Hsuan-Fu Kuo

Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes

BackgroundMeta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM).MethodsSerial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT.ResultsPostchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 μ mol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis.ConclusionsThese results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.

Areca Nut Chewing and Risk of Atrial Fibrillation in Taiwanese Men: A Nationwide Ecological Study

Background: Areca nut chewing is associated with the risk of obesity, metabolic syndrome, hypertension, and cardiovascular mortality. Although a few case reports or case series have suggested the link between areca nut chewing and cardiac arrhythmias, information about the relationship between areca nut chewing and atrial fibrillation (AF) is lacking. Thus, a nationwide ecological study was conducted to investigate this. Methods: Two national datasets, the nationwide population-based 2005 Taiwan National Health Insurance Research dataset (NHIRD) and the 2005 National Health Interview Survey (NHIS), were used for analyses. The clinical characteristics, inhabited area and medical histories for 375,360 eligible males were retrieved from the 2005 NHIRD. Health related behaviors including areca nut chewing, cigarette smoking, infrequent vegetable eating, and exercise habit were collected from the 2005 NHIS. The prevalence of AF and the areca nut chewing rate were evaluated by multivariate analysis. Results: Of the 375,360 males (mean age, 44 years old), 1,326 (0.35%) were diagnosed with AF. The higher areca nut chewing rate, the higher prevalence rate of AF in Taiwan (Spearman correlation coefficient r = 0.558, p = 0.007). After adjusting for other covariates, the current areca nut chewing rate was found to be independently associated with the prevalence of AF. The adjusted odd ratio for areca nut chewing was 1.02 (95% CI = 1.00-1.04) in risk of AF prevalence. Conclusions: Areca nut chewing is independently associated with the prevalence of AF in Taiwanese men. However, further exploration of the underlying mechanisms is necessary.

Hormone replacement therapy and risk of atrial fibrillation in Taiwanese menopause women: A nationwide cohort study.

Hormone replacement therapy (HRT) is associated with risk of vascular disease. The association between atrial fibrillation (AF), vascular events, and different HRTs, including estradiol and conjugated equine estrogens (CEE), has been controversial in previous studies. Thus, we conducted a retrospective cohort study to investigate these associations. Female patients (>45 years old) first diagnosed with menopause were enrolled from National Health Insurance Research Dataset (1998–2008). Cox regression analysis estimated risk of new-onset AF, stroke, and major adverse cardiac events (MACE) after exposure to estradiol or CEE. Of 5489 females (mean age = 55 years) enrolled, 1815 treated with estradiol and 3674 treated with CEE. Incidence per 103 person-years of AF, stroke, and MACE in CEE vs estradiol patients was 2.23 vs. 0.92, 14.0 vs. 9.09, and 15.55 vs. 10.47. As compared with patients treated with estradiol, those treated with CEE had a significantly higher incidence of AF, stroke, and MACE. The adjusted hazard ratios for each category were 1.96, 1.30, and 1.26, respectively. The significant results remained similar, even after use of propensity-score-matched strategy. In conclusion, CEE was associated with a higher risk of AF, stroke, and MACE than estradiol in menopausal females. Further exploration of underlying mechanisms is necessary.

Randomized controlled trial of heart rate variability biofeedback in cardiac autonomic and hostility among patients with coronary artery disease.

Hostility is a psychosocial risk factor that may decrease heart rate variability (HRV) in coronary artery disease (CAD) through cardiac autonomic imbalance. Heart rate variability biofeedback (HRV-BF) increases HRV indices and baroreflex gain. This study examines the effectiveness of HRV-BF in restoring cardiac autonomic balance and decreasing hostility among patients with CAD. One hundred and fifty-four patients with CAD were assigned randomly to receive 6 weeks of HRV-BF, in addition to the standard medical care received by the wait-list control (WLC) group. A 5-min electrocardiogram, blood pressure, and hostility were assessed pre-intervention, post-intervention, and at 1-month follow-up. The standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and log LF at post-intervention was significantly higher than that at pre-intervention in the HRV-BF group. Baseline log LF was significantly higher post-intervention and at follow-up after HRV-BF training than at pre-intervention. The treatment curve of log LF pre-session increased significantly after session 2, which was maintained to post-intervention. Expressive hostility, suppressive hostility, and hostility total score at post-intervention and one-month follow-up after HRV-BF were significantly lower than at pre-intervention. This study showed increased HRV and decreased expressive and suppressive hostility behavior in patients with CAD following HRV-BF.

Association of increased arterial stiffness and p wave dispersion with left ventricular diastolic dysfunction.

Background: The association between increased arterial stiffness and left ventricular diastolic dysfunction (LVDD) may be influenced by left ventricular performance. P wave dispersion is not only a significant determinant of left ventricular performance, but is also correlated with LVDD. This study is designed to compare left ventricular diastolic function among patients divided by brachial-ankle pulse wave velocity (baPWV) and corrected P wave dispersion (PWDC) and assess whether the combination of baPWV and PWDC can predict LVDD more accurately. Methods: This cross-sectional study enrolled 270 patients and classified them into four groups according to the median values of baPWV and PWDC. LVDD was defined as impaired relaxation and pseudonormal/restrictive mitral inflow patterns. Results: The ratio of transmitral E wave velocity to early diastolic mitral annulus velocity (E/Ea) was higher in group with higher baPWV and PWDC than in the other groups (all p <0.001). The prevalence of LVDD was higher in group with higher baPWV and PWDC than in the two groups with lower baPWV (p ≤ 0.001). The baPWV and PWDC were correlated with E/Ea and LVDD in multivariate analysis (p ≤ 0.030). The addition of baPWV and PWDC to a clinical mode could significantly improve the R square in prediction of E/Ea and C statistic and integrated discrimination index in prediction of LVDD (p ≤ 0.010). Conclusions: This study showed increased baPWV and PWDC were correlated with high E/Ea and LVDD. The addition of baPWV and PWDC to a clinical model improved the prediction of high E/Ea and LVDD. Screening patients by means of baPWV and PWDC might help identify the high risk group of elevated left ventricular filling pressure and LVDD.

Acupuncture-Induced Popliteal Arteriovenous Fistula Successfully Treated with Percutaneous Endovascular Intervention

A 39‐year‐old female visited our cardiovascular outpatient department with paresthesia and soreness around the right popliteal fossa, where thrill was palpable. There was no history of trauma, apart from her having undergone acupuncture several years previously. An arteriovenous fistula (AVF) was diagnosed by vascular ultrasonography and magnetic resonance imaging. Angiography confirmed the presence of an AVF fed by the medial geniculate artery. Transarterial embolization was performed to close the AVF using coils and tissue adhesive. To the best of our knowledge, acupuncture‐induced AVF has not been previously reported. We present a case demonstrating the merits of percutaneous endovascular intervention for treating this rare complication. The additional administration of a tissue adhesive can achieve complete closure of the AVF in the event of an unsatisfactory result following coil embolization. Doctors should be aware of the potential vascular complications of acupuncture, and of the management options.

A Xanthine-Derivative K + -Channel Opener Protects against Serotonin-Induced Cardiomyocyte Hypertrophy via the Modulation of Protein Kinases

This study investigated whether KMUP-1, a xanthine-derivative K+ channel opener, could prevent serotonin-induced hypertrophy in H9c2 cardiomyocytes via L-type Ca2+ channels (LTCCs). Rat heart-derived H9c2 cells were incubated with serotonin (10 μM) for 4 days. The cell size increased by 155.5%, and this was reversed by KMUP-1 (≥1 μM), and attenuated by the LTCC blocker verapamil (1 μM) and the 5-HT2A antagonist ketanserin (0.1 μM), but unaffected by the 5-HT2B antagonist SB206553. A perforated whole-cell patch-clamp technique was used to investigate Ca2+ currents through LTCCs in serotonin-induced H9c2 hypertrophy, in which cell capacitance and current density were increased. The LTCC current (ICa,L) increased ~2.9-fold in serotonin-elicited H9c2 hypertrophy, which was attenuated by verapamil and ketanserin, but not affected by SB206553 (0.1 μM). Serotonin-increased ICa,L was reduced by KMUP-1, PKA and PKC inhibitors (H-89, 1 μM and chelerythrine, 1 μM) while the current was enhanced by the PKC activator PMA, (1 μM) but not the PKA activator 8-Br-cAMP (100 μM), and was abolished by KMUP-1. In contrast, serotonin-increased ICa,L was blunted by the PKG activator 8-Br-cGMP (100 μM), but unaffected by the PKG inhibitor KT5823 (1 μM). Notably, KMUP-1 blocked serotonin-increased ICa,L but this was partially reversed by KT5823. In conclusion, serotonin-increased ICa,L could be due to activated 5-HT2A receptor-mediated PKA and PKC cascades, and/or indirect interaction with PKG. KMUP-1 prevents serotonin-induced H9c2 cardiomyocyte hypertrophy, which can be attributed to its PKA and PKC inhibition, and/or PKG stimulation.