Background: Areca nut chewing has been reported to be associated with obesity, metabolic syndrome, hypertension, and cardiovascular mortality in previous studies. The aim of this study was to examine whether chewing areca nut increases the risk of coronary artery disease (CAD) in Taiwanese men. Methods: This study is a hospital-based case-control study. The case patients were male patients diagnosed in Taiwan between 1996 and 2009 as having a positive Treadmill exercise test or a positive finding on the Thallium-201 single-photon emission computed tomography myocardial perfusion imaging. The case patients were further evaluated by coronary angiography to confirm their CAD. Obstructive CAD was defined as a ≥ 50% decrease in the luminal diameter of one major coronary artery. The patients who did not fulfill the above criteria of obstructive CAD were excluded. The potential controls were males who visited the same hospital for health check-ups and had a normal electrocardiogram but no history of ischemic heart disease or CAD during the time period that the case patients were diagnosed. The eligible controls were randomly selected and frequency-matched with the case patients based on age. Multiple logistic regression analyses were used to estimate the odds ratio of areca nut chewing and the risk of obstructive CAD. Results: A total of 293 obstructive CAD patients and 720 healthy controls, all men, were analyzed. Subjects who chewed areca nut had a 3.5-fold increased risk (95% CI = 2.0-6.2) of having obstructive CAD than those without, after adjusting for other significant covariates. The dose-response relationship of chewing areca nut and the risk of obstructive CAD was also noted. After adjusting for other covariates, the 2-way additive interactions for obstructive CAD risk were also significant between areca nut use and cigarette smoking, hypertension and dyslipidemia. Conclusions: Long-term areca nut chewing was an independent risk factor of obstructive CAD in Taiwanese men. Interactive effects between chewing areca nut and cigarette smoking, hypertension, and dyslipidemia were also observed for CAD risk. Further exploration of their underlying mechanisms is necessary.

This study evaluated the effects of heart rate (HR) on brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI). Thirty-two patients without significant organic heart disease underwent elective cardiac catheterization or electrophysiologic study, and were then enrolled in right atrial pacing (RAP; 11 men, 9 women; aged 48 ∓15 years) or right ventricular pacing (RVP; 6 men, 6 women, aged 45 ∓13 years) studies. Three different HR levels (90, 100, and 110 beats per minute) were paced in random order. By stepwise, multiple linear regression analysis, age, systolic blood pressure (SBP), and pulse pressure (PP) correlated positively with baseline baPWV. In the RAP group, as HR increased, baPWV and left brachial diastolic blood pressure increased significantly (p ≤0.015), while ABI, left ankle SBP, left brachial PP, and left ankle PP decreased significantly (p ≤0.013). In the RVP group, as HR increased, baPWV also increased significantly (p=0.001), while ABI, left ankle SBP, and PP decreased significantly (p ≤ 0.034). Values of baPWV and ABI may be influenced by HR in young and middle-aged patients without significant organic heart disease. When these values are used to evaluate and follow up cardiovascular risk in patients, HR changes should be considered.

Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0.6 mg/kg daily. All mice were sacrificed after 16 weeks of feeding. H9c2 cells were treated with adipocytokines from the pericardial and peripheral fat from the study groups. The delayed-rectifier potassium current (I_K) and L-type calcium channel current (I_Ca,L) were measured by the whole-cell patch clamp techniques. Adipocytokines from the peripheral and pericardial fat tissues of mice with MS could decrease the I_K and increase the I_Ca,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the I_K in the EMPA and GLI groups were significantly higher than that in the MS group. The I_K of the EMPA group was also significantly higher than the GLI group. The I_Ca,L of the EMPA and GLI groups were significantly decreased overload compared with that of the MS group. However, there was no significant difference of I_K and I_Ca,L among study groups after treating adipocytokines from peripheral fat. Adipocytokines from pericardial fat but not peripheral fat tissues after EMPA therapy attenuated the effects of I_K decreasing and I_Ca,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.

Background: Meta-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). Methods: Serial 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. Results: Postchallenge 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. Conclusions: These 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.

Sodium-glucose transporter 2 (SGLT2) inhibitors are new glucose-lowering agents that have been proven to be beneficial for patients with cardiovascular diseases, heart failure, and sudden cardiac death. However, the possible protective effects of cardiac arrhythmia have not yet been clarified in clinical practice. In this study, we attempted to demonstrate the effects of SGLT2 inhibitors on cardiac arrhythmia by medical records from a single center. This retrospective study included patients diagnosed with type 2 diabetes mellitus (DM) and controlled hypertension who prescribed the indicated glucose-lowering agents based on medical records from 2016 to 2019 from Kaohsiung Medical University Hospital. These patients were divided into two groups. Group one patients were defined as patients with SGLT2 inhibitor therapy, and group two patients were defined as patients without SGLT2 inhibitor therapy. Baseline characteristics were collected from medical records. Univariate, multivariate, and match-paired statistical analyses were performed for the study endpoints. The primary study outcome was the incidence of cardiac arrhythmias, including atrial and ventricular arrhythmias, after SGLT2 inhibitor therapy. The secondary study outcomes were the incidence of stroke, heart failure, and myocardial infarction after SGLT2 inhibitor therapy. From the initial 62,704 medical records, a total of 9609 people who met our experimental design criteria were included. The mean follow-up period was 51.50 ± 4.23 months. Group one included 3203 patients who received SGLT2 inhibitors for treatment, and group two included 6406 patients who received non-SGLT2 inhibitors for treatment. Multivariate analysis showed that group one patients had significantly lower incidences of total cardiac arrhythmia (hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.38–0.89, p = 0.013) and atrial fibrillation (HR: 0.56, 95% CI: 0.35–0.88, p = 0.013) than those of group two patients. The secondary outcome analysis showed that group one patients also had a significantly lower risk of stroke (HR: 0.48, 95% CI: 0.33–0.7; p < 0.001), heart failure (HR: 0.54, 95% CI: 0.41–0.7, p < 0.001), and myocardial infarction (HR: 0.47, 95% CI: 0.31–0.72, p < 0.001). A time-to-event analysis showed that treatment of type 2 DM patients with SGLT2 inhibitors could reduce the probability of total cardiac arrhythmia and related cardiovascular disease, such as atrial fibrillation, stroke, heart failure, or myocardial infarction, by 0.5%~0.8%. This databank analysis showed that SGLT2 inhibitor therapy reduced the incidence of total cardiac arrhythmia and atrial fibrillation in type 2 DM patients and decreased the incidence of related cardiovascular diseases, such as stroke, heart failure, and myocardial infarction. However, additional investigations are needed to confirm this hypothesis.