Background Data comparing outcomes in heart failure ( HF ) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN ‐HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction ( EF ; <40%) versus preserved EF (≥50%). Methods and Results The ASIAN ‐ HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced r EF ). The primary outcome was 1‐year all‐cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One‐year, crude, all‐cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One‐year, all‐cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P <0.001). Well‐known predictors of death accounted for only 44.2% of the variation in risk of mortality. Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region‐specific risk factors and gaps in guideline‐directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01633398.

Trimethylamine N-oxide (TMAO) is a metabolite originated from bacterial metabolism of choline-rich foods. Evidence suggests an association between TMAO and atherosclerosis, but the relationship between TMAO and endothelial progenitor cells (EPCs) remains unclear. This study aimed to identify the relationship between TMAO concentrations, circulating EPCs, and endothelial function in patients with stable angina. Eighty-one stable angina subjects who underwent coronary angiography were enrolled. The circulating EPCs and flow-mediated vasodilation (FMD) were measured to evaluate endothelial function. Plasma TMAO and inflammatory markers, such as hsCRP and IL-1β, were determined. Furthermore, the effect of TMAO on EPCs was assessed in vitro. Patients with lower FMD had significantly decreased circulating EPCs, elevated TMAO, hsCRP, and IL-1β concentrations. Plasma TMAO levels were negatively correlated with circulating EPC numbers and the FMD, and positively correlated with hsCRP, IL-1β concentrations. In in vitro studies, incubation of TMAO in cultured EPCs promoted cellular inflammation, elevated oxidative stress, and suppressed EPC functions. Enhanced plasma TMAO levels were associated with reduced circulating EPCs numbers, endothelial dysfunction, and more adverse cardiovascular events. These findings provided evidence of TMAO’s toxicity on EPCs, and delivered new insight into the mechanism of TMAO-mediated atherosclerosis, which could be derived from TMAO-downregulated EPC functions.

Zoledronate-attenuated Ang II induced AAA formation by suppression of MMP-2 activity and suppressed vascular inflammation and Ang II-induced Rho/ROCK activities.

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BackgroundThe pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) remains elusive. Endothelial dysfunction might play a role, but direct evidence is lacking. This study aimed to explore whether patients with RCVS have a reduced level of circulating circulating endothelial progenitor cells (EPCs) to repair the dysfunctional endothelial vasomotor control.MethodsWe prospectively recruited 24 patients with RCVS within one month of disease onset and 24 healthy age- and sex-matched controls. Flow cytometry was used to quantify the numbers of circulating EPCs, defined as KDR+CD133+, CD34+CD133+, and CD34+KDR+ double-positive mononuclear cells. The Lindegaard index, an index of vasoconstriction, was calculated by measuring the mean flow velocity of middle cerebral arteries and distal extracranial internal carotid arteries via color-coded sonography on the same day as blood drawing. A Lindegaard index of 2 was chosen as the cutoff value for significant vasoconstriction of middle cerebral arteries based on our previous study.ResultsPatients with RCVS had a reduced number of CD34+KDR+ cells (0.009 ± 0.006% vs. 0.014 ± 0.010%, p = 0.031) but not KDR+CD133+ cells or CD34+CD133+ EPCs, in comparison with controls. The number of CD34+KDR+ cells was inversely correlated with the Lindegaard index (rs = -0.418, p = 0.047). Of note, compared to controls, patients with a Lindegaard index > 2 (n = 13) had a reduced number of CD34+KDR+ cells (0.007 ± 0.005% vs. 0.014 ± 0.010%, p = 0.010), but those with a Lindegaard index ≤ 2 did not.ConclusionsPatients with RCVS had reduced circulating CD34+KDR+ EPCs, which were correlated with the severity of vasoconstriction. Endothelial dysfunction might contribute to the pathogenesis of RCVS.

Objective: This study aimed to develop machine learning-based prediction models to predict masked hypertension and masked uncontrolled hypertension using the clinical characteristics of patients at a single outpatient visit.Methods: Data were derived from two cohorts in Taiwan. The first cohort included 970 hypertensive patients recruited from six medical centers between 2004 and 2005, which were split into a training set (n = 679), a validation set (n = 146), and a test set (n = 145) for model development and internal validation. The second cohort included 416 hypertensive patients recruited from a single medical center between 2012 and 2020, which was used for external validation. We used 33 clinical characteristics as candidate variables to develop models based on logistic regression (LR), random forest (RF), eXtreme Gradient Boosting (XGboost), and artificial neural network (ANN).Results: The four models featured high sensitivity and high negative predictive value (NPV) in internal validation (sensitivity = 0.914–1.000; NPV = 0.853–1.000) and external validation (sensitivity = 0.950–1.000; NPV = 0.875–1.000). The RF, XGboost, and ANN models showed much higher area under the receiver operating characteristic curve (AUC) (0.799–0.851 in internal validation, 0.672–0.837 in external validation) than the LR model. Among the models, the RF model, composed of 6 predictor variables, had the best overall performance in both internal and external validation (AUC = 0.851 and 0.837; sensitivity = 1.000 and 1.000; specificity = 0.609 and 0.580; NPV = 1.000 and 1.000; accuracy = 0.766 and 0.721, respectively).Conclusion: An effective machine learning-based predictive model that requires data from a single clinic visit may help to identify masked hypertension and masked uncontrolled hypertension.

Objective: To investigate the role of endothelial function, inflammatory markers, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with impaired chronotropic response during exercise test. Methods: 86 subjects were enrolled. Treadmill exercise test was conducted according to the modified Bruce protocols. Brachial ultrasound was used to measure endothelium dependent flow mediated vasodilatation (FMD). Chronotropic incompetence was defined as either failure to achieve 85% of the age predicted maximum heart rate or a low chronotropic index (, 0.8).Results: Of the 86 patients, 20 (23%) exhibited chronotropic incompetence. The patients were divided into three groups according to chronotropic index: group 1, , 0.8 (n = 20); group 2, 0.8-1.0 (n = 26); and group 3, . 1.0 (n = 40). Patients with impaired chronotropic response had significantly lower FMD than those with higher chronotropic response (mean (SD) 2.8 (1.9)% v 5.0 (2.8)% v 5.3 (2.5)%, p = 0.002, for groups 1, 2, and 3, respectively). Serum concentrations of high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), and NT-proBNP were significantly higher in group 1 than in groups 2 and 3 (hsCRP: 19 (12) v 9 (6) v 9 (6) mg/l, p , 0.05; MCP-1: 140 (51) v 133 (60) v 108 (46) pg/ml, p = 0.046; NT-proBNP: 4760 (1980) v 3710 (850) v 3910 (1060) mg/l, p = 0.019, respectively). In addition, chronotropic index was significantly related to FMD (r = 0.380, p = 0.001) and inversely related to hsCRP (r = 20.267, p = 0.013). By multivariate analysis, impaired chronotropic response was significantly related to endothelial dysfunction (p = 0.012). Conclusion: Patients with impaired chronotropic response to graded exercise had endothelial dysfunction, enhanced systemic inflammation, and higher NT-proBNP concentrations. These findings may partly explain the mechanism of chronotropic incompetence as a predictor of cardiovascular risk and increased mortality.

SummaryBackground: Endothelial function plays a key role in determining the clinical manifestations of atherosclerotic lesions. Elevated high-sensitive C-reactive protein (hsCRP) relates to long-term prognosis of cardiovascular disease.Hypothesis: We test the hypothesis that combined use of endothelial function and hsCRP could increase predictive value of future cardiovascular events.Methods and Results: 205 patients were followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasound to measure endothelium-dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 205 subjects, with cardiovascular events being defined as myocardial infarction, hospitalization due to congestive heart failure, percutaneous coronary intervention, coronary artery bypass grafting, and ischemic stroke. Twenty nine (14%) developed cardiovascular events. Both FMD and hsCRP were significantly predictive of cardiovascular events (relative risk for patients with FMD < 3% as compared to those with FMD