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Increased low-density lipoprotein cholesterol (LDL-C) is the most crucial risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the mainstay therapy, but many patients need to add non-statin treatment to reach the recommended LDL-C goal. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective agents in LDL-C reduction, they are much more expensive than other lipid-lowering agents. In January 2020, the Taiwan National Health Insurance (NHI) program started to reimburse PCSK9 inhibitors for select ASCVD patients with certain conditions. Major guidelines or consensus worldwide also provide specific recommendations about how to appropriately use these agents. This review summarizes the Taiwan NHI regulations of using PCSK9 inhibitors and compared them with other guidelines or consensus around the world.

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction.

Background: Diastolic dysfunction (DD) has shown to be a hallmark pathological intermediate in the development of heart failure with preserved ejection fraction (HFpEF). We aim to establish age- and sex-stratified normal reference values of diastolic indices and to explore racial-differences. Methods: We explored age- and sex-related structural/functional alterations from 6023 healthy ethnic Asians (47.1 ± 10.9 years, 61.3% men) according to 2016 American Society of Echocardiography (ASE) diastolic dysfunction (DD) criteria. Racial comparisons were made using data from London Life Sciences Prospective Population (LOLIPOP) study. Results: Age- and sex-based normative ranges (including mean, median, 10% and 90% lower and upper reference values) were extracted from our large healthy population. In fully adjusted models, advanced age was independently associated with cardiac structural remodeling and worsened diastolic parameters including larger indexed LA volume (LAVi), lower e’, higher E/e’, and higher TR velocity; all p

Background: Atrial fibrillation (AF) is associated with a risk of ischemic stroke, and functional myocardial imaging has offered novel insights on its pathophysiology and prognosis, but its use in AF-related stroke remains limited. We aimed to evaluate the feasibility of left atrial (LA) deformations and its prognostic values of ischemic stroke in a large-scale AF population. Methods: Peak atrial longitudinal strain (LA strain), left ventricular strain (global longitudinal strain), LA strain rate (LA SR) at reservoir (LA longitudinal systolic strain rate), and early diastolic conduit (LA longitudinal early diastolic strain rate) phases were analyzed using 2-dimensional speckle tracking echocardiography. Consecutive 3-beat averaged values of strain and SR were used. The clinical end point was ischemic stroke. Results: Among 1457 AF participants, the mean LA strain, LA longitudinal systolic strain rate, and LA longitudinal early diastolic strain rate values were 12.9±4.8%, 0.80±0.28 s − 1 , and −1.17±0.46 s − 1 , respectively. There were strong positive linear relationships of 3-beat average with index-beat analysis (R=0.94, 0.94, and 0.94 for LA strain, LA longitudinal systolic strain rate, and LA longitudinal early diastolic strain rate, respectively; all P 2 DS 2 -VASc scoring ( C statistics, 0.78–0.81; P =0.006) for ischemic stroke. Overall, the prognostic performances of LA deformations were attenuated after adding global longitudinal strains in models. Conclusions: LA deformations by the 3-beat method are feasible and reproducible during AF. LA strain provided additional prognostic implication over clinical information and conventional echocardiographic measures for ischemic stroke in the AF population but not incremental to global longitudinal strains.

The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. The total diabetic population is expected to increase from 415 million in 2015 to 642 million by 2040. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of patients with type 2 diabetes died of ASCVD. The association between hyperglycemia and elevated cardiovascular (CV) risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction by conventional antidiabetic agents did not significantly reduce macrovascular outcomes.In December 2008, U.S. Food and Drug Administration issued a mandate that every new antidiabetic agent requires rigorous assessments of its CV safety. Thereafter, more than 200,000 patients have been enrolled in a number of randomized controlled trials (RCTs). These trials were initially designed to prove noninferiority. It turned out that some of these trials demonstrated superiority of some new antidiabetic agents versus placebo in reducing CV endpoints, including macrovascular events, renal events, and heart failure. These results are important in clinical practice and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases.In 2018, the Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC) published the first joint consensus on the "Pharmacological Management of Patients with Type 2 Diabetes and Cardiovascular Diseases." In 2020, TSOC appointed a new consensus group to revise the previous version. The updated 2020 consensus was comprised of 5 major parts: (1) treatment of diabetes in patients with multiple risk factors, (2) treatment of diabetes in patients with coronary heart disease, (3) treatment of diabetes in patients with stage 3 chronic kidney disease, (4) treatment of diabetes in patients with a history of stroke, and (5) treatment of diabetes in patients with heart failure. The members of the consensus group thoroughly reviewed all the evidence, mainly RCTs, and also included meta-analyses and real-world evidence. The treatment targets of HbA1c were finalized. The antidiabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.

Background: P2Y12 inhibitor monotherapy is an alternative antiplatelet strategy in patients undergoing percutaneous coronary intervention (PCI). However, the ideal P2Y12 inhibitor for monotherapy is unclear. Methods and Results: We performed a multicenter, retrospective, observational study to compare the efficacy and safety of monotherapy with clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing PCI. From 1 January 2014 to 31 December 2018, 610 patients with ACS who received P2Y12 monotherapy with either clopidogrel (n = 369) or ticagrelor (n = 241) after aspirin was discontinued prematurely were included. Inverse probability of treatment weighting was used to balance covariates between the groups. The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months after discharge. Overall, 84 patients reached the primary endpoint, with 57 (15.5%) in the clopidogrel group and 27 (11.2%) in the ticagrelor group. Multivariate adjustment in Cox proportional-hazards models revealed a lower risk of the primary endpoint with ticagrelor than with clopidogrel (adjusted hazard ratio (aHR): 0.67, 95% confidence interval (CI): 0.49&ndash, 0.93). Ticagrelor significantly reduced the risk of recurrent ACS or unplanned revascularization (aHR: 0.46, 95% CI: 0.28&ndash, 0.75). No significant difference in all-cause mortality and major bleeding events was observed between the 2 groups. Conclusions: Among patients with ACS undergoing PCI who cannot complete course of dual antiplatelet therapy, a significantly lower risk of cardiovascular events was associated with ticagrelor monotherapy than with clopidogrel monotherapy. The major bleeding risk was similar in both the groups.

Among 2085 asymptomatic subjects (age: 51.0&plusmn, 10.7 years, 41.3% female) with data available on common carotid artery diameter (CCAD) and circulating total white blood cell (WBC) counts, higher circulating leukocytes positively correlated with higher high sensitivity C-reactive protein (hs-CRP).Higher WBC/segmented cells and monocyte counts were independently associated with greater relative wall thicknesses and larger CCADs,which in generalweremore pronounced in men and obese subjects (body mass index &ge, 25kg/m2) (all P interaction: &lt, 0.05). Using multivariate adjusting models, only the monocyte count independently predicted theleft ventricularmass index (LVMi) (&szlig, Coef: 0.06, p = 0.01). Higher circulating WBC, segmented,and monocyte counts and a greater CCAD were all independently associated with a higher risk of heart failure (HF)/all-cause death during a median of 12.1 years of follow-up in fully adjusted models, with individuals manifesting both higher CCADs and monocyte countsincurring the highest risk of HF/death (adjusted hazard ratio: 2.81, 95% CI: 1.57. &minus, 5.03, p&lt, 0.001, P interaction, 0.035, lower CCAD/lower monocyte as reference). We conclude that a higher monocyte count is associated with cardiac remodeling and carotid artery dilation.Both an elevated monocyte count and a larger CCAD may indicate a specific phenotype that confers the highest risk of HF, which likely signifies the role of circulating monocytes in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

This study aimed to investigate the prognostic value of high-sensitivity creatine kinase-myocardial band or fraction (hsCK-MB) in comparison with other well-established biomarkers including heart type-fatty acid binding protein (H-FABP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary heart disease (SCHD). A total of 1,785 patients were enrolled and followed for 36 months. The primary outcome was all-cause mortality. The secondary outcomes included cardiovascular (CV) death, acute myocardial infarction (AMI), angina-related hospitalizations, and hospitalizations for heart failure. The all-cause mortality rate was significantly higher in the high hsCK-MB group compared to the low hsCK-MB group (4.64% vs. 1.88%, p = 0.0026). After adjusting for baseline covariates, there were no significant differences for the secondary outcomes. H-FABP (≥4.226 ng/mL) was the best predictor for all-cause mortality (HR = 2.68, 95% CI = 1.28–5.62, p = 0.009) and CV death (HR = 6.84, 95% CI = 1.89–22.14, p = 0.003). The high NT-proBNP group had a higher AMI-related hospitalization rate (HR = 1.91, 95% CI = 1.00–3.65, p = 0.05). Neither the addition of hsCK-MB to any other markers nor combinations of the three markers improved the prognostic significance of CV outcomes. In conclusion, hsCK-MB was an independent predictor for all-cause mortality but not CV outcomes in patients with SCHD. Combination of hsCK-MB, H-FABP and NT-proBNP failed to improve the prognostic power for all-cause mortality or CV outcomes.

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 ; 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 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.

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.

Hyperuricemia (HU) is a marker for heart failure. There are relatively few data in the Asian population regarding the effects of hyperuricemia and gouty disorders on cardiac remodeling and diastolic dysfunction (DD), an intermediate stage in the development of heart failure. We consecutively recruited asymptomatic Asian individuals to undergo cardiovascular surveys. We categorized them into Non-HU, HU, and Gout groups. We measured cardiac structure and indices for diastolic function, including tissue Doppler (TDI)-derived LV e’ and E/e’. Among 5525 participants, 1568 had HU and 347 had gout. The presence of gout and higher uric acid levels (SUA) ( = 10 mg/dL) were associated with greater LV wall thickness, greater LV mass/volumes, larger LA volume, lower LV e’ and higher E/e’. Higher SUA was associated with greater LV mass index (adjusted coefficient: 0.37), greater mass/volume ratio (adjusted coefficient: 0.01) and larger LA volume index (adjusted coefficient: 0.39, all p

Dyslipidemia is a major contributor in initiation, development and progression of atherosclerotic cardiovascular disease (ASCVD). Most lipid guidelines are from Europe and America and centered on the reduction of atherogenic lipids levels through lifestyle intervention and pharmacotherapy. Recently, the 2017 Taiwan lipid guidelines for high risk patients was published to facilitate the control of dyslipidemia in patients that are highly susceptible to ASCVD, including patients with preexisting ASCVD, diabetes, chronic kidney disease and familial hypercholesterolemia. Most recommendations outlined in the 2017 Taiwan lipid guidelines for high risk patients are in concordance with those of Western guidelines. However, based on evidence from the studies originating from Asia and local expert opinions, there are some recommendations different from the other guidelines. The purpose of the current review is to compare the similarities and differences between the perspectives of the 2017 Taiwan lipid guidelines for high risk patients and other Western guidelines in individuals at high risk of ASCVD. The definitions of high risk groups and treatment goals defined to achieve ASCVD risk reduction are specifically compared. Keywords: Dyslipidemia, Guideline, Statin, Taiwan

Summary: Background: Paraquat poisoning has high mortality rate. Hospice services have been provided by National Health Insurance program in Taiwan since 2000, and were expanded to noncancer illnesses in September 2009. The palliative care strategy and the impact of this expanded palliative care policy on patients with paraquat poisoning remain unclear. Methods: The study included 90 in-patients with paraquat poisoning, hospitalized between January 2005 and April 2016. We analyzed these patients by two factors, survivors vs. non-survivors and patients admitted between 2005 and 2010 vs. between 2011 and 2016, to compare the differences in life-sustaining treatment orders, symptom management, and use of non-beneficial life-sustaining treatments. Results: The mortality rate was 75.6% and patients progressed rapidly to death (mean time: 74.69 h). 91.2% of non-survivors had a do-not-resuscitate order. Within the 24 h before death, non-survivors in the 2011–2016 group had significantly less treatment with vasopressors (p

Background: The aim of this study is to determine the relationship between the on-treatment lipid profiles and the CV events in CKD and non-CKD population. Method: This study was a multi-center observational registry, the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. This study follows up patients with CV diseases in Taiwan who have secondary prevention therapies. The primary outcome is the time of first occurrence of a major adverse cardiac events (MACEs). Result: 5388 patients with ASCVD were included and 1478 (27.4%) had CKD without dialysis. CKD patients had higher TG and lower LDL-C levels. The incidence of recurrent MACEs per 1000 person-years in CKD patients was 19.5 (95% CI 15.5–24.9), compared with 9.1 (95% CI 7.4–11.1) in non-CKD patients. In patients with statin therapy, there were no differences in MACE risk between each level of on-treatment LDL-C, TG and HDL-C level. Higher on-treatment non-HDL-C level was a significant predictor for higher MACE risk in patients without CKD, and borderline significant in CKD patients under statin therapy. Heart failure history was also associated with higher MACE risk in both group. Lower body mass index (BMI

BACKGROUND: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) are all simple anthropometric tools used to categorize obesity status. This study aimed to determine associations between different anthropometric indices and the attainment of therapeutic lipid goals in patients with atherosclerotic cardiovascular disease (CVD) undergoing secondary prevention. METHODS: Between 2010 and 2014, this multi-center study enrolled 5718 patients undergoing secondary prevention for CVD. At study enrollment, total cholesterol, high-density lipoprotein protein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were recorded. This cross-sectional study analyzed these three anthropometric obesity indices and correlations with achieving therapeutic lipid goals. RESULTS: Among the 5718 patients, multivariate analysis revealed that those with higher BMI or WC tended not to meet their HDL-C and TG therapeutic goals. However, neither BMI nor WC showed a relationship with achieving the LDL-C target. The patients with an elevated WHR (≥ 0.98 for males and ≥ 0.97 for females) were less likely to achieve all three lipid target values, including LDL-C (p = 0.05), HDL-C (p < 0.001) and TG (p < 0.001). CONCLUSIONS: Among Taiwanese patients undergoing secondary prevention for CVD, the higher the WHR the lower the likelihood of achieving the lipid therapeutic goals.

The authors consecutively assessed various arterial pulse‐wave velocity (PWV) indices and ankle‐brachial index (ABI) by an automatic device (VP2000, OMRON Health Care Co. Ltd., Kyota, Japan) in outpatients with ≥ 1 cardiovascular risk. PAD was defined as ABI ≤ 0.9. Among 2309 outpatients (mean age 62.4 years), worse renal function was associated with higher brachial‐ankle PWV, heart‐carotid PWV, heart‐femoral PWV (hf‐PWV), and lower ABI (all P

BACKGROUND Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. AIM To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed. RESULTS The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2 , 95% confidence interval [CI]: 13.76-17.70 vs 5.96 mL/min/1.73 m2 , 95% CI: 4.72-7.19; P

Bone morphogenetic protein-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found that BMP-2 promoted cell migration and tube formation of EPCs in a concentration-dependent manner, indicating BMP-2 induced in vitro angiogenesis in human EPCs. Furthermore, BMP-2 significantly increased microvessel formation in Matrigel plug assay, and BMP-2 antagonist noggin prevented BMP-2-induced in vivo angiogenesis. Mechanistic investigations showed BMP-2 profoundly induced the expression of Id-1 and integrin α6 as well as EPCs angiogenesis by activating PI3K/Akt and MEK/ERK signaling pathways. Moreover, knockdown of Id-1 and integrin α6 by siRNA transfection obviously attenuated BMP-2-indueced tube formation of EPCs. These results suggest that BMP-2 promotes angiogenesis in human EPCs through the activation of PI3K/Akt, MEK/ERK, and Id-1/integrin α6 signaling cascades. This is the first demonstration that BMP-2 exhibits the angiogenesis property on human EPCs. BMP-2 might serve as the potential therapeutic target for treatment of angiogenesis-related diseases.

Summary: The proportion of people whose age exceeds 65 years is growing rapidly throughout the world and the prevalence of metabolic syndrome (MetS) is increasing among older adults. MetS had a two-fold increased risk for cardiovascular (CV) disease. Most patients with MetS exhibit atherogenic dyslipidemia, which includes elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C). Therefore, physicians are advised to recognize the presence of dyslipidemia in elderly patients with MetS and provide appropriate therapy to reduce CV risk. Lifestyle modification is the initial step for treating dyslipidemia. For older adults with MetS who cannot attain treatment goals by lifestyle modification, pharmacological intervention is usually considered. Treating dyslipidemia in older adults with MetS requires knowledge of the benefits and adverse effects of various pharmacologic agents in the presence of possible multiple comorbidities. The purpose of this article is to review the evidence for recognition and management of atherogenic dyslipidemia in elderly individuals with MetS. Keywords: dyslipidemia, metabolic syndrome, older adults

BACKGROUND Chronic, excessive ethanol intake has been linked with various electrical instabilities, conduction disturbances, and even sudden cardiac death, but the underlying cause for the latter is insufficiently delineated. METHODS We studied surface electrocardiography (ECG) in a community-dwelling cohort with moderate-to-heavy daily alcohol intake (grouped as >90g/day, ≤90g/day, and nonintake). RESULTS Compared with nonintake, heavier alcohol users showed markedly widened QRS duration and higher prevalence of QRS fragmentation (64.3%, 50.9%, and 33.7%, respectively, χ2 12.0, both p

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671, 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p &lt, 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p &lt, 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: &lt, 0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06–2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

Synchronous non-alcoholic fatty liver disease (NAFLD) and carotid artery plaque formation increase the risk of mortality in patients with cardiovascular disease (CVD). Metabolic status and host gut flora are associated with NAFLD and CVD, but the risk factors require further evaluation. To evaluate the risk factors associated with NAFLD and CVD, including gut-flora-related examinations. This cross-sectional study included 235 subjects aged over 40 years who underwent abdominal ultrasound examination and carotid artery ultrasound examination on the same day or within 12 months of abdominal ultrasound between January 2018 and December 2019. All subjects underwent blood tests, including endotoxin and trimethylamine-N-oxide. The synchronous NAFLD and carotid artery plaque subjects had a higher proportion of men and increased age compared with those without NAFLD and no carotid artery plaque. The synchronous NAFLD and carotid artery plaque group had increased body mass index (BMI), blood pressure, hemoglobin A1C (5.71% vs 5.42%), triglyceride (TG) (164.61 mg/dL vs 102.61 mg/dL), and low-density lipoprotein (135.27 mg/dL vs 121.42 mg/dL). In multiple logistic regression analysis, increased BMI, mean systolic blood pressure, and TG > 110 mg/dL were independent risk factors for synchronous NAFLD and carotid artery plaque formation. Endotoxin and trimethylamine-N-oxide levels were not significantly different between the 2 groups. Host metabolic status, such as elevated BMI, TG, and systolic blood pressure, are associated with synchronous NAFLD and carotid artery plaque in asymptomatic adults. Aggressive TG control, blood pressure control, and weight reduction are indicated in patients with NAFLD.

Cellular senescence is the progressive impairment of function and proliferation in response to various regulators. Dihydrolipoic acid-coated gold nanoclusters (DHLA-Au NCs), which are molecular clusters with covalently linked dihydroxyl lipoic acid, preserve cellular activities for long-term incubation. DHLA-Au NC delivery was characterized, and we determined the role of growth supplements on internalization, allowing the optimization of DHLA-Au NC bioactivity. In the optimized medium, DHLA-Au NCs attenuated the levels of the senescence-associated phenotype. Molecular mechanism analysis further indicated that during DHLA-Au NC treatment, the activation of the stress signal JNK and its downstream c-Jun were impaired under LPS induction, which led to a decline in AP-1-mediated TNF-α transactivation. Confocal microscopy and subcellular fractionation analysis suggested that DHLA-Au NCs interacted with mitochondria through their lipid moiety and attenuated mitochondria-derived reactive oxygen species. With adequate treatment, DHLA-Au NCs show protection against cellular senescence and inflammation in vitro and in vivo.

Background/Purpose The purpose of this study is to investigate the predominant clones of carbapenem-resistant Acinetobacter baumannii (CRAB) in our hospital in Taiwan by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) technique. Methods We collected 108 non-duplicate A. baumannii clinical blood isolates from January 2012 to December 2013 in MacKay Memorial Hospital. PFGE and MLST were used for typing the A. baumannii isolates and for investigation of the predominant clones. Bacteria isolates were screened by polymerase chain reaction for the presence of the carbapenemase-encoding genes. Results All 108 isolates were classified as 33 pulsotypes by PFGE. The predominant clones were pulsotype 10 (12.04%) in 2012 and pulsotype 8 (16.67%) in 2013, respectively. The 31 predominant pulsotype isolates were typed by MLST, and ST787 (54.84%) and ST455 (45.16%) were identified. All isolates carried bla OXA-51-like genes, and bla OXA-23-like genes was founded in 101 isolates (93.52%). Other identified resistance genes included bla OXA-24-like and bla OXA-IMP . Conclusion To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.

Diabetic cardiomyopathy is a well-recognized complication of diabetes, but its pathophysiology is unclear. We aimed to investigate the mechanisms underlying cardiac dysfunction in an elderly type 2 diabetic (T2DM) mouse model, using membrane proteomic analyses. Elderly mice were fed a high fat diet for 12 weeks to induce T2DM, and myocardial structure and function were assessed by echocardiography. Cardiomyocytes were isolated by Langendorff perfusion and subjected to iTRAQ-based quantitative membrane proteomic profiling, immunoblotting, and real-time quantitative reverse-transcriptase polymerase chain reaction. Compared to controls, elderly T2DM mice showed worse systolic function, more myocardial fibrosis and up-regulation of several heart failure markers (all p0.05). Cardiomyocyte membrane proteomic profiling revealed that 417 proteins had differential expressions related to perturbations in several biological processes in T2DM mice compared with the control. The most up-regulated proteins were involved in oxidative phosphorylation, whereas many down-regulated proteins were involved in cytoskeletal regulation. Differential protein expression correlated with myocardial systolic velocity by tissue Doppler. In addition, cardiomyocyte immunofluorescence staining showed greater disorganization of thick/parallel F-actin stress fibers and marked reduction in F-to-G-actin ratio in T2DM vs control (p0.05), which paralleled worsened myocardial systolic velocity. We concluded that cardiac contractile dysfunction in elderly T2DM mice was associated with impaired energetics and cytoskeletal disorganization.

Aims Excessive consumption of alcoholic beverages is associated with cardiac remodeling and cardiomyopathy. We examined the possible association of alcohol use, common Asian genetic variants in genes involved in alcohol metabolism, and cardiac structures/functions alterations. Methods A prospective, community-dwelling survey among individuals with available complete echocardiography examined the associations of alcohol use, cardiac structure/functions, and three common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1 (CYP2E1). Results Among 1577 participants (mean age: 53 ± 9, 59.7% female), we observed that in subjects with more frequent weekly ethanol intake showed greater left ventricle (LV) mass, more impaired diastolic functions, and reduced global longitudinal strain (GLS), systolic (SRs) and early diastolic strain rates (SRe) (P Conclusions Among East Asians, even moderate alcohol consumption can confer subclinical adverse effects on cardiac systolic functions, which was most pronounced in subjects carrying common variants in alcohol metabolizing genes. These findings challenge the notion of beneficial influences of less heavy ethanol consumption on the heart, especially among East Asians. Short summary This study evaluated the association of level of alcohol consumption and genetic variants in genes involved in alcohol metabolism with changes in cardiac function in East Asians. Even moderate alcohol use conferred subclinical adverse effects on cardiac systolic functions, which were most pronounced in subjects carrying common alcohol metabolizing genes.

A prospective observational study was conducted to investigate the residual risk factors to predict recurrence of major adverse cardiovascular events (MACE) in atherosclerotic cardiovascular disease (ASCVD) patients with a high prevalence under lipid-lowering therapy, particularly in the subpopulations of diabetic and nondiabetic individuals. A total of 5,483 adults (with a mean age of 66.4 and 73.3% male) with established coronary heart disease, cerebrovascular disease, or peripheral artery disease were identified from the T-SPARCLE multi-center registry. Of them, 38.6% had diabetes. The residual risk factors for MACE are divergent in these atherosclerotic patients with and without diabetes. In diabetic subpopulation, the risk of MACE was significantly increased with heart failure (HF), chronic kidney disease (CKD) stage 4–5 (vs. stage 1–2), without beta blocker use, and higher non-HDL-C, after controlling for covariates including statin use and the intensity of therapy. Increased LDL-C and TG levels were also associated with increased risk, but to a much less extent. Among nondiabetic individuals, HF, CKD stage 4–5, and history of myocardial infarction were the significant independent predictors of MACE. It is suggested that ASCVD patients with concomitant diabetes need stricter control of lipid, particularly non-HDL-C levels, to reduce cardiovascular risk when on statin therapy.

We aimed to investigate the ideal achieved blood pressure (BP) in ethnic Chinese patients with stable coronary artery disease (CAD) in Taiwan. A total of 2,045 patients (age 63.5 ± 11.9 years, 1,722 male [84.2%]) with stable CAD who had undergone percutaneous coronary interventions were enrolled. The achieved systolic BP was 130.6 ± 17.7 mmHg and diastolic BP was 74.9 ± 12.0 mmHg. In 12 months, patients with systolic BP

Background: Taiwan is an aging society by the definition of the World Health Organization. The trend of elder population is one of the fastest worldwide. The Taiwan Foundation for Geriatric Emergency and Critical Care dedicates to disseminate health promotion behaviors for community elders and middle age adults. The purpose of this study is to investigate the effects and satisfaction of the health education programs on health promotion behaviors. Methods: A one-group pretest-posttest study was conducted using purposively sampling of participants of the health education programs at five community care centers in the great Taipei metropolitan area. A structure questionnaire was developed to collect data. SPSS 20.0 was used in statistical analysis. Results: Above 40% of 136 participants were either overweight or obesity. Comparing pretest and posttest scores, the changes in mentality, perceived health, physical exercise, and blood pressure measurement were significant (p

// Chih-Jen Wu 1, 2, 3 , Cheng-Yi Chen 1, 8, 11 , Thung-S. Lai 4 , Pei-Chen Wu 1 , Chih-Kuang Chuang 5, 6, 7 , Fang-Ju Sun 8, 9 , Hsuan-Liang Liu 5 , Han-Hsiang Chen 1, 8 , Hung-I. Yeh 10 , Chih-Sheng Lin 11 and Cheng-Jui Lin 1, 5, 8 1 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College ,Taipei, Taiwan 2 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 3 Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Graduate Institute of Biomedical Science, Mackay Medical College, New Taipei City, Taiwan 5 Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan 6 Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 7 College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan 8 Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan 9 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 10 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 11 Department of Biological Science and Technology, National Chaio Tung University, Hsinchu, Taiwan Correspondence to: Cheng-Jui Lin, email: lincj@mmh.org.tw Keywords: indoxyl sulfate, chronic kidney disease, erythropoietin, renal anemia Received: April 27, 2017 Accepted: May 29, 2017 Published: June 28, 2017 ABSTRACT Renal anemia is a common complication in patients with advanced chronic kidney disease. In vitro studies have shown that indoxyl sulfate decreases erythropoietin production. Whether this effect is seen in vivo remains unclear. Our goal was to explore the role of indoxyl sulfate in renal anemia. We found serum indoxyl sulfate levels are significantly and negatively associated with erythropoietin levels in human. A multiple stepwise linear regression analyses after adjustment for other independent parameters revealed that free indoxyl sulfate, and total indoxyl sulfate were significantly associated with erythropoietin levels. In animal studies, erythropoietin gene and protein expression were markedly inhibited in rats with chronic kidney disease; however, this effect was significantly reversed by lowering serum indoxyl sulfate with AST-120. Indoxyl sulfate may also inhibit erythropoietin expression in animal models with chronic kidney disease. These findings further support the role of indoxyl sulfate in the development of renal anemia.

Aims: Elevated carotid intima-media thickness (cIMT) is a preclinical phenotype of atherosclerotic diseases. There are significant sex differences in the morbidities of cardiovascular diseases and their major determinants, and we explored the sex-specific effects of cardiovascular factors on cIMT by a community-based study. Methods: We measured the cIMT and cardiovascular profiles of 1579 residents aged 40–74 years in northern Taiwan. Multivariate regression analyses were used to assess the effects and contributions of these factors on cIMT. Results: Males had significantly higher mean (± SD) of cIMT than females (0.668 ± 0.113 vs. 0.632 ± 0.100 nm, p < 0.0001). The common factors of the best-fit regression models in both sexes were age, BMI, and LDL-/HDL-C ratio; however, their contributions and effects were different. The partial coefficients of determination (r2) were 17.9, 5.8, and 4.1%, respectively, for males and were 27.8, 1.4, and 1.2%, respectively, for females. Test statistics showed that the regression coefficients of BMI and LDL-/HDL-C ratio of males were significantly higher than those of females. As compared with females, per 1.0 SD increases of BMI and LDL-/HDL-C in males resulted in 0.0971 (p = 0.030) and 0.1177 (p = 0.0087), respectively, SD increases in cIMT. There was no difference in the means of cIMT between pre- and post-menopausal women of the same age groups. Conclusions: There was a significant sex difference in cIMT. The contributions and effects of LDL-/HDL-C ratio and BMI on cIMT were more profound in males. Our findings indicate that sex-specific factors, but possibly not menstrual status-related factors, contribute to thicker cIMT.

Background Many studies have observed an “obesity paradox” in patients with established atherosclerotic cardiovascular disease (ASCVD), in which the body mass index (BMI)-mortality curve is U-shaped. Purpose To search a better anthropometric parameter to predict the cardiovascular events in patients with ASCVD. Methods The study was conducted from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. Adult patients with stable ASCVD were enrolled. The primary composite endpoint of this study is the time of the first major cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Dose response association between primary outcome events and various traditional anthropometric parameters and a new parameter, the waist-to-BMI ratio, was examined using the Cox proportional hazards regression model. We used restricted cubic spline regression to investigate the potential nonlinear relationship between each anthropometric measure and primary outcome events. Results A total of 6921 patients with ASCVD were included in this analysis, and were followed up for a median of 2.5 years. Multivariable Cox proportional hazards regression showed a significant positive association between the waist-to-BMI ratio and the primary outcome events (adjusted hazard ratio 1.67, 95% CI 1.12–2.49, p=0.01). Other traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, did not showed significant associations (p=0.10, 0.31, 0.90, and 0.52, respectively). In the restricted cubic spline regression, the positive dose response association between the primary outcome and the waist-to-BMI ratio persisted across all the waist-to-BMI ratio, and was non-linear (the likelihood ratio test for nonlinearity was statistically significant, p3.6 cm m2/kg. Dose response curve of waist/BMI ratio Conclusion This study found the waist-to-BMI ratio to be a better predictor for major adverse cardiovascular events in established ASCVD patients than other traditional anthropometric parameters.

Purpose Metabolic syndrome (MetS) and obesity are both crucial risk factors for heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). However, the prognostic value of utilizing left atrial (LA) deformation imaging in metabolically healthy obese (MHO) or metabolically unhealthy normal weight (MUNW) subjects remains largely unexplored. Methods Speckle-tracking echocardiography was used to evaluate LA strain and strain rate among 3,915 subjects free from clinical heart failure (mean age: 50.0±10.6 years, 66.2% male) undergoing annual cardiovascular health survey. Metabolically unhealthy was defined by the presence of at least one MetS component or history of cardiovascular disease. Participants were categorized as: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy overweight/obese (MUO). Results Markedly decreased LA strain, early-diastolic LA strain rate and increased LA stiffness were observed with metabolic disorders (all trend p: Comparison between metabolic groups MHNW (N=1107) MUNW (N=255) p (MUNW vs MHNW) MHO (N=1859) MUO (N=694) p (MUO vs MHO) Age 48±10.57 54.29±11.52 Kaplan-Meier curves of adverse events Conclusion Metabolic abnormality may contribute to certain aspects of mechanistic LA dysfunction tightly linked to clinical events, even with normal lean body mass. Our observations may be insightful for targeted interventions in higher-risk patients with subclinical atrial dysfunction.

Cell cycle slowdown or arrest is a prominent feature of cellular senescence. S-phase kinase-associated protein-2 (Skp2), an F-box subunit of SCFSkp2 ubiquitin ligase, is a key regulator of G1/S transition. We investigated whether Skp2 plays a role in the regulation of endothelial progenitor cell (EPC) senescence, which is closely associated with aging-related vasculopathy. Replication-induced senescent EPCs demonstrated more pronounced senescence markers and lower Skp2 levels in comparison with those of their younger counterparts. Depletion of Skp2 induced increases in senescence-associated β-galactosidase (SA-βGal) activity and a reduction of telomere length and generated a senescent bioenergetics profile, whereas adenoviral-mediated Skp2 expression reversed the relevant senescence. EPCs isolated from older rats displayed a reduced proliferation rate and increased SA-βGal activity, both of which were significantly reversed by Skp2 ectopic expression. In addition to reversing senescence, Skp2 also rescued the angiogenic activity of senescent EPCs in the ischemic hind limbs of nude mice. The results revealed that ectopic expression of Skp2 has the potential to rejuvenate senescent EPCs and rescue their angiogenic activity and thus may be pivotal in the development of novel strategies to manage aging-related vascular disease.

Smoking is known as a powerful predictor of pathological coronary atherosclerosis. Thoracic aortic calcification (TAC), an alternative marker for pathological atherosclerosis, has also been shown to be associated unfavorable cardiovascular outcomes. We aimed to investigate the dose-response relationship between cigarette use and calcification burden in subjects free from clinical symptoms. Among 3109 patients enrolled in this analysis, we categorized study participants according to smoking exposure pattern as: non-smokers, ex-smokers and current smokers. Smoking dose (cigarette/day), duration (years) and pack-years were semi-quantified as smoking dose exposure variables. Thoracic aortic calcification burden (including TAC score, plaque volume and plaque density) were determined and related to smoking dose and pattern information. TAC burdens (including TAC score, plaque volume and density) were highest in current smoker compared to non-smoker group, with ex-smoker showing TAC burdens in-between (all ANOVA p 10 cigarettes/day) and the long-duration (> 3 years) smokers, even after adjusting for baseline demographic differences (all p

Alirocumab can provide significant reductions in low-density lipoprotein cholesterol (LDL-C). However, data regarding its efficacy and safety in Asians are limited.A subgroup analysis of Taiwanese patients (n = 116) in a randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT, clinicaltrials.gov Identifier: NCT02289963) was performed. Patients with hypercholesterolemia at high cardiovascular risk on maximally tolerated statin were randomized to alirocumab (75 mg every 2 weeks; with dose increased to 150 mg at Week 12 if LDL-C ≥ 70 mg/dL at Week 8) or placebo for 24 weeks. The primary efficacy endpoint was the percent change in LDL-C from baseline to Week 24. Safety was assessed for a total of 32 weeks.At Week 24, the percent change in calculated LDL-C in the alirocumab group (n = 57) was -51%, whereas that in the placebo group (n = 59) was 2.5%. Alirocumab significantly improved other lipid parameters, including non-high-density lipoprotein cholesterol, apolipoprotein B and A1, lipoprotein (a), high-density lipoprotein cholesterol, and total cholesterol. A significantly higher proportion of patients in the alirocumab group reached an LDL-C target below 70 mg/dL than those in the placebo group (81.3% vs 15.4%). The incidence of treatment-emergent adverse events was comparable between both groups.Alirocumab treatment provided a favorable effect on LDL-C levels and other lipid parameters, and was generally well-tolerated in patients from Taiwan. The results of current analysis were consistent with the overall ODYSSEY phase 3 program.

The combined administration of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors might be considered as a treatment for poorly responsive cancer. We report a patient with brain metastatic lung adenocarcinoma in whom fatal myocarditis developed after sequential use of PD-1 and PD-L1 inhibitors. This finding was validated in syngeneic tumor-bearing mice. The mice bearing lung metastases of CT26 colon cancer cells treated with PD-1 and/or PD-L1 inhibitors showed that the combination of anti-PD-1 and anti-PD-L1, either sequentially or simultaneously administered, caused myocarditis lesions with myocyte injury and patchy mononuclear infiltrates in the myocardium. A significant increase of infiltrating neutrophils in myocytes was noted only in mice with sequential blockade, implying a role for the pathogenesis of myocarditis. Among circulating leukocytes, concurrent and subsequent treatment of PD-1 and PD-L1 inhibitors led to sustained suppression of neutrophils. Among tumor-infiltrating leukocytes, combinatorial blockade increased CD8+ T cells and NKG2D+ T cells, and reduced tumor-associated macrophages, neutrophils, and natural killer (NK) cells in the lung metastatic microenvironment. The combinatorial treatments exhibited better control and anti-PD-L1 followed by anti-PD-1 was the most effective. In conclusion, the combinatory use of PD-1 and PD-L1 blockade, either sequentially or concurrently, may cause fulminant cardiotoxicity, although it gives better tumor control, and such usage should be cautionary.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations. Keywords: Atherosclerosis, Risk factors, Performance guide

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

To describe the relationship between a novel measurement of peri-arotic root fat and ultrasound measures of carotid artery remodeling.We studied 1492 consecutive subjects (mean age: 51.04 ± 8.97 years, 27% females) who underwent an annual cardiovascular risk survey in Taiwan. Peri-aortic root fat (PARF) was assessed by cardiac CT using three-dimensional (3D) volume assessment. Carotid artery morphology and remodeling were assessed by ultrasound. We explored the relationships between PARF volumes, cardiometabolic risk profiles and carotid morphology and remodeling.Mean PARF volume in current study was 20.8 ± 10.6 ml. PARF was positively correlated with measures of general adiposity, systemic inflammation, and several traditional cardiometabolic risk profiles (all p0.001) and successfully predicted metabolic syndrome (MetS) (AUROC: 0.75, 95%, confidence interval: 0.72-0.77). Higher PARF was independently associated with increased carotid artery intima-media thickness (IMT) (β-coef.: 0.08) and diameter (β-coef.: 0.08, both p0.05) after accounting for age, sex, BMI and other cardiovascular risk factors. The addition of PARF beyond metabolic syndrome components significantly provided incremental prediction value for abnormal IMT (ΔAUROC: 0.053, p = 0.0021).Peri-aortic root fat is associated with carotid IMT, even after adjustment for cardiometabolic risks, age and coronary atherosclerosis. Further research studies are warranted to identify the mediators of downstream pathophysiologic effects on carotid arteries by PARF and understand the mechanisms related to this correlation.

Summary Background Remote cardiac rhythm monitoring and diagnosis has been well incorporated in the telehealth service model. The prevalence and incidence of abnormal ventricular beats, based on utilizing a symptom-driven portable remote electrocardiography (ECG) device, remains less well explored. Methods We studied 339 consecutive study participants, which included 192 individuals from outpatient clinics who were enrolled via a symptom-driven protocol; 147 participated in a heart rhythm screening program. All participants underwent 24-hour data transfer using a handheld portable electrocardiogram (ECG) device (DailyCare Biomedical Inc., Taoyuan City, Taiwan) with automatic ECG wavelet data extraction software (InstantCheck, version 4.0; DailyCare Biomedical Inc., Taoyuan City, Taiwan). Results Among 1152 data transferred (98.4% success rate), we noticed 32.5% of the study participants had evidence of cardiac arrhythmias with permanent or paroxysmal atrial fibrillation (AF) constituting 50.9% of arrhythmias. Individuals with a history of heart failure (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.69–6.74), diabetes (OR, 3.03; 95% CI, 1.67–5.49), and cardiovascular disease (OR, 3.71; 95% CI, 2.05–6.7) had a higher AF risk. Both populations had an age-related increase in AF, even in multivariate models (OR, 1.72; 95% CI, 1.31–2.24 per +decade). Conclusion The handheld ECG device shows clinical feasibility with high rate for AF detection with a similar trend toward a higher prevalence with aging from different settings. These data suggested that portable ECG device via remote care system may aid in clinical diagnosis, therapeutic interventions, or patient referral for cardiac arrhythmias.

In this data, we present the details of the cross-sectional study from Mackay Memorial Hospital, Taipei, Taiwan that examined the relationship between three-dimensional (3D) peri-aortic root fat (PARF) volumes, cardiometabolic risk profiles, carotid artery morphology and remodeling. Our sample is composed of a total 1492 adults who underwent an annual cardiovascular risk survey in Taiwan. PARF was measured using images of gated non-contrast cardiac computed tomography (CT) and a dedicated workstation (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). The stratified analyses were performed in order to assess the association between carotid morphology, remodeling and PARF by tertile. For further analyses and discussion, please see “The Association among Peri-Aortic Root Adipose Tissue, Metabolic derangements and Burden of Atherosclerosis in Asymptomatic Population” by Yun et al. (2015) [1].

Obesity is a global public health problem and major risk factor for cardiovascular disease and heart failure. Due to the high prevalence of diabetes and cardiovascular risk factors in Asians with relatively normal body mass index (BMI) defined by international standards, the World Health