POA2021

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 function, 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 biomarkers will be assessed in terms of relationships of pulsatile pressure in the central aorta and peripheral arteries and pressure-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 cerebral 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.

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Systemic large arteries may be a crucial mediator between vascular health and cognitive function decline with aging. 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 cycle, 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 ventricle. Previous studies have shown that various parameters derived from the reservoir-wave analysis are associated with cardiovascular events and mortality in both high-risk individuals 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 significantly 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.

Aortic stiffness is closely related with subclinical left ventricular dysfunction. Increased central systolic blood pressure results in increasing LV afterload and makes myocyte 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 hemodynamic 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.

There is a need for imaging methods to better triage patients with acute stroke for tissue plasminogen activator-mediated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thromboemboli. Currently, magnetic resonance or computed tomography 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 thrombus more precisely, serially monitor the therapeutic effects of thrombolysis, and detect post-treatment recurrence.

I will discuss the impact of COVID-19 on cardiovascular system. I will also summarize the current status of cardiovascular medication on COVID-19 disease course.

Pulse transit time (PTT) is the time delay for the pressure wave to travel between proximal and distal arterial sites. According to the Bramwell–Hill equation, PTT varies with the arterial compliance. Since arterial compliance decreases as blood pressure (BP) increases, PTT is also often inversely correlated with BP. PTT can be estimated 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 conventional 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 systole when the waveform feet occur. Hence, by virtue of being estimated at the waveform feet, conventionally estimated PTT is precisely a marker of arterial stiffness at the level of diastolic BP (DP) and generally correlates best with DP. PTT varies with BP throughout the cardiac cycle, yet, because of wave reflection, only one PTT value at the level of DP is conventionally estimated from proximal and distal arterial waveforms. a nonlinear arterial tube-load model has been proposed and used as a technique to estimate PTT as a function of BP from proximal and distal BP waveforms. This model accounts for the BP-dependent arterial compliance (which makes it nonlinear) and the main wave reflection site at the periphery. Based on the PTT principle, there have been many innovative technologies developed to measure cuffless BP. In this talk, I will briefly introduce the current status of the development of these new cuffless BP devices.

Non-invasive continuous blood pressure monitoring is very important in terms of accurate diagnosis and monitoring of treatment progress for hypertensive patients. A continuous blood pressure measurement solution based on a wristwatch-type device has been developed and sold in the market, but the performance enough to be used in the clinical practice has not yet been confirmed. In this study, we report the current progress of the development of a non-invasive continuous blood pressure monitoring system based on a single chest-worn patch-type device. In the model for estimating blood pressure from the measured biological signals, 28 feature parameters were extracted from the ECG and PPG waveforms of the open access public dataset, Vital DB and MIMIC III, from which SBP and DBP were estimated by combining two different neural network models. (ANN & RNN) We trained the model with a total of 1,000 patient data and performed both internal and external validation with 700 patient data. Chest-worn device is a patch type that measures ECG, PPG, and SCG and transmits wirelessly through Bluetooth®. (76 x40x18 mm, 27.5 g) The performance of the developed blood pressure estimation model was evaluated after converting the chest PPG from the patch-type device into the finger PPG of total 25 subjects in three different physiological situations. The developed system showed excellent accuracy that satisfies all three international standards of AAMI, BHS, and IEEE, confirming the possibility of clinical application.

Recent accumulated evidences have demonstrated that arterial stiffness, which assessed by pulse wave velocity (PWV), is an independent risk for cardiovascular outcomes. Furthermore, PWV has been proposed a marker for the development of hypertension and also diabetes mellitus. On the other hand, central blood pressure/pressure wave reflection are also markers related to pathophysiological abnormalities in systemic arterial tree. Even so, the clinical applications of these tools for cardiovascular risk assessment are limited as compared to PWV. Here, I would like to discuss the usefulness of central blood pressure/pressure wave reflection for the assessment of cardiovascular risk in clinical practice. I explain the difference between PWV and central blood pressure/pressure wave reflection in vascular damages in systemic arterial tree. Then, the clinical implications of such difference are described.

Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionizing methods for the accurate anatomic depiction of the cardiovascular system. Based on the inherent flow sensitivity, MRI could be used to investigate hemodynamics features in patients with anatomical data within a single measurement. In particular, time-resolved and three-dimensional characterization of blood flow using 4D Flow MRI has achieved considerable progress in recent years. The presentation introduces the principle and procedures of 4D Flow MRI. Various fluid dynamic biomarkers for possible clinical usage are also described, including wall shear stress, turbulent kinetic energy, and relative pressure. Lastly, the presenter will share the experiences of MD-PhD Collaboration on 4D Flow MRI from engineer’s point of view.

Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionizing methods for the accurate anatomic depiction of the cardiovascular system. Based on the inherent flow sensitivity, MRI could be used to investigate hemodynamics features in patients with anatomical data within a single measurement. In particular, time-resolved and three-dimensional characterization of blood flow using 4D Flow MRI has achieved considerable progress in recent years. The presentation introduces the principle and procedures of 4D Flow MRI. Various fluid dynamic biomarkers for possible clinical usage are also described, including wall shear stress, turbulent kinetic energy, and relative pressure. Lastly, the presenter will share the experiences of MD-PhD Collaboration on 4D Flow MRI from engineer’s point of view.

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In 2021, accumulated coronavirus disease 2019 (COVID-19) confirmed cases exceeded 100 million worldwide. Although there is a hope for vaccination, continuous infection is observed with case fatality rate over 2%. Patients with cardiovascular disease are more susceptible 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 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, arrhythmia, acute thrombosis, and stress induced cardiomyopathy. Long-term complications are also noticed from the recent publications and need further attention.

Pulmonary arterial hypertension (PAH) is characterized by molecular heterogeneity and complicated pathology in multiple tissues, and remains incurable. In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggested 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. In mice, Sox17 deficiency induced hypoxia-triggered PAH, which was persistent even after long rest in normoxia. Mechanistically, transcriptomic 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 upregulated in Sox17-deficient lung ECs. Pharmacologic inhibition of c-Met together with a vasodilator attenuated 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. In this work, the downregulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to a hypoxic environment. Our findings suggest that the reactive upregulation of the HGF/c-Met signaling could be a novel druggable target for PAH treatment.

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 primary 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), respectively (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.

Lymphatic flow disorders 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 manifested with chylothorax and chylous ascites, and there may be lymphocutaneous fistula, chyluria, and vaginal leakage. In addition to X-ray (conventional) lymphangiography, advances in MR lymphangiography allow overall evaluation of the location of leakage and central lymphatics before intervention. 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 chylothorax and more severe leakages.

We recently investigated effects of various antihypertensive drugs on arterial stiffness as assessed by brachial-ankle 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 another 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 changes 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 treatment 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.

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-atherosclerosis therapy. In mouse models of atherosclerosis, systemically injected nanomedicine accumulates preferentially in atherosclerotic plaques and significantly reduces the amount of cholesterol crystals and the number of macrophages, 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.

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.

Multiple trials 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 patients with type 2 diabetes and left ventricular hypertrophy. Moreover, it is reported that diastolic reserve after treatment of 24 weeks SGLT-2 inhibitor in patients with early diastolic dysfunction and type 2 diabetes. Through this session, I will discuss the clinical and subclinical effects of SGLT-2 inhibitor on cardiovascular diseases.

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) monitoring, we evaluated and demonstrated that the 3D force sensor-based continuous BP shows good correlation with intermittent, noninvasive BP (NIBP). This will be especially useful in evaluating BP in patients with autonomic nervous system problem. Attachable and disposable force sensor is investigated 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.

Physical activity is associated with a dose-dependent reduction in the risk of metabolic disease, cardiovascular events, and cardiovascular and all-cause mortality. The 2018 Physical Activity Guidelines for Americans emphasize the central role of physical activity in promoting cardiovascular health and maintaining a healthy lifestyle, and recommend that adults engage in at least 150-300 minutes/week of moderate-intensity, or 75-150 minutes/week of vigorous-intensity aerobic physical activity. While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. Furthermore, men with high levels of physical activity, defined as more than 3,000 metabolic equivalents of task (MET)–minutes/week (equivalent to running approximately 6.5 km/day or 350-400 min/week), had higher CAC scores compared to men with lower levels of physical activity.5 It is still unclear if the higher CAC scores associated with high levels of physical activity are restricted to very high levels of activity, and how current levels of physical activity affect future CAC scores. This study was conducted to evaluate the prospective association between physical activity and CAC scores in a large cohort study of apparently healthy men and women who attended repeated health screening visits.

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Physical activity is associated with a dose-dependent reduction in the risk of metabolic disease, cardiovascular events, and cardiovascular and all-cause mortality. The 2018 Physical Activity Guidelines for Americans emphasize the central role of physical activity in promoting cardiovascular health and maintaining a healthy lifestyle, and recommend that adults engage in at least 150-300 minutes/week of moderate-intensity, or 75-150 minutes/week of vigorous-intensity aerobic physical activity. While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. Furthermore, men with high levels of physical activity, defined as more than 3,000 metabolic equivalents of task (MET)–minutes/week (equivalent to running approximately 6.5 km/day or 350-400 min/week), had higher CAC scores compared to men with lower levels of physical activity.5 It is still unclear if the higher CAC scores associated with high levels of physical activity are restricted to very high levels of activity, and how current levels of physical activity affect future CAC scores. This study was conducted to evaluate the prospective association between physical activity and CAC scores in a large cohort study of apparently healthy men and women who attended repeated health screening visits.

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 measure has never been taken root in the general practice in Japan, possibly because of methodological difficulties. Against this background, brachial-ankle (ba) PWV was developed. Measurement of this parameter is easy, and its reproducibility 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.

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 chronological age, called supernormal vascular aging (SUPERNOVA). In the present lecture, I will discuss the definition and clinical 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 present the first results from the SPARTE interventional trial, and what the next steps should be.

Intravital microscopy enables dynamic 3D in vivo visualization of dynamic biological processes in various tissue in a natural physiological condition in a living animal, providing unprecedented insights over conventional static 2D imaging of histological sample or in vitro culture sample. In this talk, a custom-built intravital confocal and two-photon microscopy system will be introduced, which is capable of real-time in vivo visualization of pulmonary and cardiac microcirculation and circulating cells. Based on direct imaging of rapidly flowing cells in capillaries, we newly derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the microcirculation. 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 system could serve as a useful tool for investigating pathophysiology of pulmonary and cardiac diseases with disturbed microcirculation and evaluating potential treatments.

Several societies have published guidelines to optimize the collection, analysis and interpretation of LAS data, including the recent American Heart Association Science Statement in the USA. Nevertheless, current Hypertension Guidelines notably differ about the position of assessing LAS differ in cardiovascular risk management. In general, European Guidelines recognize PWV as a marker of target organ damage, but do not recommend its systematic use in general population. Asian guidelines consider PWV as a recommended test at diagnosis of hypertension. In contrast, USA guidelines are silent on a position about its usefulness. Nevertheless, evidence continues to accumulate supporting the ability of PWV to predict cardiovascular events, and recent studies have shown that it improves risk classification adjusting for established risk factors specially for intermediate risk patients. These observations, along with continued advances relating to beneficial interventions affecting LAS in dietary, exercise, pharmacologic and other treatment areas, will be reviewed, including a summary of findings over the last 5 years that we believe are a complement to existing LAS recommendations, and continue to expand the portfolio of LAS measurement benefits.

Healthy lifestyle is a critical component to protect from vascular aging and the age-related vascular dysfunction. Cardiorespiratory fitness (fitness) is a physiological biomarker of cardiopulmonary and muscular system integrity that is reflective of physical activity behavior that has a strong protective effect against cardiovascular mortality. Physiologically, levels of fitness, like vascular aging, gradually decline with advancing age, while advancing aging also leads to a deterioration of vascular structure and function. Thus, fitness is just as powerful as vascular aging in predicting cardiovascular disease, and declines of fitness with age can be considered a sign of vascular aging. Several studies suggested that higher fitness delays the development of large elastic artery stiffness, intima-media thickening and coronary artery calcification with advancing age. Therefore, improving or maintaining relatively higher 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 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 “possible 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 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 unreasonable 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.

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 morbidity 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-related 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 developing DVT and its complications, including PE and post-thrombotic 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 validity. 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 social 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 advocated for outpatient rather than inpatient management of deep vein thrombosis, including full outpatient management 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. Second, prevention efforts specific to DVT could have contributed 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 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.

Resistant hypertension is defined as blood pressure (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, diagnosis, and treatment for patients with resistant hypertension 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 Prevention 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. Anthropometric data, medical history, medication information, the results of laboratory tests for evaluating target organ damage were collected. Patients were asked to answer questionnaires regarding lifestyle, psychological status, and cognitive 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 period 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 prevalent 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 uncontrolled hypertension. Since the prognosis of masked uncontrolled hypertension is comparable to that of sustained uncontrolled hypertension, out-of-office BP measurement is necessary to control BP in patients with resistant hypertension. 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 hypertension through this study. The achievements of this study are expected to be widely used in the treatment and research of resistant hypertension in the future.

Ectopic fat depots, such as visceral or pericardial fat, because 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 parameters. 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).

The upcoming 2022 Taiwan Hypertension Guidelines emphasize the importance of risk-based blood pressure management approach. We agree that blood pressure target of <130/80 mmHg is adequate for all hypertensive patients except 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, conducted according to the “722” rule. Details of recent progress and the new Taiwan Hypertension Guidelines will be introduced during the Talk.

Recent update of management of the hypertension and lipid and Effect of control of the hypertension and lipid using signle pill combination treatment.

Pulsatile blood pressure confers cardiovascular risk. Whether associations of cardiovascular endpoints are tighter for central than peripheral systolic or pulse pressure remains uncertain. Among 5608 participants enrolled in the International Database of Central Arterial Properties for Risk Stratification (IDCARS), 255 primary composite cardiovascular endpoints occurred during a median of 4.1 years follow-up. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% confidence interval, 1.33-1.70) for central SBP, 1.36 (1.19-1.54) for central PP, 1.49 (1.33-1.67) for brachial SBP, and 1.34 (1.19-1.51) for brachial PP (P<0.001). Adding a central or brachial SBP or PP to a base model increased the model fit (P<0.001) with generalized R2 increments ranging from 0.37 to 0.74%. Our study indicated that increased central and peripheral SBP and PP were all associated with adverse outcomes with a similar strength. A multicenter placebo-controlled randomized clinical trial on isolated central hypertension (ANTICIPATE, www.chictr.org.cn/ChiCTR2000035758) is now initiated and ongoing in China. It might help to elucidate the importance of central BP and whether controlling central SBP could bring benefit for patients with isolated central hypertension and coronary heart disease.