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Abstract Hemodynamic parameters have been correlated with stroke, hypertension, and arterial stenosis. While only a few small studies have examined the link between hemodynamics and diabetes mellitus (DM). This case-control study enrolled 417 DM patients and 3475 non-DM controls from a community-based cohort. Peak systolic velocity (PSV), end-diastolic velocity (EDV), blood flow velocity (MFV), pulsatility index (PI), and the resistance index (RI) of the common carotid arteries were measured by color Doppler ultrasonography. Generalized linear regression analyses showed that as compared to the non-DM controls, the age-sex-adjusted means of PSV, EDV, and MFV were − 3.28 cm/sec, − 1.94 cm/sec, and − 2.38 cm/sec, respectively, lower and the age-sex-adjusted means of RI and PI were 0.013 and 0.0061, respectively, higher for the DM cases (all p-values

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45–65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45–65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45–65: 14.5, >65: 31.6 %; p 65, mean difference, 77.8 m [95% confidence interval (CI), 2.1–153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37–15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45–65, mean difference, −2.1 mmHg [95% CI, −3.9 to −0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45–65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40–74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19–1.28) and 1.36 (95% CI, 1.28–1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19–1.29) and 1.38 (95% CI, 1.30–1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375–0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835–0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

Abstract Background Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). Methods We used a case–control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Early control of LDL-C to prevent ASCVD later in life is important. The Taiwan Society of Lipids and Atherosclerosis in association with the other seven societies developed this new lipid guideline focusing on subjects without clinically significant ASCVD. In this guideline for primary prevention, the recommended LDL-C target is based on risk stratification. A healthy lifestyle with recommendations for foods, dietary supplements and alcohol drinking are described. The pharmacological therapies for LDL-C reduction are recommended. The aim of this guideline is to decrease the risk of ASCVD through adequate control of dyslipidemia in Taiwan.

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.

Abstract Background The most important factor in evaluating a physician’s competence is strong clinical reasoning ability, leading to correct principal diagnoses. The process of clinical reasoning includes history taking, physical examinations, validating medical records, and determining a final diagnosis. In this study, we designed a teaching activity to evaluate the clinical reasoning competence of fourth-year medical students. Methods We created five patient scenarios for our standardized patients, including hemoptysis, abdominal pain, fever, anemia, and chest pain. A group history-taking with individual reasoning principles was implemented to teach and evaluate students’ abilities to take histories, document key information, and arrive at the most likely diagnosis. Residents were trained to act as teachers, and a post-study questionnaire was employed to evaluate the students’ satisfaction with the training activity. Results A total of 76 students, five teachers, and five standardized patients participated in this clinical reasoning training activity. The average history-taking score was 64%, the average key information number was 7, the average diagnosis number was 1.1, and the average correct diagnosis rate was 38%. Standardized patients presenting with abdominal pain (8.3%) and anemia (18.2%) had the lowest diagnosis rates. The scenario of anemia presented the most difficult challenge for students in history taking (3.5/5) and clinical reasoning (3.5/5). The abdominal pain scenario yielded even worse results (history taking: 2.9/5 and clinical reasoning 2.7/5). We found a correlation in the clinical reasoning process between the correct and incorrect most likely diagnosis groups (group history-taking score, p = 0.045; key information number, p = 0.009 and diagnosis number, p = 0.004). The post-study questionnaire results indicated significant satisfaction with the teaching program (4.7/5) and the quality of teacher feedback (4.9/5). Conclusions We concluded that the clinical reasoning skills of fourth-year medical students benefited from this training course, and the lower correction of the most likely diagnosis rate found with abdominal pain, anemia, and fever might be due to a system-based teaching modules in fourth-year medical students; cross-system remedial reasoning auxiliary training is recommended for fourth-year medical students in the future.

Background: We designed this open-pilot study to investigate the efficacy and feasibility of incorporating the Interpersonal Effectiveness skills from Dialectical Behavior Therapy (DBT-IE) into a 3-h clinical communication workshop for registered nurses. Method: A convenience sample of registered nurses were invited. The Professional Fulfillment Index, Perceived Stress Scale, Empathy Index, the Interpersonal Reactivity Index, and measures regarding quality of life, anxiety, depression, and insomnia were completed. A subgroup of participants received the Objective Structured Teaching Examinations (OSTE). Pre- and post-workshop assessments were conducted to identify the most empathetic or validated responses from case scenarios and to assess the self-rated levels of confidence regarding the capability to select the best answer. The satisfaction of the participants with respect to the workshop content, process, and the lecturer were also collected. Paired t-test was used for statistical analysis. Results: Among the 164 participants of the clinical communication workshop, 72 consented and their pre- and post-results were analyzed. Post-workshop assessment revealed significant improvement in professional fulfillment (p = 0.014), interpersonal coping ability (p = 0.038), and decrease in dysfunctional coping style (p

Background: Of the types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) may be cured through pulmonary endarterectomy (PEA). In this study, we investigated patient experiences with PEA for CTEPH treatment in Taiwan. Methods: We retrospectively reviewed the records of patients who underwent PEA in two medical centers between January 2005 and December 2019. We measured the following outcomes: in-hospital complications, improvements in cardiac function and exercise capacity, survival using Kaplan–Meier analysis after PEA. Results: Twenty-seven patients (female: 17) with a mean age of 52.6 years underwent PEA. Pre-operatively, most patients were New York Heart Association functional class (NYHA FC) III (n = 19) and IV (n = 7). The mean periods from the onset of symptoms to diagnosis and from diagnosis to operation were 22.6 and 22.3 months, respectively. After PEA, mean intubation time, and length of intensive care unit and hospital stay were 9, 11, and 20 days, respectively. Most patients' NYHA FCs improved to I (n = 15) and II (n = 10). The mean 6-min walk test (6MWT) result improved by 60.5%. The in-hospital mortality, mean follow-up period, and 5- and 10-year overall survival rates were 3.7%, 77.0 months, 96.3%, and 84.3%, respectively. Furthermore, 5- and 10-year disease-specific survival rates were both 96.3%. Conclusion: When pre-operative and post-operative statuses were compared, we found a significant improvement in NYHA FC and 6MWT distance. Our study also found a lower in-hospital mortality rate compared to other published studies, except compared to the newer data provided by the University of California, San Diego group.

Abstract The current treatment paradigm for atrial fibrillation (AF) prioritizes rate control over rhythm control; however, rhythm control has shown benefits over other AF strategies. This study compares the outcomes of rivaroxaban with and without concomitant antiarrhythmic drugs (AADs), using propensity score matching to correct for statistical effects of baseline discrepancies. This multi-center retrospective study included 1,477 patients with non-permanent AF who took rivaroxaban for at least one month between 2011 and 2016 and had not received catheter ablation. Concomitant AAD use was compared against clinical outcome endpoints for effectiveness, safety, and major adverse cardiac events (MACE). Associations with concomitant AAD use were evaluated using multivariate Cox proportional hazard analyses. Patients were divided into two matched groups: rivaroxaban alone (n = 739) and with concomitant AADs (n = 738). The cumulative incidences of safety (p = 0.308), effectiveness (p = 0.583), and MACE (p = 0.754) were similar between the two groups, and multivariate analysis showed no significant differences. The new thromboembolism and all-cause death rates were higher in rivaroxaban alone (2.7% vs 0.8%, p = 0.005; and 10% vs. 6.9%, p = 0.032, respectively). The heart failure readmission rate was higher in the concomitant-AAD group (8.4% vs. 13.3%, p = 0.003). The concomitant use of rivaroxaban with AADs appears to be well-tolerated, with lower rates of thromboembolism and all-cause death, but is associated with more occurrences of congestive heart failure.

Abstract Background Online education has been used as an adjunct modality for teaching and it attracts attention in recent years as many medical students can not accomplish their clerkship in the hospital due to COVID-19 pandemic. This study aims to collect the articles related to online surgical education for medical students, and to analyze the effectiveness of online education and the perceptions of the medical students. Method We performed a systemic literature search in PubMed, MEDLINE, EMBASE, ERIC and Cochrane library. Keywords used for searching included “medical student”, “online education”, “online teaching”, “online learning”, “distance learning”, “electronic learning”, “virtual learning” and “surgical”. Medical education research study quality instrument (MERSQI) was used for the evaluation of the quality of the searched articles. Results From 1240 studies retrieved from the databases, 13 articles were included in this study after screening. The publication year was from 2007 to 2021. The mean MERSQI score of the 13 searched articles was 12.5 +/− 1.7 (range 10.0-14.5). There were totally 2023 medical students who attended online surgical curriculum. By online course, improvement of understanding and knowledge on the studied topics could be reached. The confidence in patient encounters could be improved by online curriculum with sharing experiences, discussing, and role playing. However, students felt concentration was poor during online course. Medical students studying through video platform could get better test scores than those studying with textbooks. Regarding basic surgical skills, online teaching of suturing and knot-tying could be possible and was appreciated by the students who could practice away from the hospital and get feedbacks by instructors through online environment. The scores for the clinical competence assessment for incision, suturing and knot-tying were found to be no significant difference between the online teaching group and face-to-face teaching group. Conclusion Online surgical curriculum for medical students is not easy but inevitable in the era of COVID-19 pandemic. Although online course is not the same as physical course, there are some efforts which could be tried to increase the effectiveness. Basic surgical skills could also be taught effectively through online platform. Even if the COVID-19 pandemic is over in the future, online curriculum could still be a helpful adjunct for surgical education.

OBJECTIVE: : For competency-based medical education (CBME), there has been increasing focus on entrustable professional activities (EPA) as one of the modalities for assessment of competence. This study aims to investigate the effectiveness, the merits and the demerits of EPAs for evaluation of the competency of the surgical trainees. DESIGN: : We performed a systematic literature search in PubMed, EMBASE, MEDLINE, and ERIC. Keywords used for searching included “entrustable professional activity”, “surgery”, “surgical”, “resident” and “residency”. The search was limited to the English language but not limited to the publication time. The searched articles were included in this study if the searched articles were related to “entrustable professional activity” and “surgical residency”. SETTING: : Included studies were published from 2016 to 2022 and were written in English. PARTICIPANTS: : From 67 studies retrieved from the databases, 12 articles were included in this study after screening. There were totally 1990 surgical residents and 1165 faculty included in these studies. Results: : By EPA assessments, it was found the performance of the senior residents was better than that of the junior residents. However, there was no significant difference between junior surgical residents and medical students for the abilities of using concise, clear and comprehensive professional clinical language to do a handover with other health care professionals. There were significant amount of surgical residents had no or faint idea about EPA assessments. Regardless of pre-operative, intra-operative and post-operative assessments, EPAs could be as effective as milestones for evaluation. Conclusion: : EPAs could be a good tool for assessment of the abilities of surgical residents and could differentiate the abilities between senior and junior surgical trainees, but multiple EPAs should be used for comprehensive evaluation and the ability of communication with other professional healthcare givers by using clear, concise and comprehensive clinical language seemed to be left behind. In addition to assess the clinical abilities by EPAs, the ability of communication should not be neglected and should be emphasized.

Background: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. Methods: This study retrospectively enrolled patients in the Taiwan cohort – Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. Results: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. Conclusion: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.

Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.

Abstract The therapeutic effects of ultrasonic microbubble transfection (UMT)-based vascular endothelial growth factor 165 (VEGF165) gene delivery on young and senescent endothelial progenitor cells (EPCs) were investigated. By UMT, plasmid DNA (pDNA) can be delivered into both young EPCs and senescent EPCs. In the UMT groups, higher pDNA-derived protein expression was found in senescent EPCs than in young EPCs. Consistent with this finding, a higher intracellular level of pDNA copy number was detected in senescent EPCs, with a peak at the 2-h time point post UMT. Ultrasonic microbubble delivery with or without VEGF improved the angiogenic properties, including the proliferation and/or migration activities, of senescent EPCs. Supernatants from young and senescent EPCs subjected to UMT-mediated VEGF transfection enhanced the proliferation and migration of human aortic endothelial cells (HAECs), and the supernatant of senescent EPCs enhanced proliferation more strongly than the supernatant from young EPCs. In the UMT groups, the stronger enhancing effect of the supernatant from senescent cells on HAEC proliferation was consistent with the higher intracellular VEGF pDNA copy number and level of protein production per cell in the supernatant from senescent cells in comparison to the supernatant from young EPCs. Given that limitations for cell therapies are the inadequate number of transplanted cells and/or insufficient cell angiogenesis, these findings provide a foundation for enhancing the therapeutic angiogenic effect of cell therapy with senescent EPCs in ischaemic cardiovascular diseases.

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension. Keywords: Guideline, Pulmonary arterial hypertension, Pulmonary hypertension

The emerging data supports rhythm control to prevent major adverse cardiac events (MACE) in high-risk patients with atrial fibrillation (AF). Limited data demonstrated rivaroxaban 10 mg combining dronedarone seemed feasible. This study aimed at investigating clinical events in a dronedarone-treated cohort. This exploratory, retrospective chart review was conducted in nonpermanent AF patients receiving dronedarone for ≥ 3 months between 2009/1 and 2016/2. In Taiwan, dronedarone's labeled indication was strict to age ≥ 70 or 65 to 70 years with either hypertension, diabetes, prior stroke, or left atrium >50 mm. We divided all into 4 groups using antithrombotic strategies to evaluate the safety, effectiveness, and MACE endpoints. A total of 689 patients (mean CHA 2 DS 2 -VASc score 3.8 ± 1.4) were analyzed: rivaroxaban 10 mg (n = 93, 13.5%), warfarin (n = 89, 12.9%), antiplatelet (n = 331, 48.0%), and none (n = 176, 25.5%). During the follow-up period (mean 946 ± 493.8 days), the rivaroxaban group did not report any stroke or thromboembolism (ishcmeic stroke rate: antiplatelet [0.6%], none [1.1%]; hemorrahgic stroke rate: warfarin [2.2%]; thromboembolism rate: warfarin [2.2%]). There was no significant difference in safety, effectiveness, and MACE endpoints between groups. Also, >104 weeks of dronedarone use was the independent predictor for MACE after adjusting the strategy and other covariates (hazard ratio 0.14 [95% confidence interval 0.04-0.44], P = .001). Our findings warrant concomitant rivaroxaban 10 mg and dronedarone for further investigation. Regardless of antithrombotic strategies, a more extended persistence of dronedarone was associated with fewer MACE.

Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case–control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima–media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3′-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.

Background: Plaque in carotid arteries (CAs) is a major factor of systemic atherosclerosis and cardiovascular disease (CVD). The left and right CAs have different anatomic and geometric features and may influence the predictability of CVD. However, the site- and segment-specific prevalence of carotid plaques (CP) and study on severity of carotid atherosclerosis with CVD risks was very limited. Methods: We enrolled 1539 healthy residents aged 40-to-74 years from two northern districts in Taiwan. All volunteers received high resolution B-mode carotid ultrasound scans and CVD risk factors evaluations. Results: The prevalence rate of extracranial CP was 21.9% in females and 33.8% in males. Carotid bifurcation is the most affected segment. As compared with the right CAs, the age-sex-adjusted matched odds ratio of having plaques in the left CAs was 1.32 (95% confidence interval = 1.02–1.73). The proportions of subjects had a total plaque number≥2, maximum stenosis≥30%, and plaque score≥3 were 8.9, 10.3, and 7.2%, respectively, in females and were 17.7, 17.2, and 15.1%, respectively, in males. Among subjects with moderate and severe carotid atherosclerosis, the mean ± SD of estimated 10-year CVD risk was 19.1 ± 14.6% and more than 65% of them need intensive blood pressure, lipids, or sugar controls. Conclusion: We found that bifurcation was the most prevalent segment, and left CAs was more likely to form plaque than right CAs. The major CVD risk factors were highly prevalent and the estimated CVD risks were high in subjects with more advanced carotid atherosclerosis. The study provides further direction for CVD prevention and treatment. Keywords: Carotid plaque, Segment-specific, Cardiovascular risk factors, Community-based study

Background: Renal denervation (RDN) is effective to lower systolic blood pressure (SBP) in essential hypertension. However, patient selection under medications remains an important unmet clinical need. Methods: This multicenter study aimed at observing whether preprocedural features associated with increased renin-angiotensin-aldosterone activity influence RDN response. This study enrolled the patients who underwent RDN for uncontrolled hypertension. Medical records were reviewd and patients were divided into 2 groups depending by meeting any of the following conditions prior to RDN: (1) >10 mmHg of office SBP reduction after aldosterone inhibition, (2) aldosterone-renin ratio >30 or (3) slow flow on the renal angiogram. RDN responders were defined by a reduction in 24-hour mean ≥6 mmHg or by ≥1 class of antihypertensive drug withdraw. Results: A total of 46 patients were enrolled, of which 27 (59%) were in control group A and 19 (41%) in group B. The baseline age, gender, office and 24-hour SBP (mean 140.0 ± 12.8 mmHg vs. 144.0 ± 16.5 mmHg, p = 0.577) were comparable, while the number of prescribed drug classes was fewer in group A (4.0 ± 1.3 vs. 4.9 ± 0.9, p = 0.014). The proportion patients with prescribed aldosterone antagonist or high aldosterone-renin ratios were higher in group B. At 12 months post RDN, the results were significantly better in group B in terms of mean change in office SBP (12.4 ± 23.5 mmHg vs. 29.9 ± 25.5 mmHg, p = 0.046) and the proportion of RDN responders (51.9% vs. 89.5%, p < 0.001). Conclusion: RDN was more effective in patients with any of 3 clinical indices.

Age is a major risk factor for diseases caused by ischemic hypoxia, such as stroke and coronary artery disease. Endothelial progenitor cells (EPCs) are the major cells respond to ischemic hypoxia through angiogenesis and vascular remodeling. However, the effect of aging on EPCs and their responses to hypoxia are not well understood. CD34+ EPCs were isolated from healthy volunteers and aged by replicative senescence, which was to passage cells until their doubling time was twice as long as the original cells. Young and aged CD34+ EPCs were exposed to a hypoxic environment (1% oxygen for 48hrs) and their gene expression profiles were evaluated using gene expression array. Gene array results were confirmed using quantitative polymerase chain reaction, Western blotting, and BALB/c female athymic nude mice hindlimb ischemia model. We identified 115 differentially expressed genes in young CD34+ EPCs, 54 differentially expressed genes in aged CD34+ EPCs, and 25 common genes between normoxia and hypoxia groups. Among them, the expression of solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) increased the most by hypoxia in young cells. Gene set enrichment analysis indicated the pathways affected by aging and hypoxia most, including genes "response to oxygen levels" in young EPCs and genes involved "chondroitin sulfate metabolic process" in aged cells. Our study results indicate the key factors that contribute to the effects of aging on response to hypoxia in CD34+ EPCs. With the potential applications of EPCs in cardiovascular and other diseases, our study also provides insight on the impact of ex vivo expansion might have on EPCs.

Background: Advanced age is associated with left ventricular (LV) remodeling and impaired diastole. The association among aging, mitral leaflet closure (EF slope), cardiac structures, and diastolic indices in an asymptomatic Taiwanese population is largely unknown. Methods: We studied 8103 asymptomatic participants (49.5 ± 11.6 years, 38.2% women) from a health evaluation cohort (2004–2012) in a tertiary center in Taiwan. Echo-derived LV structure/function, and M-mode based EF slope (mm/s) and serum NT-proBNP level were obtained. The association between EF slope and the other clinical or echo-based parameters was investigated. Results: Average values for EF slope among various age groups in the Taiwanese population were determined for both genders. Advanced age was associated with reductions in EF slope (adjusted estimate: −0.35/per decade). Reduced EF slope was associated with older age, higher blood pressure and greater body mass index in multivariate models (all p

Background: Metabolic syndrome (MS) associated with systemic inflammation identifies high-risk cardiovascular diseases (CVDs). Deteriorated renal function leads to poor cardiovascular outcomes. However, the relationship between such metabolic anomaly, systemic inflammation and renal function in patients diagnosed with peripheral arterial disease (PAD) remains largely unknown. Materials and methods: A total of 249 consecutive individuals meeting the study criteria from our outpatient clinics were enrolled in the study. Baseline demographic data and information regarding metabolic abnormalities [presented as Adult Treatment Panel (ATP) III scores], high-sensitivity C-reactive protein (Hs-CRP) level, and estimated renal function [calculated by the Modification of Diet in Renal Disease (MDRD) method] were obtained. High-risk PAD was defined by utilizing the ankle–brachial index (ABI) method. Results: Of all 249 subjects, 60 had diagnostic high-risk PAD. The prevalence of PAD increased in a significant trend with worsening ATP III scores. By utilizing a multivariate adjustment model, body mass index and worse renal function were independently associated with PAD (both p

Background: The objective of this study is to determine the presence of early-stage atherosclerosis and the determinants of those with abnormal intima-media thickness (IMT) without coronary calcification assessed by carotid duplex and coronary computed tomography in a relatively healthy population and to compare the results from the two detection methods. Materials and methods: Data of 181 asymptomatic participants [mean age 50.8 (35–72) years, 131 males] regarding baseline characteristics; blood biochemistries; Framingham risk score (FRS); metabolic score (MS); either carotid intima-media thickness (CIMT) or plaque, or both; and coronary artery calcification score (CACS) were obtained. Distributional differences between categorized atherosclerosis groups defined by various methods were compared using Chi-square test, while uni- and multivariate analyses were conducted to establish independent risk of atherosclerosis. Results: For all participants, the mean MS was 1.58 and mean FRS was 5.99. Zero CACS was found in 123 individuals, of whom 75 (61%) had abnormal CIMT or plaque existence. After adjusting the confounders, both male gender and larger BMI were found to be significantly associated with abnormal CIMT or plaque existence in patients with zero CACS in multivariable regression model. Conclusion: Carotid duplex may detect subclinical vascular atherosclerosis in more than half of asymptomatic patients without coronary artery calcification detected by coronary computed tomography. These findings have important implications for early-stage atherosclerosis screening and implementation of primary preventive intervention.

Background: Aging is known to play a key role in the development of cardiovascular diseases (CVDs). Although aging is associated with mitochondria dysfunction, the impact of mitochondria-related aging on CVDs has remained unclear in Taiwan. Methods: The Mitochondria-AGing in NorthErn Taiwan (MAGNET) study, a prospective study, was initiated in December 2010 to investigate the prevalence, determinants and the progress of CVDs and related risks in a community-dwelling sample of about 3000 men and women from suburban areas of northern Taiwan. The middle-aged population comprises the majority of the whole cohort in a 3-year collection period. This study also examines a link between baseline characteristics and the development of subclinical atherosclerosis. Data obtained will include information regarding baseline demographics, body surface electrocardiography, blood bio-specimen components, measurement of cardiac and carotid structure and function by ultrasonography, socioeconomic status, life styles, and life quality scoring including short-form SF-36. Additional survey of blood samples, including analysis of endothelial progenitor cells and the mitochondria function, and biomarkers, for a nested case-control study will be performed. All participants will be followed for incidence and characterization of related cardiovascular events. Conclusion: This study is expected to clarify the role of mitochondria-related aging in the development of CVDs and functional changes in sub-urban areas of Taiwan.

Gold has been used in medicine for thousands of years. Nowadays, gold compounds contribute to the treatment of rheumatoid arthritis; gold alloys are used in implants in various fields of medicine; and colloid gold is used in immunogold electron microscopy. Advances in nanotechnology have resulted in novel gold nanoparticles, which possess distinct physical properties such as fluorescence. We have developed fluorescent gold nanoclusters (FANCs) that contain gold nanoparticles with a core dimension < 2 nm. Initial studies have shown that FANCs are a highly biocompatible marker with a fluorescence half-life of 9 days, and are suitable for in vitro and in vivo tracking of endothelial and endothelial progenitor cells. FANCs may also have novel chemical properties involved in regulation of endothelial cell function. This minireview discusses the future directions of biomedical research for FANCs.

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: Age has been shown to be related with increased vascular stiffness, cardiac structural alterations, and geometric remodeling. Data regarding the relationship between clinical heart failure (HF) symptoms and aging-related alterations of ventricular geometries are scarce. We therefore investigated this issue. Methods: We subsequently studied 1,577 participants without cardiovascular or chronic lung disorders. Echocardiography-defined cardiac structures and left ventricular (LV) geometries, including LV mass, relative wall thickness, and mass-to-volume ratio were all determined. Baseline clinical variables, medical histories, and functional impairment in terms of HF symptoms during exercise were all obtained. Multivariate bootstrapping derived odds ratio from various models were used to represent the independent predictors for HF. Results: Of all, 1,459 participants (age: 49.3±10.8; 36% female) with normal ejection fraction (66.8±4.7%) were enrolled in our study. Cardiac structural alterations, ventricular geometric remodeling, and diastolic dysfunction were significantly related to aging process, along with increasing cardiovascular morbidities and risk factors. After adjusting for confounders and LV mass, change in ventricular geometries in terms of mass-to-volume ratio remained an independent risk, whereas relative wall thickness had a borderline significance for HF symptoms (odds ratio: 2.79 and 1.04, p=0.047 and 0.08, respectively). Conclusion: Cardiac structure, function, and various ventricular remodeling patterns were age-related. Such remodeling process is not only associated with a higher incidence of cardiovascular morbidities but also more likely to develop HF symptoms, which are independent of clinical variables and LV mass.

Background: Nonalcoholic fatty liver disease (NAFLD), which represents metabolic abnormality and reflects extra visceral fat deposition, has been shown to be a threat to public health and associated with cardiovascular risks. However, data regarding the differences in clinical presentation and related metabolic abnormalities in the aging group population remained scarce in the Taiwanese population. Methods: We subsequently examined 8,658 subjects participating general health evaluation in Mackay Memorial hospital from 2003 to 2007. Baseline characteristics, anthropometrics, medical history, and biochemical markers were all collected. Abdominal ultrasonography was performed in all subjects. Two estimated cardiovascular risk scores were calculated according to criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III as metabolic score and Framingham risk score. Univariate logistic regression model was used to examine whether the baseline characteristics, anthropometrics, histories, and biochemical markers were independently associated with NAFLD from various age groups (young vs. aging groups) classified by 60 years of age. Respective receiver operating characteristic curves (ROC) with area under the curve were generated to test the capability of both cardiovascular risk scores in NAFLD discrimination from different age groups. Results: Totally 7,204 subjects (mean age: 44.5±11 years, 36% female) were finally enrolled in our study. Subjects with NAFLD were observed to have high body weight, body mass index, and circumferential waist and significantly abnormal biochemical markers accompanying worsening lipid profiles when compared with those without NAFLD in both the young and aging group populations (all p

The clinical benefits of percutaneous coronary intervention, the most prevalent procedure nowadays for the treatment of symptomatic coronary artery disease, are frequently offset by the occurrence of vascular restenosis. Although the introduction of drug-eluting stents has significantly reduced restenotic rates, the rare, but potentially fatal, delayed thrombosis remains a clinical threat. Further refinement of the drug-eluting stent based on a better understanding of cell cycle regulation between the vascular smooth muscle cell (VSMC) and endothelial cell (EC) is required. In this review, we discuss the role of S-phase kinase-associated protein-2 (Skp2), previously known as an oncoprotein, in the regulation of VSMC proliferation and its signaling axis. The currently available evidence suggests that the Rac1-Skp2-p27Kip1 signaling axis acts as a common final pathway for many factors that regulate VSMC proliferation, such as growth factors, extracellular matrices and cyclic nucleotides. Importantly, although EC proliferation is also shown to be regulated by the same axis, cAMP seems to regulate this axis differentially between VSMC and EC, rendering the underlying mechanism of this differential regulation a promising target for the development of a new generation of drug-eluting stent.

BACKGROUND: The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized. MATERIALS AND METHODS: In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines. RESULTS: TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p

Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7±7.0 years) met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X2=6.12, trend P