Long-term oral nitrate therapy is associated with adverse outcome in diabetic patients following elective percutaneous coronary intervention

<p>Abstract</p> <p>Background</p> <p>To assess the impact of long-term oral nitrate therapy on clinical outcome following percutaneous coronary intervention (PCI) in patients with type II diabetes.</p> <p>Methods</p> <p>The incidence of major adverse cardiovascular events (MACEs) following elective PCI for stable coronary artery disease was evaluated in 108 patients with type II diabetes (age 64.6 ± 10.5 years, 67.7% men). Major adverse cardiovascular events were defined as the need for revascularization, non-fatal myocardial infarction or cardiovascular death. Multivariate Cox regression analysis was used to evaluate the predictive value of MACEs by clinical characteristics and the prescription of long-term nitrate therapy.</p> <p>Results</p> <p>Isosorbide mononitrate (ISMN) was prescribed to 46 patients with an average dose of 44.3 ± 15.2 mg/day. After a mean follow up of 25.3 ± 25 months, 16 patients developed MACEs. Patients who received ISMN were more likely to suffer from MACEs (26.1% vs. 6.5%, P = 0.01), mainly driven by a higher rate of acute coronary syndrome (13.0 vs 0%, P = 0.01). Average daily dose of nitrate and other cardiovascular medication was not associated with MACEs. Multivariate Cox regression analysis revealed that prescription of only ISMN (Hazard Ratio 3.09, 95% CI 1.10-10.21, P = 0.04) was an independent predictor for the development of MACEs.</p> <p>Conclusion</p> <p>Long-term oral nitrate therapy was associated with MACEs following elective coronary artery revascularization by PCI in patients with type II diabetes.</p

Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.</p> <p>Methods</p> <p>We measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls.</p> <p>Results</p> <p>Patients with DM had significantly lower circulating Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts, and higher Log baPWV compared with controls (all <it>P < 0.05</it>). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all <it>P < 0.05)</it>. The circulating levels of Log CD34/KDR⁺EPC (r = -0.46, <it>P < 0.001</it>) and Log CD133/KDR⁺EPC counts (r = -0.45, <it>P < 0.001</it>) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, <it>P < 0.05</it>) and negatively correlated with circulating levels of Log CD34/KDR⁺EPC (r = -0.40, <it>P < 0.001</it>) and Log CD133/KDR⁺EPC (r = -0.41, <it>P < 0.001</it>). Multivariate analysis revealed that HbA1c, Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts were independent predictors of Log baPWV (<it>P < 0.05</it>).</p> <p>Conclusions</p> <p>In patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.</p

Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells

The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway

Cardiovascular outcomes associated with use of clarithromycin: population based study

Study question What is the association between clarithromycin use and cardiovascular outcomes? Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke. Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients. What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population

Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with type 2 diabetes.

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Plasma apixaban levels in Chinese patients with chronic kidney disease—Relationship with renal function and bleeding complications

Introduction: Accumulation of apixaban in plasma is a major concern in patients with chronic kidney disease (CKD). Studies that investigated plasma apixaban level in CKD patients and its association with clinically significant events are scarce.Methods: Patients with CKD Stage 1–4 who were taking apixaban, either 2.5 mg BD or 5 mg BD were recruited. The peak and trough plasma apixaban level were measured after 2 h and 12 h of last dose respectively. The results were correlated with renal function and clinical events during the period of follow-up from 1 January 2018 to 31 October 2021.Results: 141 patients (CKD Stage 1, n = 12; Stage 2, n = 74; Stage 3, n = 48, stage 4, n = 7) were included for analysis. The plasma peak and trough apixaban were significantly higher in patients with CKD stage 3 when compared with those having CKD stage 2 and 1 (peak levels: 223.4 ± 107.8 ng/ml vs. 161.0 ± 55.2 ng/ml vs. 126.6 ± 30.2 ng/ml; trough levels: 118.3 ± 67.9 ng/ml vs. 81.2 ± 33.0 ng/ml vs. 51.9 ± 31.1 ng/ml, p &lt; 0.05 or all) in patients taking 5 mg BD. Plasma trough apixaban level was negatively correlated with eGFR in patients taking 5 mg BD (r2 = −0.174, p &lt; 0.001) and 2.5 mg BD (r2 = −0.215, p &lt; 0.05). The plasma peak and trough apixaban level correlated with PT (r2 = 0.065, p = 0.003 and r2 = 0.096, p &lt; 0.01 respectively). Multivariate analysis showed that plasma trough apixaban levels were associated with the risk of bleeding complications (Odd ratio: 1.011, 95% CI:1.002–1.021, p = 0.023).Conclusion: The plasma apixaban level shows a trend of increase with worsening renal function, and an increase in the plasma apixaban level is suggestive of an increased risk of bleeding complications in patients with CKD. Further large-scale prospective studies are needed to evaluate relationship between plasma apixaban level and renal function as well as safety outcome in CKD patients. Moreover, the role of drug level monitoring should be prospectively evaluated for dosage optimization and the minimization of bleeding risks in CKD patients

Roles of the CHADS2 and CHA2DS2-VASc scores in post-myocardial infarction patients: Risk of new occurrence of atrial fibrillation and ischemic stroke

Background: Patients with myocardial infarction (MI) are at risk of the development of atrial fibrillation (AF) and ischemic stroke. We sought to evaluate the prognostic performance of the CHADS2 and CHA2DS2-VASc scores in predicting new AF and/or ischemic stroke in post-ST segment elevation MI (STEMI) patients. Six hundred and seven consecutive post-STEMI patients with no previously documented AF were studied.Methods and Results: After a follow-up of 63 months (3,184 patient-years), 83 (13.7%) patients developed new AF (2.8% per year). Patients with a high CHADS2 and/or CHA2DS2-VASc score were more likely to develop new AF. The annual incidence of new AF was 1.18%, 2.10%, 4.52%, and 7.03% in patients with CHADS2 of 0, 1, 2, and ≥ 3; and 0.39%, 1.72%, 1.83%, and 5.83% in patients with a CHA2DS2-VASc score of 1, 2, 3 and ≥ 4. The CHA2DS2-VASc score (C-statistic = 0.676) was superior to the CHADS2 (C-statistic = 0.632) for discriminating new AF. Ischemic stroke occurred in 29 patients (0.9% per year), the incidence increasing in line with the CHADS2 (0.41%, 1.02%, 1.11%, and 1.95% with score of 0, 1, 2, and ≥ 3) and CHA2DS2-VASc scores (0.39%, 0.49%, 1.02%, and 1.48% with score of 1, 2, 3 and ≥ 4). The C-statistic of the CHA2DS2-VASc score as a predictor of ischemic stroke was 0.601, superior to that of CHADS2 score (0.573). CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and stroke.Conclusions: The CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and ischemic stroke. This enables close surveillance and prompt anticoagulation for stroke prevention

PLASER: Pronunciation Learning via Automatic Speech Recognition

PLASER is a multimedia tool with instant feedback designed to teach English pronunciation for high-school students of Hong Kong whose mother tongue is Cantonese Chinese. The objective is to teach correct pronunciation and not to assess a student&apos;s overall pronunciation quality. Major challenges related to speech recognition technology include: allowance for non-native accent, reliable and corrective feedbacks, and visualization of errors