD and 152 healthy subjects. The MTHFR genotypes and plasma homocysteine levels were determined. No significant difference in mutation of the MTHFR gene between two groups was observed (P>0.05). While the homozygous mutant genotype (V/V) had the highest homocysteine levels compared to wild (A/A) and heterozygous mutant (A/V) genotypes, there were no significant differences in homocysteine levels among the MTHFR genotype groups. Homocysteine was significantly and inversely related to folate levels, the significant association in V/V genotype (beta coefficient=-1.954, P=0.04). Our data suggested that MTHFR polymorphism was not associated with homocysteine levels, implying no association between gene polymorphism and CAD in Koreans.

Sang-Ho Park, Seung-Woon Rha, Ung Jun, Se-Whan Lee, Won-Yong Shin, Seung Jin Lee, Dong-Kyu Jin, Byoung Geol Choi, Se Yeon Choi, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh Cardiology Department, Soonchunhyang university cheonan hospital, Cheonan, Korea, Republic of, Cardiovascular Center, Korea University Guro Hospital, Seoul, Korea, Republic of