Book Reviews

Increased production of reactive oxygen species (ROS) in the vascular wall is a characteristic feature of disease states, including atherosclerosis, diabetes and hypertension. ROS, such as superoxide, reduce nitric oxide bioactivity by scavenging and cause oxidation of lipids and target proteins. In addition, recent work has revealed that ROS mediate a wide range of pathological processes in the endothelium, smooth muscle cells, and inflammatory cells.1 ROS are generated by enzyme systems present in cells in the vascular wall, including NAD(P)H oxidase, xanthine oxidase, and nitric oxide synthase. The activities and levels of these enzyme systems are increased in association with vascular disease risk factors2 and in vascular disease states in which oxidative stress is prominent, for example, in diabetes3 and atherosclerosis. See page 1838 The NAD(P)H oxidases appear to be particularly important sources of ROS production in blood vessels,4 where they are constitutively active, producing relatively low levels of ROS under basal conditions, but generating higher levels of oxidants in response to stimuli such as growth factors and cytokines. These factors are consistent with a role for nonphagocytic NAD(P)H oxidases in cellular signaling rather than the high-level burst activity characteristic of the phagocyte NAD(P)H oxidase. The NAD(P)H oxidases are multimeric enzymes composed of plasma membrane associated–proteins as well as cytosolic factors. In the phagocytic-type NAD(P)H oxidase, the plasma membrane–associated proteins gp91phox and p22phox compose the flavocytochrome b558 complex, which forms the catalytic subunit of the oxidase. The cytosolic subunits, including p47phox, p67phox, and the G-protein Rac, provide regulatory function. Azumi and colleagues,5 in this issue of Arteriosclerosis, Thrombosis and Vascular Biology …

This reference summarizes recent advancements in knowledge about cardiovascular disease and pharmacology. The goal of the book is to inform readers about recent findings on cardiovascular therapeutics and how to conduct experiments to evaluate natural products. It presents 10 chapters that cover basic clinical research on cardiovascular diseases and therapeutic agents derived from natural sources. The book concludes with a series of experiments that demonstrate the methods to test the ameliorative effects of 3 phytochemicals: Biochanin A (red clover), Zingiberene (ginger oil) and Betaine (sugar beet). Key Features - 10 chapters that highlight recent research cardiovascular medicine and pharmacology - Covers knowledge about basic cardiovascular physiology, congestive heart failure treatment and the treatment of heart inflammation. - Covers uses, benefits, and drawbacks of numerous rodent and non-rodent animal models for studying CVD - Updates readers about 21st-century CRISPR-cas9 technology and its uses in CVD. - Covers the significance of Indian Ayurvedic techniques on the cardiovascular system, - Covers information about nutraceuticals for CVD therapy - Includes experiments to evaluate 3 phytochemicals for the treatment of different heart diseases such as hypertension, obesity-cardiomyopathy and the mitigation of inflammatory cytokines in myocardial infarction. This book is an informative resource for cardiologists, and researchers working in the field of cardiovascular pharmacology. It also helps readers to understand the benefits of herbal medications that are commonly available for consumption in homes.

The Clinical Efficacy Assessment Subcommittee of the American College of Physicians–American Society of Internal Medicine acknowledges the scientific validity of this product as a background paper and as a review that captures the levels of evidence in the management of patients with chronic stable angina as of November 17, 2002. The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or a full revision is needed. This process gives priority to areas in which major changes in text, and particularly recommendations, are merited on the basis of new understanding or evidence. Minor changes in verbiage and references are discouraged. The ACC/AHA/American College of Physicians–American Society of Internal Medicine (ACP-ASIM) Guidelines for the Management of Patients With Chronic Stable Angina, which were published in June 1999, have now been updated. The full-text guideline incorporating the updated material is available on the Internet (www.acc.org or www.americanheart.org) in both a track-changes version showing the changes in the 1999 guideline in strike-out (deleted text) and highlighting …

Despite aggressive dietary modification, lipid-lowering medications, and other interventional medical therapy, vascular disease continues to be a leading cause of mortality in the western world. It is a significant medical and socioeconomic problem contributing to mortality of multiple diseases including myocardial infarction, stroke, renal failure, and peripheral vascular disease. Morbidity and mortality of vascular disease are expected to worsen with the increasing number of patients with comorbid conditions such as obesity, metabolic syndrome, and diabetes mellitus type 2. Vascular diseases such as atherosclerosis, restenosis, and allograft vasculopathy are recognized to be driven by inflammation, and as such, cytokines which mediate inflammation not only represent important targets of rational therapy, but also can be considered as possible therapeutic modalities themselves. In this paper, we will examine the role of inflammatory cytokines and lymphocyte Th1/Th2 polarity in vascular inflammation, with a focus on atherosclerotic vascular disease. We will then introduce a recently described Th2 interleukin, interleukin-19 (IL-19), as a previously unrecognized mediator of vascular inflammatory disorders. We will review our current understanding of this interleukin in health and disease and present the possibility that IL-19 could represent a potential therapeutic to combat vascular inflammatory disease.

To assess whether prior interventional treatment for benign prostatic hyperplasia (BPH) influences oncologic or functional outcomes following primary whole-gland prostate cryoablation. Among 3831 men with prostate cancer who underwent primary whole-gland prostate cryoablation, we identified 160 with a history of prior BPH interventional therapy including transurethral needle ablation (n = 6), transurethral microwave thermotherapy (n = 9), or transurethral resection of the prostate (n = 145). Patients with a history of medically treated or unspecified BPH therapy were excluded from the study. Oncological and functional outcomes were compared between men with and without prior BPH interventional therapy. In unadjusted analyses, prior interventional BPH therapy was associated with higher risks of postoperative urinary retention (17.5% vs. 9.6%, p = 0.001) and new-onset urinary incontinence (39.9% vs. 19.4%, p > 0.001) compared with no prior therapy. Interventional BPH therapy was not correlated with the risk of developing a rectourethral fistula (p = 0.84) or new-onset erectile dysfunction (ED) at 12 months (p = 0.08) following surgery. On multivariable regression, prior interventional BPH therapy was associated with increased risk of urinary retention (OR 1.9, 95%, p = 0.015) and new-onset urinary incontinence (OR 2.13, p < 0.001). The estimated 5 years Kaplan-Meier survival analysis showed no statistically significant difference (p = 0.3) in biochemical progression free survival between those who underwent interventional BPH therapy compared with those who did not. Local disease recurrence assessed by post cryoablation positive for-cause prostate biopsy showed no significant difference between the two groups (25.4% vs. 28.7%, p = 0.59). Prior interventional BPH therapy did not affect the oncologic outcomes nor did it increase the risk of rectourethral fistula or ED in sexually performing patients prior to cryosurgery. Prior interventional BPH therapy was associated with increased risk of urinary retention and incontinence after primary whole-gland prostate cryoablation for prostate cancer.

Percutaneous angioscopy, using high resolution fiberoptic imaging, allows direct and two-dimensional visualization of the vascular interior, thereby enabling macroscopic pathological diagnosis. Percutaneous angioscopy has revealed that the vascular luminal surface exhibits various colors and morphologies characteristic of different vascular diseases. This imaging technique is used for evaluation of the severity of vascular diseases, staging of atherosclerosis, analysis of thrombus composition, evaluation of interventional and surgical therapies, and for guidance of intravascular interventions such as angioplasty, venous valvuloplasty and aortic stentgrafting. Recently, dye-image angioscopy has been used clinically for analyses of thrombus composition, endothelial damage and plaque composition. Intravascular microscopy was also developed for cellular imaging of vascular disease. Furthermore, fluorescent angioscopy was developed for molecular imaging of substances comprising atherosclerotic plaques. In this article, we describe the history of the development of angioscopy, angioscopic systems and techniques, angioscopic changes associated with vascular diseases, angioscope-guided intravascular therapies, and evaluation of intravascular and surgical therapies. Angioscopic pictures, except those of the coronary arteries, have rarely been published in the literature, so we have included many representative angioscopic pictures obtained by the authors in this article.

During the past decade, numerous experimental and clinical studies have demonstrated that many common conditions predisposing to atherosclerosis, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a reduced vascular availability of nitric oxide (NO•). Nitric oxide not only produces vasodilation but also has potent antiatherogenic properties. These properties include inhibition of platelet aggregation, prevention of smooth muscle cell proliferation, reduction of lipid peroxidation, and inhibition of adhesion molecule expression. Thus, the loss of NO• observed in these various conditions not only alters vascular tone but also may explain in part why these conditions are risk factors for atherosclerosis. See p 2673 Given this apparent link between loss of nitric oxide and atherosclerosis, several groups have been interested in the concept that endothelium-dependent vasodilation, a surrogate for NO• bioavailability, may predict cardiovascular events. Indeed, Suwaidi et al1 followed 157 patients with mildly diseased coronary arteries for an average of 28 months and observed cardiac events only in the patients with the lowest tertile of coronary vasodilation to acetylcholine. Similarly, in a study of 147 patients, Schachinger et al2 used 3 different stimuli for endothelial release of NO: acetylcholine, cold pressor testing, and increased blood flow. The authors showed that responses to each of these stimuli were independent predictors of cardiovascular events during a follow-up period of ≈8 years. Perticone et al3 also demonstrated that endothelial dysfunction in the forearm circulation predicts cardiovascular events in hypertensive subjects. There have been several explanations for why the various risk factors impair endothelial function. One that has received substantial attention is increased production of reactive oxygen species within the vessel.4 In particular, superoxide (O2•-) reacts rapidly with NO•, resulting in the formation of the peroxynitrite anion and loss of NO• …

F(2)-isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. Their quantification as a pathophysiological biomarker provides a unique opportunity to investigate lipid peroxidation in vascular diseases. Their measurement also provides an interesting biomarker for the rational dose selection of antioxidants in vascular diseases where oxidative stress might be involved. In addition to their use as biomarkers, some isoprostanes possess a biological activity. The 15-series F(2)- and E(2)-isoprostanes mediate vasoconstriction in different vascular beds and species. In addition, 15-F(2t)-IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. The data available supports but does not prove the hypothesis that isoprostanes are involved in vascular physiology and pathogenesis.

Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

A series of interdependent advances in knowledge and technology over recent years has fueled significant progress in management of diseases of the peripheral arteries and veins. Contributions have come from many sources but most importantly from vascular surgeons and interventional vascular radiologists working separately and increasingly together. Advances in traditional surgical strategies of thromboendarterectomy, resection, and bypass have been supplemented by growth of endovascular therapeutic modalities such as fibrinolysis, percutaneous transluminal angioplasty, atherectomy, stenting, and recent pioneering efforts at intraluminal prosthetic grafting. Over the last several years, it has become abundantly clear that vascular therapy is best when involved physicians from all disciplines work together to bring their techniques and expertise to bear on the chronic complexities and challenges of vascular disease. Since vascular surgeons and interventional radiologists have found themselves working together on nearly every patient with vascular disease, it is remarkable that a significant text combining the wisdom

Elevated low-density lipoprotein cholesterol (LDLC) levels in the plasma is the most important causative factor of atherosclerosis and associated ischemic cardiovascular diseases. The LDL receptor (LDLR) is the preferential pathway through which LDLs are cleared from the circulation. LDLs bound to the LDLR are internalized into clathrin-coated pits and subsequently undergo lysosomal degradation, whereas the LDLR is recycled back to the plasma membrane. See accompanying article on page 1333 Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with elevated LDL levels and premature coronary heart disease. FH is caused primarily by mutations of the LDLR or of apolipoprotein B100 (apoB100), the protein component of LDL that interacts with the LDLR. In 2003, “gain of function” mutations on a newly identified gene, proprotein convertase subtilisin/kexin type 9 ( PCSK9), were associated with FH. In 2005, a causative association was established between “loss of function” mutations in PCSK9 and low LDLC levels in 2% of the African-American population. The coronary heart disease risk in these individuals was reduced by 88%. As a result of these landmark studies (reviewed in Reference 1), PCSK9 became the subject of intensive research to discover the underlying mechanisms. PCSK9 is a serine protease mainly expressed in the liver and the intestine. It acts by reducing the amount of LDLR in hepatocytes. This was demonstrated in vitro and in mouse models …

Atherosclerosis is now widely accepted as an inflammatory disease that involves both the innate and acquired immune systems.1 Several types of immune cells have been identified in the atherosclerotic lesions of humans and animal models. Numerous studies have shown a role for T and B lymphocytes in atherogenesis.2–6 Most studies have shown that T lymphocytes are proatherogenic, whereas B lymphocytes are associated with protection from atherosclerosis.2–6 The mechanisms for T and B lymphocyte–mediated modulation of atherosclerosis remain undefined, but may involve the production of proatherosclerotic cytokines, such as interferon (IFN)-γ, and the secretion of atheroprotective autoantibodies, respectively. See page 1049 Macrophages are particularly important to the atherosclerotic disease process. They are among the first cells to infiltrate the artery wall and regulate lesion growth from its inception through uptake of modified lipoproteins, production of apolipoprotein (apo)-E and regulation of cholesterol efflux, secretion of matrix metalloproteinases, and contribution to the inflammatory process.7,8 The importance of macrophages to atherosclerosis has been emphasized in animal models with defective macrophage biology such as the op/op and monocyte chemoattractant protein-1–deficient mice.9–11 In these cases, reduction in macrophage accumulation in the artery wall led to significant protection against atherosclerosis. Although the role of macrophages in atherosclerosis is now undisputed, the importance of other cells of the innate immune system has not yet been solidified. Few studies have looked at mast cells and neutrophils in atherosclerosis, and, until recently, not much had been determined regarding natural killer (NK) cells.1 NK cells are members of the innate immune system and are defined by their ability to lyse tumor cells in vivo.12 In addition, and perhaps more relevant to the atherogenic process, NK cells participate in innate immunity through the production of cytokines such as IFN-γ in response to interleukin (IL)-12 and …

Surgical Pain Management: A Complete Guide to Implantable and Interventional Pain Therapies, S Narang, A Weisheipl and EL Ross (editors)

The article “Hypertension in Sub-Saharan Africa” by Addo et al has documented both the high prevalence of hypertension, especially in urban areas, and poor control of hypertension in sub-Saharan Africa.1 In 1992, we reported the high prevalence of hypertensive disease in a population sample from Benin, Nigeria and the strong association with higher socioeconomic class and body weight.2 Previous reports from the World Health Organization (WHO) and other groups have warned of the growing epidemic of hypertension and vascular disease and, most important, the need for both population-based approaches to reduce the epidemic, including the reduction of salt in the diet and treatment of BP using inexpensive drug therapies.3,4 There is a need for better data on the prevalence of hypertension and risk factors related to both hypertension and vascular disease in sub-Saharan Africa. The most important imperative at the present time is to effectively blunt this growing epidemic of vascular disease. This epidemic of vascular disease is following the path characteristic of many other countries and especially in the United States, with initial high rates of hypertension and vascular disease among the upper socioeconomic groups and then explosive epidemics of both hypertension and vascular disease among lower income populations, especially the black population in the United States.5 The key variables that drive the epidemics are the greater use of processed foods, higher intake of calories, decreased physical activity leading to weight gain, and the reduction of foods high in potassium.6 The epidemic, as noted, has begun in the upper social classes and in urban …