Activation of the renin-angiotensin-aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers [ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)] yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: 'Do not use ACEI and ARB in combination'. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations.

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Cuffless technique enables continuous blood pressure (BP) measurement in an unobtrusive manner, and thus has the potential to revolutionize the conventional cuff-based approaches. This study extends the pulse transit time (PTT) based cuffless BP measurement method by introducing a new indicator – the photoplethysmogram (PPG) intensity ratio (PIR). The performance of the models with PTT and PIR was comprehensively evaluated in comparison with six models that are based on sole PTT. The validation conducted on 33 subjects with and without hypertension, at rest and under various maneuvers with induced BP changes, and over an extended calibration interval, respectively. The results showed that, comparing to the PTT models, the proposed methods achieved better accuracy on each subject group at rest state and over 24 hours calibration interval. Although the BP estimation errors under dynamic maneuvers and over extended calibration interval were significantly increased for all methods, the proposed methods still outperformed the compared methods in the latter situation. These findings suggest that additional BP-related indicator other than PTT has added value for improving the accuracy of cuffless BP measurement. This study also offers insights into future research in cuffless BP measurement for tracking dynamic BP changes and over extended periods of time.

Sudden cardiac death, frequently due to ventricular arrhythmias, is a significant problem globally. Most affected individuals do not arrive at hospital in time for medical treatment. Therefore, there is an urgent need to identify the most-at-risk patients for insertion of prophylactic implantable cardioverter defibrillators. Clinical risk markers derived from electrocardiography are important for this purpose. They can be based on repolarization, including corrected QT (QTc) interval, QT dispersion (QTD), interval from the peak to the end of the T-wave (Tpeak - Tend), (Tpeak - Tend)/QT, T-wave alternans (TWA), and microvolt TWA. Abnormal repolarization properties can increase the risk of triggered activity and re-entrant arrhythmias. Other risk markers are based solely on conduction, such as QRS duration (QRSd), which is a surrogate marker of conduction velocity (CV) and QRS dispersion (QRSD) reflecting CV dispersion. Conduction abnormalities in the form of reduced CV, unidirectional block, together with a functional or a structural obstacle, are conditions required for circus-type or spiral wave re-entry. Conduction and repolarization can be represented by a single parameter, excitation wavelength (λ = CV × effective refractory period). λ is an important determinant of arrhythmogenesis in different settings. Novel conduction-repolarization markers incorporating λ include Lu et al.' index of cardiac electrophysiological balance (iCEB: QT/QRSd), [QRSD× (Tpeak - Tend)/QRSd] and [QRSD × (Tpeak - Tend)/(QRSd × QT)] recently proposed by Tse and Yan. The aim of this review is to provide up to date information on traditional and novel markers and discuss their utility and downfalls for risk stratification.

61Background: The Tpeak -Tend interval, an electrocardiographic marker reflecting transmural

The Rho/rho-kinase (ROCK) pathway has an important role in the pathogenesis of several cardiovascular diseases. The activation of ROCK is involved in the regulation of vascular tone, endothelial dysfunction, inflammation and remodeling. The inhibition of ROCK has a beneficial effect in a variety of cardiovascular disorders. Evidence from animal models and from clinical use of ROCK inhibitors, such as Y-27632, fasudil and statins (i.e. pleiotropic effects), supports the hypothesis that ROCK is a potential therapeutic target. This review provides a current understanding of the role of ROCK pathway in the regulation of vascular function and the use of ROCK inhibitors in the treatment of cardiovascular disorders.

Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors. Moreover, pathophysiological changes can be induced either genetically or pharmacologically to study the harmful effects of these interventions. There is no single ideal animal model, as different systems are suitable for different research objectives. A good understanding of the similarities and differences to humans enables effective extrapolation of data for translational application. In this article, we will examine the different mouse models for the study and elucidation of the pathophysiological mechanisms underlying atherosclerosis. We also review recent advances in the field, such as the role of oxidative stress in promoting endoplasmic reticulum stress, mitochondrial dysfunction and mitochondrial DNA damage, which can result in vascular inflammation and atherosclerosis. Finally, novel therapeutic approaches to reduce vascular damage caused by chronic inflammation using microRNA and nano-medicine technology, are discussed.