The tether function of the anoctamins.

The core functions of the anoctamins are Cl- channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.

Intravascular imaging-guided percutaneous coronary intervention in patients with acute myocardial infarction and cardiogenic shock.

INTRODUCTION AND OBJECTIVES: There are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock. METHODS: Among a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis. RESULTS: Among the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88). CONCLUSIONS: In AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death.

Intracoronary antithrombotic therapy during primary percutaneous coronary intervention in patients with STEMI: A systematic review and network meta-analysis.

INTRODUCTION: The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents. MATERIALS AND METHODS: This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models. RESULTS: Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24-4.13; OR 2.06, 95 % CrI 1.17-3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48-7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20-0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31-0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed. CONCLUSIONS: IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods.

The role and medical prospects of long non-coding RNAs in cardiovascular disease.

Cardiovascular disease (CVD) has reached epidemic proportions and is a leading cause of death worldwide. One of the long-standing goals of scientists is to repair heart tissue damaged by various forms of CVD such as cardiac hypertrophy, dilated cardiomyopathy, myocardial infarction, heart fibrosis, and genetic and developmental heart defects such as heart valve deformities. Damaged or defective heart tissue has limited regenerative capacity and results in a loss of functioning myocardium. Advances in transcriptomic profiling technology have revealed that long noncoding RNA (lncRNA) is transcribed from what was once considered "junk DNA." It has since been discovered that lncRNAs play a critical role in the pathogenesis of various CVDs and in myocardial regeneration. This review will explore how lncRNAs impact various forms of CVD as well as those involved in cardiomyocyte regeneration. Further, we discuss the potential of lncRNAs as a therapeutic modality for treating CVD.

PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function.

The membrane contact site ER/PM junctions are hubs for signaling pathways, including Ca2+ signaling. Phosphatidylserine (PtdSer) mediates various physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca2+ signaling and Ca2+-dependent gene regulation are not understood. Here, we show that STIM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal lipid exchange modes and function as a rheostat that sets the junctional PtdSer/PI(4)P ratio. Targeting the ORP5 and ORP8 and their lipid transfer ORD domains to PM subdomains revealed that ORP5 sets low and ORP8 high junctional PI(4)P/PtdSer ratio that controls STIM1-STIM1 and STIM1-Orai1 interaction and the activity of the SERCA pump to determine the pattern of receptor-evoked Ca2+ oscillations, and consequently translocation of NFAT to the nucleus. Significantly, targeting the ORP5 and ORP8 ORDs to the STIM1 ER subdomain reversed their function. Notably, changing PI(4)P/PtdSer ratio by hydrolysis of PM or ER PtdSer with targeted PtdSer-specific PLA1a1 reproduced the ORPs function. The function of the ORPs is determined both by their differential lipid exchange modes and by privileged localization at the ER/PM subdomains. These findings reveal a role of PtdSer as a signaling lipid that controls the available PM PI(4)P, the unappreciated role of ER PtdSer in cell function, and the diversity of the ER/PM junctions. The effect of PtdSer on the junctional PI(4)P level should have multiple implications in cellular signaling and functions.

Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis.

BACKGROUND: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. METHODS: Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. RESULTS: Of 184 patients who agreed to participate in the study, 151 were finally analyzed. Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63-0.80) for CCTA, 0.65 (95% CI, 0.56-0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70-0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55-0.71) for CCTA alone, 0.66 (0.58-0.74) for algorithm A, and 0.76 (0.68-0.82) for algorithm B. CONCLUSION: This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.

Intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in patients with STEMI: a systematic review and meta-analysis.

BACKGROUND: Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI. METHODS: We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included. RESULTS: The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37-0.80) and heart failure (RR: 0.48, 95% CI: 0.25-0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration. CONCLUSIONS: When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered.

Prognostic value of reactive hyperemia index using peripheral artery tonometry in patients with heart failure.

Given the high prevalence and poor prognosis of heart failure (HF), finding prognostic factors for patients with HF is crucial. This study investigated the prognostic value of reactive hyperemia index (RHI), a measure of endothelial function, in HF. A total of 90 HF patients (mean age, 63.7 ± 13.2 years; female, 25.6%) with a history of hospitalization for HF treatment were prospectively enrolled. RHI was measured using digital arterial tonometry in a stable condition. Clinical events, including all-cause death and HF admission, were assessed. During the median follow-up of 3.66 years (interquartile range, 0.91-4.94 years), 26 clinical events (28.9%) occurred. Although there were no significant differences in risk factors and laboratory findings according to the occurrence of clinical events, the RHI value was significantly lower in patients with clinical events than in those without (1.21 ± 0.34 vs. 1.68 ± 0.48; P < 0.001). Kaplan-Meier survival analysis showed that a lower RHI value (< 1.48) was associated with a significantly higher incidence rate of clinical events (log-rank P < 0.001). In multivariable cox regression analysis, a low RHI value (< 1.48) was associated with an increased risk of clinical events (hazard ratio, 14.09; 95% confidence interval, 3.61-54.99; P < 0.001) even after controlling for potential confounders. Our study showed that reduced RHI was associated with an increased risk of adverse clinical outcomes in HF. This suggests that endothelial dysfunction may be an important prognostic marker in patients with HF.

The sun, cholesterol and Orai1 conspire in melanoma.

How does skin cancer become metastatic? A recent study by Gross et al (2022) reports a novel pathway by which UV radiation acts on cholesterol biosynthesis to control Ca2+ influx by Orai1, causing protein O-GlcNAcylation that promotes transformation to invasive melanoma.

Efficacy and Safety of 3 Versus 6 Months of Dual-Antiplatelet Therapy in Patients Implanted With a Coroflex ISAR Stents: A Prospective, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES), especially recently developed polymer-free DESs, is unknown. This study examined the efficacy and safety of 3- versus 6-month DAPT in patients implanted with Coroflex ISAR polymer-free DESs. METHODS: Between May 2015 and August 2020, 488 patients who underwent Coroflex ISAR stent implantation were enrolled in the study and randomly assigned to the 3-month (n=244) or 6-month (n=244) DAPT group. RESULTS: At 1 year, the primary endpoint (composite of cardiovascular death, myocardial infarction, target vessel revascularization, and Bleeding Academic Research Consortium [BARC] type 2-5 bleeding) occurred in 9 (3.7%) patients in the 3-month DAPT group and in 7 (2.9%) patients in the 6-month DAPT group (hazard ratio 1.31; P=.60). There was no difference between the 3- and 6-month DAPT groups in either BARC type 2-5 bleeding (1.6% vs 0.8%; hazard ratio 2.00; P=.42) or any bleeding (2.9% vs 3.3%; hazard ratio 0.87; P=.80). CONCLUSION: Compared with 6 months of DAPT, 3 months of DAPT did not increase the risk of primary endpoint 1 year after Coroflex ISAR stent implantation, although it should be noted that the trial has limited power to see differences due to low event rate and low recruitment rate.

Public Reporting on the Quality of Care in Patients with Acute Myocardial Infarction: The Korean Experience.

Public reporting is a way to promote quality of healthcare. However, evidence supporting improved quality of care using public reporting in patients with acute myocardial infarction (AMI) is disputed. This study aims to describe the impact of public reporting of AMI care on hospital quality improvement in Korea. Patients with AMI admitted to the emergency room with ICD-10 codes of I21.0 to I21.9 as the primary or secondary diagnosis were identified from the national health insurance claims data (2007-2012). Between 2007 and 2012, 43,240/83,378 (51.9%) patients manifested ST segment elevation myocardial infarction (STEMI). Timely reperfusion rate increased (ß = 2.78, p = 0.001). The mortality rate of STEMI patients was not changed (ß = -0.0098, p = 0.384) but that of NSTEMI patients decreased (ß = -0.465, p = 0.001). Public reporting has a substantial impact on the process indicators of AMI in Korea because of the increased reperfusion rate. However, the outcome indicators such as mortality did not significantly change, suggesting that public reporting did not necessarily improve the quality of care.

Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis.

PURPOSE: Although clinically driven low-dose (CDLD) treatment with direct oral anticoagulants (DOACs) is frequently administered to Asian patients with atrial fibrillation, clinical evidence confirming its efficacy remains insufficient. We evaluated the clinical efficacy and safety of CDLD treatment with DOACs compared to on-label dose treatment in Asian patients with atrial fibrillation and assessed the differences in the baseline characteristics between patients receiving these treatments. METHODS: We searched the MEDLINE, CENTRAL, EMBASE, Web of Science, and Scopus databases for articles from inception through July 2020. RESULTS: Thirteen studies were included in this meta-analysis. The baseline characteristics of the CDLD group were significantly different from those of the standard dose (STD) and standard low-dose (SLD) groups. The incidences of thromboembolic events (risk ratio [RR] 0.46, 95% confidence interval [CI] 0.29-0.73, p < 0.001) and major bleeding (RR 0.55, 95% CI 0.35-0.87, p = 0.01) in the CDLD group were lower than those in the SLD group; however, they were comparable with those in the STD group. The incidence of a composite endpoint in the CDLD group was not significantly different from that in the STD group but was significantly lower than that in the SLD group (RR 0.50, 95% CI 0.38-0.65, p < 0.001). CONCLUSION: The clinical outcomes of CDLD treatment showed no difference compared to those of the STD treatment despite the vulnerable baseline characteristics of the CDLD group for thromboembolic and major bleeding events.

Modeling of Statistical Variation Effects on DRAM Sense Amplifier Offset Voltage.

With the downscaling in device sizes, process-induced parameter variation has emerged as one of the most serious problems. In particular, the parameter fluctuation of the dynamic random access memory (DRAM) sense amplifiers causes an offset voltage, leading to sensing failure. Previous studies indicate that the threshold voltage mismatch between the paired transistors of a sense amplifier is the most critical factor. In this study, virtual wafers were generated, including statistical VT variation. Then, we numerically investigate the prediction accuracy and reliability of the offset voltage of DRAM wafers using test point measurement for the first time. We expect that this study will be helpful in strengthening the in-line controllability of wafers to secure the DRAM sensing margin.

Blood lead levels in relation to smoking and chronic obstructive pulmonary disease (COPD): a study from Korean National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05). CONCLUSIONS: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.

Validation of the diagnostic performance of 'HeartMedi V.1.0', a novel CT-derived fractional flow reserve measurement, for patients with coronary artery disease: a study protocol.

INTRODUCTION: Coronary CT angiography (CCTA) is widely used for non-invasive coronary artery evaluation, but it is limited in identifying the nature of functional characteristics that cause ischaemia. Recent computational fluid dynamic (CFD) techniques applied to CCTA images permit non-invasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischaemia. However, this technology has limitations, such as long computational time and the need for expensive equipment, which hinder widespread use. METHODS AND ANALYSIS: This study is a prospective, multicentre, comparative and confirmatory trial designed to evaluate the diagnostic performance of HeartMedi V.1.0, a novel CT-derived FFR measurement for the detection of haemodynamically significant coronary artery stenoses identified by CCTA, based on invasive FFR as a reference standard. The invasive FFR values ≤0.80 will be considered haemodynamically significant. The study will enrol 184 patients who underwent CCTA, invasive coronary angiography and invasive FFR. Computational FFR (c-FFR) will be analysed by CFD techniques using a lumped parameter model based on vessel length method. Blinded core laboratory interpretation will be performed for CCTA, invasive coronary angiography, invasive FFR and c-FFR. The primary objective of the study is to compare the area under the receiver-operator characteristic curve between c-FFR and CCTA to non-invasively detect the presence of haemodynamically significant coronary stenosis. The secondary endpoints include diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value and correlation of c-FFR with invasive FFR. ETHICS AND DISSEMINATION: The study has ethic approval from the ethics committee of Seoul National University Bundang Hospital (E-1709/420-001) and informed consent will be obtained for all enrolled patients. The result will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: KCT0002725; Pre-results.

Peripheral arterial endothelial dysfunction predicts future cardiovascular events in diabetic patients with albuminuria: a prospective cohort study.

BACKGROUND: Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. METHODS: Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). RESULTS: In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00-119.91 for the primary outcome; HR, 4.12; 95% CI 1.37-12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14-9.17). CONCLUSIONS: PED can independently predict future cardiovascular events among diabetic patients with albuminuria.

Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina.

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR's diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.

Ca2+ Signaling in Exocrine Cells.

Calcium (Ca2+) and cyclic AMP (cAMP) signaling cross talk and synergize to stimulate the cardinal functions of exocrine cells, regulated exocytosis, and fluid and electrolyte secretion. This physiological process requires the organization of the two signaling pathways into complexes at defined cellular domains and close placement. Such domains are formed by membrane contact sites (MCS). This review discusses the basic properties of Ca2+ signaling in exocrine cells, the role of MCS in the organization of cell signaling and in cross talk and synergism between the Ca2+ and cAMP signaling pathways and, finally, the mechanism by which the Ca2+ and cAMP pathways synergize to stimulate epithelial fluid and electrolyte secretion.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Three-year clinical outcome of biodegradable hybrid polymer Orsiro sirolimus-eluting stent and the durable biocompatible polymer Resolute Integrity zotarolimus-eluting stent: A randomized controlled trial.

AIMS: We compared long-term clinical outcomes between patients treated with Orsiro sirolimus-eluting stent (O-SES) and those treated with durable biocompatible polymer Resolute Integrity zotarolimus-eluting stent (R-ZES). METHODS AND RESULTS: The ORIENT trial was a randomized controlled noninferiority trial to compare angiographic outcomes between O-SES and R-ZES. We performed a post hoc analysis of 3-year clinical outcomes and included 372 patients who were prospectively enrolled and randomly assigned to O-SES (n = 250) and R-ZES (n = 122) groups in a 2:1 ratio. The primary endpoint was target lesion failure defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. At 3 years, target lesion failure occurred in 4.7% and 7.8% of O-SES and R-ZES groups, respectively (hazard ratio, 0.58; 95% confidence intervals, 0.24-1.41; p = .232 by log-rank test). Secondary endpoints including cardiac death, myocardial infarction, and target lesion revascularization showed no significant differences between the groups. Stent thrombosis occurred in two patients in R-ZES group (0.0% vs. 1.6%, p = .040). CONCLUSION: This study confirms long-term safety and efficacy of the two stents. We found a trend for lower target lesion failure with O-SES compared to R-ZES, although statistically insignificant.