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Mark Creager noticed that how we teach students to reason mathematically may be counterproductive to our teaching goals. Sometimes a linear approach, focusing on sub-processes leading to a proof works well. But not always. Students should be made aware that reasoning is not always a straight forward process, but one filled with false starts and mistakes. He outlines some useful strategies to help students understand and develop mathematical reasoning. [ABSTRACT FROM AUTHOR]

A task force composed of American Heart Association (AHA) Research Committee members established processes to measure the performance of the AHA's research portfolio and evaluated key outcomes that are fundamental to the overall success of the program. This report reviews progress that the AHA research program has had in achieving its goals relevant to the research programs in the AHA's research portfolio from 2008 to 2017. Comprehensive performance metrics were identified to assess the impact of AHA funding on researchers' career progress and research outcomes. Metrics included bibliometric analysis (ie, tracking of publications and their impact) and career development measures (ie, subsequent grant funding, intellectual property, faculty appointment/promotion, or industry position). Publication rates ranged from ≈0.5 to 4 publications per year, with a strong correlation between number of publications per year and later career stage. The Field-Weighted Citation Index, a metric of bibliometric impact, was between 1.5 and 3.0 for all programs, indicating that AHA awardee publications had a higher citation impact compared with similar publications. To gain insight into the career progression of AHA awardees, a 2-year postaward survey was distributed. Of the Postdoctoral Fellowship recipient respondents, 72% obtained academic research positions, with the remaining working in industry or government research settings; 72% of those in academic positions obtained additional funding. Among respondents who were Beginning Grant-in-Aid and Scientist Development Grant awardees, 45% received academic promotions and 83% obtained additional funding. Measuring performance of the AHA's research portfolio is critical to ensure that its strategic goals are met and to show the AHA's commitment to high-quality, impactful research. [ABSTRACT FROM AUTHOR]

Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and 2009, the amputation rate increased by 50% from 2009 to 2015. A number of evidence-based diagnostic and therapeutic approaches for PAD can reduce amputation risk. However, their implementation and adherence are suboptimal. Some racial/ethnic groups have an elevated risk of PAD but less access to high-quality vascular care, leading to increased rates of amputation. To stop, and indeed reverse, the increasing trends of amputation, actionable policies that will reduce the incidence of critical limb ischemia and enhance delivery of optimal care are needed. This statement describes the impact of amputation on patients and society, summarizes medical approaches to identify PAD and prevent its progression, and proposes policy solutions to prevent limb amputation. Among the actions recommended are improving public awareness of PAD and greater use of effective PAD management strategies (eg, smoking cessation, use of statins, and foot monitoring/care in patients with diabetes). To facilitate the implementation of these recommendations, we propose several regulatory/legislative and organizational/institutional policies such as adoption of quality measures for PAD care; affordable prevention, diagnosis, and management; regulation of tobacco products; clinical decision support for PAD care; professional education; and dedicated funding opportunities to support PAD research. If these recommendations and proposed policies are implemented, we should be able to achieve the goal of reducing the rate of nontraumatic lower-extremity amputations by 20% by 2030. [ABSTRACT FROM AUTHOR]

Three iterative, 18-episode design experiments were conducted after school with groups of 6–9 middle school students to understand how to differentiate mathematics instruction. Prior research on differentiating instruction (DI) and hypothetical learning trajectories guided the instruction. As the experiments proceeded, this definition of DI emerged: proactively tailoring instruction to students' mathematical thinking while developing a cohesive classroom community. Analysis of 10 episodes across experiments yielded five teaching practices that facilitated DI: using research-based knowledge of students' mathematical thinking, providing purposeful choices and different pathways, inquiring responsively during group work, attending to small group functioning, and conducting whole class discussions across different thinkers. The latter three practices, at times, impeded DI. This study is a case of using second-order models of students' mathematical thinking to differentiate instruction, and it reveals that inquiring into research-based knowledge and inquiring responsively into students' thinking are at the heart of differentiating mathematics instruction. [ABSTRACT FROM AUTHOR]

Clinical Experience Level III training in vascular medicine should provide the knowledge and skills to function as a vascular specialist, including the ability to interpret patients' clinical presentation, plan diagnostic testing, apply clinical and laboratory information, and develop appropriate management plans for patients across the entire range of vascular diseases. For patients with atherosclerotic cerebrovascular disease, trainees should define and apply appropriate risk stratification and medical therapies to reduce risk of stroke, including managing the most common risk factors for development and progression of cerebrovascular disease (e.g., smoking, diabetes, hypertension, hypercholesterolemia). They should know the diagnostic and management strategies relevant to specific patient populations, such as pregnant women, patients with cancer, patients with severe obesity, and patients with chronic kidney disease. They should be able to initiate compression therapy, refer to a physical therapist specialized in manual lymphatic therapy and multimodal lymphedema therapy, and determine if a patient would benefit from advanced therapies such as compression pumps or referral for surgery. [Extracted from the article]

The article provides an overview of the current state of care for patients with peripheral artery disease (PAD) and emphasizes the need for improved diagnosis and management. It discusses the American Heart Association's PAD Collaborative and the updated PAD guidelines, which include new recommendations for treatment. The article highlights the importance of considering the diversity of PAD and the role of health equity in patient care. It also raises some controversial issues and calls for a comprehensive and personalized approach to PAD management. The article acknowledges the challenges of implementing guidelines and calls for collaboration among healthcare professionals, researchers, and policymakers to ensure equitable access to care for PAD patients. [Extracted from the article]

The process of peer review has been the gold standard for evaluating medical science, but significant pressures from the recent COVID-19 pandemic, new methods of communication, larger amounts of research, and an evolving publication landscape have placed significant pressures on this system. A task force convened by the American College of Cardiology identified the 5 most significant controversies associated with the current peer-review process: the effect of preprints, reviewer blinding, reviewer selection, reviewer incentivization, and publication of peer reviewer comments. Although specific solutions to these issues will vary, regardless of how scientific communication evolves, peer review must remain an essential process for ensuring scientific integrity, timely dissemination of information, and better patient care. In medicine, the peer-review process is crucial because harm can occur if poor-quality data or incorrect conclusions are published. With the dramatic increase in scientific publications and new methods of communication, high-quality peer review is more important now than ever. [Display omitted] • Peer review of medical science is critical to providing clinicians with fairly vetted and accurate information. • The current process of peer review is often opaque, slow, and susceptible to conscious and unconscious bias. • Peer-review processes must evolve to incorporate contemporary methods of communication and respond to increasing clinical demands. [ABSTRACT FROM AUTHOR]

The article focuses on increasing the efficiency of vascular medicine. Topics discussed include treating and managing vascular disease; improving the vascular health of patients, and the public; and contributing to the vascular education of other physician specialties. It also talks about improving quality of life of the patients.

Net US spending on pharmaceuticals reached $309.5 billion in 2015, an 8.5% increase from the year before, and is expected to reach between $370 and $400 billion by 2020. These current and projected levels have raised serious concerns by policy makers, providers, payers, and patient groups that they are unsustainable and threaten the affordability of and accessibility to much-needed therapies for patients. Two trends related to drugs/biologics and generic drugs/biosimilars underlie this overall increase in spending. First, the market entry prices of innovator pharmaceutical products, or brand drugs and biologics, are at levels that some assessments consider unaffordable to the healthcare system. Second, prices for some established generic drugs such as digoxin and captopril have seen sharp and rapid increases. As an evidence-based patient advocacy organization dedicated to improving the cardiovascular health of all Americans, the American Heart Association has a unique role in advocating for treatments, including medicines that are available, affordable, and accessible to patients. This advisory serves to lay out a set of principles that will guide association engagement in pursuit of this goal. [ABSTRACT FROM AUTHOR]

Although coronary obstruction due to atherosclerosis is the most common cause of myocardial ischemia, a significant proportion of patients have myocardial ischemia in the absence of obstructive epicardial coronary artery disease (CAD). This finding is more common among women and alternative causes can mediate myocardial ischemia. Abnormalities in vascular structure, alterations in coronary vasomotion and dysfunction of the coronary microcirculation can all cause ischemia in the absence of obstructive CAD due to atherosclerosis. In this review, we provide an update on three alternative causes of myocardial ischemia: spontaneous coronary artery dissection (SCAD), vasospastic angina (VSA) and coronary microvascular dysfunction (CMVD). We review pathophysiology, clinical presentation, diagnosis, treatment and outcomes related to these important clinical entities. There is increasing interest in better defining this patient population with use of advanced imaging and testing tools. Despite the increased associated risk with future cardiac events, evidencebased treatments for these diagnoses remain under-studied and poorly defined. These alternative diagnoses should be kept in mind when evaluating women with myocardial ischemia without obstructive CAD due to atherosclerosis. [ABSTRACT FROM AUTHOR]

The article presents a speech by Mark A. Creager, president of the American Heart Association (AHA), delivered at the 2015 Scientific Sessions of the AHA held in Orlando, Florida in November 2015. Topics discussed include the crisis of vascular disease and the journey to vascular health, advances in technology leading to innovative approaches to treat vascular diseases such as optical coherence tomography, intravascular ultrasonography, and positron emission tomography-computed tomography.

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (J Am Coll Cardiol 2010;55:e27-130) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (J Am Coll Cardiol 2014;63:e57-185). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline. [ABSTRACT FROM AUTHOR]

The article focuses on the COCATS 4 Task Force 9, which is a training designed for vascular medicine. Topics discussed include an overview of cardiovascular physicians, the guidelines and requirements for vascular medicine training, the several levels of the training, and the developments and evaluation of core competencies.

The article discusses role of low-density lipoprotein cholesterol in lowering with evolocumab and outcomes in patients with peripheral artery disease. Topics discussed include ways in which lowering low-density lipoprotein cholesterol to very low levels reduces major adverse cardiovascular event; consistent relative reductions in patients with and without peripheral artery disease; and major adverse cardiovascular events in patients with symptomatic lower extremity peripheral artery disease.

The Society for Vascular Medicine was founded in 1989. During the subsequent 25 years, the Society has grown to approximately 500 members and has achieved international recognition while making important contributions to vascular disease education, clinical vascular medicine and biology research, and patient care. In celebration of the Society’s 25th anniversary, its past and current presidents reflect on the Society’s history, challenges, and achievements, and emphasize the vital role of the SVM in the discipline of vascular medicine. [ABSTRACT FROM PUBLISHER]

The article discusses the case of a 57-year-old man who was diagnosed with acute limb ischemia. His symptoms include left foot pain, numbness and partial loss of function. To address disabling claudication, the patient underwent endocascular treatment. Complete occlusion of the stent was detected via angiography. Information on the incidence of acute limb ischemia is provided. Amputation occurs in 10% to 15% of patients in spite of urgent revascularization with thrombolytic agents or surgery.

Background--Hypoxia-inducible factor-la (HIF-l&agr;) is a transcriptional regulatory factor that orchestrates cellular responses to hypoxia. It increases collateral vessel growth and blood flow in models of hind-limb ischemia. This study tested whether intramuscular administration of Ad2/HIF-1 &agr;/VP 16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-l&agr;, improves walking time in patients with peripheral artery disease and intermittent claudication. Methods and Results--Two hundred eighty-nine patients with claudication were randomized in a double-blind manner to 1 of 3 doses of Ad2/HIF-l&agr;/VP 16 (2×109 2×1010, or 2×1011 viral particles) or placebo, administered by 20 intramuscular injections to each leg. Graded treadmill tests were performed at baseline and then 3,6, and 12 months after treatment. The primary end point was the change in peak walking time from baseline to 6 months. The secondary end point was change in claudication onset time, and tertiary end points included changes in ankle-brachial index and quality-of-life assessments. Median peak walking time increased by 0.82 minutes (interquartile range, --0.05-1.93 minutes) in the placebo group and by 0.82 minutes (interquartile range, -0.07-2.12 minutes), 0.28 minutes (interquartile range, -0.37-1.70 minutes), and 0.78 minutes (interquartile range, --0.02-2.10 minutes) in the HIF-l&agr; 2×109, 2×1010, and 2×1011 viral particle groups, respectively (P=NS between placebo and each HIF-la treatment group). There were no significant differences in claudication onset time, ankle-brachial index, or quality-of-life measurements between the placebo and each HIF-la group. Conclusions--Gene therapy with intramuscular administration of Ad2/HIF-l&agr;/VP16 is not an effective treatment for patients with intermittent claudication. [ABSTRACT FROM AUTHOR]

Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 μg, 100 μg, or 150 μg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 μg, 100 μg, and 150 μg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication. [ABSTRACT FROM AUTHOR]

An editorial is presented in which author discusses use of VOYAGER PAD (Vascular Outcomes Study of acetylsalicylic acid) to reduce adverse limb events in patients undergoing peripheral revascularization. Topics include risk of the primary efficacy outcome, a composite of acute limb ischemia; information on COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial for limb ischemia; and role of low-dose rivaroxaban to aspirin to reduce risk of adverse limb events.

Hydroxymethylglutaryl-coenzyme A reductase inhibitors or statins constitute one of the wonder drugs of the last 2 decades. Use of this hypolipidemic medication class reduces morbidity and mortality in patients with a wide variety of cholesterol levels. Beneficial effects of the medication are seen in advance of changes in lipids suggesting nonlipid mechanisms may play a role in mediating these benefits of statins. One important nonlipid mechanism by which statins may improve vascular outcomes is restoration of normal endothelial cell function. This review will discuss the nonlipid effects of statins on endothelial cell function to highlight other avenues of benefit conferred by these medications. [Copyright &y& Elsevier]

The vascular endothelium is a crucial regulator of vascular function and homeostasis. Nitric oxide (NO) is an important paracrine substance released by the endothelium to regulate vasomotor tone. Risk factors for atherosclerosis, as well as atherosclerosis per se, are associated with endothelial dysfunction and decreased bioavailablilty of NO. Indeed, endothelial dysfunction is integral to the pathogenesis of atherosclerosis and other cardiovascular diseases. Moreover, endothelial dysfunction relates to an increased risk of adverse cardiovascular outcomes. L-Arginine is an essential amino acid required by the constitutive enzyme, endothelial NO oxide synthase (eNOS), to produce NO. Administration of L-arginine improves endothelial function in animal models and in humans with hypercholesterolemia and with atherosclerosis. Clinical trials to date support potential clinical applications of L-arginine in the treatment of coronary artery disease and peripheral arterial disease, as well as in the prevention of in-stent restenosis. The mechanism of benefit of L-arginine on endothelial function is unclear, because intracellular concentrations of L-arginine far exceed that required by eNOS. One potential explanation of this ‘arginine paradox’ is that L-arginine restores endothelial function in atherosclerotic patients, in whom there are elevated levels of asymmetric dimethylarginine, an endogenous inhibitor of eNOS. Given the promising findings of early studies of L-arginine as a potential therapy for cardiovascular disorders, large-scale clinical trials are warranted. [ABSTRACT FROM AUTHOR]

Focuses on the requirements and standards of postgraduate training in vascular medicine. Guidelines of medicine training for cardiologists; Outlines of specific training methods in vascular medicine; Topics to be covered in vascular medicine.

Context: Complications of atherosclerosis cause most morbidity and mortality in patients with diabetes mellitus. Despite the frequency and severity of disease, proven medical therapy remains incompletely understood and underused. Objective: To review the epidemiology, pathophysiology, and medical and invasive treatment of atherosclerosis in patients with diabetes mellitus. Data Sources: Using the index terms diabetes mellitus, myocardial infarction, peripheral vascular diseases, cerebrovascular accident, endothelium, vascular smooth muscle, platelets, thrombosis, cholesterol, hypertension, hyperglycemia, insulin, angioplasty, and coronary artery bypass, we searched the MEDLINE and EMBASE databases from 1976 to 2001. Additional data sources included bibliographies of identified articles and preliminary data presented at recent cardiology conferences. Study Selection: We selected original investigations and reviews of the epidemiology, pathophysiology, and therapy of atherosclerosis in diabetes. We selected randomized, double-blind, controlled studies, when available, to support therapeutic recommendations. Criteria for data inclusion (168 of 396) included publication in a peer-reviewed journal or presentation at a national cardiovascular society–sponsored meeting. Data Extraction: Data quality was determined by publication in peer-reviewed literature. Data extraction was performed by one of the authors. Data Synthesis: Diabetes mellitus markedly increases the risk of myocardial infarction, stroke, amputation, and death. The metabolic abnormalities caused by diabetes induce vascular dysfunction that predisposes this patient population to atherosclerosis. Blood pressure control, lipid-lowering therapy, angiotensin-converting enzyme inhibition, and antiplatelet drugs significantly reduce the risk of cardiovascular events. Although diabetic patients undergo revascularization procedures because of acute coronary syndromes or critical limb ischemia, the... [ABSTRACT FROM AUTHOR]

BACKGROUND: In the BEST-CLI trial (Best Endovascular Versus Best Surgical Therapy for Patients With Chronic Limb-Threatening Ischemia), a prespecified secondary objective was to assess the effects of revascularization strategy on health-related quality of life (HRQoL). METHODS: Patients with chronic limb-threatening ischemia were randomized to surgical bypass (Bypass) or endovascular intervention (Endo) in 2 parallel trials. Cohort 1 included patients with single-segment great saphenous vein; cohort 2 included those lacking suitable single-segment great saphenous vein. HRQoL was assessed over the trial duration using Vascular Quality-of-Life (VascuQoL), European Quality-of-Life-5D (EQ-5D), the Short Form-12 (SF-12) Physical Component Summary (SF-12 PCS), SF-12 Mental Component Summary (SF-12 MCS), Utility Index Score (SF-6D R2), and numeric rating scales of pain. HRQoL was summarized by cohort and compared within and between groups using mixed-model linear regression. RESULTS: A total of 1193 and 335 patients in cohorts 1 and 2 with a mean follow-up of 2.9 and 2.0 years, respectively, were analyzed. In cohort 1, HRQoL significantly improved from baseline to follow-up for both groups across all measures. For example, mean (SD) VascuQoL scores were 3.0 (1.3) and 3.0 (1.2) for Bypass and Endo at baseline and 4.7 (1.4) and 4.8 (1.5) over follow-up. There were significant group differences favoring Endo when assessed with VascuQoL (difference, –0.14 [95% CI, –0.25 to –0.02]; P =0.02), SF-12 MCS (difference, –1.03 [95% CI, –1.89 to –0.18]; P =0.02), SF-6D R2 (difference, –0.01 [95% CI, –0.02 to –0.001]; P =0.03), numeric rating scale pain at present (difference, 0.26 [95% CI, 0.03 to 0.49]; P =0.03), usual level during previous week (difference, 0.26 [95% CI, 0.04 to 0.48]; P =0.02), and worst level during previous week (difference, 0.29 [95% CI, 0.02 to 0.56]; P =0.04). There was no difference between treatment arms on the basis of EQ-5D (difference, –0.01 [95% CI, –0.03 to 0.004]; P =0.12) or SF-12 PCS (difference, –0.41 [95% CI, –1.2 to 0.37]; P =0.31). In cohort 2, HRQoL also significantly improved from baseline to the end of follow-up for both groups based on all measures, but there were no differences between Bypass and Endo on any measure. CONCLUSIONS: Among patients with chronic limb-threatening ischemia deemed eligible for either Bypass or Endo, revascularization resulted in significant and clinically meaningful improvements in HRQoL. In patients with an available single-segment great saphenous vein for bypass, but not among those without one, Endo was statistically superior on some HRQoL measures; however, these differences were below the threshold of clinically meaningful difference. [ABSTRACT FROM AUTHOR]

Discusses the pathogenesis of atherosclerosis. Regression of coronary atherosclerotic lesions; Importance of hemodynamically severe stenosis; Stabilization of rupture-prone plaques; Endothelial dysfunction; Cholesterol lowering and plaque stability; Effect of lipid-lowering treatment on the incidence of myocardial ischemia.

The author discusses updates of the journal. He provides overview of the history of the journal such as the changes of its name to reflect its focus as medical and cardiovascular periodical. The author also expresses thanks to the authors of the journal who have made significant contributions on various researches, and shares his plan for the journal for its continued service.

In this article the authors criticize the study on the efficacy of percutaneous revascularization when combined with medical therapy for renal-artery stenosis. They investigate the efficacy of the technique after treating 806 patients confirmed to have antomical atherosclerotic stenosis. The authors conclude that the study suggests to exclude patients with the most severe clinical consequences of renal artery stenosis when conducting this kind of study.

Representation of women in interventional vascular fields (interventional cardiology, interventional radiology, and vascular surgery) lags behind that in other specialties. With women representing half of all medical school graduates, encouraging parity of women in these fields needs to start in medical school. Barriers to pursuing careers in vascular intervention include insufficient exposure during core clerkships, early mentorship, visibility of women in the field, length of training, lifestyle considerations, work culture and environment, and concerns about radiation exposure. This scientific statement highlights potential solutions for both the real and perceived barriers that women may face in pursuing careers in vascular intervention, including streamlining of training (as both interventional radiology and vascular surgery have done with a resultant increase in percentage of women trainees), standardization of institutional promotion of women in leadership, and professional and industry partnerships for the retention and advancement of women. [ABSTRACT FROM AUTHOR]

The article focuses on how lack of public awareness about the symptoms and risk factors of venous thromboembolism, especially among the poor population, causes delay in the diagnosis and affects the outcome of the treatment. It also discusses the risk factors for the disease including obesity and sickle cell traits, and its prevention and treatment options like anticoagulation therapy.

Venous thromboembolism (VTE), composed of pulmonary embolism and deep venous thrombosis, is a significant cause of maternal mortality in the developed world. Normal physiological changes of pregnancy increase coagulability, which is compounded by patient-inherited and acquired risk factors. Depending on these risks and peripartum stage, the benefits of thromboprophylaxis can outweigh potential side effects. Diagnosis requires cautious clinical acumen because many symptoms of normal pregnancy mimic those of VTE and algorithmic tools used in the nonpregnant population are not equally applicable. Choice of imaging technique must account for potential risk to the fetus and altered test accuracy (sensitivity and specificity) in the setting of pregnancy. When VTE is diagnosed, anticoagulation is the backbone of treatment, with more advanced therapies being options for those with right ventricular dysfunction or unstable hemodynamics. Overall, pregnancy-associated VTE is complex, and management decisions should be individualized and informed by patient preferences. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Venous thromboembolism is a major cause of morbidity and mortality. The impact of the US Surgeon General's The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in venous thromboembolism, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiological causative mechanisms for the 50% of patients with unprovoked venous thromboembolism and to better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing venous thromboembolism will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter-based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence-based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population-based cohort studies can elucidate the biological and environmental underpinnings of venous thromboembolism and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of venous thromboembolism. [ABSTRACT FROM AUTHOR]

The article discusses several important clinical trials that have significantly influenced treatment for common vascular disorders. Topics discussed include health risks faced by patients with peripheral artery disease, effectiveness of aspirin therapy, and the efficacy of endovascular repair of large abdominal aortic aneurysms (AAAs). Information is also presented on studies that investigated the efficacy of new oral anticoagulants.

Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (–2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474 [ABSTRACT FROM AUTHOR]

The article presents an obituary for Jay Denton Coffman, founder and second president of the Society for Vascular Medicine and Biology.

This article reports that peripheral arterial disease (PAD) and its most common manifestation, intermittent claudication (IC), are associated with considerable morbidity and mortality. The patient with PAD has well-documented risk factors for atherosclerosis. Because of these, combined with the systemic nature of atherosclerosis and the high cardiovascular event rate in these patients, all should be considered for secondary prevention strategies that include antiplatelet therapy and aggressive risk factor modification.

Peripheral artery disease (PAD) affects over 200 million people globally and is a cause of significant morbidity, mortality, and disability due to limb loss. Although secondary prevention with antithrombotic therapy is a mainstay of treatment to prevent adverse cardiovascular events, PAD patients are often undertreated with antithrombotic agents. Furthermore, there is a paucity of high-quality data from randomized controlled trials of PAD patients, leading to wide variations in clinical practice and guideline recommendations. Recently, there have been important advances that have further increased the number of antiplatelet and anticoagulant choices potentially available for patients with PAD. In this context, this paper aims to summarize the current available evidence for the safety and efficacy of various antithrombotic agents in PAD, and discuss how to integrate this emerging evidence into actual clinical practice. An evidenced-based approach to PAD patients is essential to achieve optimal outcomes, weighing cardiovascular and limb benefits against bleeding risks. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplatelet therapy reduces VTE risk beyond aspirin monotherapy is unknown.Methods: TRA2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction) (vorapaxar) and PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) (ticagrelor) were blinded, randomized placebo-controlled trials of antiplatelet therapy for the prevention of ischemic events in stable patients with symptomatic atherosclerosis. Two blinded vascular specialists systematically identified symptomatic venous thromboembolic events in both trials.Results: Of 47 611 patients with stable vascular disease followed for 3 years in both studies there were 343 VTE events in 301 patients (Kaplan-Meier rate at 3 years, 0.9% for placebo). The risk of VTE was independently associated with age, body mass index, polyvascular disease, chronic obstructive pulmonary disease, and malignancy. The burden of atherosclerosis manifested as an increasing number of symptomatic vascular territories was associated with a graded increase in the 3-year rates of VTE (0.76% for 1, 1.53% for 2, and 2.45% for 3 territories). More intensive antiplatelet therapy (vorapaxar and ticagrelor pooled) significantly reduced the risk of VTE by 29% compared with background antiplatelet therapy, from 0.93% to 0.64% at 3 years (hazard ratio, 0.71; 95% confidence interval, 0.56-0.89; P=0.003).Conclusions: The rate of VTE in patients with atherosclerosis is ≈0.3% per year while on treatment with ≥1 antiplatelet agent, with increased risk independently associated with the number of symptomatic vascular territories. More intensive antiplatelet therapy reduces the risk of VTE. These data suggest a relationship between atherosclerosis burden and VTE risk, and they support inclusion of VTE as a prospective end point in long-term secondary prevention trials evaluating the risks and benefits of antiplatelet therapies in patients with atherosclerosis.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562. [ABSTRACT FROM AUTHOR]