The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review.

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.

Most Promising Therapies in Interventional Cardiology.

PURPOSE OF REVIEW: The last 40 years of clinical research in interventional cardiology were extraordinarily innovative. This article will review the most promising up and coming interventional cardiovascular therapies, with a primary focus on the treatment of coronary artery disease. RECENT FINDINGS: From the first stent, to the first transcatheter aortic valve implantation (TAVI), and the left appendage closure technique, percutaneous interventions revolutionized the treatment of multiple diseases and dramatically improved the prognosis of many patients. While these advances have decreased the risk of mortality in some patients (such as ST-elevation myocardial infarction), 15% of acute coronary syndrome (ACS) patients still experience recurrent ischemic events within the first year, challenging us to develop new pharmaceutical targets and new devices. The continued emergence of data supporting inflammation as a risk factor and pharmacologic target as well as data supporting the importance of cholesterol efflux have identified novel therapeutic targets that may play a major role in the improvement of prognosis of patients with coronary artery disease. In addition, novel medical devices are being developed to allow even earlier detection of acute cardiac events and to support high-risk percutaneous coronary interventions. Advances in computing and the ability to analyze large datasets will allow us to use artificial intelligence to augment the clinician patient experience, both in and out of the catheterization laboratory, with live procedural guidance as well as pre- and post-operative prognostication tools.

Light chain cast nephropathy caused by plasmablastic lymphoma of the bladder.

INTRODUCTION: Plasmablastic lymphoma (PBL) is a rare form of B-cell lymphoma typically seen in patients with underlying immunosuppression such as HIV, autoimmune disease, and organ transplantation. PBL in HIV-positive patients usually originates from the gastrointestinal tract, with a predilection for the oral cavity. Bladder involvement by PBL is exceedingly rare, and cast nephropathy due to κ light chain-secreting PBL has not been reported previously. CASE REPORT: We report a patient who presented with acute kidney injury (AKI) in the setting of HIV, and was found to have a bladder tumor. Bladder pathology revealed a high-grade PBL with κ light chain restriction. Renal biopsy showed κ light chain cast nephropathy, presumably secondary to κ light chain-secreting PBL. CONCLUSION: Although the prognosis of PBL is poor, our patient recovered from AKI, achieved complete hematologic remission with chemotherapy, and underwent successful autologous stem cell transplant.

Coronary artery tortuosity: a narrative review.

Coronary artery tortuosity (CAT) is a prevalent angiographic finding commonly associated with aging, hypertension, atherosclerosis and other conditions. Preliminary evidence suggests that degradation of elastin, a key component of extracellular matrix in the vascular wall, may be responsible for the development of CAT. The clinical significance of CAT should be considered in several aspects. First, coronary flow alteration associated with CAT may result in myocardial ischemia owing to reduced perfusion pressure distal to the tortuous segment. Second, increased and oscillatory shear stress in the tortuous vessel may promote atherosclerotic plaque formation and acute coronary syndrome. Third, as one of the criteria for coronary lesion complexity, the presence of severe tortuosity proximal to the culprit lesion may pose a challenge to wiring and stent or balloon delivery, thereby increasing the risk of periprocedural complications. Last, the presence of CAT may serve as a diagnostic clue of concurrent vasculopathy such as fibromuscular dysplasia or spontaneous coronary artery dissection. In general, CAT represents a benign entity that does not require specific treatment or intervention. Further research is warranted to elucidate the pathogenesis and prognostic effect of coronary tortuosity.

Extended-duration betrixaban versus shorter-duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients: an APEX trial substudy.

PURPOSE: To assess the efficacy and safety of betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. METHODS: The APEX trial randomized 7513 acutely ill hospitalized patients to betrixaban for 35-42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35-42 days and at 77 days. RESULTS: At 35-42 days, extended betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). CONCLUSIONS: Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration betrixaban had fewer VTE without more major bleeding events. The benefit of betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Eosinophilic inflammation in spontaneous coronary artery dissection: A potential therapeutic target?

Spontaneous coronary artery dissection (SCAD), defined as non-traumatic, non-iatrogenic dissociation of coronary vessel wall resulting from intimal disruption or intramural hemorrhage, represents an important cause of sudden death and myocardial infarction among young or middle-aged women without conventional risk factors for atherosclerosis. On histopathological examination, SCAD is featured by prominent eosinophilic infiltration of the adventitia or periadventitial layer of coronary artery. It has been estimated that approximately 15-30% of SCAD patients experience recurrent episodes of dissection despite medical therapy. Preliminary evidence suggests that injury to the vascular endothelium and myocytes in the arterial wall may be explained by cytotoxic products released from eosinophils in response to inflammatory mediators. In addition, neovascularization of vasa vasorum and dilatation of intimal capillaries may be stimulated by localized eosinophils. Newly formed fragile vasa vasorum may disrupt due to high intraluminal pressure from the interconnected capillary network, leading to the expansion of intramural hemorrhage. It is hypothesized that anti-inflammatory therapy targeting eosinophilic coronary periarteritis would be effective in preventing the recurrence of SCAD by promoting the healing of dissection. The article delineates the biological plausibility, empirical data, and future perspective regarding eosinophilic inflammation as a potential therapeutic target for SCAD.

Dual antithrombotic plus adjunctive antiinflammatory therapy to improve cardiovascular outcome in atrial fibrillation patients with concurrent acute coronary syndrome: A triple-pathway strategy.

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1ß-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Betrixaban for first-line venous thromboembolism prevention in acute medically ill patients with risk factors for venous thromboembolism.

INTRODUCTION: Compared to other direct oral anticoagulants, betrixaban has a longer half-life, smaller peak-trough variance, minimal renal clearance, and minimal hepatic Cytochrome P (CYP) metabolism. The Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial evaluated the efficacy and safety of extended duration betrixaban compared to standard duration enoxaparin in acutely ill hospitalized patients. Areas covered: This article describes the role of betrixaban in the prevention of venous thromboembolism (VTE) in acutely ill medical patients. This article provides a consolidated summary of the primary APEX study findings as well as prespecified and exploratory substudies. This article also provides a review of the results of studies in which other direct factor Xa inhibitors have been evaluated in an extended duration regimen in this patient population. Expert commentary: While previous agents have demonstrated that extended duration VTE prophylaxis can be efficacious, betrixaban is the first agent to demonstrate efficacy without an increase in major bleeding. The totality of the data from the APEX trial supports extended duration betrixaban for VTE prophylaxis in the acute medically ill patient population. As such, betrixaban has been approved in the USA for extended VTE prophylaxis in at-risk acute medically ill patients.

Prevalence and predictors of atherosclerotic renal artery stenosis in hypertensive patients undergoing simultaneous coronary and renal artery angiography; a cross-sectional study.

INTRODUCTION: According to the non-specific presentation of atherosclerotic renal artery stenosis (ARAS), this disease is usually an under-diagnosed in clinical conditions. OBJECTIVES: The aim of the presence study was to evaluate the prevalence of renal artery stenosis (RAS) and its related risk factors in hypertensive patients undergoing coronary angiography. PATIENTS AND METHODS: In a cross-sectional study, between March 2009 and October 2010, all of hypertensive patients candidate for diagnostic cardiac catheterization, underwent nonselective renal angiography before completion of their coronary angiography procedure. A standardized questionnaire was used to collect demographics, cardiac history, indications for cardiac catheterization and angiographic data. The degree of ARAS was estimated visually by skilled cardiologist. Narrowing greater than 50% of the arterial lumen considered as arterial stenosis. Data was analyzed by SPSS version 19, and by chi-square test and logistic regression model. RESULTS: In overall 274 patients with mean age of 60.75 ± 10.92 years 108 (39.4%) were male and 166 (60.61%) were female. The prevalence of ARAS calculated 18.2%. According to the present study, heart failure and smoking were predictors of ARAS. However, old age, gender, diabetes mellitus, hyperlipidemia and family history of cardiovascular disease were not clinical predictors of significant ARAS in hypertensive patients, candidate for coronary angiography. CONCLUSION: According to present data, we suggest to consider renal artery angiography in combination with coronary artery angiography especially in hypertensive patients who are smoker or individuals who have heart failure.

Restless Legs Syndrome: Associated Risk Factors in Hemodialysis Patients.

BACKGROUND: Restless legs syndrome (RLS) may be associated with increased morbidity and mortality among end-stage renal disease (ESRD) patients; however, it is a disorder that is neglected in dialysis centers. OBJECTIVES: The goal of this study was to investigate the clinical factors associated with RLS among ESRD patients. PATIENTS AND METHODS: This cross-sectional study was conducted on ESRD patients undergoing maintenance hemodialysis (HD) in three HD centers in Ahvaz city in Southwest Iran. Blood samples were obtained prior to a dialysis session to check the routine laboratory test results and assess the adequacy of dialysis. The presence of RLS was assessed by using the international RLS study group (IRLSSG) diagnostic criteria. The IRLSSG rating scale was also used to evaluate the severity of the RLS symptoms. RESULTS: Of the 139 HD patients enrolled in this study, 60 were female (43.2%) and 79 were male (56.8%), with a mean age of 51.82 ± 13.31 years. The prevalence of RLS was 15.8% (22 patients), with 50% of them (11 patients) having severe or very severe symptoms. There was a significant relationship between RLS and longer durations of dialysis (P < 0.001). The mean level of serum ferritin was lower in patients without RLS, but it was not significant (P = 0.065). No significant differences were found according to age, gender, dialysis shifts, and hemoglobin (Hb) level among patients with and without RLS. CONCLUSIONS: We conclude that a significant percentage of ESRD patients undergoing maintenance HD have severe or very severe RLS symptoms. The presence of RLS is associated to longer durations of dialysis.