Invited Lecture Summary - Karger Publishers

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Invited Lecture SummarySummary I-02-I-27

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I-02Need of Noninvasive, Continuous BP Monitoring in the “Digital Hypertension” EraKazuomi KarioDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan

The synergistic resonance theory proposes that each form of blood pressure (BP) variability (beat-by-beat, diurnal, day-by-day, seasonal and yearly) with different time-phases has the potential to create dynamic surges in BP, which could coincide with peak BP and different external triggers (eg, temperature, mental stress, sleep apnea, exercise) to precipi-tate cardiovascular events, especially in patients with arterial stiffness who are less able to absorb BP surges in the periph-eral arteries (Kario, et al. Prog Cardiovasc Dis 2020;63:22-32). The optimal approach would be a wearable device that allows noninvasive cuff-less, beat-by-beat BP monitoring, with simultaneous determination of environmental condi-tions. There is therefore a need for more scientifically based and validated approaches to wearable BP technology to allow continuous monitoring of BP in an ambulatory setting. We have developed the beat-by-beat continuous BP monitoring device and Surge BP detection program with OmronHealth Inc. (Kyoto, Japan) (Kario. Hypertension. 2020;76:640-650). This devices using the applanation tonometry method have been used to monitor nighttime BP and detect BP surges that are common in patients with sleep apnea. An algorithm to detect pathological surge BP (BP surge in seconds) was developed based on beat-by-beat BP readings obtained over one night. This device detected the surge BPs and confirmed successful treatment of SGLT2 inhibitor in the hypertensive diabetic patients with obstructive sleep apnea [Figure left (before treatment) and right (after treatment)]. Before and after treatment Kario. Hypertension. 2020;76:640-650). In this session, I will introduce the up-dated data of our re-search and development on beat-by-beat BP monitoring de-vice and its clinical implication for the future management of hypertension in the era of digital hypertension.

Need of Noninvasive, Continuous BP Monitoring in the “Digital Hypertension” Era

Kazuomi KarioDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine,

Tochigi, Japan

The synergistic resonance theory proposes that each form of blood pressure (BP) variability (beat-by-beat, diurnal,day-by-day, seasonal and yearly) with different time-phases has the potential to create dynamic surges in BP,which could coincide with peak BP and different external triggers (eg, temperature, mental stress, sleep apnea,exercise) to precipitate cardiovascular events, especially in patients with arterial stiffness who are less able toabsorb BP surges in the peripheral arteries (Kario, et al. Prog Cardiovasc Dis 2020;63:22-32). The optimalapproach would be a wearable device that allows noninvasive cuff-less, beat-by-beat BP monitoring, with simultaneous determination of environmental conditions. There is therefore a need for more scientifically basedand validated approaches to wearable BP technology to allow continuous monitoring of BP in an ambulatorysetting. We have developed the beat-by-beat continuous BP monitoring device and Surge BP detection programwith OmronHealth Inc. (Kyoto, Japan) (Kario. Hypertension. 2020;76:640-650). This devices using theapplanation tonometry method have been used to monitor nighttime BP and detect BP surges that are common inpatients with sleep apnea. An algorithm to detect pathological surge BP (BP surge in seconds) was developedbased on beat-by-beat BP readings obtained over one night. This device detected the surge BPs and confirmedsuccessful treatment of SGLT2 inhibitor in the hypertensive diabetic patients with obstructive sleep apnea [Figureleft (before treatment) and right (after treatment)]. Before and after treatment Kario. Hypertension. 2020;76:640-650). In this session, I will introduce the up-dated data of our research and development on beat-by-beat BPmonitoring device and its clinical implication for the future management of hypertension in the era of digitalhypertension.

I-03Non-invasive Continuous Arterial Blood Pressure Monitoring System Using Single Chest-worn DeviceSeungman Yanga, Hee Chan Kimb

aInterdisciplinary Program in Bioengineering, The Graduate School,Seoul National University, Republic of Korea, bDepartment of Biomedical Engineering, Seoul National University College of Medicine, Republic of Korea

Objective The goal of this study is to develop a wear-able blood pressure(BP) monitoring system which facilitates non-invasive continuous arterial BP monitoring in daily life. Design and Method The developed system consists of aBP estimation model (S/W) and a chest-worn device (H/W). Clinically applicable BP estimation model was developed us-ing 2.4 million cardiac cycles of two commonly used non-in-vasive biosignals, electrocardiogram (ECG) and photoplethys-mogram (PPG) from 1376 surgical patients (Vital DB, Seoul National University Hospital, Korea). Total 28 waveform fea-tures including pulse arrival time(PAT), heart rate, and vari-ous PPG morphological parameters, were used to construct models of systolic BP(SBP) and diastolic BP(DBP) using var-ious machine learning algorithms such as linear regression, random forest, artificial neural network (ANN), and recurrent neural network (RNN). A wireless chest-worn device mea-suring ECG and PPG simultaneously was in-house fabricated and ECG and PPG data from 25 healthy subjects wearing the device in their daily life were acquired. The developed BP estimation models were then applied to this dataset after mapping the chest PPG morphology features to the corre-sponding finger PPG morphology features through an appro-priate transfer function. Results Internal dataset validationof the BP estimation models resulted in mean errors of 0.05 ± 6.92 mmHg for SBP, and 0.05 ± 3.99 mmHg for DBP. Exter-nal validation of the model using another biosignal database

Pulse 2021;9(suppl 1):1-44DOI: 10.1159/000517557 Published online: June 30, 2021

Abstracts: The Pulse of Asia 2021 Seoul

© 2021 S. Karger AG, Baselwww.karger.com/pls

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consisting of 334 intensive care unit patients (MIMIC critical Care DB) led to similar results, satisfying three standards for accuracy of BP monitors (AAMI, BHS and IEEE). Mean errors of 0.54 ± 7.47 mmHg for SBP, and 0.29 ± 4.33 mmHg for DBP were achieved in performance testing of the BP estimation models using data measured from the chest-worn device, which also satisfies three standards for accuracy of BP moni-tors. Conclusions The proposed non-invasive continuous BP monitoring system can be clinically applicable by showing acceptable performance of BP estimation errors in daily life use as a form of single wearable device.

Keywords: Noninvasive blood pressure, Continuous blood pressure monitoring, Electrocardiogram, Photoplethys-mogram

I-04Continuous Blood Pressure Monitoring by Tactile SensorJong-Mo SeoDepartment of Electrical and Computer Engineering, Seoul National University School of Engineering, Seoul National University Hospital, Republic of Korea

Arterial blood pressure (BP) measurement with catheter type pressure sensor is a gold standard for the continuous BP monitoring. However, due to its invasiveness and the risk of infection, it is adopted in operation theater or in intensive care unit. For the non-invasive continuous BP (NICBP) moni-toring, we evaluated and demonstrated that the 3D force sen-sor-based continuous BP shows good correlation with inter-mittent, noninvasive BP (NIBP). This will be especially useful in evaluating BP in patients with autonomic nervous system problem. Attachable and disposable force sensor is investi-gated recently, and this can broaden the application of NICBP avoiding risk of infection and pain. In this talk, reliability of the 3D force sensor-based NICBP during postural change will be addressed and the preliminary results of the attachable force sensor will be introduced.

I-05Continuous Monitoring of Blood Pressures Using Cuffless Device: Present and FutureHao-min Chenga,b

aDepartment of Medicine, National Yang Ming Chiao Tung University College of Medicine, Taiwan, bCenter

for Evidence-based Medicine, Taipei Veterans General Hospital, Taiwan

Objective To review the current status of continuous blood pressure monitoring using cuffless device and discuss its future directions. Background Pulse transit time (PTT) is the time delay for the pressure wave to travel between prox-imal and distal arterial sites. According to the Bramwell–Hill equation, PTT varies with the arterial compliance. Since arte-rial compliance decreases as blood pressure (BP) increases, PTT is also often inversely correlated with BP. PTT can be es-timated simply via the relative timing between proximal and distal waveforms reflecting the arterial pulse. Hence, PTT has proven to be a convenient marker of arterial stiffness and could potentially permit cuff-less BP monitoring. The conven-tional technique for estimating PTT is to detect the trough-to-trough or foot-to-foot time delay between the proximal and distal waveforms. The premise is that arterial wave reflection interference is negligible during late diastole and early sys-tole when the waveform feet occur. However, PTT varies with BP throughout the cardiac cycle, yet, because of wave reflec-tion, only one PTT value at the level of DP is conventionally estimated from proximal and distal arterial waveforms. Re-cently, we have proposed a nonlinear arterial tube-load mod-el, which is used as a technique to estimate PTT as a function of BP from proximal and distal BP waveforms. Based on the PTT principle, there have been many innovative technologies developed to measure cuffless BP. Conclusion In this talk, I will briefly introduce the current status of these new cuffless BP devices, the limitation, and the future development of this promising technique.

Keywords: Cuffless blood pressure monitoring, Pulse transit time, Blood pressure measurements

I-06Future of Arterial Stiffness Measurement, Clinical ApplicationsPierre BoutouyrieDepartment of Pharmacology, Université de PARIS, INSERM U970, Assistance Publique Hopitaux de Paris, France

Arterial stiffness is the best surrogate for vascular aging. We have put forward the notion of early vascular aging (EVA), in which subjects have arteries older than chronological age. On the opposite, subjects can be resilient to the effect of age and risk factors, and present arteries younger than chrono-logical age, called supernormal vascular aging (SUPERNOVA).

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Keywords: Central blood pressure, Cardiovascular risk, Meta-analysis, Trial

I-08Prognostic Evidence on Brachial-ankle Pulse Wave Velocity: Why It Is Better than Initially Expected? Masanori MunakataResearch Center for Lifestyle-related Disease, Tohoku Rosai Hospital, Japan

Arterial stiffness has now been well recognized as a new risk measure for cardiovascular events. Carotid-femoral (cf)PWV is a gold-standard PWV measure. However, this mea-sure has never been taken root in the general practice in Ja-pan, possibly because of methodological difficulties. Against this background, brachial-ankle (ba) PWV was developed. Measurement of this parameter is easy, and its reproducibil-ity is good. The generality and validity of the methodology is guaranteed. baPWV has been reported to consistently increase with most traditional cardiovascular risk factors. Prognostic significance has been reported in many Asian countries. We recently reported the results of an individual participant data meta-analysis including 14 673 Japanese participants. The results clearly established that baPWV is an independent predictor of the risk of cardiovascular events in Japanese subjects. Prognostic significance of baPWV was first questioned because it includes large part of leg artery, which is considered as poor prognostic value. So real world results were very different from theoretical consideration. In this symposium, I will talk about the possible reasons of why the prognostic value of baPWV is better than initial expectation.

I-09Cardiorespiratory Fitness and Vascular AgingSae Young JaeDepartment of Sport Science, University of Seoul, Republic of Korea

Healthy lifestyle is a critical component to protect from vascular aging and the age-related vascular dysfunction. Car-diorespiratory fitness is a physiological biomarker of cardio-pulmonary and muscular system integrity that is reflective of physical activity behaviors. Directly measured peak oxygen

In the present lecture, I will discuss the definition and clin-ical utility of EVA and SUPERNOVA, how we can practically measure EVA and SUPERNOVA in clinics, and what measures can be applied to correct for EVA, and promote SUPERNOVA, especially in the context of COVID pandemic. I will also pres-ent the first results from the SPARTE interventional trial, and what the next steps should be.

I-07Central Blood Pressure as a Predictor of Cardiovascular RiskYan LiShanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China

Objective High blood pressure (BP) confers cardiovas-cular risk. However, the clinical value of central BP remains uncertain. Design and Method Among 5608 participants enrolled in the International Database of Central Arterial Properties for Risk Stratification (IDCARS), 255 primary composite cardiovascular endpoints occurred during a me-dian of 4.1 years follow-up. A multicenter placebo-controlled randomized clinical trial on isolated central hypertension (ANTICIPATE, www.chictr.org.cn/ ChiCTR2000035758) has been initiated and is ongoing in China. Results The multivari-able-adjusted hazard ratios for the composite cardiovascu-lar endpoint, expressing the risk per 1-SD increment in BP, were 1.50 (95% confidence interval, 1.33-1.70) for central systolic BP, 1.36 (1.19-1.54) for central pulse pressure, 1.49 (1.33-1.67) for brachial systolic BP, and 1.34 (1.19-1.51) for brachial pulse pressure (P<0.001). Adding a central or bra-chial BP to a base model increased the model fit (P<0.001) with generalized R2 increments ranging from 0.37 to 0.74%. In the ANTICIPATE trial, 2000 patients with coronary heart disease and isolated central arterial hypertension, defined as a normal non-invasive brachial BP (<140/90 mmHg) but a high central SBP of at least 130 mmHg measured with in-vasive catheters, will be randomly assigned into the active treatment with alisartan or amlodipine besilate or to their placebos for 48 weeks. The primary composite outcome includes myocardial infarction, stroke, cardiac revasculariza-tion procedures, hospitalization due to heart failure or an-gina, or death from cardiovascular causes. Conclusions The IDCARS study indicated that increased central and peripheral BPs were all associated with adverse outcomes with a similar strength. The ANTICIPATE trial might help to elucidate the clinical value of central BP and whether controlling central BP could bring benefit to patients with coronary heart disease.

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uptake (VO2peak) during cardiopulmonary exercise testing is the gold standard for assessing cardiorespiratory fitness. Higher levels of cardiorespiratory fitness have been associat-ed with lower risk of all cause and cardiovascular mortality in healthy populations as well as patients with cardiomet-abolic diseases. Although cardiorespiratory fitness exhibits beneficial effects on traditional and nontraditional cardio-vascular risk factors, the benefit of vascular conditioning has recently been proposed as potential cardioprotective benefits of high cardiorespiratory fitness levels. Physiologically, lev-els of cardiorespiratory fitness, like vascular aging, gradually decline with advancing age, while advancing aging also leads to a deterioration of vascular structure and function. Thus, cardiorespiratory fitness is just as powerful as vascular aging in predicting cardiovascular disease, and declines of cardio-respiratory fitness with age can be considered a sign of vas-cular aging. Previous studies suggested that the association between cardiorespiratory fitness and arterial stiffness was independent of lifestyle variables. Moreover, relatively higher cardiorespiratory fitness delays the development of artery stiffness, intima-media thickening and coronary artery calci-fication with advancing age. Therefore, improving or main-taining relatively higher cardiorespiratory fitness level based on the value of age-specific VO2peak may serve as an effective approach to prevent or attenuate the age-related vascular dysfunction. In this presentation, available scientific evidence regarding the favorable role of cardiorespiratory fitness on healthy vascular aging will be introduced.

I-10Cardiovascular System and COVID-19Hae-Young LeeDepartment of internal medicine, Seoul National University College of Medicine, Republic of Korea

Objective Different hypotheses suggest a contradictory association of statins, angiotensin receptor blockers(ARBs) or angiotensin-converting enzyme(ACE) inhibitors with potential adverse or favorable effects in patients with Coronavirus disease 2019(COVID-19). This study aimed to compare the association of statins, ARB, and ACE inhibitors in COVID-19 and in pneumonia. Design and Method All patients with laboratory-confirmed COVID-19 through April 16, 2020, in Korea were retrieved. We evaluated the associ-ation of statins, ARBs, and ACE inhibitors on COVID-19-re-lated mortality within 60 days. Furthermore, a comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of patients hospitalized

with pneumonia between January and June 2019 in Korea. Lastly, meta-analysis was performed to compare the results of this study and other reports. Results The median age of the 10,448 COVID-19 patients was 45 years, and statins, ARBs and ACE inhibitors were prescribed in 533 (5.1%), 1,231(11.8%) and 47(0.4%) patients, respectively. As of April 24, 228 patients (2.2%) succumbed to death. After adjusting age, sex, residential area, the history of comorbidities, Cox regression showed significant decrease in HR by 36% asso-ciated with statin use (HR 0.635, 95% CI 0.424 – 0.951, p = 0.0274). However, ARBs group showed neutral association (HR 1.034, 95% CI 0.765 – 1.399, p = 0.8270) and ACE inhib-itor groups showed insignificant results mainly due to small sample size (HR 0.736, 95% CI 0.314 – 1.726, p = 0.4810). When comparing the HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019, the trend of statins and ACE inhibitors showed similar benefit, whereas the protective effect of ARBs observed in the retrospective cohort was lost in the COVID-19 patients. Meta-analysis including the results of this study showed significant benefit of statins and ACE inhibitors, whereas neutral association with ARBs and the mortality. Conclusions Statins were associated with signifi-cantly lower mortality of COVID-19, consistent with usual pneumonia patients. While ARBs or ACE inhibitors were not associated with fatal outcome, the possible beneficial effect of ARBs observed in usual pneumonia was attenuated in COVID-19.

Keywords: COVID-19, Statin, Angiotensin receptor blocker, Angiotensin converting enzyme inhibitor, Mortality

I-11Long Term Sequale on COVID-19In-Cheol KimDivision of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea

Objective In 2021, accumulated coronavirus disease 2019 (COVID-19) confirmed cases exceeded 100 million worldwide. We sought the long term sequale on COVID-19. Design and Method Although there is a hope for vaccina-tion, continuous infection is observed with case fatality rate over 2%. Patients with cardiovascular disease are more sus-ceptible to COVID-19 and show more severe clinical course after the infection. COVID-19 related myocardial injury evidenced by increased troponin plasma levels occur in at

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Syndrome (TTS)” in scientific term. Unreasonable fears and myths is widely reported in Korean journals about this very rare side effect. The most important issue about this unrea-sonable fear is improper use of terminology for blood clots or thrombosis. In this presentation, I will explain the exact meaning of this TTS in Korea.

I-14US Update on Arterial StiffnessRaymond R. TownsendDepartment of Medicine, University of Pennsylvania, USA

Objective The goal of this presentation is to provide an informational update on the field of large artery stiffness building on the prior 2015 American Heart Association Sci-ence Statement. Design and Method In this presentation three areas are covered: what hypertension guidelines cur-rently recommend regarding large artery stiffness, studies of how stiffness can alter cardiovascular risk classification, and a brief overview of recent publications of interventions that impart large artery stiffness. Results Global hypertension guidelines acknowledge arterials stiffness as a reflection of target organ damage, but are mixed, or silent, in their recom-mendations about the role of assessment of arterial stiffness in clinical practice. Measurements of pulse wave velocity reclassify about 10-15% of patients particularly those with intermediate (~10% 10yr risk of an event) cardiovascular risk. Interventions include diet, exercise, medications and renal denervation. Reductions in arterial stiffness are mainly less than 1 meter/sec of carotid-femoral pulse wave velocity, with similar magnitude reductions in brachial-ankle pulse wave velocity. Diet interventions involve alteration of min-eral intake (sodium and potassium) and the Atlantic Diet. Exercise includes aerobic, resistive and combined aerobic-re-sistive approaches. Medication interventions include statins, antihypertensives, anti-inflammatory agents for rheumatoid arthritis, and SGLT2 inhibitors. Renal denervation has main-ly been with radiofrequency ablation. Conclusions Arterial stiffness measurements provide independent prediction of cardiovascular events and complement office blood pressure readings in this regard. Recommendations to use stiffness measurements in office-based evaluations of hypertension and cardiovascular risk assessment remain scant, partially due to the challenge of demonstrating the value of reducing stiffness independently of reducing blood pressure. Howev-er, an increasing number of interventions are using large ar-tery stiffness measurements as an outcome, and we continue to hope that interest in this important area of measurement

least 10% of hospitalized patients and 25% to 35% or more, of critically ill patients. Patients with SARS-CoV-2 infection related cardiac complications are heart failure, arrhyth-mia, acute thrombosis, and stress induced cardiomyopathy. Results Myocardial injury is an important entity that cause long term sequale. The extent of the local tissue damage and cytokine storm triggered by the host immune response both contribute to the severity of the myocarditis. An exag-gerated inflammatory response can be extremely fatal, and immunomodulators such as corticosteroids are considered in selected cases even though the efficacy and safety is ques-tionable. Combined with these mechanisms related to a host immune response, multiple factors are responsible for the cardiac consequence of COVID-19, such as an oxygen supply and demand imbalance (with or without coronary artery dis-ease), increased right ventricular afterload due to respiratory acidosis, hypoxemia and positive pressure ventilation. Even though it is difficult to discriminate all the possible mecha-nisms related to myocarditis, accordingly the effort to iden-tify the dominant cause is necessary for the selection of the proper target treatment. Conclusions Substantial evidence has suggested a non-negligible incidence of cardiac injury re-lated to COVID-19. Although the clinical significance and ex-act mechanisms are under investigation, we should be aware of the potentially fatal cardiac manifestations when dealing with patients with COVID-19. Long-term complications are also noticed from the recent publications and need further attention.

Keywords: COVID-19, Myocarditis, Sequale, Myocardial injury

I-12Adverse Effects on COVID-19 Vaccination: Myth or Fact?Sang Hoon NaDepartment of Internal Medicine, Seoul National University Hosipital, Republic of Korea

In the pandemic era, we have started use the vaccination to prevent COVID-19 infection 3-4 months ago. COVID-19 vaccinations may have some unexpected adverse effects in the same as other all medications. In Europe, unusual blood clot after Astrazeneca COVID-19 vaccination (AZ vaccine) were reported to European Medical Agency (EMA) on early March. On 7th April 2021, EMA has declared this event “pos-sible side effect of AZ vaccine’. The name of this very rare side effect is known as blood clots with low platelet count in common term, and “Thrombosis with Thrombocytopenia

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will continue to develop.

Keywords: Large artery stiffness, Arterial compliance, High blood pressure, Cardiovascular risk, Epidemiology

I-15Fighting Vascular Disease: Thoughts about 2022 Taiwan Hypertension GuidelinesTzung-Dau WangDepartment of Internal Medicine, National Taiwan University Hospital, Taiwan

The upcoming 2022 Taiwan Hypertension Guidelines emphasize the importance of risk-based blood pressure man-agement approach. We agree that blood pressure target of <130/80 mmHg is adequate for all hypertensive patients ex-cept those at low-moderate risk (with <3 risk factors and no organ damage). To obtain more accurate assessment of blood pressure profiles, home blood pressure monitoring will be recommended as the foundation throughout all phases of blood pressure management, from diagnosis to long-term care. The diagnosis of hypertension (<130/80 mmHg) should be based on results of home blood pressure monitoring, con-ducted according to the “722” rule. Details of recent progress and the new Taiwan Hypertension Guidelines will be intro-duced during the Talk.

I-16Nanomedicine for the Treatment of AtherosclerosisJi-Ho ParkDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Republic of Korea

Atherosclerosis is a chronic inflammatory disease that progresses with the accumulation of interrelated cholesterol crystals (CC) and macrophages in the arterial wall. These are not only the main components of atherosclerotic plaques, but also key inflammation-triggering sources that promote their own accumulation. However, existing therapeutics have not achieved effective removal of both CC and macrophages from plaques for the treatment of atherosclerosis. In this lecture, I will introduce a new class of nanomedicine that delivers the anti-inflammatory drug to plaques and carries away

cholesterol from there at the same time for effective anti-ath-erosclerosis therapy. In mouse models of atherosclerosis, systemically injected nanomedicine accumulates preferen-tially in atherosclerotic plaques and significantly reduces the amount of cholesterol crystals and the number of macro-phages, thus leading to inhibition of atherosclerotic plaque development and regression of the established plaques. I believe that this nanomedicine offers a powerful therapeutic option for the treatment of atherosclerosis.

I-17Quantification of Hemodynamic Parameters Using 4D Flow MRIHojin HaDepartment of Mechanical and Biomedical Engineering, Kangwon National University, Republic of Korea

Objective The purpose of this presentation is to discuss recent advances in 4D Flow MRI. This briefly overviews the principles and procedures of 4D Flow MRI. Later it intro-duces various fluid dynamic biomarkers that can be used for hemodynamic assessment. Lastly, clinical applications in various cardiovascular diseases will be discussed. Design and Method Time-resolved and three-dimensional char-acterization of blood flow using 4D Flow MRI has achieved considerable progress in recent years. Various fluid dynamic biomarkers for possible clinical usage are also described, including wall shear stress, turbulent kinetic energy, and relative pressure. Results 4D Flow MRI has been improved by the rapid development of sequence, reconstruction, and post-processing techniques. Multidirectional velocity flow measurement with volumetric acquisition enables various retrospective analyses, which might be useful in clinical prac-tice. Multidisciplinary researchers have developed several potential biomarkers based on fluid dynamics, and these bio-markers are being validated in various clinical investigations. Conclusions While 4D Flow MRI is still being used only for research purposes, it will no doubt soon be available for rou-tine clinical applications as the clinical evidence accumulates.

Keywords: 4D Flow MRI, 3D Phase Contrast MRI

I-18Direct Thrombus ImagingDong-Eog KimDepartment of Neurology, Dongguk University Ilsan

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a living animal model in real time in vivo. Briefly, intravital microscopic imaging of various organs will be introduced. Based on direct imaging of rapidly flowing individual cells in pulmonary and cardiac microcirculation, we newly derived the functional capillary ratio (FCR) as a quantitative param-eter for assessing the in vivo function of microvasculature in various organs. In a murine model of sepsis-induced acute lung injury, the intravital imaging revealed that a prolonged neutrophil entrapment within the capillaries and cluster for-mation induced the generation of dead space and decreased FCR. The circulating neutrophils had an extended seques-tration time and showed an arrest-like dynamic behavior. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved the hypoxemia in vivo. This imaging method can serve as a useful tool for investigating pathophysiology of pulmonary and cardiac diseases with dis-turbed microcirculation and evaluating potential treatments.

Keywords: Intravital microscopy, Confocal microscopy, Two-photon microscopy, Microcirculation, In vivo imaging

Real-time Intravital Microscopy for Visualization of Microcirculation

Pilhan Kim1,2,3

1Graduate School of Medical Science and Engineering, KAIST, Republic of Korea 2Graduate School of Nanoscience and Technology, KAIST, Republic of Korea

3KI Institute for Health Science and Technology, KAIST, Republic of Korea

Intravital microscopy can visualize various in vivo cellular-level dynamics such as cell trafficking, cell-to-cell or cell-to-microenvironment interactions in a living animal. Intravital imaging of pathophysiological cellular dynamics in natural in vivo microenvironment in various preclinical animal model can provide an unprecedented insight in the dynamic processes of human diseases beyond conventional static observation of histological sample or in vitro culture sample. Additionally, it can accelerate the development of new therapeutics and diagnostics by providing improved accuracy and reliability in in vivo validation with delivery monitoring and efficacy assessment. During the last decade, intravital microscopy has become a highly valuable, indispensable technique in wide areas of biomedical sciences such as immunology, neuroscience, developmental and tumor biology. In this talk, a custom-built video-rate laser-scanning intravital confocal and two-photon microscopy system will be introduced, which can acquire the multi-color microscopic fluorescence images with sub-micron resolution in a living animal model in real time in vivo. Briefly, intravital microscopic imaging of various organs will be introduced. Based on direct imaging of rapidly flowing individual cells in pulmonary and cardiac microcirculation, we newly derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the in vivo function of microvasculature in various organs. In a murine model of sepsis-induced acute lung injury, the intravital imaging revealed that a prolonged neutrophil entrapment within the capillaries and cluster formation induced the generation of dead space and decreased FCR. The circulating neutrophils had an extended sequestration time and showed an arrest-like dynamic behavior. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved the hypoxemia in vivo. This imaging method can serve as a useful tool for investigating pathophysiology of pulmonary and cardiac diseases with disturbed microcirculation and evaluating potential treatments. Keywords: Intravital microscopy, Confocal microscopy, Two-photon microscopy, Microcirculation, In vivo imaging

I-20Imaging Based Diagnosis and Treatment on Lymphatic Flow DisordersJi Hoon ShinDepartment of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Republic of Korea

Objective To present imaging based diagnosis and treatment on lymphatic flow disorders. Design and Meth-od Based on conventional and MR lymphangiography, many cases of lymphatic flow disorders have been treated using interventional techniques. Results Lymphatic flow disor-ders can be largely divided into 1) lymphedema secondary to disturbance and damage to the lymphatic system and 2) lymphatic flow leakage. Lymphatic leakage is mainly mani-fested with chylothorax and chylous ascites, and there may be lymphocutaneous fistula, chyluria, and vaginal leakage. In addition to X-ray (conventional) lymphangiography, advanc-

Hospital, Republic of Korea

There is a need for imaging methods to better triage pa-tients with acute stroke for tissue plasminogen activator-me-diated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thrombo-emboli. Currently, magnetic resonance or computed tomog-raphy angiography visualizes the obstruction of blood flow within the vessel lumen rather than the thrombus itself. The present visualization method, which relies on observation of the dense artery sign (the appearance of cerebral thrombi on a non-enhanced computed tomography, suffers from low sensitivity. When translated into the clinical setting, direct thrombus imaging is likely to enable individualized acute stroke therapy by allowing clinicians to detect the thrombus with high sensitivity, assess the size and nature of the throm-bus more precisely, serially monitor the therapeutic effects of thrombolysis, and detect post-treatment recurrence.

I-19Real-time Intravital Microscopy for Visualization of MicrocirculationPilhan Kima,b,c

aGraduate School of Medical Science and Engineering, KAIST, Republic of Korea, bGraduate School of Nanoscience and Technology, KAIST, Republic of Korea, cKI Institute for Health Science and Technology, KAIST, Republic of Korea

Intravital microscopy can visualize various in vivo cel-lular-level dynamics such as cell trafficking, cell-to-cell or cell-to-microenvironment interactions in a living animal. Intravital imaging of pathophysiological cellular dynamics in natural in vivo microenvironment in various preclinical animal model can provide an unprecedented insight in the dynamic processes of human diseases beyond conventional static observation of histological sample or in vitro culture sample. Additionally, it can accelerate the development of new therapeutics and diagnostics by providing improved accuracy and reliability in in vivo validation with delivery monitoring and efficacy assessment. During the last decade, intravital microscopy has become a highly valuable, indis-pensable technique in wide areas of biomedical sciences such as immunology, neuroscience, developmental and tumor biology. In this talk, a custom-built video-rate laser-scanning intravital confocal and two-photon microscopy system will be introduced, which can acquire the multi-color micro-scopic fluorescence images with sub-micron resolution in

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es in MR lymphangiography allow overall evaluation of the location of leakage and central lymphatics before interven-tion. In particular, contrast-enhanced MR lymphangiography provides dynamic information. In the case of chylothorax, the antegrade approach to the cisterna chyli is traditionally used, and retrograde transvenous access and pleural access are also possible. In the case of chylous ascites, in addition to the direct percutaneous approach, there is a reversed approach, which is accessed through lymphatic fluid collection, and transhepatic or mesenteric embolization may be required. The addition of embolization improves the clinical success in resolving lymphatic leakages, especially in patients with chy-lothorax and more severe leakages. Conclusions Most lym-phatic flow disorders can be diagnosed and interventionally treated.

Keywords: MR lymphangiography, Chylothorax, Chylou-sascites, Interventional treatment

I-21Aortic Stiffness and Subclinical Left Ventricular DysfunctionChi Young ShimDivision of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

Aortic stiffness is closely related with subclinical left ventricular dysfunction. Increased central systolic blood pressure results in increasing LV afterload and makes myo-cyte hypertrophy and impaired relaxation. Simultaneously, central aortic diastolic blood pressure decreases. It reduces coronary perfusion and induces subendocardial ischemia and fibrosis. These adverse effects finally lead to left ventricular diastolic dysfunction and longitudinal systolic dysfunction. Therefore, increased arterial stiffness is now considered a principal contributor to the pathophysiology of heart failure with preserved ejection fraction. It also has been suggested the potential additive value of pulsatile arterial hemodynam-ic evaluation for the diagnosing heart failure with preserved ejection fraction. For a decade, there have been many studies on arterial stiffness and LV diastolic function. In this lecture, we will review the results of several clinical research about aortic stiffness and subclinical LV dysfunction.

Keywords: Aortic stiffness, Left ventricle, Subclinical Dysfunction

I-22Fatty Liver Index (FLI) and Cardiovascular DiseaseJang Young KimDepartment of Cardiology, Wonju College of Medicine, Yonsei University, Republic of Korea

Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), whether NAFLD predicts future CVD events, especially CVD mortality, remains uncertain. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACEs) in a large population-based study. We identified 3,011,588 subjects in the Korean National Health Insurance System cohort without a history of CVD who underwent health examinations from 2009 to 2011. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. A Cox proportional hazards regression analysis was performed to assess association between the FLI and the primary endpoint. During the median follow-up period of 6 years, there were 46,010 cases of MACEs (7148 cases of cardiovascular death, 16,574 of non-fatal MI, and 22,288 of ischemic stroke). There was a linear association between higher FLI values and higher incidence of the prima-ry endpoint. In the multivariable models adjusted for factors, such as body weight and cholesterol levels, the hazard ratio for the primary endpoint comparing the highest vs. lowest quartiles of the FLI was 1.99 (95% confidence interval [CIs], 1.91–2.07). The corresponding hazard ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9–2.06), 2.16 (2.01–2.31), and 2.01 (1.90–2.13), re-spectively (p < 0.001). In conclusion, our findings indicate that the FLI, which is a surrogate marker of NAFLD, has prognostic value for detecting individuals at higher risk for cardiovascular events.

I-23A Cohort Study of Resistant Hypertension in KoreaSungha ParkDivion of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Republic of Korea

Resistant hypertension is defined as blood pressure

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resistant hypertension in the future.

Keywords: Resistant hypertension, Cohort study, Uncon-trolled hypertension, Blood pressure

I-24Clinical Outcome in Patients with Deep Vein ThrombosisSung-Ai KimDepartment of Cardiology, Hallym Sacred Heart Hospital, Republic of Korea

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a major health problem in the World. DVT is a frequent cause of mor-bidity among hospitalized patients who underwent surgical interventions. Approximately 25% to 50% of patients who have DVT might develop post-thrombotic syndrome resulting in impaired quality of life. PE is often diagnosed in patients with lower limb DVT. However, silent PE can develop in up to 50% of those patients. In a necropsy-based study, fatal PE (10% of total hospital deaths) was found to be related to nonsurgical illness (mainly acute infection) in 75% of PE-re-lated deaths. The established risk factors for VTE include advanced age, prolonged immobility, cancer, major surgery, severe trauma, prior VTE, chronic heart failure, pregnancy, use of contraceptive pills, and hormone replacement therapy. DVT is associated with high health care costs and a high rate of recurrence. Older adults are particularly at risk of develop-ing DVT and its complications, including PE and post-throm-botic syndrome with the risk of DVT estimated to double for each 10-year increase in age after age 50 years. Because of its life-threatening consequences, and yet availability of effective preventive measures, DVT has been cited as one of the most treatable diseases and preventable causes of death. There have been medical advancements in the diagnosis and treatment of DVT since key clinical trials were published in the late 1990s that have the potential to improve patient outcomes. For instance, widespread application of diagnostic tests helps identify DVT more quickly and with greater validi-ty. Moreover, findings from randomized trials have made DVT treatment at home or in outpatient settings a possibility for many patients. This may be particularly important for older adults as hospital admission poses a greater risk of adverse event and iatrogenic disease, including psychomotor and so-cial consequences. Recently, the adjusted DVT hospitalization rate decreased by nearly 35%. There are several hypotheses to account for this decrease. First, changes in clinical practice

(BP) above target BP despite the concurrent use of three or more antihypertensive drugs including diuretics, and also includes patients whose BP achieves target values on four or more antihypertensive drugs. The prevalence of resistant hypertension is known to be 10-20% of all hypertensive patients. Since the risk of cardiovascular disease in patients with resistant hypertension is higher than in patients with non-resistant hypertension, thorough identification of causes and blood pressure control should be needed. However, there are very few relevant studies for preventive management, di-agnosis, and treatment for patients with resistant hyperten-sion in Korea. Therefore, in 2018, a cohort study of patients with resistant hypertension was started with the support of research funding from the Korea Disease Control and Pre-vention Agency to create evidence for the proper diagnosis and management of resistant hypertension. Twelve domestic university hospitals participated in this study and enrolled patients over 20 years of age with resistant hypertension. An-thropometric data, medical history, medication information, the results of laboratory tests for evaluating target organ damage were collected. Patients were asked to answer ques-tionnaires regarding lifestyle, psychological status, and cog-nitive function. In addition, investigator-reported causes of resistant hypertension were collected. During the follow-up period, office BP, 24-hour ambulatory BP, and home BP were measured regularly, and the occurrence of clinical events was investigated. From 2018 to 2020, a total of 806 patients were enrolled, and 757 were followed up. The mean follow-up pe-riod was 504 ± 251 days (median 519 [IQR 282-701] days). When discrimination was made after 12 months of follow-up, 13.6% were classified as pseudo-resistant hypertension, 11.2% were classified as secondary hypertension, and 75.2% were diagnosed as true resistant hypertension. The average age of patients with resistant hypertension was 60 years old. Most of them were obese. Dyslipidemia was the most prev-alent comorbidity, followed by diabetes. Spironolactone as a fourth-line drug for resistant hypertension is recommended, but beta-blocker was more widely used in Korea. When the office BP threshold was 140/90 mmHg, among the subjects with controlled BP with 4 or more agents, 64% of patients with resistant hypertension were classified as masked un-controlled hypertension. Since the prognosis of masked un-controlled hypertension is comparable to that of sustained uncontrolled hypertension, out-of-office BP measurement is necessary to control BP in patients with resistant hyperten-sion. Reviewing the results of the one-year follow-up study, BP of patients with resistant hypertension enrolled in this cohort decreased. It may be due to the improvement in the physician’s inertia and the patient’s awareness of hyperten-sion through this study. The achievements of this study are expected to be widely used in the treatment and research of

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advocated for outpatient rather than inpatient management of deep vein thrombosis, including full outpatient manage-ment or earlier hospital discharge. The length of hospital stay for DVT decreased from 1999 to 2010, and the proportion of patients discharged to home decreased with more patients discharged to skilled nursing facilities in aging groups. Sec-ond, prevention efforts specific to DVT could have contribut-ed to a decrease in new adverse events and thereby the DVT hospitalization rate over time. For instance, health promotion education efforts may have informed older adults about the signs and symptoms of DVT, thus encouraging patients to avoid prolonged sedentary periods. Further, increased utili-zation of pharmacological prophylaxis, coincident with the widespread use of electronic medical records that encom-pass frequent VTE prophylaxis alerts, may have contributed to lower rates of DVT during other hospitalizations or post discharge, and thereby lowering the rates of subsequent hos-pitalizations for DVT.

*Predictors of overall mortality in patients with acute symptomatic pulmonary embolism

signs and symptoms of DVT, thus encouraging patients to avoid prolonged sedentary periods. Further,

increased utilization of pharmacological prophylaxis, coincident with the widespread use of electronic

medical records that encompass frequent VTE prophylaxis alerts, may have contributed to lower rates

of DVT during other hospitalizations or post discharge, and thereby lowering the rates of subsequent

hospitalizations for DVT.


** Clinical outcome of deep vein thrombosis


signs and symptoms of DVT, thus encouraging patients to avoid prolonged sedentary periods. Further,

increased utilization of pharmacological prophylaxis, coincident with the widespread use of electronic

medical records that encompass frequent VTE prophylaxis alerts, may have contributed to lower rates

of DVT during other hospitalizations or post discharge, and thereby lowering the rates of subsequent

hospitalizations for DVT.



REFERENCES1. Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP

et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4:4693-4738.

2. Nishiwaki S, Morita Y, Yamashita Y, Morimoto T, et al. Impact of no, distal, and proximal deep vein thrombo-sis on clinical outcomes in patients with acute pulmonary embolism: From the COMMAND VTE registry. J Cardiol. 2021;77:395-403

3. van Rij AM, Hill G, Krysa J, Dutton S, et al. Prospective study of natural history of deep vein thrombosis: early pre-dictors of poor late outcomes. Ann Vasc Surg. 2013;27:924-31.

4. Bauersachs RM.Bauersachs RM. Best Pract Res Clin Haematol. Clinical presentation of deep vein thrombosis and pulmonary embolism. 2012;25:243-51.

I-25Analysis of Plasma and Fat Tissue Omics in Patients with Atherosclerosis and DiabetesSung Hee ChoiDepartment of Internal Medicine, Seoul National University Bundang Hospital, Republic of Korea

Ectopic fat depots, such as visceral or pericardial fat, be-cause it is important key feature of many metabolic diseases including diabetes and cardiovascular diseases. In humans. There were many studies that higher amounts of ectopic fats are significantly associated with altered metabolic parame-ters. Despite their pathological significance, proteomic and lipodomic analysis of human adipose tissue that characterize their functions and are associated with metabolic diseases were lacking. We want to find the pathological difference of human ectopic fat proteomes and plasma proteome markers in non-DM and T2DM patients with coronary artery disease (CAD).

I-26Sox17 Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met SignalingChan Soon Parka, Jun-Bean Parkb, Ralph Schermulyc, Injune Kima

aGraduate School of Medical Science and Engineering, KAIST, Republic of Korea, bDepartment of Internal Medicine, Seoul Natl University College of Medicine, Republic of Korea, cDepartment of Internal Medicine, Justus-Liebig University Giessen, Germany

Objective Pulmonary arterial hypertension (PAH) is characterized by molecular heterogeneity and complicated pathology in multiple tissues, and remains incurable without general therapeutics. In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggest-

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ed as one of the causal genes of PAH. However, the functional impacts and acting mechanisms of impaired Sox17 pathway in the pulmonary endothelial cells (ECs) remain unexplored. Design and Method To know the role of Sox17 in PAH de-velopment, we deleted endothelial Sox17 in adult mice and maintained them under hypoxia for 3 weeks for triggering PAH. PAH phenotypes were evaluated by assessing vascular pathology, inflammation, and cardiac remodeling. Pulmonary arterial pressure was measured using intracardiac hemody-namic catheter. For transcriptomic profiling, we performed in vivo RNA sequencing using endothelial-specific RiboTaq sys-tem. We examined explanted lung tissues from PAH patients and control subjects. Results In adult mice, Sox17 deletion from ECs did not induce PAH spontaneously, but hypox-ia-triggered PAH with high penetrance and severity. This PAH featured hypermuscularization and EC hyperplasia in lung arterioles, pulmonary inflammation, right ventricular hyper-trophy, and elevated pulmonary arterial pressure persistent even after long rest in normoxia. Mechanistically, transcrip-tomic profiling predicted activation of c-Met signaling in Sox17-deficient lung ECs under hypoxic stress. Importantly, hepatocyte grow factor (HGF), a ligand of c-Met, was upreg-ulated in Sox17-deficient lung ECs. Pharmacologic inhibition of c-Met together with a vasodilator effectively attenuated and reversed pulmonary cardiovascular pathology. In line with our findings, Sox17 levels were repressed in pulmonary ECs in a substantial fraction of PAH patients compared with non-PAH controls. HGF levels in pulmonary arterioles were increased in 13 of 15 PAH patients as seen in the mouse models. Conclusions Here, we demonstrated that the down-regulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to a hy-poxic environment. Our findings further suggest the reactive upregulation of HGF/c-Met signaling as a novel druggable target for PAH treatment.

Keywords: Pulmonary arterial hypertension, Sox17, HGF, c-Met signaling

I-27Cardiovascular Benefits of SGLT-2 InhibitorJiwon SeoDepartment of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Republic of Korea

Multiple trials have demonstrated that sodium-glucose co-transporter-2 (SGLT-2) inhibitor reduced the combined risk of cardiovascular death or hospitalization for heart

failure in patients with heart failure with reduced ejection fraction. Both empagliflozin and dapagliflozin treatment have shown significantly reduced left ventricular (LV) mass in pa-tients with type 2 diabetes and left ventricular hypertrophy. Although the actual mechanism responsible for these benefi-cial effects are not completely clear, Accumulating evidences taking a bedside-to-bench approach, have suggested several potential theses to explain the cardioprotective effects of SGLT-2 inhibitor, which included diuresis/natriuresis, blood pressure reduction, prevention of ischemia/reperfusion injury, inflammation reduction, and suppression of fibrosis. In an animal study, treatment with the SGLT-2 inhibitor im-proves cardiac diastolic function, cardiac interstitial fibrosis, cardiomyocyte hypertrophy, intermyofibrillar ultrastructure in the diabetic mouse. SGLT-2 inhibitors have been shown to reduce the cardiac workload by decreasing plasma volume and to have the cardioprotective effects of erythropoietin by SGTL-2 inhibition in clinical studies. Recently, improvement of LV diastolic function after SGLT-2 inhibitor treatment for 24 week compared with that of placebo treatment in pa-tients with diabetes and diastolic dysfunction was reported. In this study, LV diastolic function was assessed by supine bicycle diastolic exercise stress chocardiography. A post-hoc subgroup analysis of the CANVAS programme suggested that canagliflozin may reduce the rates of HFpEF hospitalisation or mortality events and DECLARE-TIMI 58 study also found a signal for reduced risk of hospitalisation for HFpEF. The ongoing DELIVER study and EMPEROR-Preserved are evalu-ating the use of SGLT-2 inhibitors specifically in people with heart failure with preserved ejection fraction (HFpEF). As there are very limited weapons against HFpEF, the results of these two trials are very promising. Although the actual mechanism responsible for cardiovascular beneficial effects is not completely clear, SGLT-2 inhibitor has been established as a heart medication. To maximize the beneficial effects on the cardiovascular system, an effort to synthesize and pri-oritize the mechanisms related to clinical event reduction is required.

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Featured Scholar Invited Lecture SummaryFI-01-FI-05

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FI-01Basic Concepts and New Evidence of Vascular BiomarkersAlberto AvolioDepartment of Biomedical Sciences, Macquarie University, Australia

One of the most basic features of the circulation is the beating of the heart, which is the fundamental sign of life. It is also responsible for pulsatile phenomena of blood pressure and flow in the arterial vasculature. In describing arterial func-tion, vascular biomarkers are associated with the interaction of vascular properties and the pulsatile function of the heart. This presentation will address underlying hemodynamic concepts involved in relationships of pulsatile pressure and flow and arterial stiffness. Pulse propagation phenomena will be discussed in the context of effect of pulsatile stress on the vasculature and effects in organs of high flow. Vascular bio-markers will be assessed in terms of relationships of pulsatile pressure in the central aorta and peripheral arteries and pres-sure-dependent and pressure independent indices of arterial stiffness. In relation to pulsatile stress on the vasculature affecting organ function, novel experimental evidence will be presented that suggests that cyclic mechanical stretch on cere-bral vascular endothelial cells can potentiate expression of the amyloid precursor protein, thus establishing a possible link between large artery function, arterial stiffness and pulsatility with potential vascular causes of cognitive impairment and dementia.

FI-02Implication of 24-hour Central Blood Pressure MonitoringJinho ShinDivision of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea

Central blood pressure was the key component of phys-ical stress causing major target organs in hypertension. It is more strongly associated with hypertension mediated organ damages than brachial blood pressure. Recently, ambulatory central blood pressure measurement was made possible in clinical practice. But its clinical implications are not estab-lished with some controversies to be resolved. Firstly, the physical principles for measurement of ambulatory central

BP were established by ARC-Solver algorithm, which was de-rived from Navier-Storkes equations. But clinical validation might not be sufficient at the moment. Secondly, the protocol issues for central blood pressure measurement can be chal-lenging because it should be measured at resting state at least for 10~20 minutes, preferably on a fasting state. How to interpret central BP measured in ambulatory states is not known yet. With this respect, if central BP measured during sleep could represent the resting state should be studied fur-ther. Thirdly, the normal reference value issue has not been resolved yet. Nevertheless, those limitations, some clinical studies showed that changes in ambulatory central BP, specif-ically, nocturnal one was contributing the changes in vascular stiffness.

Keywords: Blood pressure monitoring, Hypertension, Diagnosis, Vascular stiffness, Target organ damage

FI-03Antihypertensive Treatment and Arterial StiffnessJiguang WangThe Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China

We recently investigated effects of various antihyperten-sive drugs on arterial stiffness as assessed by brachial-an-kle pulse wave velocity (PWV). In a 12-week randomized multicenter study, brachial-ankle PWV was significantly reduced by the valsartan/amlodipine 80/5 mg combination (n=59, -1.1±0.3 m/s, P<0.0001) but not nifedipine GITS 30 mg (n=59, -0.5±0.3 m/s, P=0.06). The mean ambulatory systolic/diastolic blood pressure (BP) reductions tended to be a few mmHg greater in the valsartan/amlodipine than nifedipine group. The changes in PWV were associated with that in ambulatory systolic BP and pulse pressure in the nifedipine (P≤0.0008) but not valsartan/amlodipine group (P≥0.57), with a significant interaction (P≤0.045). In anoth-er trial of double-blind design, treatment with lacidipine (4–6 mg, n=109) or amlodipine (5–7.5 mg, n=109) for 20 weeks reduced PWV similarly (-1.98±0.45 vs. -1.74±0.44 m/s, P=0.45). These two drugs also similarly reduced clinic and ambulatory BP. In both groups, the treatment-induced chang-es in PWV were associated with that in clinic and ambulatory systolic and diastolic BP (P≤0.007). Taken the results of these two studies together, it appears that antihypertensive treat-ment with the use of a calcium channel blocker alone or in combination with an angiotensin-receptor blocker reduces arterial stiffness, with a greater effect for the combination.

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FI-04Central Blood Pressure and Pressure Wave Reflection in Cardiovascular Abnormalities: Do Not Put Them in ShadeHirofumi TomiyamaDepartment of Cardiology, Tokyo Medical University, Japan

Background In PubMED, the number of articles hit by “pressure wave reflection” is smaller as compared that hit by “pulse wave velocity”. Question Is pulse wave velocity enough for cardiovascular risk assessment related to arterial stiffness/pulse pressure hemodynamics? Main talk Pres-sure wave reflection and pulse wave velocity are differently association with the elevation of systolic and diastolic blood pressure. Summary 1. Augmentation index has limitations to assess pressure wave reflection from peripheral. 2. Even so, pulse wave velocity may not be enough to assess abnormal hemodynamics in arterial tree. 3. The combination of aug-mentation index with pulse wave velocity may provide some useful information for cardiovascular abnormalities. 4. In-creased augmentation index without accompanying increase in pulse wave velocity is related to elevation of diastolic blood pressure and its development.

Keywords: Pressure wave reflection, Pulse wave veloci-ty, Diastolic blood pressure

FI-05Association between Excess Pressure and Cognitive Function among Elderly PopulationChen-Huan ChenNational Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan

Systemic large arteries may be a crucial mediator be-tween vascular health and cognitive function decline with ag-ing. Carotid-femoral pulse wave velocity (cf-PWV) estimates mainly the reservoir function of descending aorta and has been inconsistently associated with cognitive dysfunction. In contrast, arterial reservoir-wave analysis integrates both reservoir and conduit function of the systemic arterial tree. According to the reservoir-wave model, reservoir pressure is determined by the aortic volume change during a cardiac cy-cle, and excess pressure is the summation of the forward and backward pressure waves. Excess pressure integral (XSPI) calculated from excess pressure quantifies the redundant

and detrimental arterial hemodynamic load to the left ven-tricle. Previous studies have shown that various parameters derived from the reservoir-wave analysis are associated with cardiovascular events and mortality in both high-risk indi-viduals and general populations. Whether reservoir-wave analysis is useful in investigating the relationship between vascular aging and cognitive dysfunction remains unknown. In our community-based study, XSPI was consistently and significantly associated with cognitive dysfunction after adjusting for covariates. In contrast, none of other systemic arterial function parameters, including cf-PWV, were sig-nificantly associated with cognitive dysfunction. Our study results suggest that XSPI from the reservoir-wave analysis may be a useful indicator in elucidating the mechanisms of age-related cognitive dysfunction.

Keywords: Arterial stiffness, Reservoir function, Excess pressure, Cognitive dysfunction

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Oral Abstracts

Outstanding Abstracts

O-01 Carotid-femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the ElderlyDe-Wei An (China)

O-02 Associations between Arterial Aging and Muscle-to-fat Ratio among Middle-aged and Older Adults: Results from the Longitudinal Aging Study of TaipeiHsin-Yu Liu (Taiwan)

Moderated Session

O-03 Visceral Adipose Tissue, Coronary Artery Calcification and Heart Failure: A Moderated Mediation AnalysisChun-Wei Lee (Taiwan)

O-04 Ambulatory Pulse Pressure Components and Ambulatory Arterial Stiffness Index in Chinese OutpatientsMingxuan Li (China)

O-05 Early and Supernormal Vascular Aging: Associations with Cognitive Dysfunction in a Community-based Healthy PopulationChen-Hua Lin (Taiwan)

O-06 Comparison of Vascular Characteristic Impedance Estimation in Time Domain or Frequency DomainAudrey Adji (Australia)

O-07 Moderate to Severe Obstructive Sleep Apnea Is Independently Associated with Inter-arm Systolic Blood Pressure Difference -Tokyo Heart Sleep Study-Kazuki Shiina (Japan)

O-08 The Cardio-ankle Vascular Index Was Associated with CHADS2 Score in Patients with Atrial Fibrillation: A Coupling Registry StudyTomoyuki Kabutoya (Japan)

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O-01Carotid-femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the ElderlyDe-Wei Ana, Iram Faqir Muhammadb, Ming-Xuan Lia, Yan Borneb, Chang-Sheng Shenga, Margaretha Perssonb, Ren-Zhi Caic, Qian-Hui Guoa, Ji-Guang Wanga, Gunnar Engstromb, Yan Lia, Peter Nilssonb

aDepartment of Cardiovascular Medicine, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China, bDepartment of Clinical Science, Lund University, and Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden, cDepartment of Vital Statistics, Division of Health Information, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

Objective The carotid-to-femoral pulse wave velocity (cf-PWV), determined by pulse transit time (PTT) and distance, is a well-established measure of arterial stiffness and predicts adverse outcomes. However, its predictive value decreases with aging. To explore new risk indicator in the elderly, we investigated if the variation of cf-PWV, registered as beat-to-beat variability of cf-PTT, could predict outcome. Design and Method Totally 3,015 (median age, 72.4 years; 39.6% men) and 1,181 (75.6 years; 42.2% men) subjects from communities of Malmo, Sweden and Shanghai, China were analyzed, respec-tively. Continuous pulse waves for 10 seconds were recorded sequentially at carotid and femoral arterial sites with applana-tion tonometry (Sphygmocor, Atcor, Australia). Results During a median 6.6 and 10.2 years, 389 and 427 deaths occurred in the Malmo and Shanghai cohorts, respectively. Each one-stan-dard deviation increase in the log-transformed coefficient of variation (CV) of cf-PTT was associated with 25% (95% confi-dence interval, 13-37%) and 22% (10-36%) increased risk for all-cause mortality in the Malmo and Shanghai subjects, and 60% (34-92%) for cardiovascular mortality in the Malmo sub-jects. Adding the CV of cf-PTT to the models including conven-tional risk factors and cf-PWV significantly (p0.05) improved prediction for all-cause mortality in both cohorts (integrated discrimination improvement [IDI], 0.005-0.008) and cardio-vascular mortality in the Malmo cohort (net reclassification improvement [NRI], 0.225). In both cohorts, a CV of cf-PTT 6% was not associated with increased mortality risk. Conclusions The beat-to-beat variability of cf-PTT predicted mortality and improved risk stratification, which might be a novel risk indi-cator for elderly people.

Keywords: Elderly, Mortality, Pulse transit time, Pulse wave velocity, Risk stratification

O-02Associations between Arterial Aging and Muscle-to-fat Ratio among Middle-aged and Older Adults: Results from the Longitudinal Aging Study of TaipeiHsin-Yu Liua,b,c, Chen-Hua Linb,c, Li-Ning Penga,b, Ming-Hsien Lina,b, Hao-Min Chengc,d, Liang-Kung Chena,b,g, Chen-Huan Chene,f

aCenter for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan, bAging and Health Research Center, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan, cInstitute of Public Health, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan, dCenter for Evidence-Based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, eDepartment of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, fDepartment of Medicine, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan, gTaipei Municipal Gan-Dau Hospital, Taipei, Taiwan

Objective This study aims to evaluate the associations between different hemodynamic parameters of arterial aging and unfavorable body composition among community-dwell-ing middle-aged and older adults. Design and Method Data from the Longitudinal Aging Study of Taipei (LAST) were ex-cerpted for study. Participants underwent physical examina-tions, functional assessment and venous blood sampling after 10-hour overnight fast, as well as body composition (using bioimpedance analysis) and hemodynamic study using the tonometry and echocardiography. Both wave-transmission and reservoir-wave theories were applied for wave form analysis. Results Data of 985 participants aged 65 years and older (67.22±0.22 years, 29.7% men) were excepted for the study. Men had more muscle mass, less fat mass, and higher MFR. The systolic and diastolic blood pressure and carot-id-femoral pulse wave velocity (cfPWV) were higher in men, and the augmented pressure and carotid augmented index were higher in women. The excess pressure integral (XSPI), amplitude of reservoir pressure, systolic rate constant and di-astolic rate constant were similar in men and women, where-as men had higher magnitudes of the forward wave (Pf) and backward wave (Pb), peak of reservoir pressure (PRI) and reservoir pressure integral. Multivariate linear regression discovered a negative association between MFR and XSPI (men, coef: -0.025, p0.05; women, coef: 0.007, p0.05) among

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participants after adjustment for potential confounding fac-tors. Conclusions XSPI, a novel cardiovascular indicator for arterial aging, is independently associated with muscle-to-fat ratio in community-dwelling middle-aged and older adults. Further outcome-based studies are needed to explore the pathophysiological and longitudinal effects between arterial aging and unfavorable body composition.

Keywords: Arterial aging, Atherosclerosis, Body compo-sition, Cardiovascular diseaseTable

Figure

Table

Figure

O-03Visceral Adipose Tissue, Coronary Artery Calcification and Heart Failure: A Moderated Mediation AnalysisChun-Wei Leea,b,c, Yu-Hsuan Leed, Chern-En Chiange,f, Wen-Chung Yue,g, Shih-Hsien Sunge,g, Chen-Huan Chena,h,i, Hao-Min Chenga,d,e,i

aInstitute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, bCardiovascular Division, Department of Internal Medicine, MacKay Memorial Hospital, MacKay Medical College, New Taipei City, Taiwan, cMacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan, dCenter for Evidence-based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, eFaculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, fGeneral Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, gDivision of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, hSchool of Medicine, National Yang Ming Chiao Tung University, iDepartment of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan

Objective The purpose of this study was to elucidate the relationship between VAT, coronary artery calcification (CAC), and incident HF, and using causal mediation analysis investi-gate whether the VAT’s effect on heart failure was mediated through CAC. Design and Method This was a retrospective analysis of the longitudinal follow-up data of JHS. For CAC were modeled as continuous variables. To examine the asso-ciation between VAT and HF, CAC were performed after loga-rithmic transformation of the Agatston score plus. The asso-

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Table

Figure

Table

Figure

O-04Ambulatory Pulse Pressure Components and Ambulatory Arterial Stiffness Index in Chinese OutpatientsLi Mingxuan, Huang Jianfeng, An Dewei, Cheng Yibang, Guo Qianhui, Zhang Dongyan, Huang Qifang, Sheng Changsheng, Xu Tingyan, Wang Jiguang, Li YanThe Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective Ambulatory arterial stiffness index (AASI) is a

ciation between measures of VAT and CAC was investigated by using multivariable-adjusted linear regression models. We used Cox proportional hazards models to estimate hazard ratios of CAC and VAT for the risk of incident HF and adjusted for age, sex, hypertension, diabetes, and statin medication status. Causal mediation analysis was performed to examine CAC mediator underlying association between VAT and HF. An accelerated failure time (AFT) model with Weibull distri-bution was fitted in the weighted cohort, adjusting for covari-ates. The total effect of VAT on heart failure was decomposed into its indirect effect, direct effect, and total effect. Results A total of 1952 participants (mean age: 59.9 years, 35.1% men) from the Jackson Heart Study without prevalent HF who had received CAC and VAT quantification by computed tomogra-phy were investigated. The association between measures of VAT and CAC was investigated by multivariable-adjusted linear regression models. Cox proportional hazards models were used to estimate hazard ratios of VAT and CAC for HF by adjusting age, sex, hypertension, diabetes, and statin med-ication status. VAT was associated with CAC (β coefficient ± standard error : 0.114 ± 0.053, p=0.031). Increased CAC and VAT were associated with a higher risk of incident heart failure (adjusted hazard ratio: 1.126 [95% CI: 1.038-1.221]; p 0.001 and 1.217 [1.014-1.461]; p =0.035; respectively). The causal mediation analysis showed that CAC was a significant mediator of the relationship between VAT and heart failure with a medi-ated proportion of 5.68%. Conclusions VAT may contribute to the development of heart failure partly through the effects of CAC. Efforts to prevent HF can be made by targeting VAT and considering the presence of CAC in the African American patients.

Keywords: Visceral adipose tissue, Heart failure, Coro-nary artery calcification

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surrogate measure of arterial stiffness, and closely correlated with pulse pressure (PP), which was recently proposed to be decomposed into pressure-dependent (‘elastic’, elPP) and pressure-independent (‘stiffening’, stPP) PP. The aim of this study is to investigate with which PP component that AASI most correlated. Design and Method Consecutive ambula-tory blood pressure monitoring (ABPM) recorded with val-idated monitors (Mobil-O-Graph, Germany) from February 2017 to February 2018 in the Hypertension Clinic of Ruijin hospital, Shanghai was obtained from a remote online ABPM platform (www.shuoyun.com.cn, Shanghai). The 24-hour ambulatory PP was divided into elPP and stPP as previously described. Results Among the 5408 participants (mean age, 53.0±14.3 years; 45.6% men), 1861 (34.4%) patients had an AASI ≥0.55. AASI was significantly correlated with the 24-hour ambulatory PP (r=0.56, P0.001). The Pearson cor-relation coefficient of AASI with the stPP was greater than that with the eIPP (0.66 vs 0.26, P0.001). Multiple linear re-gression analyses revealed that age, sex, smoking, body mass index, 24-hour mean heart rate and stPP were independent determinants for AASI and AASI ≥ 0.55. The stPP explained 43% of the total variance of AASI. Conclusions AASI was more closely associated with stPP than elPP, indicating it re-flects pressure-independent stiffening.

Keywords: Arterial stiffness, Ambulatory, Pulse pres-sure, Hypertension

O-05Early and Supernormal Vascular Aging: Associations with Cognitive Dysfunction in a Community-based Healthy PopulationChen-Hua Lina, Shao-Yuan Chuangc, Hao-Min Chenga,b, Li-Ning Pengd, Liang-Kung Chend, Chen-Huan Chena,b aInstitute of Public Health, National Yang Ming Chiao Tung University College of Medicine, Taiwan, bDepartment of Internal Medicine, National Yang Ming Chiao Tung University College of Medicine, Taiwan, cPublic Health Sciences Institute, National Health Research Institutes, Taiwan, dCenter for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taiwan

Objective The difference between chronological and vascular age (Δage) has been used to identify subjects with early vascular aging (EVA) and supernormal vascular aging (SUPERNOVA). In the present study, we investigated the associations of EVA and SUPERNOVA with cognitive dys-function in a healthy community population. Design and Method A total of 929 subjects aged between 50 to 90 years

were enrolled (68.4% female, mean age 67.6 years, mean education 13.5 years). Vascular age was estimated in general additive model including classical cardiovascular risk factors, treatment, and carotid-femoral pulse wave velocity (cf-PWV) from another community cohort (n=664). Variables showing nonlinear relationship with age were transformed by penal-ized spline. Δ age was calculated as chronological age minus vascular age, and EVA was defined as Δage -7.5 years, normal vascular aging as Δage -7.5 to 7.47 years, and SUPERNOVA as Δage7.47 years. Cognitive function was assessed using the Montreal cognitive assessment (MoCA), and a total score26 was considered as cognitive dysfunction. Associations of dif-ferent vascular aging categories with cognitive dysfunction were examined using logistic regression analysis. Results Subjects with EVA (n=81, mean age 59.1±6.4 years) were significantly younger, and SUPERNOVA (n=77, mean age 75.6±5.6 years) were significantly older than those with nor-mal vascular aging (n=771, mean age 67.7±5.6 years). EVA had the highest cf-PWV (11.9 m/s). Subjects with SUPER-NOVA (29.9%) had the highest prevalence of cognitive dys-function, followed by EVA (21.0%). As compared to normal vascular aging with adjustment for age, sex and educational years, subjects with EVA (Standardized OR and 95% CI, 2.46, 1.24-4.75) had significantly higher odds of cognitive dysfunc-tion and those with SUPERNOVA had a standardized OR of 0.73 (0.38-1.35) of cognitive dysfunction. Conclusions Mid-dle-aged subjects with EVA defined by Δage were associated with an increased odds of cognitive dysfunction. Subjects with SUPERNOVA defined by Δage were elderly who had a higher crude prevalence but an insignificantly lower odds of cognitive dysfunction when compared with the younger sub-jects with normal vascular aging.

Keywords: EVA, SUPERNOVA, Vascular aging, Cognitive dysfunction

O-06Comparison of Vascular Characteristic Impedance Estimation in Time Domain or Frequency DomainA Adjia,b,c, S Hungerforda,b, M Namasivayama,b, M O’Rourkeb, A Jabboura,b, C Haywarda,b, D Mullera,b

aVictor Chang Cardiac Research Institute, Sydney, Australia, bDepartment of Cardiology, St Vincent’s Hospital, Sydney, Australia, cDepartment of Biomedical Engineering, FMHHS, Macquarie University, Sydney, Australia

Objective Characteristic impedance (Zc) is an import-

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Figure

Figure

O-07Moderate to Severe Obstructive Sleep Apnea Is Independently Associated with Inter-arm Systolic Blood Pressure Difference - Tokyo Heart Sleep Study-Kazuki Shiina, Kento Kumai, Takamichi Takahashi, Hiroki Nakano, Masatsune Fujii, Taishiro Chikamori, Hirofumi Tomiyama Department of Cardiology, Tokyo Medical University, Japan

Objective Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference, inter-ankle systolic blood pressure difference, and ankle-bra-chial index are all known predictors of cardiovascular events. However, the association of OSA with these four-limb blood pressure parameters have not yet been fully clarified. We conducted this cross-sectional study in the Tokyo Sleep Heart Study, from a high-volume center. Design and Method We conducted the cross-sectional study from a high-volume center sleep cohort. In 2643 consecutive patients who visit-ed sleep clinic to perform polysomnography in 2005-2017, blood pressure in four-limb were measured simultaneously by oscillometric methods. The IAD and IAND were defined as absolute value of the systolic blood pressure difference in both arms and ankles. Results The prevalence rate of IAD ≥ 10 mm Hg was significantly higher in the severe OSA (AHI ≥ 30) group (4.6%) than in the no/mild (AHI 15) group (1.6%). Multivariate logistic regression analysis also identified mod-erate to severe OSA as being significantly associated with in-ter-arm systolic blood pressure difference ≥ 10 mm Hg, even

ant hemodynamic marker. Historically, Zc is estimated in the frequency domain to characterise properties of the vascular bed and to express the relationship between pulsatile pres-sure and flow in an artery. Zc can also be estimated in the time domain using the “up-slope method”, by utilising the initial upstroke of arterial pressure and flow waves during the early phase of left ventricular ejection. We compare Zc determined in time (Zct) and frequency (Zcf) domains, using data acquired from simultaneously-recorded non-invasive radially-derived aortic pressure and cardiovascular magnetic resonance (CMR) ascending aortic flow velocity. Design and Method Seventy-eight participants (37 healthy volunteers, 21 patients with cardiac symptoms undergoing investiga-tions, and 20 patients with aortic stenosis) had their pressure and flow acquired simultaneously. Applanation tonometric radial pressure was recorded then converted offline to aortic pressure using SphygmoCor 8.1 (AtCor Medical) and calibrat-ed using brachial cuff values. CMR provided ascending aortic flow velocity. Zct was calculated with 3 approaches (figure); (1) ZcVmax = P1 ÷ Vmax; (2) Zc95 = P95% ÷ V95%; (3) Zc-slope = Pslope ÷ Vslope. Zcf was calculated as average ratio of pressure to flow harmonic modulus from 2 to 8 Hz. Results There were no significant differences between Zcf (652 dyne.s.cm-3) with ZcVmax (665 dyne.s.cm-3) and Zc95 (669 dyne.s.cm-3) in normal group. However, Zc-slope was significantly higher by 157 mmHg (809 dyne.s.cm-3, p=0.002). In contrast, for the clinical participants, there were significant differences between all Zct calculation and Zcf (p0.001) (table). Conclu-sions The optimal assessment of cardiovascular performance requires the assessment of arterial conduit/cushion function to determine the efficiency of the cardiovascular system as a whole. The “gold standard” approach for quantification of cardiac load historically has been in the frequency domain, allowing for the pulsatile feature of the pressure and flow waves to be expressed appropriately. While Zct may be con-venient and less cumbersome, an approximation of load in the time domain, or steady state load, may not be appropri-ate, especially in the clinical cohort.

Keywords: Hemodynamics, Cardiac load

Figure

Table

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after adjustments for confounding variables. However, there were no significant associations of the OSA severity with inter-ankle systolic blood pressure difference ≥ 15 mm Hg or ankle-brachial index 0.9. Conclusions Moderate to severe OSA was independently associated with the inter-arm sys-tolic blood pressure difference, not but with the inter-ankle systolic blood pressure difference or ankle-brachial index. A plausible explanation is that the negative intrathoracic pres-sure generated in patients with obstructive sleep apnea may exert an adverse impact on the structural characteristics of the thoracic aorta.

Keywords: Sleep apnea, Hypertension, Atherosclerosis

O-08The Cardio-ankle Vascular Index Was Associated with CHADS2 Score in Patients with Atrial Fibrillation: A Coupling Registry StudyTomoyuki Kabutoya, Satoshi Hoshide, Kazuomi KarioDivision of Cardiovascular Medicine, Jichi Medical University, Japan

Objective The cardio-ankle vascular index (CAVI) is used as an indicator of atherosclerosis. A comparison of the CAVI values of patients with and without atrial fibrillation (AF) has not been conducted, and the association between CAVI and the CHADS2 (Congestive heart failure, High blood pressure, Age, Diabetes, Stroke) score has been unclear. The aim of this study was to evaluate the association between CAVI and CHADS2 score. Design and Method We enrolled 290 patients with AF and 290 control patients matched for age and gender from the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry). We obtained the pulse wave and CAVI in five beats of all patients and evalu-ated the average, standard deviation (SD), and coefficient of variation (CV) values. Results In both the AF and non-AF groups, the average age was 73.8±8.9 yrs and the percentage of males was 71%. The AF patients’ CAVI values were signifi-cantly higher than those in the control group (9.77±1.44 vs. 9.16±1.39, p0.001). The SD and CV of CAVI in the AF group were significantly higher than those in the control group (SD: 0.98±0.89 vs. 0.60±0.81, p0.001; CV: 9.7±9.6 vs. 5.4±6.7%, p0.001). In both groups, the CAVI was associated with the CHADS2 score (AF: r=0.25, p0.001; control: r=0.28, p0.001). Conclusions The CAVI in the patients with AF was signifi-cantly higher than that in the controls matched for age and gender. The beat-by-beat variation of CAVI in the AF group was high, and the AF patients’ CAVI values were associated

with their CHADS2 scores.

Keywords: CAVI, Atrial fibrillation

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e-Poster Abstracts

eP-01 Improved Prognostic Value in Predicting Long-term Cardiovascular Events by a Combination of C-reactive Protein and Brachial-ankle Pulse Wave VelocityHack-Lyoung Kim (Republic of Korea)

eP-02 Association of Changes of Pulse Wave Velocity and Augmentation Index after Isometric Handgrip Exercise with Coronary Lesion Extent and RevascularizationSeung-Jae Joo (Republic of Korea)

eP-03 Clinical Significance of Subclinical Atherosclerosis in Retinal Vein OcclusionMinhyung Lyu (Republic of Korea)

eP-04 Association of Urinary Sodium Excretion, Home and Office Blood Pressure, and Vascular Function in Patients with Hypertension: Flow-mediated Dilatation Japan Study (fmd-j) Study BAkio Ishida (Japan)

eP-05 Central Blood Pressure Lowering Effect of Telmisartan/Rosuvastatin Single Pill Combination in Hypertensive Patients Combined with DyslipidemiaJungMin Choi (Republic of Korea)

eP-07 Serum Uric Acid Change in Relation to Antihypertensive Therapy with Calcium Channel BlockersDi Zhang (China)

eP-09 Transient Receptor Potential Melastatin 7 Promotes Vascular Adventitial Fibroblasts Phenotypic Transformation and Inflammatory Reaction Induced by Mechanical Stretching Stress via p38 MAPK/JNK PathwayShujie Guo (China)

eP-14 Dilation-responsive Microshape Programing Prevents Vascular Graft StenosisHyun-Su Ha (Republic of Korea)

eP-15 A Double-blind, Placebo-controlled Trial on the Antihypertensive Treatment Effect of a Quadruple Single-pill CombinationLei-Xiao Hu (China)

eP-16 A Prospective Comparative Study on Cardiac Structure and Function after Surgery and Drug Treatment of Primary AldosteronismYi-Lin Chen (China)

eP-17 The Relationship of Aging and Arterial Impedance Mismatch with Target Organ DamageJui-Tzu Huang (Taiwan)

eP-19 Long-term Clinical Outcomes and Diastolic Function as a Predictor in Diabetic Patients with Negative Treadmill Stress EchocardiographySo Young Yang (Republic of Korea)

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eP-20 Continuous Positive Airway Pressure Adherence and Blood Pressure Lowering in Patients with Obstructive Sleep Apnoea Syndrome and Nocturnal HypertensionJia-Hui Xia (China)

eP-21 Peptide Programming of Nanoparticle as a Theranostic Toolbox towards Anti-atherosclerosisSeungeun Yu (Republic of Korea)

eP-22 Supernormal Vascular Aging and Long-term Incidence of Cardiovascular Disease in a Taiwanese CohortShao-Yuan Chuang (Taiwan)

eP-25 Differences between Brachial Oscillometric Arterial Blood Pressure Measured during Cuff Inflation and Cuff DeflationJames Cox (Australia)

eP-26 Associations between Choriocapillaris Flow on Optical Coherence Tomography Angiography and Cardiovascular Risk Profiles in Patients with Acute Myocardial InfarctionByung Sik Kim (Republic of Korea)

eP-33 Retrograde Pressure Gradient in the Brachial Artery Is Associated with Severity of Myocardial Perfusion Defect in Patients with Ischemic Heart DiseaseSmriti Badhwar (India)

eP-34 Contrast-enhanced Magnetic Resonance Lymphangiography and Interventional Treatment for Various Thoracoabdominal Lymphatic DiseasesJi Hoon Shin (Republic of Korea)

eP-35 A Count-based Binary Decision Method for Target Blood Pressure Achievement in Interpretation of Home Blood Pressure Monitoring RecordsYonggu Lee (Republic of Korea)

eP-37 Metformin Alleviates Left Ventricular Diastolic Dysfunction in a Rat Myocardial Ischemia Reperfusion Injury ModelWoori Jo (Republic of Korea)

eP-38 Quarterly Versus Annual ECG Screening for Atrial Fibrillation in Older Chinese (AF-CATCH): A Prospective, Randomised, Controlled TrialWei Zhang (China)

eP-39 Depression Was Associated with Atherosclerosis and Cardiovascular Events, Especially in Male Patients at Risk for Cardiovascular DiseaseTomoyuki Kabutoya (Japan)

eP-41 Alcohol Consumption in Relation to Cardiovascular and Non-cardiovascular Mortality in an Elderly Male Chinese PopulationXiao-Fei Ye (China)

eP-42 Brachial-ankle PWV for Predicting Clinical Outcomes in Patients with ST-elevation Myocardial InfarctionKye Taek Ahn (Republic of Korea)

eP-43 Differential Impact of Home Blood Pressure Variability for Cardiovascular Events between Patients with and without Advanced Arterial Stiffness: Results of the J-HOP StudySatoshi Hoshide (Japan)

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eP-45 Estimated Pulse Wave Velocity and the Risk of Cardiovascular Events: A Nationwide Population-based Study of More Than 4 Million Men and WomenDong-Hyuk Cho (Republic of Korea)

eP-46 The Associations between Endothelial Dysfunction, Arterial Stiffness and the Development of Carotid Atherosclerosis in Hypertensive SubjectsHiroki Nakano (Japan)

eP-47 Biomechanical Characterization of the Arteries in Type 2 Diabetic MiceJungsil Kim (Republic of Korea)

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eP-01Improved Prognostic Value in Predicting Long-term Cardiovascular Events by a Combination of C-reactive Protein and Brachial-ankle Pulse Wave VelocityHack-Lyoung Kim, Woo-Hyun Lim, Jae-Bin Seo, Sang-Hyun Kim, Joo-Hee Zo, Myung-A KimDivision of Cardiology, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea

Objective Both C-reactive protein (CRP) and arterial stiff-ness are associated with the development of cardiovascular disease (CVD). This study was performed to investigate wheth-er a combination of these 2 measurements could improve cardiovascular risk stratification. Design and Method A total of 6,572 consecutive subjects (mean age, 60.8 ± 11.8 years; female, 44.2%) who underwent both CRP and brachial-ankle pulse wave velocity (baPWV) measurement within 1 week were retrospectively analyzed. Major adverse cardiovascular events (MACE), including cardiovascular death, acute myocar-dial infarction, coronary revascularization and stroke, were assessed during the clinical follow-up. Results During a mean follow-up period of 3.75 years (interquartile range, 1.78-5.31 years), there were 182 cases of MACE (2.8%). The elevated baPWV (≥ 1,505 cm/s) (hazard ratio [HR], 4.21; 95% confi-dence interval [CI], 2.73-6.48; P 0.001) and CRP (≥ 3 mg/L) (HR, 1.57; 95% CI, 1.12-2.21; P 0.001) levels were associated with MACE even after controlling for potential confounders. The combination of baPWV and CRP further stratified the subjects’ risk (subjects with low baPWV and CRP vs. subjects with high baPWV and CRP; HR, 7.08; 95% CI, 3.76-13.30; P 0.001). Adding baPWV information to clinical factors and CRP had an incremental prognostic value (global Chi-square score, from 126 to 167, P 0.001). Conclusions The combination of CRP and baPWV provided better prediction of future CVD than either one by itself. Taking these 2 simple measurements simultaneously is clinically useful in cardiovascular risk strati-fication.

Keywords: Arterial stiffness, C-reactive protein, Major adverse cardiovascular event, Major adverse cardiovascular event, Risk stratification

Figure

eP-02Association of Changes of Pulse Wave Velocity and Augmentation Index after Isometric Handgrip Exercise with Coronary Lesion Extent and RevascularizationJong-Wook Beom, Ki Yung Boo, Jae-Geun Lee, Joon-Hyouk Choi, Song-Yi Kim, Seung-Jae JooDepartment of Internal Medicine, Jeju National University Hospital, Republic of Korea

Objective Arterial stiffness is associated with myocardi-al ischemia and incident coronary artery disease (CAD), and indexes of arterial stiffness are usually increased in patients with CAD. However, these indexes are often increased in el-derly without CAD. Arterial stiffness in patients with CAD may become more evident after isometric handgrip exercise which increases systolic pressure and ventricular afterload. We in-vestigated the association of the change of stiffness indexes after isometric handgrip exercise with the lesion extent of CAD and the necessity for coronary revascularization. Design and Method Patients who were scheduled a routine coro-nary angiography via a femoral artery were enrolled. Arterial waveforms were traced at aortic root and external iliac artery using coronary catheters at baseline and 3 minutes after hand-grip exercise. Augmentation index (AIx) was measured on the recorded aortic pressure waveform, and pulse wave velocity (PWV) was calculated using the ECG-gated time difference of the upstroke of arterial waveforms and distance between aortic root and external iliac artery. Results Total 37 patients were evaluated. Both PWV and AIx increased after handgrip exercise. ΔPWV was significantly correlated with ΔAIx (r = 0.344, P = 0.037). Patients were divided into higher and lower ΔPWV or ΔAIx groups based on the median values of 0.4 m/sec and 3.3%, respectively. Patients with higher PWV had more 2- or 3-vessel CAD (69% vs. 27%, P = 0.034), and underwent percutaneous coronary intervention (PCI) more frequently

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(84% vs. 50%, P = 0.038), but higher ΔAIx was not associated with either the lesion extent or PCI. Area under curve (AUC) of ΔPWV in association with PCI by C-statistics was 0.70 (95% confidence interval [CI] 0.51-0.88; P = 0.056). In multiple logistic regression analysis, ΔPWV was significantly associat-ed with PCI (odds ratio 7.78; 95% CI 1.26-48.02; P = 0.027). Conclusions Higher ΔPWV after isometric handgrip exercise was associated with the lesion extent of CAD and the necessity for coronary revascularization, but higher ΔAIx was not.

Keywords: Arterial stiffness, Pulse wave velocity, Pulse wave analysis, Isometric exercise, Percutaneous coronary in-tervention

Figure

eP-03Clinical Significance of Subclinical Atherosclerosis in Retinal Vein OcclusionMinhyung Lyua, Yonggu Leea, Byung Sik Kima, Hyun-Jin Kima, Yong Un Shinb, Heeyoon Chob, Jeong-Hun Shina

aDivision of Cardiology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea, bDepartment of Ophthalmology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea

Objective Retinal vein occlusion (RVO) is known to be associated with atherosclerotic cardiovascular risk factors, but the association between specific markers of subclinical atherosclerosis has not been established. In this study, we investigated the subclinical atherosclerosis of patients with RVO compared to control subjects without known retinal dis-

eases. Design and Method To investigate this association, we compared 70 patients with RVO to age- and sex-matched 70 patients without RVO. They were undergone cardiovascular examinations including 24-hour ambulatory blood pressure monitoring, carotid ultrasonography, and brachial-ankle pulse wave velocity (baPWV) measurement. Age and sex were matched between the patients with RVO and the control using a propensity score. Results Low-density lipoprotein choles-terol (LDL-C) level and brachial-ankle pulse wave velocity (baPWV) were significantly higher in the RVO group than in the control group. Carotid plaque (54.3% vs. 28.6%, p = 0.004) was more frequent in the RVO group. Multivariate logistic re-gression analysis showed that the presence of carotid plaque [odds ratio (OR) 3.15, 95% confidence interval (CI) 1.38-7.16, p = 0.006], as well as smoking, LDL-C level, and baPWV was associated with RVO. Additionally, a multinomial logistic regression model showed that the presence of carotid plaque (OR 3.94, 95% CI 1.65-9.41, p = 0.002) and LDL-C level were associated with branch RVO, whereas smoking and baPWV were associated with central RVO. Conclusions RVO is associ-ated with subclinical atherosclerosis markers, including carot-id plaques and baPWV. These results support the hypothesis of atherosclerosis on the etiology of RVO and suggest the evalua-tion of subclinical atherosclerosis in patients with RVO.

Keywords: Atherosclerosis, Retinal vein occlusion, Sub-clinical atherosclerosis, Carotid plaque, Pulse wave velocity

Table

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had hypertension or diabetes mellitus were enrolled, and 324 of them who had at least 5 days morning home BP measure-ments were analyzed in this study. FMD of the brachial artery was measured using an ultrasound semi-automatic measuring system (UNEXEF18G, UNEX Co., Nagoya, Japan). We used the Tanaka formula to estimate 24-hour urinary sodium excretion. Results A total of 315 (97%) patients were being treated with antihypertensive drugs and 52 patients (18%) had diabetes mellitus. Mean age of patients was 62.7 years (45% women), and mean BP was 133/79 mmHg at office and 132/85 mmHg at home. Estimated sodium excretion was positively correlated with home systolic BP (r=0.15, P=0.006) and inversely asso-ciated with FMD (r=-0.14, P=0.012). Neither office systolic BP nor brachial-ankle pulse wave velocity (baPWV) was associ-ated with sodium excretion. Univariate analysis revealed that FMD was inversely associated with home systolic BP (r=-0.14, P=0.013) but not with office systolic BP. baPWV was positively associated with home (r=0.14, P=0.014) and office systolic BP (r=0.22, P0.001). After adjusting several factors, home systolic BP but not office systolic BP was inversely associated with FMD, whereas home and office systolic BP were positively as-sociated with baPWV. Conclusions In patients with hyperten-sion, sodium excretion was associated with increase in home systolic BP and decrease in endothelial function.

Keywords: Endothelial function, Arterial stiffness, Sodi-um, Out-of-office blood pressure, Hypertension

eP-05Central Blood Pressure Lowering Effect of Telmisartan/Rosuvastatin Single Pill Combination in Hypertensive Patients Combined with DyslipidemiaJungMin Choi a, Ki-Chul Sungb, Sang-Hyun Ihmc, Chang-Hwan Yoond, Seung Woo Parke, Sung-Ha Parkf, Jang-Young Kimg, Sung-Uk Kwonh, Hae-Young Leea

aDepartment of Internal Medicine, Seoul National University Hospital, Republic of Korea, bDivision of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Republic of Korea, cDivision of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea, dCardiovascular Center & Department of Internal Medicine, Seoul National University Bundang Hospital, Republic of Korea, eDivision of Cardiology, Department of Internal Medicine, Samsung Medical Center, Heart Vascular Stroke Institute, Sungkyunkwan University School of Medicine, Republic of Korea, fDivision of

Figure

eP-04Association of Urinary Sodium Excretion, Home and Office Blood Pressure, and Vascular Function in Patients with Hypertension: Flow-mediated Dilatation Japan Study (fmd-j) Study BAkio Ishidaa, Tetsuya Ishiki a, Hirofumi Tomiyamab, Akira Yamashinab, Satoshi Hoshidec, Tomoyuki Kabutoyac, Kazuomi Karioc, Takuzo Hanod, Bonpei Takasee, Tomoo Furumotof, Yusuke Ohyaa

aDepartment of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan, bSecond Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan, cDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan, dDepartment of Medical Education and Population-based Medicine, Postgraduate School of Medicine, Wakayama Medical University, Wakayama, Japan, eDivision of Biomedical Engineering, National Defense Medical College Research Institute, Saitama, Japan, fDepartment of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

Objective The aim of this study is to evaluate the relation-ship between urinary sodium excretion, home and office blood pressure, and endothelial function and arterial stiffness in pa-tients with hypertension. Design and Method A cross-section-al analysis was conducted to examine the utility of flow-medi-ated dilatation (FMD) in the management of patients at risk of cardiovascular disease. A total of 966 Japanese patients who

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Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Republic of Korea, gDepartments of Cardiology, Wonju College of Medicine, Yonsei University, Korea, Institute of Genomic Cohort, Yonsei University, Republic of Korea, hDepartment of Internal Medicine, Inje University Ilsan Paik Hospital, Republic of Korea

Objective This study aimed to evaluate the safety and efficacy of telmisartan/rosuvastatin single pill combination therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia. Design and Method This multicenter, phase 4, PROBE (Prospective Randomized Open, Blinded End-point) study was conducted in Korea. After run-in period with telmis-artan, those who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovas-cular Disease Risk Score over 5%) were randomized to telmis-artan/rosuvastatin group or telmisartan monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (PWV), and augmentation index (AIx) were assessed at base-line and 16 weeks later. Results Of the screened 125 patients, 80 were randomized into two groups. The mean brachial SBP changed from 135.80±14.22mmHg to 130.69±13.23mmHg in telmisartan/rosuvastatin group and from 134.37±12.50mmHg to 133.75±12.30mmHg in telmisartan monotherapy group with no statistically significant difference between the two groups (between-group difference p = 0.149). In contrast, the reduction in central SBP was significantly greater in the tel-misartan/rosuvastatin group as the mean central SBP changed from 126.72±14.44mmHg at baseline to 121.56±14.56mmHg at week 16 while telmisartan monotherapy group changed from 124.33±14.20mmHg to 126.27±16.36mmHg at week 16 (between-group difference -6.41mmHg; 95% CI: -12.08 to -0.73mmHg; p = 0.028) (Figure). The bra-chial-ankle PWV changed from 1672.57±371.72m/sec to 1591.75±272.16m/sec in telmisartan/rosuvastatin group and from 1542.85±263.70m/sec to 1586.12±297.45m/sec in tel-misartan monotherapy group with no statistical significance (between-group difference of 86.10m/s; 95% CI: -182.09 to 9.90m/s; p = 0.078). The change of AIx had no significant dif-ference (between-group difference p = 0.314). Both groups showed excellent compliance rate of 96.9±4.5% with no signif-icant difference. There were 9 adverse events from telmisartan group, 7 from telmisartan/rosuvastatin group (between-group difference p=0.494). Conclusions Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP com-pared with the telmisartan monotherapy. The results of this study showed another benefit of additive statin therapy in hy-pertensive patients combined with dyslipidemia.

Keywords: Telmisartan, Rosuvastatin, Hypertension, Dys-

lipidemia, Angiotensin II receptor blocker

Figure

Figure

eP-07Serum Uric Acid Change in Relation to Antihypertensive Therapy with Calcium Channel BlockersDi Zhang, Qi-Fang Huang, Chang-Sheng Sheng, Yan Li, Ji-Guang WangCentre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective We investigated serum uric acid changes in relation to the achieved clinic and ambulatory blood pressure after 8 weeks of antihypertensive therapy with two calcium channel blockers. Design and Method The study partici-pants were patients with clinic and ambulatory hypertension, who were enrolled in a randomized controlled trial that com-pared efficacy of amlodipine (5-10 mg, n=216) and nifedipine gastrointestinal therapeutic system (GITS, 30-60 mg, n=204). Analysis of covariance and multiple regression analyses were performed to study the associations between serum uric acid changes and the achieved clinic and ambulatory blood pres-sure during follow-up. Results At baseline, 68 (16.2%) pa-tients had hyperuricemia (serum uric acid concentration ≥420 μmol/L in men and ≥360 μmol/L in women). Antihypertensive treatment reduced clinic and 24-h, daytime and nighttime systolic/diastolic blood pressure by a mean (±standard error [SE]) change of -17.5±0.6/-8.6±0.4 mm Hg, -13.7±0.5/-8.3±0.3 mm Hg, -13.8±0.6/-8.3±0.4 mm Hg, -12.8±0.7/-8.0±0.4 mm Hg, respectively. Serum uric acid significantly (P≤0.04) de-creased at ranges of the achieved clinic (130-139/≥90 mm Hg) and 24-h (130/75-84 mm Hg), daytime (145/80-84 mm Hg) and nighttime systolic/diastolic blood pressure (120/65-

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(TNF-α). Pharmacological and RNA interference approaches using the TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB) and specific anti-TRPM7 small interfering RNA (siR-NA-TRPM7) abrogated these changes significantly. Further exploration uncloaked that inhibition of TRPM7 reduced the phosphorylation of p38 MAP kinase (p38MAPK) and c-Jun Nterminal kinase (JNK) in the AFs stimulated with MSS. Fur-thermore, inhibition of the phosphorylation of p38MAPK or JNK could also alleviate the MSS-induced expression of α-SMA and secretion of inflammatory factors. Conclusions These observations indicate that activated TRPM7 participates in the phenotypic transformation and inflammatory action of AFs in response to MSS through the p38MAPK/JNK pathway and suggest that TRPM7 may be a potential therapeutic target for vascular remodeling caused by hemodynamic changes in hy-pertension.

Keywords: TRPM7, Vascular adventitial fibroblasts, Me-chanical stretching stress, Phenotypic transformation, Over-load pressure

eP-14Dilation-responsive Microshape Programing Prevents Vascular Graft StenosisHyun-Su Haa, Se Won Yi b, Young Min Shina, Jung Bok Leec, Ju Young Parkb, Dae-Hyun Kima, Mi-Lan Kanga,b, Jae Won Yangd, and Hak-Joon Sunga

aDepartment of Medical Engineering, Yonsei University College of Medicine, Republic of Korea, bResearch Institute, TMD LAB Co., Ltd., Republic of Korea, cDepartment of Biological Science, Sookmyung Women’s University, Republic of Korea, dDivision of Nephrology, Yonsei University Wonju College of Medicine, Republic of Korea

Objective In hemodialysis patients, a significant cause of vascular access failure is stenosis. In particular, vein dilation triggers this hyperplastic vascular stenosis with formation of disturbed blood flow upon grafting. As a breakthrough design point, our approach used vein dilation in a positive way to minimize stenosis. Self-enclosable external support (SES) was designed in cooperation with computational modeling to wrap around the dilated vascular out-wall using shape memory polymers (SMPs). Based on unprecedented points of device design, micropore shape programing in collaboration with elastic shape-fixity played key roles in adjusting vein overdi-lation and consequently, inducing regenerative inflammation, thereby preventing stenosis. Design and Method During fabrication of photo-crosslinkable SMP-based SES, microshape

69 mm Hg) by a mean (±SE) change of -20.6±6.6 to -11.2±2.9 μmol/L. Conclusions Our study showed that antihypertensive therapy with a calcium channel blocker reduced serum uric acid, especially when 24-h ambulatory systolic blood pressure was controlled.

Keywords: Serum uric acid, Antihypertensive therapy, Clinic blood pressure, Ambulatory blood pressure, Calcium channel blocker

eP-09Transient Receptor Potential Melastatin 7 Promotes Vascular Adventitial Fibroblasts Phenotypic Transformation and Inflammatory Reaction Induced by Mechanical Stretching Stress via p38 MAPK/JNK PathwayShujie Guoa, Jiachen Liua, Jun Huanga, Laijiang Chenb, Wenda Xi a, Pingjin Gaoa, Dingliang Zhua

aShanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, bDepartment of Cardiology, Ningbo Medical Center Lihuili Hospital, Zhejiang, Ningbo, ChinaObjective Remodeling of the arteries is one of the patho-

logical bases of hypertension and is implicated in the whole process of hypertension, especially refractory hypertension. So, reversal or restraint of vascular remodeling has become a novel therapeutic strategy. We have previously shown that transient receptor potential melastatin 7 (TRPM7) aggra-vates the vascular adventitial remodeling caused by pressure overload in the transverse aortic constriction (TAC) model. It is known that in an artery under pressure overload, the adventitia undergoes an increase of mechanical stretching stress (MSS). In this study, we sought to explore the functional expression and downstream signaling of TRPM7 in vascular adventitial fibroblasts (AFs) stimulated by MSS. Design and Method The expression of TRPM7 was inhibited by siRNA. The primary cultured rat vascular adventitial fibroblasts were treated with 20%MSS. The protein expression was measured by western blot, ELISA and immunofluorescence, and the chemotaxis characteristics of macrophages were measured by Transwell assay. Results The expression of TRPM7 was upreg-ulated with a concomitant translocation to the cytoplasm in the AFs stimulated with 20% MSS. Meanwhile, the expression of α-smooth muscle actin (α-SMA), a marker of transformation from AFs to myofibroblasts (MFs) was also increased. More-over, AF-conditioned medium caused a significant migration of macrophages after treatment with MSS and contained high levels of monocyte chemotactic protein-1 (MCP-1), interleu-kin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α

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programing was carried out using gelatin and punching as small and large micro-porogens, respectively. This shape pro-graming aimed to pre-set pore interconnectivity and size, and thereby to induce regenerative inflammation by controlling vein dilation. In rabbit vein graft model(end-to-end) and ca-nine vein graft model(side-to-side), vein grafts and anastomo-sis sites were automatically wrapped with SES in response to body temperature. On day 28 post surgery, the vein grafts were harvested and analyzed by a series of tissue staining. Results The results of in vitro experiments indicate that micropore shape programing of SES enables efficient adjustment of pore size and interconnectivity upon vein dilatation. Consequently, regenerative inflammation, pro-angiogenesis, and vascular smooth muscle cell (SMC) migration were improved. The in vivo performance of SES significantly controlled vein dilation with results of reduced neointima formation and blood flow disturbance. The collaborative effects of regenerative inflam-mation with vasa vasorum regeneration efficiently rescued the ischemic disorders and induced migration of healthy SMCs to-wards adventitia instead of the intima side (vein maturation), resulting successful prevention of stenosis. Conclusions This study suggest a previously unconsidered strategy to treat ste-nosis in vein-artery grafting.

Keywords: Dilation-responsive, Microscale shape pro-gramming, Self-enclosable external support, Shape-fixity, Vein-to-artery grafting

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eP-15A Double-blind, Placebo-controlled Trial on the Antihypertensive Treatment Effect of a Quadruple Single-pill CombinationLei-Xiao Ha, Dian Wanga, Hua-Ling Liub, Qing-Tao Zhangb, Dong-Sheng Sunc, Li Zhangc, Xin Chend, Gui-Li Changd, Ji-Guang Wanga

aDepartment of Cardiovascular Medicine, Centre for

Epidemiological Studies and Clinical Trials, Shanghai Key Laboratory of Hypertension, The Shanghai Institute of Hypertension, Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, bDepartment of Hypertension, Zhoukou Central Hospital, Zhoukou, Henan Province, China, cDepartment of Geriatrics, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, China, dDepartment of Hypertension, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective In a randomized, double-blind, placebo-con-trolled trial, we investigated antihypertensive treatment effect of a quadruple single- pill combination of reserpine 0.1 mg, di-hydralazine 12.5 mg, hydrochlorothiazide 12.5 mg, and triam-terene 12.5 mg, and changes in plasma levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in patients with grade 1 hypertension. Design and Method Eligible patients with a systolic/diastolic blood pressure (BP, average of six readings at two clinic visits during a 4-week run-in period) of 140- 159/90–99 mmHg were randomly as-signed to the quadruple combination (n = 30) or placebo (n = 30). The randomized patients were instructed to take a pill of the combination or placebo once daily and followed up at 4, 8, and 12 weeks, respectively. Results After 12-week treatment, systolic/diastolic BP significantly (p ≤ .0001) decreased from 140.8 ± 7.9/89.5 ± 7.5 mmHg at baseline by 9.8 ± 1.8/6.4 ± 1.3 mmHg in the combination group. The corresponding values in the placebo group were 141.3 ± 7.9/90.3 ± 7.3 mmHg and 5.2 ± 1.8/0.4 ± 1.3 mmHg, respectively. The between- group differ-ences in systolic/diastolic BP changes were −4.6/−6.0 mmHg (95% CI, −9.7 to 0.6/−9.7 to −2.2 mmHg, p ≤ .08). The control rate of hypertension was higher in the combination than place-bo group (63.3% vs. 16.7%, p = .0002). Plasma serotonin, but not norepinephrine or dopamine, changed in both treatment and placebo groups (p ≤ .01). Nonetheless, plasma norepi-nephrine tended to decrease in the treatment group (−34.4 pg/ml, p = .09). Adverse events occurred in 5 (16.7%) and 3 (10.0%) patients in the combination and placebo groups, re-spectively. Conclusions Our study showed that the quadruple combination reduced BP and caused some changes in plasma neurotransmitters.

Keywords: Single-pill combination, Reserpine, Blood pressure, Monoamine neurotransmitters

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study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed con-ventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up. Results During follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass in-dex and left atrial volume index. However, only in the surgery group, global wasted work significantly decreased (200.8±86.7 at baseline vs. 142.1±58.1 mmHg% at 6 months), and global work efficiency (91.5±3.1 vs. 93.6±2.3%) and global longitu-dinal strain (-18.3±2.7 vs. -19.2±1.9%) significantly (P0.01) increased at 6 months of follow-up. The corresponding differ-ences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), -1.64% (95% CI, -2.56, -0.71%) and -0.85% (95% CI, -1.51, -0.20%), respectively. In addition, the changes in global wasted work at 6 months of fol-low-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group (r=0.54) and two groups combined (r=0.55), but not surgery group. Conclusions In spite of similar serum potassium normaliza-tion and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function.

Keywords: Primary aldosteronism, Adrenalectomy, Mineralocorticoid receptor antagonist, Eft ventricular pres-sure-strain loop

eP-17The Relationship of Aging and Arterial Impedance Mismatch with Target Organ DamageJui-Tzu Huanga, Chen-Huan Chena,b,c, Hao-Min Chenga,b,c

aDepartment of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan, bDepartment of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, cFaculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Objective Aortic stiffening has been known to be strong-ly associated with age and hypertension. The proximal aorta plays an important role in modulating the amount of pressure and flow pulsatility transmitted into the microcirculation of brain, which may contribute to early cognitive decline and further vascular dementia. However, the hemodynamic mecha-nisms contributing to cognitive impairment in the presence of high aortic stiffness remain controversial. Hypothesis with dis-proportionate stiffening of the proximal aorta comparing to the

Table

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eP-16A Prospective Comparative Study on Cardiac Structure and Function after Surgery and Drug Treatment of Primary AldosteronismYi-Lin Chen, Ting-Yan Xu, Jian-Zhong Xu, Li-Min Zhu, Yan Li, Ji-Guang WangThe Shanghai Institute of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective We performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocar-dial deformation and LV pressure. Design and Method Our

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carotid arteries reduces wave reflection had been proposed. We therefore investigated the relation between aortic-carot-id impedance mismatch and cognitive impairment, vascular aging and target organ dysfunction. Design and Method A total of 722 patients (51.5% male; mean age: 65.4±8.5 years) was enrolled between November 2017 to August 2020. Aortic and carotid arterial waveforms were obtained and analyzed to calculate aortic and carotid artery impedance. Cognition and lifestyle questionnaire of each participant was measured. Amnestic Mild Cognitive Impairment (aMCI) was defined as a Mini–Mental State Examination (MMSE) score no more than 27. Target organ indices including renal and cardiac functions were defined as estimated Glomerular filtration rate (eGFR) and left ventricular mass index (LVMI). Results Significant associations were noted between stroke volume, cardiac out-put, systemic vascular resistance (SVR), aortic impedance and age (P0.0001). However, there was no significant correlation between total peripheral resistance (TPR), carotid impedance and age. Impaired renal and cardiac remodeling were not as-sociated with increased arterial impedance. Both SVR and TPR were significantly lower in patients with aMCI. Compared with subjects with normal cognitive function, subjects with aMCI had a higher carotid impedance, the difference between carot-id and aortic impedance, and the ratio of carotid-over-aortic impedance in those patients. Conclusions Increased SVR and TPR but not aortic and carotid impedance associated aMCI.

Keywords: Arterial impedance mismatch, Vascular aging, Target organ damage, Hemodynamics, Cognitive function im-pairment

eP-19Long-term Clinical Outcomes and Diastolic Function as a Predictor in Diabetic Patients with Negative Treadmill Stress EchocardiographySo Young Yang, Narae Kim, Hui-Jeoung Hwang, Il Suk SonDepartment of Cardiology, Kyung Hee University Hospital at Gangdong, Republic of Korea

Objective Cardiovascular morbidity and mortality rates are considered to be high in diabetic patients, despite negative stress test results; however, there is little data to support this supposition. We compared the long-term clinical outcomes of diabetic and non-diabetic patients with negative treadmill stress echocardiographic findings and evaluated the prognos-tic value of treadmill-related data in diabetic patients. Design and Method We evaluated 1,243 consecutive patients (mean

age, 56 ± 10 years; non-diabetics: diabetics, 975:268; mean follow-up of 5 years) with negative treadmill stress echocar-diography. Clinical and treadmill-related data were examined, and major adverse cardiovascular events (MACEs, a composite of coronary revascularization, acute myocardial infarction, and cardiovascular death) between the non-diabetic and diabetic groups were compared. Results In the population matched by clinical characteristics, the diabetic and non-di-abetic groups had similar MACEs occurrence (non-diabetics vs. diabetics = 5% vs. 7%) and event-free survival (incidence rate per person-years, 0.010 in non-diabetics vs. 0.014 in dia-betics; p value = 0.289). An independent predictor of MACEs in the diabetic group was elevated early diastolic velocity of the mitral inflow/mitral annulus (E/e’ ratio). Conclusions During the long-term follow-up, clinical outcomes of diabetic patients with negative stress echocardiographic results were benign and similar to those of non-diabetic patients. On the other hand, the transition toward diastolic dysfunction was an independent predictor of worse clinical outcomes. Therefore, diabetic patients with negative stress echocardiography may be considered to have low cardiovascular risk, especially when their diastolic function is normal.

Keywords: Diabetes mellitus, Prognosis, Echocardiogra-phy, Stress echocardiography, Diastolic disfunction

able

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the CPAP and sham CPAP groups combined, statistical sig-nificance was achieved for the adjusted between adherence and non-adherence differences in home systolic/diastolic BP (5.0/3.8 mmHg) and 24-h, daytime and night-time ambulatory pulse rate (6.2, 7.8 and 4.4 beats/min, respectively, p≤0.04). Conclusions CPAP adherence was associated with the BP lowering and pulse rate slowing effects, especially the CPAP frequency.

Keywords: Obstructive sleep apnoea syndrome, Noctur-nal hypertension, Continuous positive airway pressure, Adher-ence, Blood pressure

eP-21Peptide Programming of Nanoparticle as a Theranostic Toolbox towards Anti-atherosclerosisSeung Eun Yua, Seyong Chunga, Dae-Hyun Kimb, Hyun-Su Haa, Joon-Sang Parkc, Chang-Soo Kimd, Hak-Joon Sunga

aDepartment of Medical Engineering, Yonsei University College of Medicine, Republic of Korea, bDepartment of Veterinary Surgery, College of Veterinary Medicine, Chungnam National University, Republic of Korea, cDepartment of Computer Engineering, Hongik University, Seoul, Republic of Korea, dNumais Co., Ltd., Republic of Korea

Objective Continuous progress has been made in the field of nanodelivery to enable diagnosis and therapy together (“theranostic”) and to set nanoparticle as major depot and vehicle of therapeutics. Increasing demands lie in improving the therapeutic potential because currently, nanoparticle themselves are used as the sole spot to load therapeutics. When peptides are displayed on nanoparticles, the peptides can serve as not only a navigator to find a molecular zip code but also a potent therapeutic to improve synergistically with inter-nanoparticle contents. Moreover, this peptide strategy improves the diagnostic power due to the zip code targeting in addition to saving a room to load diagnostic agents in nanopar-ticles. When applied to a vascular system, this strategy appears to be more effective because atherosclerosis occurs in an irre-versible cascade fashion and thus, requires a theranostic tool as a last option to treat, representing a breakthrough point of the present study. Design and Method As a key factor of the diagnostic strategy, a unreported peptide with 10 amino acid sequence was used to target a site of disturbed blood as one of the earliest atherosclerotic events, thereby treating athero-sclerosis. Its targeting efficiency and therapeutic effects were

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eP-20Continuous Positive Airway Pressure Adherence and Blood Pressure Lowering in Patients with Obstructive Sleep Apnoea Syndrome and Nocturnal HypertensionJia-Hui Xia, Yuan-Yuan Kang, Yi-Bang Cheng, Qi-Fang Huang, Ting-Yan Xu, Yan Li, Ji-Guang WangDepartment of Cardiovascular Medicine, Centre for Epidemiological Studies and Clinical Trials, Shanghai Key Laboratory of Hypertension, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective We investigated continuous positive airway pressure (CPAP) adherence and its association with the blood pressure (BP) and pulse rate changes in patients with obstruc-tive sleep apnoea syndrome (OSAS) and hypertension. Design and Method In a single-blind trial, patients were randomly assigned to CPAP or sham CPAP treatment for 3 months. We performed clinic, ambulatory and home BP measurements at baseline and during follow-up. CPAP adherence was as-sessed as the CPAP frequency per week and time per night. Non-adherence was defined as a CPAP use for 5 days/week or 4 h/night. Results In the CPAP (n=26) and sham CPAP groups (n=21), the CPAP frequency was 5.5 and 4.8 days/week (p=0.17), respectively, and the CPAP time was 5.0 and 4.1 h/night (p=0.03), respectively. The corresponding prevalence of non-adherence was 46.2% and 66.7% (p=0.16), respectively. The CPAP frequency but not time tended to be associated with the changes in BP and pulse rate at 3 months of follow-up, es-pecially home systolic/diastolic BP in the CPAP group (3.2/1.3 mmHg greater reductions per 1 day increment, p≤0.01). Ad-herent, compared with non-adherent patients, had greater reductions in BP or pulse rate at 3 months of follow-up. In

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determined using cone-in-plate-based cell culture model and mouse partial carotid ligation model, followed by examination of anti-atherosclerotic and anti-inflammatory actions. The peptides were displayed on nanoparticles with high concentra-tion of iodine contrast and tested for the diagnostic precision of vascular lesion formation by computed tomography (CT) in the mouse model. Results The peptides enabled efficient targeting to sites of disturbed flow in the in vitro and in vivo models of atherosclerosis. The strategy served as an effective treatment to neointima formation by decreasing expression of adhesion molecules to recruit inflammatory cells. Moreover, the diagnostic efficiency was validated by concentrating the iodine contrast concentration and by CT-imaging the contrast signals in the sites of disturbed flow to detect vascular occlu-sion. Conclusions As an unprecedented strategy of theranos-tic nanotechnology, peptide-based programming of targeting and therapeutic functions is suggested to diagnose and treat early stages of atherosclerosis in the present study.

Keywords: Peptide programming, Theranostic, Nanopar-ticle, Blood flow disturbance, Atherosclerosis

eP-22Supernormal Vascular Aging and Long-term Incidence of Cardiovascular Disease in a Taiwanese CohortShao-Yuan Chuanga, Hao-Min Chenb,c, Chen-Hua Linb, Chi-Jung Huangc, Shu-Mei Yangc, Wan-Yu Yehc, Chen-Huan Chenb,c

aPublic Health Sciences Institute, National Health Research Institutes, Miaoli, Taiwan, bInstitute of Public Health, Taiwan, cDepartment of Internal Medicine, National Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan

Objective Arterial stiffening with age beyond expecta-tions implies early vascular aging (EVA) and contributes to the development of cardiovascular diseases. On the other hand, whether supernormal vascular aging (SNOVA) defined by less than expected age-related arterial stiffening predicts a lower incidence of cardiovascular diseases remains to be estab-lished. Design and Method A community-based cohort of 1850 Taiwanese adults enrolled during years 1991-1993 were followed until year 2017. Carotid-femoral pulse wave velocity (CF-PWV) was measured and conventional cardiovascular risk factors were collected at baseline. Age- and sex-specific CF-PWV cut-off points were used to define EVA, general vascular aging (GVA), and SNOVA. Cardiovascular diseases (coded as ICD-9-CM 390-459) were ascertained from the National Health

Insurance Dataset. Cox proportion model was used to evaluate the associations of EVA and SNOVA with incident cardiovascu-lar diseases. Results The three groups (EVA, n = 182; GVA, n = 1483; SNOVA, n = 185) had similar age, sex, height, smoking, drinking, and levels of serum creatinine and high-density li-poprotein cholesterol. A total of 664 adults developed one or more cardiovascular events during 40,626 person-years fol-low-up period. The SNOVA group (15.1 per 1000 person-years) had a significantly lower incidence of cardiovascular disease than the EVA group (21.8 per 1000 person-years, p0.05). SNOVA had a significantly lower cardiovascular risk than EVA (hazard ratio: 0.67, 95% confidence intervals, 0.46-0.97, p-val-ue =0.032), independent of the conventional cardiovascular risk factors, including age, male gender, brachial systolic and diastolic blood pressure, glucose, lipids, body mass index, uric acid, smoking, and drinking. Conclusions In this Taiwanese community-based cohort, SNOVA had a significantly lower long-term risk of cardiovascular disease than EVA, and the risk difference was independent of conventional cardiovascular risk factors. Identifying subjects with SNOVA may help discov-er novel cardiovascular protection factors.

Keywords: Early vascular aging, Carotid-formal Pulse wave Velocity, Cardiovascular risk, Prospective design

eP-25Differences between Brachial Oscillometric Arterial Blood Pressure Measured during Cuff Inflation and Cuff DeflationJames Coxa, Alberto P. Avolioa, Ahmad Qasemb, Isabella Tana, Mark Butlina

aDepartment of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia, bAtCor Medical-CardieX, Sydney, NSW, Australia

Objective Brachial oscillometric arterial blood pressure (BP) assessment offers greater convenience and less user dependence compared to auscultatory and invasive BP assess-ment. More recent devices have adopted the method of esti-mating BP using the oscillometric waveform obtained during inflation of the pneumatic cuff rather than during deflation. At present there is a lack in awareness and understanding of dif-ferences between these two methods in the context of oscillo-metric BP estimation. This study aims to determine if there are differences in the arterial brachial BP measurements obtained during cuff inflation compared to cuff deflation. Design and Method Brachial oscillometric BP was measured at baseline using two separate devices in triplicate in a randomised order

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capillary plexus (DCP), choriocapillaris flow void features, and cardiovascular profiles were assessed. The patients were divided into tertiles according to OCTA parameter. Results 60 patients with acute myocardial infarction were enrolled for analysis. The VD in SCP and DCP was not associated with the cardiovascular profiles. However, choriocapillaris flow void features (count, average size, and signal void area) significantly correlated with cardiovascular risk scores (Figure). Patients in the highest tertile of the average size of choriocapillaris were older, and more frequently had hypertension and dyslipidemia. Moreover, the 10-year risk of atherosclerotic cardiovascular disease (ASCDV) and Global Registry of Acute Coronary Events (GRACE) scores as well as B-type natriuretic peptide were higher in these patients. In multivariate analysis, GRACE score (odds ratio, 1.021; 95% confidence interval, 1.001?1.042; P = 0.042) and hypertension (odds ratio, 6.763; 95% confidence interval, 1.741?26.274; P = 0.006) were significantly associat-ed with the highest tertile of average size of choriocapillaris. Conclusions Choriocapillaris measured on OCTA was asso-ciated with the cardiovascular risk profiles in patients with acute myocardial infarction. This study suggests the possibility of OCTA as an indicator of the cardiovascular risk profile and could improve cardiovascular risk assessments.

Keywords: OCT-Angiography, Acute myocardial infarc-tion, Cardiovascular risk, Choriocapillaris

in seated participants (n=27, 42±17 years, 12 female). One de-vice estimated BP during cuff inflation whilst the other device estimated BP during cuff deflation. Differences were expressed as mean±standard deviation and compared using Bland-Alt-man plots and linear regression analysis. Results The average difference between devices for systolic BP (SBP) was -1.1±6.4 mmHg and for diastolic BP (DBP) it was 0.8±3.8 mmHg. There were no significant within-device BP differences across all measurements (p0.05). Despite no significant between-device differences observed in either SBP or DBP (p0.05), there was a large proportion of differences greater than 5 mmHg (SBP: 51% and DBP: 30%), with some differences greater than 10 mmHg (SBP: 22% and DBP: 6%). Heart rate was a con-tributing factor to the variation in SBP differences (p=0.02). Conclusions There were no significant differences between oscillometric brachial BP measured during cuff inflation or cuff deflation. However, the large variations in the readings that can be caused by differences in heart rate have implications when oscillometric BP devices are used as a reference for BP measurements, such as in the context of cuffless BP estimation.

Keywords: Blood pressure, Measurement, Devices

eP-26Associations between Choriocapillaris Flow on Optical Coherence Tomography Angiography and Cardiovascular Risk Profiles in Patients with Acute Myocardial InfarctionByung Sik Kima, Yong Un Shinb, Jeong-Hun Shina

aDivision of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Guri Hospital, Guri, Republic of Korea, bDepartment of Ophthalmology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri Hospital, Republic of Korea

Objective The aim of this study was to evaluate the association between macular perfusion assessed by retinal optical coherence tomography angiography (OCTA) and the cardiovascular risk profiles hospitalized for acute myocardial infarction. Design and Method Patients with acute myocar-dial infarction who had undergone OCTA and comprehensive ophthalmological examinations were evaluated retrospective-ly. Retinal OCTA was performed for each patient within 3 days after admission. Quantitative analyses of the vessel density of superficial retinal capillary and deep retinal capillary plexus layers was performed using the ImageJ software package. As-sociations between retinal OCTA parameters including, vessel density (VD) in the superficial capillary plexus (SCP) and deep

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Table

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eP-33Retrograde Pressure Gradient in the Brachial Artery Is Associated with Severity of Myocardial Perfusion Defect in Patients with Ischemic Heart DiseaseSmriti Badhwara, Dinu S Chandrana, Ashok K Jaryala,

Rajiv Narangb, Chetan Patelc, Kishore Kumar Deepaka

aDepartment of Physiology, All India Institute of Medical Sciences, New Delhi, India, bDepartment of Cardiology, All India Institute of Medical Sciences, New Delhi, India, cDepartment of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India

Objective Retrograde flow in endothelial cell cultures has shown to induce a pro-atherogenic phenotype. Pressure-gra-dient drives flow in peripheral arteries therefore, brachial artery retrograde blood flow should follow a reversal in pres-sure-gradient. The aim of the study was to evaluate associa-tion between retrograde blood flow and pressure gradient in brachial artery and assess the potential clinical significance of retrograde-pressure gradient as a tool for estimating cardio-vascular disease severity in patients. Design and Method Brachial artery retrograde blood flow velocity (RBFV) and pressure gradient was quantified using doppler ultrasound and non-invasive beat-to-beat blood pressure waveform in 31 healthy subjects and 45 patients with IHD. Area under curve of negative peak of the first derivative of brachial pressure waveform was used to calculate retrograde dP/dt (R-dP/dt). Carotid-radial pulse wave velocity (cr-PWV) measured using applanation tonometry was used to calculate retrograde-pres-sure gradient (R-dP/dx) using the formula; dP/dx = 1/cr-PWV *R-dP/dt. Extent of myocardial perfusion defect for patients was defined based on summed stress score (SSS) during ex-ercise-stress single positron emission computerized tomog-raphy (SPECT). Results Both R-dP/dt and R-dP/dx showed a significant positive correlation with RBFV (r = 0.56, p =0.001 and r = 0.56, p =0.001 respectively) in healthy subjects. R-dP/dx also correlated positively with RBFV in patients (r = 0.35, p =0.03) but was not independent of the association between RBFV and cr-PWV. In multiple regression analysis, including conventional cardiovascular risk factors (Age, gender, systolic BP, Heart Rate, Total Cholesterol and BMI) and cr-PWV, R-dP/dx emerged as an independent predictor of SSS and contrib-uted 72% of the total variance (23.5% of 32.5%), explained by the best-fit model. Conclusions An increase in retrograde pressure gradient would suggest an alteration in both central (aortic) and peripheral waveforms. The results of the study indicate that retrograde pressure gradient could be a valuable tool for assessing myocardial perfusion severity in patients with IHD.

Keywords: Retrograde blood flow, Ischemic heart dis-ease, Brachial pressure waveform, Myocardial perfusion

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eP-35A Count-based Binary Decision Method for Target Blood Pressure Achievement in Interpretation of Home Blood Pressure Monitoring RecordsYonggu Leea, Jinho Shinb, Jeong-Hun Shina, Hyun-Jin Kima, Young-Hyo Limb, Ran Heob

aDepartment of Cardiology, Hanyang University Guri Hosptial, Guri City, Republic of Korea, bDepartment of Cardiology, Hanyang University Medical Center, Seoul, Republic of Korea

Objective Home blood pressure monitoring (HBPM) is a useful tool to decide whether a patient’s blood pressure (BP) is controlled. However, applying HBPM to daily clinical practices is still challenging, because many patients with hypertension are not familiar to digital devices and high BP criteria using average HBPs are useless without easy accesses to average HBP. Therefore, we developed a simple method to make a bi-nary decision for an uncontrolled HBP through high BP counts. Design and Method We simulated 100 cases of HBPM series at 3 BP readings (K =16, 20 ,24) and 4 SD levels (SD=5, 10, 15, 20) using a random number generator function in statistical software R. Simulated mean systolic BPs (SBPs) and diastolic BPs were 130-140 mmHg and 80-90 mmHg. A high BP was de-fined as an individual BP ≥135/85 mmHg and an uncontrolled BP was defined as the mean BP ≥135/85 mmHg. Validation of the decision method was conducted using actual HBPM data from 412 patients on antihypertensive medications. Results In the simulated cohort, C-statistics of the high SBP counts were 0.970, 0.933, 0.933 and 0.868, when SDs were 5, 10, 15 and 20 mmHg at K=24, respectively. When ≥12 of 24 SBPs were high, the sensitivity, specificity and accuracy were 90.7%, 89.5% and 90.0% at K=24 and SD=5 mmHg. For the other combinations of K and SD levels, C-statistics and the accuracies ranged be-tween 0.8-1.0 and decreased as SDs increased while remained steady as Ks increased (Table 1). The validation cohort simi-larly showed that C-statistics of the ratio between the high BP counts to the total BP readings (count/reading ratio; CRR) was 0.985 (0.976-0.994) and CRR ≥0.5 had a sensitivity of 0.957, a specificity of 0.907 and an accuracy of 0.927. The SBP and diastolic BP (DBP) CCRs were highly correlated with mean SBP and DBP in the HBPM data (Linear regression R2 =0.736 for mean SBP; R2=0.821 for mean DBP) in the mean SBP of 124-145 mmHg and the mean DBP of 75-95 mmHg, respectively (Figure 1). Conclusions The count-based decision method can provide accurate assessments for HBP. A CCR of ≥0.5 is a simple and accurate marker of uncontrolled HBP and could be a useful tool to quickly assess the controlledness of HBP.

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eP-34Contrast-enhanced Magnetic Resonance Lymphangiography and Interventional Treatment for Various Thoracoabdominal Lymphatic DiseasesJi Hoon Shin, Hyun Jung Koo, Jooae Choe, Hee Ho ChuDepartment of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Korea, Republic of Korea

Objective To present experiences of contrast-enhanced magnetic resonance lymphangiography and interventional treatment for various thoracoabdominal lymphatic diseases.Design and Method Out of more than 100 lymphatic inter-ventional treatment cases, representative cases of contrast-en-hanced magnetic resonance lymphangiography and inter-ventional treatment for various thoracoabdominal lymphatic diseases will be presented. Results Normal anatomy and function of the central lymphatics and protocol of contrast-en-hanced dynamic MR lymphangiography are presented. MR lymphangiography findings and interventional treatment for various lymphatic diseases, such as plastic bronchitis, congen-ital chylothorax, iatrogenic thoracic duct injury, chylous asci-tes, lymphocele, and other lymphatic leakages are presented. Conclusions Contrast-enhanced dynamic MR lymphangiogra-phy accurately show anatomy of the central lymphatics includ-ing cisterna chyli and thoracic duct and nature/location of the lymphatic leakage / abnormality, and provide pivotal role in planning interventional treatment.

Keywords: Lymphatic intervention, MR, Chylothorax, Chylous ascites

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Keywords: Count-based binary decision method, Home blood pressure monitoring, Diagnostic performances, Simula-tion, Validation

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eP-37Metformin Alleviates Left Ventricular Diastolic Dysfunction in a Rat Myocardial Ischemia Reperfusion Injury ModelWoori Joa, Kyung-Ku Kanga, Sehyun Chaeb, Woo-Chan Sonc

aLaboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Republic of Korea, bDevelopmental disorders & rare diseases Research G, Korean Brain Research Institute, Republic of Korea, cUniversity of Ulsan College of Medicine, Asan Medical Center, Republic of Korea

Objective An increased incidence of myocardial infarc-tion (MI) has recently emerged as the cause of cardiovascular morbidity and mortality worldwide. Acute myocardial infarc-tion (AMI) is strongly related to metabolic syndrome, including dyslipidemia, smoking, diabetes mellitus, and hypertension. Left ventricular function is the best indicator of prognosis in MI patients, and patients with left ventricular diastolic dys-function have poorer surgical outcomes than patients with left ventricular systolic dysfunction in the perioperative period. Therefore, echocardiography is a well-established, non-inva-sive diagnostic tool for the accurate evaluation of myocardial dysfunction, cardiac anatomy and hemodynamic function in

clinical practice. A rat myocardial ischemia/reperfusion (I/R) injury model has recently been developed, which has been widely used to evaluate new drugs or stem cell therapies. The cardio-protective action of metformin cannot be entirely attributed to its anti-hyperglycemic actions, and a short-term treatment study of metformin using an isoproterenol-induced myocardial infarction rat model has been conducted to assess the mechanism. However, it is necessary to evaluate cardiac function in the early phase after MI because I/R injury is a common cause of AMI; furthermore, therapeutic strategies for the prevention of myocardial I/R injury can improve clinical outcomes in patients. This study aimed to show the effective-ness of metformin on left ventricular diastolic function using echocardiography in a rat myocardial I/R injury model. De-sign and Method In this in vivo model, the positive effect of metformin on the early stage of MI was confirmed by assessing total weight change over the study period, the relative heart weight, left ventricular systolic and diastolic function using echocardiography on Days 1, 3, and 7 as well as the degree of fibrosis. Sprague-Dawley rats (8-week-old adult males, mean weight: 287.90 _ 6.62 g) were purchased from Koatech (Kyun-gki, South Korea); the study design was approved by the Insti-tutional Animal Care and Use Committee of Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF-19022001-00, 17 02 2019). The rats were housed at a temperature of 22℃ and relative humidity of 50%, using 12 h light/dark cycles, illumi-nation at 150?300 Lux and with ventilation 10?20 times/hour. These conditions were monitored every hour for 24 h and maintained within an acceptable range throughout the study. The rats were housed three per cage at the beginning of the study and fed an autoclaved pellet diet (SAFE + 40RMM; SAFE Diets, Augy, France) ad libitum. The experimental design is shown in Figure 1A. The rats were divided into four groups (six rats/group) as follows: A) Sham group, B) MI group, C) Sham + MET group and D) MI + MET group. The rats in groups A and B received reverse osmosis (RO) drinking water, and the rats in groups C and D were treated with 200 mg/kg metformin (Sig-ma-Aldrich, St Louis, MO, USA) dissolved in RO drinking water by oral injection daily for 11 days (3 days before the surgery to 7 days post-surgery). Results Metformin administration significantly increased ejection fraction and fractional shorten-ing values on Days 3 and 7 when MI occurred, indicating that metformin improved left ventricular systolic function. In the Sham + MET and MI + MET groups, the E’ value was signifi-cantly different up to Day 3 but not at Day 7. This may mean that left ventricular diastolic function was effectively restored to some extent by Day 7 when metformin was administered. These results suggest that diastolic dysfunction, assessed by echocardiography, does not recover in the early phase of isch-emic reperfusion injury in the rat myocardial I/R model. How-ever, administering metformin resulted in recovery in the early phase of ischemic reperfusion injury in this model. Further

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Figure

eP-38Quarterly Versus Annual ECG Screening for Atrial Fibrillation in Older Chinese (AF-CATCH): A Prospective, Randomised, Controlled TrialWei Zhang, Yi Chen, Ji-Guang WangDepartment of Cardiovascular Medicine, Center for Epidemiological Studies and Clinical Trials, Shanghai Key Laboratory of Hypertension, The Shanghai Institute of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective Screening for atrial fibrillation before symp-toms manifested and subsequent initiation of oral antico-agulants (OACs), could prevent stroke and death. The most cost-effective strategy to screen atrial fibrillation in high-risk population aged 65 and over remains unknown. Design and Method We performed a randomised controlled trial that compares different screening frequencies of 30-second single-lead ECG (AliveCor® Heart Monitor) in the detection of atrial fibrillation in Chinese residents (≥65 years old) in 5 community health centres in Shanghai. Only participants without atrial fibrillation history and atrial fibrillation rhythm

gene expression profiling of left ventricle tissues revealed that the metformin-treated group had notably attenuated immune and inflammatory profiles. To sum up, a rat myocardial I/R injury model and ultrasound-based assessment of left ventric-ular systolic and diastolic function can be used in translational research and for the development of new heart failure-related drugs, in addition to evaluating the potential of metformin to improve left ventricular (LV) diastolic function. Conclusions The current study highlighted the positive effects of metformin on acute MI; the weight loss associated with metformin treat-ment was confirmed, and the increased heart weight/body weight (%) in the MI-induced groups reflects cardiac hypertro-phy, as reported in previous studies. Echocardiographic data showed that left ventricular cardiac dysfunction does not re-cover in the early phase of ischemic reperfusion injury in this rat model throughout the experimental period, but metformin administration significantly improved left ventricular systol-ic function on Day 7. In addition, E/E’ values, an important indicator of cardiac diastolic function and poor outcomes in humans, significantly improved in the early stage of MI onset when metformin was administrated. There are some limita-tions to using E’ and E/E’, which show only the global function of the LV. However, further studies are planned using quantita-tive evaluation of regional function and the filling dynamics of the LV using strain, strain rate and speckle tracking with color tissue doppler.

Keywords: Acute myocardial infarction, Coronary artery ligation, Myocardial ischemia/reperfusion, Systolic function, Diastolic function

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at baseline were eligible for inclusion in the trial. Randomis-ation was done with the use of a random number table, and stratified for study site. Participants were randomised in a 1:1 ratio into annual (G1) and quarterly screening (G2) groups: the quarterly screening group was further randomised in a 3:1 ratio into subgroups of quarterly screening (G2-1) and quarterly screening PLUS (G2-2, ECG weekly for 1-month then quarterly). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was per-formed for all randomised patients who had at least one ECG recording during follow-up. This trial was registered at Clin-icalTrials.gov, number NCT02990741, and terminated on 31 October, 2020. Results Between April 17, 2017, and June 26, 2018, a total of 8240 participants were randomised into G1 (n=4120), G2-1 (n=3090) and G2-2 (n=1030), with a mean of 1.6, 3.5 and 5.2 ECG records respectively during a median of 2.1 years follow-up (13,284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in G1 (4.1/1000 person-years) and 47 in G2 (6.7/1000 person-years; hazard ratio with G1, 1.71; 95% confidence interval [CI] 1.06-2.76; P=0.03). 40 in-cident cases were detected in G2-1 (7.2/1000 person-years; hazard ratio with G1, 1.83; 95% CI 1.12-3.00; P=0.02) and 7 in G2-2 (4.8/1000 person-years; hazard ratio with G1, 1.24; 95% CI 0.54-2.86; P=0.61). No significant difference was noted between G2-1 and G2-2 (hazard ratio with G2-1, 0.68; 95% CI 0.30-1.52; P=0.35). Conclusions Quarterly 30-second sin-gle-lead ECG screening significantly increased the detection rate of incident atrial fibrillation, additional weekly screening in the first month did not yield added predictive value.

Keywords: Atrial fibrillation, ECG, Screening

eP-39Depression Was Associated with Atherosclerosis and Cardiovascular Events, Especially in Male Patients at Risk for Cardiovascular DiseaseTomoyuki Kabutoya, Satoshi Hoshide, Kazuomi KarioDivision of Cardiovascular Medicine, Jichi Medical University, Japan

Objective Depression is known to be associated with poor prognosis in hypertensive patients, but the associa-tions between depression status and vascular properties in patients at risk of cardiovascular disease have been unclear. We hypothesized that the depression score is associated with atherosclerosis and cardiovascular events. Design and Method We studied 2,695 outpatients who had at least one cardiovascular risk factor (mean age 65±11 years; male, 46%).

We examined the relationship between depressive symptoms, as measured by the Beck Depression Inventory (BDI), and each of atherosclerosis and cardiovascular events. Depression was defined as having a BDI score ≥ 16. We measured brachi-al-ankle pulse wave velocity (baPWV) in 2,176 patients and intima-media thickness (IMT) in 1,165 patients. The primary endpoints were fatal/nonfatal cardiovascular events (myocar-dial infarction, hospitalization for heart failure, and aortic dis-section) and were assessed separately in males and females. Results The BDI scores and the prevalence of depression were significantly higher in women compared to men (BDI scores: 10.3±7.4 vs. 7.5±6.3, p0.001; prevalence of depression: 21.9 vs. 10.8%, p0.001). In males, the depression group (n=84) had higher baPWV but similar IMT compared to the nondepres-sion group (baPWV: 17.7±4.7 vs. 16.6±3.2m/s, p=0.001; mean IMT: 1.14±0.44 vs. 1.07±0.52mm, p=0.27), and in females, the depression group had slightly higher baPWV and IMT than the nondepression group (baPWV: 17.1±3.8 vs. 16.7±3.5m/s, p=0.072; mean IMT: 1.13±0.75 vs. 0.97±0.34mm, p=0.09). The mean follow-up period was 49±27 months; 124 patients suffered primary endpoints. Among males, patients with de-pression (n=120) had a greater incidence of cardiovascular events than patients in the nondepression group (n=995) (log rank 8.62, p=0.003). Among females, the incidence of cardio-vascular events was similar between the depression (n=298) and nondepression groups (n=1063, p=0.88). Conclusions Depression is associated with cardiovascular events in male patients, but not female patients, with a cardiovascular risk factor. The associations between depression and PWV or IMT differed between the sexes.

Keywords: Depression, Atherosclerosis

eP-41Alcohol Consumption in Relation to Cardiovascular and Non-cardiovascular Mortality in an Elderly Male Chinese PopulationXiao-Fei Ye, Chao-Ying Miao, Wei Zhang, Chang-Sheng Sheng, Qi-Fang Huang, Ji-Guang WangDepartment of Cardiovascular Medicine, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objective We investigated the association of alcohol con-sumption with cardiovascular and non-cardiovascular mortal-ity in elderly Chinese men. Design and Method Our partici-pants were recruited from residents living in a suburban town of Shanghai (≥60 years of age, n=1702). Alcohol intake was

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myocardial infarction (STEMI) has not been is not demonstrat-ed well. Design and Method Total 490 patients with STEMI who underwent a primary percutaneous coronary interven-tion and baPWV measurement were enrolled between Novem-ber 2011 and December 2015. We evaluated the prognostic value of baPWV predicting the major adverse cardiovascular events including cardiac death, recurrent MI, revasculariza-tion, hospitalization for heart failure, and stroke. Results Cut off value of high baPWV was 17.37m/sec in the receiver op-erating characteristic curve analysis for MACCE (area under the curve: 0.662; 95% confidence interval [CI]: 0.618-0.704; p value 0.001). MACCE occurred 11 patients (3.7%) in low baPWV group and 29 (14.8%) in high baPWV group during follow-up periods (median 375 days). Multivariate Cox regres-sion analysis revealed that high baPWV group had higher risk for MACCE than low baPWV group (hazard ratio with 95% CI: 3.004 [1.117-8.083], p=0.029). Conclusions High baPWV was a strong prognostic value of MACCE in patients with STEMI.

Keywords: baPWV, STEMI, PCI

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eP-43Differential Impact of Home Blood Pressure Variability for Cardiovascular Events between Patients with and without Advanced Arterial Stiffness: Results of the J-HOP StudySatoshi Hoshide, Yusuke Ishiyama, Kazuomi KarioDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Tochigi, Japan

Objective This study sought to investigate whether the relation between increased blood pressure (BP) variability and increased arterial stiffness confers a risk for cardiovas-cular disease (CVD) events. Design and Method We ana-lyzed 2648 patients from a practitioner-based population (mean±SD age 64.9?11.4 years: 75.8% taking antihyperten-sive medication) with at least one cardiovascular risk factor who underwent home BP monitoring in the Japan Morning Surge-Home Blood Pressure Study. The standard deviation (SDSBP), coefficient of variation (CVSBP), and average real

classified as non-drinkers, past drinkers (stopped drinking for ≥12 months), and current light-to-moderate (1 to 299 g/week) and heavy drinkers (≥300 g/week). Alcoholic beverages were classified as beer/wine, rice aperitif and liquor/mix drinking. Results During 5.9 years (median) of follow-up, all-cause, cardiovascular and non-cardiovascular deaths occurred in 211, 98 and 113 participants, respectively. The corresponding incidence rates were 23.6/1000, 10.9/1000 and 12.6/1000 person-years, respectively. Both before and after adjustment for confounding factors, compared with non-drinkers (n=843), past drinkers (n=241), but not the current light-to-moderate (n=241) or heavy drinkers (n=377), had a higher risk of all-cause (adjusted hazard ratio [HR] 1.90, 95% confidence inter-val [CI] 1.35-2.68, P=0.0003) and non-cardiovascular mortality (HR 2.46, 95% CI 1.55-3.91, P=0.0001). Similar trends were observed for cardiovascular mortality (HR 1.44, 95% CI 0.85-2.44, P=0.18). In similar unadjusted and adjusted analyses, compared with the current beer/wine drinkers (n=203), li-quor/mix drinkers (n=142), but not aperitif drinkers (n=273), had a significantly higher risk of all-cause (HR 3.07, 95% CI 1.39-6.79, P=0.006), and cardiovascular mortality (HR 10.49, 95% CI 2.00-55.22, P=0.006). Similar trends were observed for non-cardiovascular mortality (HR 1.94, 95% CI 0.73-5.16, P=0.18). Conclusions Our study showed risks of mortality as-sociated with past drinking and liquor drinking in the elderly Chinese men.

Keywords: Alcohol consumption, Mortality, All-cause mortality, Cardiovascular mortality

eP-42Brachial-ankle PWV for Predicting Clinical Outcomes in Patients with ST-elevation Myocardial InfarctionKye Taek Ahna, Sang Yeub Leeb, Seon Ah Jina, Mi Joo Kima, Seok-Woo Seonga, Pil Sang Songa, Si Wan Choi a, Jin-Ok Jeonga

aDepartment of internal medicine, Division of cardiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea, bDepartment of internal medicine, Division of cardiology, Chungbuk National University Hospital, Chungbuk National University School of Medicine, Daejeon, Republic of Korea

Objective Brachial-ankle pulse wave velocity (baPWV) is the vastly used good modality to estimate arterial stiffness and predict the cerebro-cardiovascular morbidity and mortality. However, its anticipated value to the patients with ST-elevation

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variability (ARVSBP) were assessed as indexes of day-by-day home systolic BP (SBP) variability. We assessed arterial stiffness by brachial-ankle pulse wave velocity (baPWV) and divided patients into lower (1800 cm/s, n=1837) and higher (≥1800 cm/s, n=811) baPWV groups. Results During a mean follow-up of 4.4 years, 95 cardiovascular events occurred (8.1 per 1000 person-years). In Cox proportional hazard models adjusted for traditional cardiovascular risk factors including average home SBP, the highest quartiles of SDSBP (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.33-4.67), CVSBP (HR, 2.93; 95%CI, 1.61-5.32) and ARVSBP (HR, 2.76; 95%CI, 1.48-5.14) were predictive of CVD events compared to the other quartiles in the higher baPWV group. Moreover, 1SD increases in SDSBP (HR, 1.39; 95%CI, 1.07-1.82), CVSBP (HR, 1.44; 95%CI, 1.09-1.89) and ARVSBP (HR, 1.34; 95%CI, 1.03-1.74) were also predictive of CVD events. These associations remained even after N-terminal pro-brain natriuretic peptide was added to the models. However, these associations were not observed in the lower baPWV group. Conclusions We conclude that arterial stiffness contributes to the association between home BP variability and CVD incidence.

Keywords: Home blood pressure, Blood pressure vari-ability, Arterial stiffness, Brachial-ankle pulse wave velocity, Cardiovascular disease

eP-45Estimated Pulse Wave Velocity and the Risk of Cardiovascular Events: A Nationwide Population-based Study of More Than 4 Million Men and WomenDong-Hyuk Cho, Sae Young Jae, Jang Young KimCardiology, Yonsei University Wonju College of Medicine, Republic of Korea

Objective Pulse wave velocity (PWV), an index of aortic stiffness, is a predictor of cardiovascular (CV) events, but its measurement demands cost-intensive equipment and sophis-ticated testing skills in clinical practice. This study aimed to evaluate whether estimated PWV (ePWV) would be associat-ed with CV events in a large nationwide population. Design and Method We identified 4,668,405 individuals without previous CV disease who underwent a health screening exam-ination in 2009 and 2011 from the Korean National Health In-surance Cohort database. ePWV was estimated using a prag-matic and previously validated equation from age and mean blood pressure. The primary composite endpoint (CE) was a composite of non-fatal myocardial infarction (MI), ischemic stroke, and CV mortality. Results During a median 6 years of

follow-up, 81,558 developed CEs. In multivariable-adjusted models including systolic blood pressure, the hazard ratio (95% confidence interval) for incident CE comparing the high-est to the lowest quartiles of ePWV levels was 1.38(1.31- 1.44, P for trend 0.01). The corresponding hazard ratios (95% con-fidence interval) for non-fetal myocardial infarction, ischemic stroke, and CV mortality were 1.59(1.45-1.74), 1.30(1.23-1.38), and 1.53(1.17-2.01), respectively. Conclusions ePWV is independently associated with increased risk of CV events, indicating that ePWV may reflect the residual risk of age and blood pressure on arterial stiffness and subsequently cardio-vascular risk. ePWV may be a simple and cost-effective ap-proach to assess CVD risk.

Keywords: Pulse wave velocity, Cardiovascular eventsFigure

Figure

eP-46The Associations between Endothelial Dysfunction, Arterial Stiffness and the Development of Carotid Atherosclerosis in Hypertensive SubjectsH Nakano, K Shiina, T Takahashi, K Kumai, M Fujii, Y Iwasaki, C Matsumoto, A Yamashina, T Chikamori, H TomiyamaDepartment of Cardiology, Tokyo Medical University, Japan

Objective While arterial stiffness and endothelial dys-function, which are diffuse vascular damage, are phenotypes of vascular damage, their associations with the progression of atherosclerosis, which is focal vascular damage, has not been fully clarified. The present prospective observational study was conducted to examine whether arterial stiffness and endothelial dysfunction predict the progression of carotid atherosclerosis in subjects medicated for hypertension with/without carotid atherosclerosis. Design and Method We conducted flow-mediated dilation Japan study, which is mul-ticenter prospective observational study. In 617 subjects re-

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outer diameter of metformin treated db/db aorta are greater than db/db aorta and control. This resulted in an increase of compliance in metformin treated aorta. Interestingly, these findings are not consistent in the carotid artery. Untreated db/db carotid artery shows larger outer diameter compared to the control, according to the lumen pressure increase. However, metformin treatment leads a less increase in outer diameter and circumferential stretch compared to untreated db/db carotid during the inflation. It suggests that metformin could prevent the abnormal increase of lumen in type 2 di-abetes. There is no difference in tangent modulus between untreated and metformin treated db/db carotid artery. It in-dicates that metformin does not alter the material properties. Conclusions Metformin is a typical medicine used to type 2 diabetes. To understand the effect of metformin to the arterial mechanics, we compared the mechanical behavior of the aorta and common carotid artery with and without treatment. This study elucidates that metformin treatment alters the arterial mechanics in a different way, in a different location.

Key words: Type 2 diabetes, Arterial mechanics, Met-formin, Aorta, Carotid artery

ceiving antihypertensive treatment, we performed flow-medi-ated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV) and common carotid artery intima-media thickness mean and maximal (IMTmean and IMTmax) at the baseline and the end (3 years’ later) of study periods. Results During the study period, FMD was decreased and baPWV, IMTmean and IMTmax were increased significantly. In subjects without carotid atherosclerosis (IMTmax <1.1mm, n=416), baPWV, but not FMD, at baseline had significant associations with IMTmean and IMTmax at both the baseline and end of study period. As shown in Figure, the changes of IMTmean and also IMTmax during the study period were higher in the highest tertile ranges of baPWV at the baseline than in the lowest tertile range of baPWV. On the other hand, in subjects with carotid atherosclerosis (IMTmax >1.1mm, n=201), both baP-WV and FMD were not associated with any markers of carotid atherosclerosis and also their changes during the study period. Conclusions In subjects with hypertension, arterial stiffness rather than endothelial dysfunction may be associated with the progression of carotid atherosclerosis, and this association may be significant in the premature stage of atherosclerosis.

eP-47Biomechanical Characterization of the Arteries in Type 2 Diabetic MiceJungsil Kima,b, Mi-kyung Leec

aDepartment of Biosystems Machinery Engineering, Sunchon National University, Republic of Korea, bDepartment of Intelligent Biomedical Technology, Sunchon National University, Republic of Korea, cDepartment of Food and Nutrition, Sunchon National University, Republic of Korea

Objective Diabetes mellitus (DM) is linked to an in-creased prevalence of cardiovascular complications. In this study, we investigated the impact of type 2 DM on arterial mechanics using type 2 diabetic (db/db) mice with metformin treatment. Design and Method Male mice from three groups (m+/db mice as control, db/db mice, and db/db mice with metformin treatment for 6 weeks) were used. Aortae and common carotid arteries dissected from 13-week-old mice were used for mechanical testing. Outer diameter of the artery, lumen pressure, and axial force were collected for the me-chanical analysis, applying lumen pressure ranging from 0 to 175 mmHg. Mean circumferential stress, stretch, compliance to represent a structural property of the arterial wall, and tan-gent modulus to indicate a material property were calculated and compared among groups. Results During the inflation, the

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