ABI
: ankle–brachial index
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
AGREE
: Appraisal of Guidelines Research and Evaluation
AHA
: American Heart Association
apoA1
: apolipoprotein A1
apoB
: apolipoprotein B
CABG
: coronary artery bypass graft surgery
CARDS
: Collaborative AtoRvastatin Diabetes Study
CCNAP
: Council on Cardiovascular Nursing and Allied Professions
CHARISMA
: Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance
CHD
: coronary heart disease
CKD
: chronic kidney disease
COMMIT
: Clopidogrel and Metoprolol in Myocardial Infarction Trial
CRP
: C-reactive protein
CURE
: Clopidogrel in Unstable Angina to Prevent Recurrent Events
CVD
: cardiovascular disease
DALYs
: disability-adjusted life years
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Trial
ED
: erectile dysfunction
eGFR
: estimated glomerular filtration rate
EHN
: European Heart Network
EPIC
: European Prospective Investigation into Cancer and Nutrition
EUROASPIRE
: European Action on Secondary and Primary Prevention through Intervention to Reduce Events
GFR
: glomerular filtration rate
GOSPEL
: Global Secondary Prevention Strategies to Limit Event Recurrence After MI
GRADE
: Grading of Recommendations Assessment, Development and Evaluation
HbA1c
: glycated haemoglobin
HDL
: high-density lipoprotein
HF-ACTION
: Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing
HOT
: Hypertension Optimal Treatment Study
HPS
: Heart Protection Study
HR
: hazard ratio
hsCRP
: high-sensitivity C-reactive protein
HYVET
: Hypertension in the Very Elderly Trial
ICD
: International Classification of Diseases
IMT
: intima-media thickness
INVEST
: International Verapamil SR/Trandolapril
JTF
: Joint Task Force
LDL
: low-density lipoprotein
Lp(a)
: lipoprotein(a)
LpPLA2
: lipoprotein-associated phospholipase 2
LVH
: left ventricular hypertrophy
MATCH
: Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke
MDRD
: Modification of Diet in Renal Disease
MET
: metabolic equivalent
MONICA
: Multinational MONItoring of trends and determinants in CArdiovascular disease
NICE
: National Institute of Health and Clinical Excellence
NRT
: nicotine replacement therapy
NSTEMI
: non-ST elevation myocardial infarction
ONTARGET
: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
OSA
: obstructive sleep apnoea
PAD
: peripheral artery disease
PCI
: percutaneous coronary intervention
PROactive
: Prospective Pioglitazone Clinical Trial in Macrovascular Events
PWV
: pulse wave velocity
QOF
: Quality and Outcomes Framework
RCT
: randomized clinical trial
RR
: relative risk
SBP
: systolic blood pressure
SCORE
: Systematic Coronary Risk Evaluation Project
SEARCH
: Study of the Effectiveness of Additional Reductions in Cholesterol and
SHEP
: Systolic Hypertension in the Elderly Program
STEMI
: ST-elevation myocardial infarction
SU.FOL.OM3
: SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids
Syst-Eur
: Systolic Hypertension in Europe
TNT
: Treating to New Targets
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use
VITATOPS
: VITAmins TO Prevent Stroke
VLDL
: very low-density lipoprotein
WHO
: World Health Organization

### 1.1 Introduction

Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

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European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

/pdf/nitric-oxide-and-peroxynitrite-in-health-and-disease-3uuuqgfdcz.pdf

Nitric Oxide and Peroxynitrite in Health and Disease

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules).

In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below.

The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

/pdf/european-guidelines-on-cardiovascular-disease-prevention-in-17acj3uib4.pdf

European guidelines on cardiovascular disease prevention in clinical practice (version 2012) : the fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).

The pathophysiology of cigarette smoking and cardiovascular disease: An update

Other experts who contributed to parts of the guidelines: Edmond Walma, Schoonhoven (The Netherlands), Tony Fitzgerald, Dublin (Ireland), Marie Therese Cooney, Dublin (Ireland), Alexandra Dudina, Dublin (Ireland) European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG):, Alec Vahanian (Chairperson) (France), John Camm (UK), Raffaele De Caterina (Italy), Veronica Dean (France), Kenneth Dickstein (Norway), Christian Funck-Brentano (France), Gerasimos Filippatos (Greece), Irene Hellemans (The Netherlands), Steen Dalby Kristensen (Denmark), Keith McGregor (France), Udo Sechtem (Germany), Sigmund Silber (Germany), Michal Tendera (Poland), Petr Widimsky (Czech Republic), Jose Luis Zamorano (Spain)Document reviewers: Irene Hellemans (CPG Review Coordinator) (The Netherlands), Attila Altiner (Germany), Enzo Bonora (Italy), Paul N. Durrington (UK), Robert Fagard (Belgium), Simona Giampaoli(Italy), Harry Hemingway (UK), Jan Hakansson (Sweden), Sverre Erik Kjeldsen (Norway), Mogens Lytken Larsen ...

/pdf/european-guidelines-on-cardiovascular-disease-prevention-in-4vlgh0a6w5.pdf

European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).

An attempt was made to elucidate the molecular targetfor the antitumor effects of cordycepin (3'-deoxyadenosine) using non-selective and selective adenosine A1, A2a, A2b and A3 receptor agonists and antagonists. Although adenosine and 2'-deoxyadenosine (up to 100 microM) had no effect, cordycepin showed remarkable inhibitory effects on the growth curves of B16-BL6 mouse melanoma (IC50= 39 microM) and mouse Lewis lung carcinoma (IC50 = 48 microM) cell lines in vitro. Among the adenosine receptor agonists and antagonists used (up to 100 microM), only 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective adenosine A3 receptor agonist, notably inhibited the growth of both mouse tumor cell lines (B16-BL6; IC50 = 5 microM, LLC; 14 microM). In addition, the tumor growth inhibitory effect of cordycepin was antagonized by 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191), a selective adenosine A3 receptor antagonist. These results suggest that cordycepin exerts inhibitory effects on the growth of mouse melanoma and lung carcinoma cells by stimulating adenosine A3 receptors on tumor cells.

Antitumor effect of cordycepin (3'-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation.

Cordyceps sinensis is one of the most valued herbs in traditional Chinese medicine. We investigated the antioxidant activities of the cultured fruiting bodies of Cordyceps sinesis. The water and ethanol extracts of Cordyceps sinensis were found to possess a potent antioxidant activity. The scavenging effects of the extracts on superoxide were very weak, but the extracts moderately inhibited malondialdehyde formation via hydroxyl radical induced by SIN-1, a peroxynitrite generator. Of the extracts examined, the hot water extract (70 degrees C for 5 min) showed the greatest oxygen free radical scavenging activity. Also, when low-density lipoprotein (LDL) was incubated with macrophages in the presence of CuCl2 (1 microM), the hot water extract showed a strong inhibitory effect against lipid peroxidation in the medium and consequent accumulation of cholesteryl ester in macrophages. Their activities were comparable to that of authentic Cu/Zn SOD. These results suggest that the extracts of cultured Cordyceps sinensis possess potent antioxidant and anti-lipid peroxidation activities and inhibit accumulation of cholesteryl ester in macrophages via suppression of LDL oxidation.

Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis.

Conventional noninvasive blood pressure in conscious rats or mice are typically measured using the tail-cuff method after heating the animal. The goal of this study was to assess the validity of a novel tail-cuff method without animal heating when compared with the conventional heating tail-cuff method (unanesthetized rats with heating), telemetry method (unanesthetized restrained rats without heating), or carotid arterial catheter method (anesthetized rats, carotid arterial cannulation). The blood pressure and heart rate of spontaneously hypertensive rats were measured at 13:00-17:00 h for all experiments. Experiments demonstrated similar systolic blood pressure measurements when comparing the unheated-animal tail-cuff method and the telemetry method. Further, values obtained by both methods were lower than those obtained by the heated-animal tail-cuff method. Systolic blood pressure measurements obtained through carotid arterial cannulation were lower than those obtained by any other method. The heart rate was highest using the unheated-animal tail-cuff method when compared with the other methods. These data suggest that the novel unheated-animal tail-cuff method is a sensitive and accurate approach for the noninvasive measurement of blood pressure in conscious rats.

Evaluation of blood pressure measured by tail-cuff methods (without heating) in spontaneously hypertensive rats.

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits

Satomi Kagota

Papers

Antitumor effect of cordycepin (3'-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation.

Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis.

Evaluation of blood pressure measured by tail-cuff methods (without heating) in spontaneously hypertensive rats.

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits