Aortic Characteristic Impedance and Suspected Mild Cognitive Impairment in a Community-Based Healthy Population.

BACKGROUND: Aging of the proximal aorta can lead to increased pressure and flow pulsatility in the cerebral microcirculation, which may cause cognitive impairment. This study investigated the association between aortic characteristic impedance (Zc), an indicator of regional stiffness of the proximal aorta, and suspected mild cognitive impairment (MCI), compared with carotid-femoral pulse wave velocity (CFPWV). METHODS AND RESULTS: A total of 1461 healthy community residents (46.4% men; age range, 35-96 years [mean±SD, 59.9±11.8 years]) without a history of cardiovascular events or stroke were included in the study. Zc was estimated using applanation tonometry and echocardiography. Cognitive function was assessed using the Mini-Mental State Examination. Education-adjusted cut points were used to define suspected MCI. Subjects with suspected MCI (n=493 [33.7%]) had significantly higher Zc and CFPWV than those without. In multivariable analysis, both Zc and CFPWV were inversely associated with Mini-Mental State Examination score. Zc (odds ratio per 1 SD, 1.22 [95% CI, 1.09-1.37] and CFPWV (odds ratio per 1 SD, 1.18 [95% CI, 1.01-1.38]) was also significantly associated with suspected MCI, after adjusting for age, sex, education level, mean arterial pressure, hypertension, diabetes, low-density lipoprotein cholesterol, and smoking status. In joint analysis, Zc was significantly associated with suspected MCI, but CFPWV was not. In the age subgroups of <50 years and 50 to 70 years, only Zc was significantly associated with suspected MCI. CONCLUSIONS: This study found that Zc was significantly associated with Mini-Mental State Examination score and suspected MCI, especially in younger and middle-aged adults. These findings suggest that Zc may be a useful biomarker for identifying individuals at risk for MCI.

Surgery for severe mitral regurgitation: The etiology matters.

BACKGROUND: While surgery has been the standard treatment for patients with severe primary mitral regurgitation (PMR), the role of surgery for severe secondary mitral regurgitation (SMR) remained debated. We therefore investigated the prognostic differences of surgery for patients with either severe PMR or SMR. METHODS: Subjects hospitalized for heart failure were enrolled from 2002 to 2012. The severity of MR was assessed by continuity equation, and an effective regurgitant orifice area of ≥40 mm 2 was defined as severe. Long-term survival was then identified by the National Death Registry. RESULTS: A total of 1143 subjects (66.4 ± 16.6 years, 65% men, and 59.7% PMR) with severe MR were analyzed. Compared with PMR, patients with SMR were older, had more comorbidities, greater left atrial and ventricular diameter, and less left ventricular ejection fraction (all p < 0.05). While 47.8% of PMR patients received mitral valve surgery, only 6.9% of SMR patients did. Surgical intervention crudely was associated with 54% reduction of all-cause mortality in PMR (hazard ratio, 0.46; 95% confident interval, 0.32-0.67), and 48% in the subpopulation with SMR (0.52, 0.30-0.91). Propensity score matching analysis demonstrated the survival benefits of mitral valve surgery was observed in patients with PMR (log rank p = 0.024), but not with SMR. Among the unoperated subjects, age, renal function, and right ventricular systolic pressure were common risk factors of mortality, regardless of MR etiology. CONCLUSION: Mitral valve surgery for patients with heart failure and severe MR was associated with better survival in patients with PMR, but not in those with SMR.

The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis.

CONTEXT: Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. OBJECTIVE: To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. METHODS: We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). RESULTS: In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. CONCLUSION: Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.

Who should be screened for primary aldosteronism? A comprehensive review of current evidence.

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone-producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug-resistant hypertension, hypertensive with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first-degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well-established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.

Hypertensive emergencies in Asia: A brief review.

Hypertensive emergency is one of the most challenging conditions to treat in the emergency department (ED). From previous studies, about 1%-3% of hypertensive individuals experienced hypertensive emergencies. Its prevalence varied by country and region throughout Asia. Asian populations have more different biological and cultural backgrounds than Caucasians and even within Asian countries. However, there is a scarcity of research on clinical features, treatment, and outcomes in multinational Asian populations. The authors aimed to review the current evidence about epidemiology, clinical characteristics and outcomes, and practice guidelines in Asia. Five observational studies and nine clinical practice guidelines across Asia were reviewed. The prevalence of hypertensive emergencies ranged from .1% to 1.5%. Stroke was the most common target organ involvement in Asians who presented with hypertensive emergencies. Although most hypertensive emergency patients required hospitalization, the mortality rate was low. Given the current lack of data among Asian countries, a multinational data repository and Asian guidelines on hypertensive emergency management are mandatory.

Impaired renal function and mortalities in acute heart failure with different phenotypes.

AIMS: Impaired renal function (IRF) prevails in patients with acute heart failure. The study aimed to investigate the prevalence of on-admission IRF and its association with short-term and long-term mortalities in patients hospitalized for HF with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) left ventricular ejection fraction (LVEF). METHODS: Patients hospitalized for acute heart failure were enrolled and stratified by LVEF into three phenotypes as HFpEF (≥50%), HFmrEF (40-49%), and HFrEF (<40%). IRF was defined as an estimated glomerular filtration rate of ≤60 mL/min/1.73m2 on admission. National Death Registry was linked for the identification of mortality. RESULTS: Of 2613 patients enrolled, 673 (25.7%) had HFrEF, 367 (14.0%) had HFmrEF, and 1573 (60.1%) had HFpEF, whereas IRF was prevalent among 63.7, 68.6, and 67.5% of them, respectively. IRF significantly correlated with higher long-term mortality in each phenotype of HF. However, IRF was associated with 90-day and 1-year mortality in subjects with HFrEF and HFmrEF, but not HFpEF. After accounting for age, gender, hypertension, diabetes, coronary artery disease, atrial fibrillation, stroke, serum sodium, de novo heart failure, date of enrolment, and systolic blood pressure <90 mmHg or use of inotropic agents, IRF remained related to 5-year mortality in patients with HFrEF (hazard ratio and 95% confidence interval: 1.346, 1.034-1.751), HFmrEF (2.210, 1.435-3.404), and HFpEF (1.493, 1.237-1.801). CONCLUSIONS: On-admission IRF was independently predictive of long-term mortality in patients hospitalized for HF, irrespective of HF phenotypes. Furthermore, IRF was also associated with short-term mortality in HFrEF and HFmrEF, but not in HFpEF.

Prognostic Role of Pulmonary Function in Patients With Heart Failure With Reduced Ejection Fraction.

Background Both ventilatory abnormalities and pulmonary hypertension (PH) are frequently observed in patients with heart failure with reduced ejection fraction. We aim to investigate the association between ventilatory abnormalities and PH in heart failure with reduced ejection fraction, as well as their prognostic impacts. Methods and Results A total of 440 ambulatory patients (age, 66.2±15.8 years; 77% men) with left ventricular ejection fraction ≤40% who underwent comprehensive echocardiography and spirometry were enrolled. Total lung capacity, forced vital capacity, and forced expiratory volume in the first second were obtained. Pulmonary arterial systolic pressure was estimated. PH was defined as a pulmonary arterial systolic pressure of >50 mm Hg. The primary end point was all-cause mortality at 5 years. Patients with PH had significantly reduced total lung capacity, forced vital capacity, and forced expiratory volume in the first second. During a median follow-up of 25.9 months, there were 111 deaths. After accounting for age, sex, body mass index, renal function, smoking, left ventricular ejection fraction, and functional capacity, total lung capacity (hazard ratio [HR] per 1 SD, 0.66; 95% CI per 1 SD, 0.46-0.96), forced vital capacity (HR per 1 SD, 0.64; 95% CI per 1 SD, 0.48-0.84), and forced expiratory volume in the first second (HR per 1 SD, 0.72; 95% CI per 1 SD, 0.53-0.98) were all significantly correlated with mortality in patients without PH. Kaplan-Meier curve demonstrated impaired pulmonary function, defined as forced expiratory volume in the first second ≤58% of predicted or forced vital capacity ≤65% of predicted, was associated with higher mortality in patients without PH (HR, 2.85; 95% CI, 1.66-4.89), but not in patients with PH (HR, 1.05; 95% CI, 0.61-1.82). Conclusions Ventilatory abnormality was more prevalent in patients with heart failure with reduced ejection fraction with PH than those without. However, such ventilatory defects were related to long-term survival only in patients without PH, regardless of their functional status.

Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework.

BACKGROUND: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. METHODS: Between 2013-2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). RESULTS: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient-Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. CONCLUSIONS: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.

Associations Between Cerebral Vasoreactivity and Cognitive Function in the Middle-Aged Non-Demented Population.

BACKGROUND: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer's disease (AD) in elderly population. OBJECTIVE: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population. METHODS: We recruited 490 middle-aged community-based participants (30-60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter. RESULTS: In 369 participants (median age 52 years [IQR 47-56], 48.8% men) with robust acoustic windows, the factors related to poorer MoCA scores were older age, less education extent, and the habitats of cigarette smoking or alcohol consumption. Multivariate analyses did not show a significant association between any intracranial hemodynamic parameters in both MCAs and MoCA scores in the total study population. Left MCA BHI was found to be significantly and independently correlated with the MoCA scores only in people aged 55-60 years (n = 111, B = 0.70, 95% confidence interval, 0.13-1.26, p = 0.017), however, not in people younger than 55 years. CONCLUSION: Our results emphasize the role of neurovascular abnormalities in the early pathophysiology of cognitive impairment and suggest cerebral vasoreactivity as the earliest detectable cognition-associated hemodynamic parameter.

Machine learning of treadmill exercise test to improve selection for testing for coronary artery disease.

BACKGROUND AND AIMS: The high false-positive rate of the treadmill exercise test (TET) may lead to unnecessary invasive coronary angiography. We aimed to develop a machine learning-based algorithm to improve the diagnostic performance of TET. METHODS: Study included 2325 patients who underwent TET and subsequent coronary angiography within one-year interval. The mean age was 58.7 (48.1-69.3) years, 1731 (74.5%) were male, 1858 (79.9%) had positive TET result, and 812 (34.9%) had obstructive coronary artery disease (≥70% stenosis in at least one vessel). The study population were randomly divided into training (70%) and testing (30%) groups for algorithm development. A total of 93 features, including exercise performance, hemodynamics and ST-segment changes were extracted from the TET results. Clinical features included comorbidity, smoking, height, weight, and Framingham risk score. Support vector machine, logistic regression, random forest, k-nearest neighbor and extreme gradient boosting machine learning algorithms were used to build the predictive models. The performance of each model was compared with that of conventional TET. RESULTS: Four of the five models exhibited comparable diagnostic performance and were better than conventional TET. The random forest algorithm had an area under the curve (AUC) of 0.73. When used with clinical features, the AUC improved to 0.74. The major advantage of the algorithm is the reduction of the false-positive rate compared with conventional TET (55% vs. 76.3%, respectively), while maintaining comparable sensitivity (85%). CONCLUSIONS: Using the information obtained from conventional TET, a more accurate diagnosis can be made by incorporating an artificial intelligence-based model.

TIFA protein expression is associated with pulmonary arterial hypertension.

Tumor necrosis factor receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA), a key regulator of inflammation, may be involved in the pathogenesis of pulmonary arterial hypertension (PAH). A total of 48 PAH patients (age 50.1 ± 13.1 years, 22.9% men), 25 hypertensive subjects, and 26 healthy controls were enrolled. TIFA protein expression in peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured. Pulmonary arterial hemodynamics were derived from right heart catheterization. PAH patients had the highest expression of TIFA, TNF-α, and IL-1ß. TIFA protein expression was significantly associated with IL-1ß (r = 0.94; P < 0.001), TNF-α (r = 0.93; P < 0.001), mean pulmonary artery pressure (r = 0.41; P = 0.006), and pulmonary vascular resistance (r = 0.41; P = 0.007). TIFA protein expression could independently predict the presence of PAH (odds ratio [95% confidence interval per-0.1 standard deviation]: 1.72 [1.37-2.16]; P < 0.001) and outperformed echocardiographic estimation. Ex vivo silencing of TIFA protein expression in PBMCs led to the suppression of the cellular expression of IL-1ß and TNF-α. IL-1ß and TNF-α mediated 80.4% and 56.6% of the causal relationship between TIFA and PAH, respectively, supporting the idea that TIFA protein is involved in the pathogenesis of PAH.

Impact of dietary intake of sodium and potassium on short-term blood pressure variability.

BACKGROUND: Dietary Approaches to Stop Hypertension (DASH)-Sodium trial showed that dietary sodium and potassium affect blood pressure (BP). We aimed to investigate whether dietary sodium and potassium affect short-term BP variability (BPV) in addition to BP. METHODS: A total of 343 participants from the DASH-Sodium trial (age 48.4 ±â€Š9.7, 42.5% men) and 323 individuals from the Jackson Heart Study (JHS) (age 56.7 ±â€Š11.2, 30.7% men) with satisfactory ambulatory BP monitoring records and 24-h urine collection were included. Average real variability (ARV) was calculated as a measure of short-term BPV. RESULTS: By estimating dietary intake from urinary excretion, we observed that higher urinary sodium-to-potassium ratio was significantly associated with higher diastolic ARV in both studies. Among the DASH-Sodium trial, potassium-rich DASH diet alone had insignificant effect on both systolic (-0.1 ±â€Š1.7 mmHg, P = 0.343) or diastolic ARV (-0.2 ±â€Š1.5 mmHg, P = 0.164), whereas combined DASH diet and low sodium intake significantly reduced both systolic (8.5 ±â€Š1.6 vs. 8.9 ±â€Š1.7 mmHg, P = 0.032) and diastolic ARV (7.5 ±â€Š1.5 vs. 7.8 ±â€Š1.6 mmHg, P = 0.025) as compared with control diet and high sodium intake. As the reduction of systolic ARV was majorly derived from the change of mean SBP, diastolic ARV was significantly determined by urinary sodium-to-potassium ratio (ß coefficient ±â€Šstandard error: 0.012 ±â€Š0.004; P = 0.006) after adjusting for age, sex, smoking, mean DBP, BMI, and race. CONCLUSION: Dietary sodium and potassium can jointly modulate short-term BPV in addition to BP. Combined DASH diet and low sodium intake may reduce systolic and diastolic ARV via different mechanisms.

Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF), the largest and most inclusive global HFpEF trial. METHODS: We studied differences in clinical characteristics, outcomes, and treatment effects of sacubitril/valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region. RESULTS: Regional differences in patient characteristics and comorbidities were observed: patients from Western Europe were oldest (mean 75±7 years) with the highest prevalence of atrial fibrillation/flutter (36%); Central/Eastern European patients were youngest (mean 71±8 years) with the highest prevalence of coronary artery disease (50%); North American patients had the highest prevalence of obesity (65%) and diabetes (49%); Latin American patients were younger (73±9 years) and had a high prevalence of obesity (53%); and Asia-Pacific patients had a high prevalence of diabetes (44%), despite a low prevalence of obesity (26%). Rates of the primary composite end point of total hospitalizations for HF and death from cardiovascular causes were lower in patients from Central Europe (9 per 100 patient-years) and highest in patients from North America (28 per 100 patient-years), which was primarily driven by a greater number of total hospitalizations for HF. The effect of treatment with sacubitril-valsartan was not modified by region (interaction P>0.05). CONCLUSIONS: Among patients with HFpEF recruited worldwide in PARAGON-HF, there were important regional differences in clinical characteristics and outcomes, which may have implications for the design of future clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Regional differences in office and self-measured home heart rates in Asian hypertensive patients: AsiaBP@Home study.

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all-cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self-measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM-7130-AP/HEM-7131-E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta-blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.

Feasibility of the transcatheter mitral valve repair for patients with severe mitral regurgitation and endangered heart failure.

BACKGROUND: The transcatheter edge-to-edge mitral valve repair using MitraClip has been a safe and effective treatment for severe mitral regurgitation (MR). In patients with severe MR and cardiogenic shock under hemodynamic supporting devices, emergent surgical mitral valve interventions carry extremely high risk for peri-operative morbidities and mortalities. The feasibility and efficacy of emergent MitraClip to rescue patients in critical conditions remains elucidate. METHODS: Patients with severe MR and high or prohibitive surgical risks were referred for MitraClip procedures. Emergent MitraClip were conducted in patients with unstable hemodynamics and under mechanical or inotropic support. The hemodynamic measures, transthoracic echocardiography, transesophageal echocardiography, and blood tests were performed before MitraClip procedures. Procedural success was defined as having mild mitral regurgitation immediately after MitraClip, and patients were free from in-hospital mortality. Clinical and echocardiographic outcomes were followed by telephones and clinics. RESULTS: Among 50 consecutive patients (74.7 ± 11.2 years, 74% male), 8 emergent MitraClip procedures were conducted to rescue patients with cardiogenic shock. Extracorporeal membrane oxygenations were used in 2 patients and intra-aortic balloon pump were applied in 4 patients (50%). Compare to those who underwent elective procedures, patients underwent emergent MitraClip had higher surgical risk profile (EuroSCORE II 34.8% vs 5.1% and STS score 19.7% vs 5.1%), poorer renal function and higher right atrial pressure. There was no peri-procedural death, myocardial infarction, stroke or any adverse events requiring emergent cardiac surgery in both groups. Mild mitral regurgitation was achieved in 87.5% patients from the emergent group and 95.2% patients in the elective group (P = 0.514). The Kaplan-Meier analysis showed patients who underwent emergent procedures have poorer long-term survival rate as compare to those who received elective procedures. (P value = 0.008). CONCLUSION: When open-heart surgery is not feasible, trans-catheter mitral valve repair is an alternative way to rescue patients in cardiogenic shock status.

Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe.

Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.

The feasibility of polypill for cardiovascular disease prevention in Asian Population.

Polypill is a fixed-dose combination of medications with proven benefits for the prevention of cardiovascular disease (CVD). Its role in CVD prevention has been extensively debated since the inception of this concept in 2003. There are two major kinds of polypills in clinical studies. The first is polypill that combines multiple low-dose medications for controlling only one CVD risk factor (such as high blood pressure or high serum cholesterol). These "single-purpose" polypills were mostly developed from original producers and have higher cost. The polypill that combines 3-4 pharmaceutical components, each with potential to reduce one major cardiovascular risk factors is "multi-purpose" or "cardiovascular" polypill. Using data from various clinical trials and from meta-analysis, Wald and Law claimed that this "cardiovascular" polypill when administered to every individual older than 55 years could reduce the incidence of CVD by more than 80%. Several short and intermediate to long-term studies with different cardiovascular polypills in phase II and III trials showed that they could provide better adherence, equivalent, or better risk factor control and quality of life among users as compared to usual care. One recently published randomized controlled clinical trial demonstrated the effectiveness and safety of a four-component polypill for both primary and secondary CVD prevention with acceptable number needed to treat (NNT) to prevent one major cardiovascular event. Considering the slow achievement of CVD prevention in many poor- and middle-income Asian countries and also the need to further improve compliance of antihypertensive and lipid lowering medications in many high-income Asian countries, the concept of "cardiovascular polypill" could be very useful. With further support from ongoing polypill cardiovascular outcome trials, polypill could be the foundation of the population-based strategies for CVD prevention.

Effect of Acoustic Cardiography-guided Management on 1-year Outcomes in Patients With Acute Heart Failure.

BACKGROUND: The electromechanical activation time (EMAT) normalized by cardiac cycle length (%EMAT) and the third heart sound (S3) strength, as measured by automated acoustic cardiography, are predictive of postdischarge adverse events in patients with acute heart failure (AHF). The aim of this study was to evaluate whether the acoustic cardiography-guided management improves outcomes in patients with AHF when it is compared with the conventional therapy. METHODS AND RESULTS: This prospective single-blind study randomized 225 patients with AHF (74.1 ± 14.5 years of age, 26.2% women, and left ventricular ejection fraction 38.4 ± 14.4%) before discharge to the EMAT-guided group (n = 114) with the postdischarge treatment goals to reduce %EMAT to < 15% and S3 < 5, and the symptom-guided group (n = 111) to adjust medications without knowledge of the results of acoustic cardiography. The primary endpoints were rehospitalization for heart failure and total mortality during 1-year follow-up. The 2 groups were well matched in age and predischarge %EMAT and S3 strength. After a mean follow-up period of 238.1 ± 140.8 days, a significant reduction in the primary endpoints was seen in the EMAT-guided group compared with the symptom-guided group (43 events vs 61 events, P = 0.0095). Kaplan-Meier curves demonstrated significant differences in the time to first event, favoring the EMAT-guided group in the total study population (n = 225, hazard ratio and 95% confidence interval: 0.61, 0.42-0.91, log-rank P = 0.0129), as well as in the prespecified subgroup of patients with predischarge %EMAT > 15% (n = 85; 0.32, 0.16-0.65, P = 0.0008). CONCLUSIONS: In patients hospitalized due to AHF, EMAT-guided postdischarge management was superior to the conventional symptoms-driven therapy in terms of 1-year outcomes (ClinicalTrials.gov number NCT01298232).

Carotid Flow Velocities and Blood Pressures Are Independently Associated With Cognitive Function.

BACKGROUND: Few studies simultaneously addressed associations between carotid flow velocities, blood pressure (BP), and cognitive function. MATERIALS AND METHODS: Subject without dementia (N = 1,684) underwent measurements of BP and biochemical markers. Mini-Mental State Examination (MMSE) and comprehensive neuropsychological tests were used to evaluate cognitive function. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured in common and internal carotid artery. Subjects with MMSE score of ≤24 (25th percentile) was defined as low MMSE. Multivariable linear and logistic regression were used to evaluate the relationship of cognitive function with carotid flow velocities and BP. RESULTS: Carotid flow velocities (PSV: standardized ß = 0.067, P = 0.0009; and EDV: standardized ß = 0.067, P = 0.0021) and systolic blood pressure (standardized ß = -0.061, P = 0.005) were positively and negatively associated with MMSE, respectively, in the model with adjustments for age, sex, educational attainment, nutritional status, and smoking. Similar trends were noted for the associations between flow velocities and different neuropsychological tests. By multivariable logistic regression, the group with the lowest quartile (<25th percentile) of flow velocities had increased probability of low MMSE (odds ratio: 1.538; 95% confidence intervals: 1.142 to 2.071, P = 0.0046 for PSV; and odds ratio: 1.699; 95% confidence intervals: 1.233 to 2.341; P = 0.0012 for EDV), compared to those with the highest quartile (≥75th) flow velocities. CONCLUSION: Both low carotid flow velocity and high BP were independently and comparably associated with cognitive dysfunction.