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The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5,p 208) dropped from 23.5 to 10% (p

Background: The literature emphasizes the importance of matching the demand and supply of endocrinology and metabolism (EM) specialists. This study analyzed the current status of EM specialists in Taiwan. The gender effects on the workplace of EM specialists were also evaluated. Methods: The number of internal medicine (IM) specialists was obtained from the websites of the Ministry of Health and Welfare. Data about EM specialists were retrieved from the database of the Endocrine Society of the Republic of China (ESROC; Taiwan). Differences in age distribution and workplace levels or locations between female and male EM specialists were analyzed. Results: Since 1988, 809 physicians were certified as EM specialists. The average age of 739 EM specialists (509 male, 230 female) who remained as active members of the ESROC was 49.9 ± 11.1 years. The age distribution (p

Aims Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region‐specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored. Methods and results Among 1326 asymptomatic individuals, region‐specific VAT including peri‐aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri‐aortic adipose tissue (TAT), was assessed using multiple‐detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle‐tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI‐e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17–2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440–1927 days) of follow‐up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log‐rank P

ObjectiveWe aimed to investigate the influence of income level on guideline-directed medical therapy (GDMT) prescription rates and prognosis of patients with heart failure (HF) following implementation of a nationwide health insurance programme.MethodsA total of 633 098 hospitalised patients with HF from 1996 to 2013 were identified from Taiwan National Health Insurance Research Database. Participants were classified into low-income, median-income and high-income groups. GDMT utilisation, in-hospital mortality and postdischarge HF readmission, and mortality rates were compared.ResultsThe low-income group had a higher comorbidity burden and was less likely to receive GDMT than the other two groups. The in-hospital mortality rate in the low-income group (5.07%) was higher than in the median-income (2.47%) and high-income (2.51%) groups. Compared with the high-income group, the low-income group had a significantly higher risk of postdischarge HF readmission (adjusted HR (aHR): 1.29, 95% CI 1.27 to 1.31), all-cause mortality (aHR: 1.98, 95% CI 1.95 to 2.02) and composite HF readmission/all-cause mortality (aHR: 1.54, 95% CI 1.52 to 1.56). These results were generally consistent among the population after propensity matching (low vs high: HR=2.08 for mortality and 1.36 for HF readmission; median vs high: HR=1.23 for mortality and 1.12 for HF readmission; all pConclusionsLow-income patients with HF had nearly a twofold increase in the risk of in-hospital mortality and postdischarge events compared with the high-income group, partly due to lower GDMT utilisation. The differences between postdischarge HF outcomes among various income groups appeared to mitigate over time following the implementation of nationwide universal health coverage.

Aims This study aimed to investigate the functional correlate, clinical relevance, and prognostic implications of novel left ventricular (LV) deformations in patients with atrial fibrillation (AF). Methods and results LV deformational indices, including peak global longitudinal strain (GLS), systolic strain rates (SRs), and early diastolic strain rates (SRe) were measured in a large‐scale AF population. We related such measures to key clinical heart failure (HF) markers, conventional echocardiographic ventricular parameters, and clinical outcomes. Among 1483 subjects with newly diagnosed AF (mean age, 71.6 ± 12.4 years; 55.5% male), worsened GLS (mean, − 12.6 ± 3.9%) and strain rates (SRs and SRe: mean, − 0.86 ± 0.27 and 1.25 ± 0.41 1/s, respectively) by our three‐beat measures were independently correlated with higher C‐reactive protein, N‐terminal pro‐B‐type natriuretic peptide, higher E/e′, more impaired LV ejection fraction (LVEF − 14.7%) was common in our cohort (67.8%) despite an averaged preserved LVEF (58.4 ± 14.2%), with worse GLS and SRe being associated with higher composite HF re‐admissions/death during the 2.9 year follow‐up (inter‐quartile range, 1.6–4.1 years) in multivariate models incorporating key LV indices (LVEF, LV mass index, and E/e′) (all P

Aims We aimed to investigate the functional alterations, diagnostic utilization, and prognostic implication of carotid arterial deformations in subjects with cardiovascular risk factors and heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results Among 251 prospectively participants (mean age 66.0 ± 9.8 years, 65.7% female) in a single centre between December 2011 and September 2014, carotid artery deformations including circumferential strain (CCS)/strain rate and radial strain were analysed by two‐dimensional speckle tracking. We further related these carotid artery deformation indices to HF biomarkers and cardiac structure and function by echocardiography and explored their prognostic values. Significant reductions of CCS, circumferential strain rate, and circumferential radial strain were observed across control (n = 52), high risk (n = 147), and HFpEF (n = 52) (trend P ≤ 0.001). Aging, hypertension, HFpEF, and higher pulse rate showed independent associations with reduced CCS by stepwise multivariate regressions (all P

Background: Hypothyroidism is reportedly associated with increased cardiovascular risk and heart failure. We aimed to elucidate the mechanistic influence of atrio-ventricular deformations and their prognostic utilizations in asymptomatic subclinical hypothyroidism (SCH). Methods: We assessed speckle-tracking of deformations among 4173 population-based asymptomatic individuals classified as euthyroid (0.25< thyroid-stimulating hormone [TSH] ≤4.0 μIU/mL, n=3799) or having mild (4< TSH ≤10.0 μIU/mL, n=349) or marked (TSH >10 μIU/mL, n=25) SCH. We further related deformational indices to outcomes of atrial fibrillation and heart failure. Results: Despite borderline differences in indexed left ventricular mass and left atrial volume ( P =0.054 and 0.051), those classified as mild and marked SCH presented with modest but significant reductions of global longitudinal strain, and showed elevated E/tissue Doppler imaging (TDI)-e′, markedly diminished peak atrial longitudinal strain and higher left atrial stiffness (all P P P Conclusions: Hypothyroidism, even when asymptomatic, may widely influence subclinical atrio-ventricular mechanical functions that may lead to higher heart failure and atrial fibrillation risk. We proposed the potential usefulness and prognostic utilization of myocardial strains in such population.

Background: Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. Methods: We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles.Result: Patients with moderate and mild NAFLD have greater volume of PCF (100.7±26.3vs. 77.1±21.3 vs. 61.7±21.6ml, P < 0.001) and TAT (11.2±4.1 vs. 7.6±2.6 vs. 5.5±2.6ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82-0.89 and 0.84-0.90). Conclusion: Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, are currently approved for clinical use by Taiwan National Health Insurance (NHI) in patients who had a recent atherosclerotic cardiovascular disease with persistent LDL-C levels >135 mg/dL despite high-intensity statin (HIS) or maximally tolerated statin in combination with ezetimibe treatment. Since January 2020 to July 2020, total of 10 patients who had received coronary revascularization received NHI-approved alirocumab or evolocumab in our institution. The mean reduction of LDL-C following PCSK9 inhibitors treatment at 6-month and 12-month were respectively 62.5% and 60.2%. The patients in our study were younger, had more frequently received HIS/ezetimibe, and had higher baseline LDL-C levels with a greater LDL-C reduction following PCSK9 inhibitors treatment compared with those patients in previously studies. Our findings highlight that the NHI's regulation of PCSK9 inhibitors application should be re-evaluation to increase the use of NHI-approved PCSK9 inhibitors in high-risk patients.

Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test p = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04–1.63, p = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05–3.22, p &lt, 0.001), age &gt, 65 (aHR = 9.25, 95% C.I. 7.46–11.50, p &lt, 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20–2.58, p = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52–2.29, p &lt, 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient’s best interest for physicians to be aware of this potential complication and offer preventative measures.

BACKGROUND This study aims to explore the clinical correlates of myocardial deformations using speckle-tracking algorithm and to determine the prognostic utility of such measures in asymptomatic ethnic Chinese population. METHODS Global longitudinal (GLS), circumferential strain (GCS), and torsion were analyzed using featured tissue-tracking algorithm among 4049 symptom-free ethnic Chinese population. Hypertrophy (LVH) was classified into 4 tiers: indeterminate, dilated, thick and thick/dilated, by gender-stratified partition of end-diastolic volume index (EDVi) and LV mass/EDV0.67. RESULTS LVH (7.3%) showed substantially lower GLS (-20.3 ± 1.82% vs. -18.9 ± 2.08%) yet higher torsion (2.20 ± 0.90 vs. 2.39 ± 1.01, p

Background New-onset atrial fibrillation (NOAF) is associated with adverse outcomes in patients with coronary artery disease (CAD). Although newer generation drug-eluting stents (NG-DESs) are more beneficial than bare-metal stents (BMSs) in reducing the risk of in-stent restenosis and revascularization, whether NG-DES implantation in patients with stable CAD reduces NOAF risk compared with BMS implantation remains unknown. Methods This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching was used to select 18,423 pairs of patients with stable CAD receiving NG-DES implantation and BMS implantation with similar baseline characteristics for evaluation. A competing risk model was used to evaluate the risk of NOAF between the NG-DES and BMS groups in which death was considered a competing risk. Results After adjustment for patients' clinical variables, the use of NG-DESs was associated with a decreased risk of NOAF at 1-year follow-up (adjusted subdistribution hazard ratio [SHR] = 0.79, 95% confidence interval [CI] = 0.68–0.93, P = 0.005) compared with the use of BMSs. Similar results indicated that NG-DESs were beneficial for reducing the risk of NOAF (adjusted SHR = 0.81, 95% CI = 0.67–0.97, P = 0.020) in patients with a CHA2DS2-VASc score of ≥2. These findings were also consistent with those for patients who received dual antiplatelet therapy for an undefined duration of >1 month following stent implantation. Conclusions Our findings suggest that NG-DESs might reduce the risk of NOAF in patients with stable CAD.

Aims This study aimed to evaluate the prognostic significance of nutritional status in post‐discharge Asians with heart failure with preserved ejection fraction (HFpEF). Methods and results We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C‐reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53–0.85)], higher PNI [HR: 0.97 (95% CI: 0.95–0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97–0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02–1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re‐hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut‐off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted P interaction for both SA level and PNI

Purposes: We investigated the influences of prognostic factors on long-term survival of patients with follicular thyroid cancer (FTC) based on all-cause mortality and two exclusive causes of death, FTC and non-FTC. Methods: In this retrospective cohort study, we collected data of 204 patients with FTC diagnosed between 1985 and 2007 at National Taiwan University Hospital. For all-cause mortality, Cox proportional hazards models were used to estimate hazard ratios for prognostic factors. Cause-specific hazard and cumulative incidence function models were used to determine the influences of prognostic factors on FTC and non-FTC death, respectively. The dynamic processes of distant metastases and locoregional recurrences were included as time-varying factors in all models. Results: The cumulative incidence of all-cause death was 24% and 45% at 10 and 20-years, respectively. Multivariate analyses identified that distant metastases, locoregional recurrences, and positive surgical margins were significant independent risk factors for overall survival, hazard, and cumulative incidence of FTC death. Age at diagnosis >60 years increased the risks of all-cause and non-FTC death as well as cumulative incidence of non-FTC death. Tumor size >4 cm had a harmful effect on overall survival. Female patients had higher risk and cumulative incidence of FTC death, but male patients had a higher cumulative incidence of non-FTC death. Lymph node metastases significantly increased the cumulative incidence of FTC death. Conclusion: Dynamic distant metastases and locoregional recurrences were the most dominant risk factors influencing FTC-specific hazard and cumulative incidence for FTC death by accounting for non-FTC death as a competing risk for FTC patients. Keywords: Thyroid cancer, Follicular thyroid cancer, Prognosis, Distant metastasis, Locoregional recurrence

Aims Left atrial (LA) remodelling is an important predictor of cardiovascular events of heart failure (HF) and atrial fibrillation. Data regarding diagnostic value of LA remodelling on diastolic dysfunction (DD) and preclinical HF remain largely unexplored. Methods and results We assessed LA dimension (LAD) in 8368 consecutive asymptomatic Asians (mean age: 49.7, 38.9% women) and related such measure to updated American Society of Echocardiography (ASE) DD criteria and newly revised N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) cut‐off (≥125 pg/mL) and HF with preserved ejection fraction criteria incorporating NT‐proBNP and echocardiography parameters by the European Society of Cardiology (ESC). LAD and indexed LAD (LADi) were both inversely correlated with myocardial relaxation e′ and positively associated with indexed LA volume, left ventricular E/e′, and tricuspid regurgitation velocity (all P 34 mL/m2; positive predictive value: 96%) and well‐discriminated ESC‐recommended NT‐proBNP (≥125 pg/mL, LAD: 37 mm) for HF. Conclusions Single utilization of atrial remodelling is highly useful for ruling out presence of DD and provides practical threshold for identifying preclinical HF based on most updated guidelines.

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75–2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

There is an established link between cardiometabolic abnormality, central arterial stiffness, and preserved ejection fraction heart failure (HFpEF). Adipocyte free fatty acid binding protein (a-FABP) has been shown to signal endothelial dysfunction through fatty acid toxicity, though its role in mediating ventricular-arterial dysfunction remains unclear. We prospectively examined the associations of a-FABP with central arterial pressure using non-invasive applanation tonometry (SphygmoCor) and cardiac structure/function (i.e., tissue Doppler imaging [TDI] and global longitudinal myocardial strain [GLS]) in patients with cardiometabolic (CM) risk (n = 150) and HFpEF (n = 50), with healthy volunteers (n = 49) serving as a control. We observed a graded increase of a-FABP across the healthy controls, CM individuals, and HFpEF groups (all paired p

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions &lt, 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement &lt, 0.05) mainly in the NW phenotypes (p interaction &lt, 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.

The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29&ndash, 45.63, 43.55, 95% CI: 23.38&ndash, 63.73 for MUNO and MUO (MHNO as reference), both p &lt, 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both pinteraction &lt, 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean - 18.2 ± 48.1; 95% confidence interval - 24.9 to - 11.5, p 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU 208) dropped from 23.5 to 10% (p 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

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.

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).

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

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a primary genetic cardiomyopathy with morphologically unique characteristics, including loose “spongy” meshwork. Subjects carrying these disorders were typically presented with triad of heart failure, cardiac arrhythmias, and consequences of mural thrombi formation. The clinical and echocardiographic features regarding LVNC, however, are not widely known. Methods: A retrospective survey involving 11 patients who fulfilled echocardiographic criteria for LVNC defined by Jenni et al. was conducted at MacKay Memorial Hospital from January 2009 to March 2017. Parameters assessed by echocardiography and clinical data were further analyzed. Results: Significantly depressed left ventricular systolic function assessed by echocardiography was noticed in a majority of our adult study cases. Conclusion: Considering the fatal complications LVNC may lead to, it is essential for clinical cardiologists to early identify suspicious individuals, and the establishment of definitive criteria and early treatment is essential.

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.

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.

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.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Background— Left atrial (LA) function is tightly linked to several cardiovascular diseases and confers key prognostic information. Speckle tracking-based deformation as a feasible and sensitive LA mechanical assessment has proven its clinical significance beyond volume measures; however, the reference values remain largely unknown. Methods and Results— We studied 4042 participants undergoing annual cardiovascular survey. Among them, 2812 healthy participants (65% men; mean age, 47.4±9.9 years) were eligible for speckle tracking analysis. Peak atrial longitudinal systolic strain and strain rate (SR) at systolic (SRs), early diastolic (SRe), and late diastolic atrial contraction phases (SRa) were analyzed by dedicated software (EchoPAC, GE) and compared in terms of age, sex, and blood pressure. Overall, women demonstrated higher peak atrial longitudinal systolic strain (39.34±7.99% versus 37.95±7.96%; P Conclusions— Our findings suggest LA mechanical functional decays in association with increasing age and higher blood pressure, which seem to be compensated for by augmentation of atrial pump function. We have also provided age- and sex-stratified reference values for strain and SR based on a large-scale Asian population.

Background: Diabetes mellitus and pre–diabetes mellitus are associated with lower body mass indices and increased risk of cardiovascular events (including heart failure) at lower glucose thresholds in Chinese compared with Western cohorts. However, the extent of cardiac remodeling and regulation on cardiac mechanics in lean and nonlean dysglycemic Chinese adults is understudied. Methods and Results: We studied 3950 asymptomatic Chinese (aged 49.7±10.7 years; 65% male; body mass index: 24.3±3.5 kg/m 2 ) with comprehensive echocardiography including speckle tracking for left ventricular global longitudinal strain/torsion, with plasma sugar, glycosylated hemoglobin (HbA1c), and insulin resistance (homeostasis model assessment of insulin resistance) obtained. Participants were classified as (1) nondiabetic (fasting glucose 2 ; n=1445) or nonlean (n=2505). Higher sugar, HbA1c, and homeostasis model assessment of insulin resistance were independently associated with higher left ventricular mass, greater mass-to-volume ratio, more impaired diastolic indices, and worse global longitudinal strain even after adjusting for clinical covariates (adjusted coefficient value: 0.28/0.12 for global longitudinal strain per 1 U HbA1c/homeostasis model assessment of insulin resistance increment; both P P Conclusions: These data demonstrate the presence of preclinical cardiac remodeling and systolic dysfunction in prediabetic and diabetic Chinese adults, occurring at lower thresholds of glycemic indices than defined by international standards, particularly in lean individuals.

Coronary heart disease (CHD) is a leading cause of death in developed countries. Exploration of indicators to identify high risk individuals who develop adverse outcomes despite stable baseline condition is important. This study is to evaluate the association between serum albumin concentration and cardiovascular (CV) outcomes in individuals of stable CHD.Seven-hundred-thirty-four participants from Biosignature study, a nationwide prospective cohort study aimed to identity risk factors among patients with stable CHD, were enrolled for analysis. They were divided into low serum albumin group (baseline albumin concentration3.5g/dL, n=98) and normal albumin group (baseline albumin concentration ≥3.5g/dL, n=636). The relations between baseline albumin and adverse CV outcomes within 18months of follow-up were analyzed.Compared baseline characteristics with normal albumin group, subjects in low albumin group are older, having more diabetic patients, lower hemoglobin level, lower estimated glomerular filtration rate, lower total cholesterol level, lower left ventricular ejection fraction, and higher blood glucose. While there is no significant difference of total CV events between two groups, low serum albumin concentration is associated with an increased risk of all-cause mortality (10.2% vs. 0.5%, p0.001) and hard CV events (7.1% vs. 1.4%, p0.001). The association remains significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95% CI: 1.01-45.62; hard CV events, HR: 3.68, 95% CI: 1.03-13.19).Low serum albumin concentration (3.5g/dL) worsens prognosis of patients with stable CHD.

Objective Some patients with papillary thyroid carcinoma (PTC) would suffer from locoregional recurrences or distant metastases. This study was aimed to elucidate the impacts of locoregional recurrences and distant metastases on these patients' survival. Design Retrospective hospital-based cohort study. Population Data were collected from 1636 subjects with PTC at National Taiwan University Hospital between 1985 and 2007. Measurements Overall and disease-specific survival curves were estimated by the Kaplan-Meier method. Time-independent and time-dependent prognostic factors were included simultaneously in multivariate analyses using Cox models. Results Overall survival (OS) rates at 10- and 20-years were 90% and 76%, respectively. The 10- and 20-year disease-specific survival (DSS) rates were 95% and 90%, respectively. Our multivariate analyses identified that older age, distant metastases (hazard ratio, HR: 6·69, 95% CI: 4·40-10·18), locoregional recurrences (HR: 1·88, 95% CI: 1·22-2·89), lymph node metastases, massive extrathyroid extension, male gender and larger tumour size (>4 cm) were significantly associated with poorer OS. Older age, distant metastases (HR: 15·03, 95% CI: 8·31-27·21), locoregional recurrences (HR: 3·63, 95% CI: 2·03-6·51), massive extrathyroid extension, male gender and larger tumour size (>4 cm) were independently related to worse DSS. The performance of high-dose (131) I ablation had a protective effect on OS and DSS. Conclusion The locoregional recurrences had a moderately harmful impact on OS and DSS, but age and distant metastases were the major decisive factors for OS and DSS. High-dose (131) I ablation had a protective role. However, lymph node dissection did not alter the prognosis whenever lymph node metastases only influenced OS.

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C 40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3–5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

MKP-1 dephosphorylates and inactivates MAPKs, whose constitutive activations have been associated with human cancers.We found that total MKP-1 protein levels were decreased in 63.7 % of breast cancer tissues compared with the paired noncancerous breast tissues. Decreased MKP-1 protein levels were correlated with increased tumor stage and positive recurrence and were associated with poor survival, even when using a multivariate Cox regression model. Intriguingly, nuclear MKP-1 staining was positively correlated with ER status. In vitro, tamoxifen increased MKP-1 expression in ER-positive but not ER-negative breast cancer cells. ER-specific siRNA was able to attenuate tamoxifen-induced MKP-1 expression. Furthermore, tamoxifen prolonged the duration of MKP-1 elevation and the binding time of ER to the promoter of the MKP-1/DUSP-1 gene compared with estrogen.Our results suggest that alterations of MKP-1 may serve as a prognostic factor in breast cancer. In addition, the regulation of MKP-1 may be related to the ER.

Purpose: Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. Methods: This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, p]USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. Results: All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (ß-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (ß-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. Conclusion: Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population.

We compared the cardiovascular diseases (CVD) and risk factors in patients with stage 3–5 chronic kidney disease (CKD) and those with diabetes mellitus by analyzing the MAGNET study data of residents in northern Taiwan. The reimbursement of lipid-lowering therapy was also examined. Of the 1607 participants, 63 (31 men) were found to have eGFR

Background Visceral adipose tissue, a biologically active fat depot, has been proposed as a reliable marker for visceral adiposity and metabolic abnormalities. Effects of such adiposity on LV diastolic function and dyssynchrony remained largely unknown. Methods We assessed pericardial fat (PCF) and thoracic peri-aortic fat (TPAF) by three-dimensional (3D) volume-vender multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Echo-derived diastolic parameters and tissue Doppler imaging (TDI) defined mitral annular systolic (S’), early diastolic (E’) velocities as well as LV filling (E/E’) were all obtained. Intra-ventricular systolic (Sys-D) and diastolic (Dias-D) dyssynchrony were assessed by TDI method. Results A total of 318 asymptomatic subjects (mean age: 53.5 years, 36.8 % female) were eligible in this study. Greater PCF and TPAF were both associated with unfavorable diastolic indices and higher diastolic dyssynchrony (all p

To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex.Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex.Median leptin concentrations were significantly higher (p0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004).Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.

Growth hormone is a growth factor for normal and abnormal tissues. Patients with acromegaly are postulated to be at greater risk for cancer development. To date, small cell lung cancer in such patients is not reported in the literature. We report a 76-year-old man with frank acromegaly resu

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been described in many types of cancers. However, the role of phospho-STAT3 (p-STAT3) at serine residue 727 is in large part undetermined. Our purposes of this study were to evaluate the expression patterns of p-STAT3 (ser727) in cervical intraepithelial neoplasia (CIN) and to explore its possible role in the progression of cervical cancer.Paraffin-embedded sections from 56 patients including 20 CIN 1, 10 CIN 2, and 26 CIN 3 were collected in this study. Immunohistochemical analysis was performed, and the expression patterns of p-STAT3 (ser727) were categorized by semiquantitative method and further correlated with the CIN histopathologic grade using the chi(2) test with Bonferroni adjustment for multiple comparisons and with the proliferation marker Ki-67 expression using Fisher's Exact Test.The categorized high p-STAT3 (ser727) expression group in nuclei of dysplastic cells was significantly higher in CIN 3 (76.92%), in comparison with CIN 1/2 (13.33%, P0.001). Moreover, both the nuclear and cytoplasmic p-STAT3 (ser727) expressions were correlated with Ki-67 nuclear staining (P0.001 and0.001, respectively).Our result revealed that aberrant expression levels of p-STAT3 (ser727) were significantly correlated with CIN lesion grade and cell proliferation. Evaluation of p-STAT3 (ser727) expression may provide additional prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for cervical cancer.

Objective . Leptin and its receptor are the key players in the regulation of energy balance and body weight control. However, their roles in gynecological malignancies are mostly unclear. In this study, we analyzed the expression and possible involvement of leptin and the leptin receptor in the pathogenesis of endometrial cancer. Methods . Radioimmunoassay was performed to analyze the serum leptin levels in the endometrial cancer patients, while RT-PCR, immunoblotting, and immunohistochemistry techniques were applied to study the expression of leptin receptor in the endometrioid-type endometrial cancer tissues. Furthermore, BrdU labeling followed by immunofluorescent analysis was used to analyze the effect of leptin receptor overexpression on endometrial cancer cell proliferation. Results . Serum leptin levels are elevated in endometrial cancer patients, but show no significant difference to those of normal controls when normalized by body mass index. On the other hand, lower expression levels of leptin receptor short form (Ob-Ra) were observed in most endometrial cancer tissues, especially in the poorly differentiated ones, and the forced expression of Ob-Ra in RL95-2 endometrial cancer cells prevented them from entering the S-phase. Conclusion . In summary, our data demonstrates for the first time that the leptin receptor is aberrantly expressed in endometrial cancer tissues and is possibly involved in the pathogenesis of endometrial cancer.

Objective. To measure adiponectin levels in maternal serum and umbilical cord serum at delivery, and examine whether or not there are correlations between adiponectin levels and neonatal birthweights, maternal body weights and body mass indexes. Study design. The study included 84 healthy mothers who had given birth to healthy neonates. Adiponectin levels in maternal serum and umbilical cord serum were determined by radioimmunoassay and compared. Results. The ranges of adiponectin levels for umbilical cord serum and maternal serum were 22.7-78.4 µg/ml and 4.0-43.3 µg/ml, respectively. Umbilical serum adiponectin levels (46.9 ± 1.2 µg/ml) were significantly higher than maternal serum adiponectin levels (16.1 ± 0.8 µg/ml) ( p < 0.001). No correlation was found between the adiponectin levels in maternal serum and those in umbilical cord serum ( r = 0.158, p = 0.151). Umbilical serum adiponectin levels were significantly correlated with both neonatal birthweights ( r = 0.454, p < 0.001) and gestational ages a...

Objectives : To study the correlation between amniotic fluid leptin levels and maternal serum leptin levels during the early second trimester, and to determine whether the ratios of amniotic fluid leptin levels to maternal serum leptin levels are elevated in pregnant women who subsequently develop preeclampsia. Study design : Samples from 120 pregnant women were included in this prospective study, of which 20 were from pregnant women who subsequently developed preeclampsia and 100 were from normal pregnant women. Both the amniotic fluid and the maternal serum leptin levels were ascertained by radioimmunoassay (RIA). Results : A strong correlation between amniotic fluid leptin levels and maternal serum leptin levels was observed in both preeclamptic and normal pregnant women. In addition, the ratios of amniotic fluid leptin levels to maternal serum leptin levels were positively correlated to amniotic fluid leptin levels, but negatively correlated to maternal serum leptin levels. Furthermore, the ratios of amniotic fluid leptin levels to maternal serum leptin levels in preeclamptic women were significantly higher than those in normal pregnant women. Conclusions : Amniotic fluid leptin levels correlated with maternal serum leptin levels during the early second trimester. The ratios of amniotic fluid leptin levels to maternal serum leptin levels were elevated in preeclamptic women. However, the maternal serum leptin levels themselves showed no such elevation. Therefore, this elevated ratio may be a marker at the early stage of pregnancy in preeclamptic women.

Objective. To analyze the possible involvement of leptin in uterine leiomyomas. Study design. Serum leptin levels, determined by radioimmunoassay, were compared in myomatic ( n = 50) and the normal ( n = 50) women. Results. A significant correlation was found between serum leptin levels and body mass index in both the myomatic women ( r = 0.76, p < 0.001) and the normal women ( r = 0.56, p < 0.001). Serum leptin levels in the myomatic women (9.3 ± 0.6 ng/mL) were significantly lower ( p < 0.001) than those in the normal women (13.6 ± 1.2 ng/mL). In addition, the ratios of serum leptin levels/body mass index in the myomatic women (0.38 ± 0.02) were significantly lower than those in the normal women (0.57 ± 0.04) ( p < 0.001). A significant correlation was found between the ratios of serum leptin levels/body mass index and body mass index ( r = 0.59, p < 0.001) in the normal women, but not in the myomatic women ( r = 0.27, p = 0.061). Conclusion. The lower plasma leptin levels observed in the women with myo...

Background Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive. Methods A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA). Results Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029). Conclusion A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage.