The Beneficial Effect of the SGLT2 Inhibitor Dapagliflozin in Alleviating Acute Myocardial Infarction-Induced Cardiomyocyte Injury by Increasing the Sirtuin Family SIRT1/SIRT3 and Cascade Signaling.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have a variety of cardiovascular and renoprotective effects and have been developed as novel agents for the treatment of heart failure. However, the beneficial mechanisms of SGLT2i on cardiac tissue need to be investigated further. In this study, we established a mouse model of acute myocardial infarction (AMI) using coronary artery constriction surgery and investigated the role of dapagliflozin (DAPA) in protecting cardiomyocytes from hypoxic injury induced by AMI. In vitro experiments were done using hypoxic cultured H9c2 ventricular cells to verify this potential mechanism. Expression of the SIRT family and related genes and proteins was verified by qPCR, Western blotting and immunofluorescence staining, and the intrinsic potential mechanism of cardiomyocyte death due to AMI and hypoxia was comprehensively investigated by RNA sequencing. The RNA sequencing results of cardiomyocytes from AMI mice showed that the SIRT family may be mainly involved in the mechanisms of hypoxia-induced cardiomyocyte death. In vitro hypoxia-induced ventricular cells showed the role of dapagliflozin in conferring resistance to hypoxic injury in cardiomyocytes. It showed that SIRT1/3/6 were downregulated in H9c2 cells in a hypoxic environment, and the addition of dapagliflozin significantly increased the gene and protein expression of SIRT1, 3 and 6. We then verified the underlying mechanisms induced by dapagliflozin in hypoxic cardiomyocytes using RNA-seq, and found that dapagliflozin upregulated the hypoxia-induced gene downregulation, which includes ESRRA, EPAS1, AGTRAP, etc., that associated with SIRTs-related and apoptosis-related signaling to prevent H9c2 cell death. This study provides laboratory data for SGLT2i dapagliflozin treatment of AMI and confirms that dapagliflozin can be used to treat hypoxia-induced cellular necrosis in cardiomyocytes, in which SIRT1 and SIRT3 may play an important role. This opens up further opportunities for SGLT2i in the treatment of heart disease.

Enhancing Therapeutic Efficacy of Cinnamon Essential Oil by Nanoemulsification for Intravaginal Treatment of Candida Vaginitis.

Background: Due to its prevalence, recurrence, and the emergence of drug-resistance, Candida vaginitis significantly impacts the well-being of women. Although cinnamon essential oil (CEO) possesses antifungal activity, its hydrophobic properties limit its clinical application. Purpose: To overcome this challenge, a nanoemulsification technology was employed to prepare cinnamon essential oil-nanoemulsion (CEO@NE), and its therapeutic efficacy and action mechanism for Candida vaginitis was investigated in vivo and in vitro. Materials and Methods: CEO@NE, composed of 4% CEO, 78% distilled water, and 18% Tween 80, was prepared by ultrasonic nanoemulsification. The physical properties, anti-Candida activity, cytotoxicity, immunomodulatory potential and storage stability of CEO@NE were explored. Subsequently, the effect of intravaginal CEO@NE treatment on Candida vaginitis was investigated in mice. To comprehend the possible mechanism of CEO@NE, an analysis was conducted to ascertain the production of intracellular reactive oxygen species (ROS) in C. albicans. Results: CEO@NE, with the droplet size less than 100 nm and robust storage stability for up to 8 weeks, exhibited comparable anti-Candida activity with CEO. CEO@NE at the concentration lower than 400 µg/mL had no cytotoxic and immunomodulatory effects on murine splenocytes. Intravaginal treatment of CEO@NE (400 µg/mL, 20 µL/day/mouse for 5 consecutive days) curbed Candida colonization, ameliorated histopathological changes, and suppressed inflammatory cytokine production in mice intravaginally challenged with C. albicans. Notably, this treatment preserved the density of vaginal lactic acid bacteria (LAB) crucial for vaginal health. Co-culturing C. albicans with CEO@NE revealed concentration-dependent augmentation of intracellular ROS generation and ensuing cell death. In addition, co-culturing LPS-stimulated murine splenocytes with CEO@NE yielded a decrease in the generation of cytokines. Conclusion: This discovery provides insight into the conceivable antifungal and anti-inflammatory mechanisms of CEO@NE to tackle Candida vaginitis. CEO@NE offers a promising avenue to address the limitations of current treatments, providing novel strategy for treating Candida vaginitis.

Preparation and evaluation of Cordyceps militaris polysaccharide- and sesame oil-loaded nanoemulsion for the treatment of candidal vaginitis in mice.

BACKGROUND: Candida albicans is the most prevalent fungal pathogen, affecting over 75% of women who have experienced candidal vaginitis. Given the identification of drug-resistant C. albicans strains, there is an urgent need to develop therapeutic methods for treating vaginal Candida infection. Polysaccharide is the major bioactive component of Cordyceps militaris, known to modulate immune responses and alleviate inflammation. Sesame oil is known with anti-microbial and anti-inflammatory activities. METHODS: C. militaris polysaccharide was prepared and formulated with sesame oil to prepare emulsion and nanoemulsion, which are ideal mucosal delivery systems for both hydrophobic and hydrophilic compounds concurrently. The physical property and storage stability of these formulations were illustrated, and their effects on ameliorating vaginitis were investigated in a murine model of vaginal Candida infection. RESULTS: C. militaris polysaccharide-containing nanoemulsion showed smaller particle size, lower polydispersity index, higher zeta-potential and better stability than emulsion. Intravaginal administration of C. militaris polysaccharide-containing nanoemulsion significantly attenuated C. militaris colonization and vaginitis. Notably, these formulations exerted distinct effects on modulating cell infiltration and splenic cytokine production. Moreover, different profile of vaginal microflora was observed among the treatment groups, revealing the potential action mechanisms of these formulations to mitigate vaginal Candida infection. CONCLUSION: C. militaris polysaccharide- and sesame oil-containing nanoemulsion is potential to be developed as intravaginal therapeutic strategy for C. albicans-induced vaginitis.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes.

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Tumor Necrosis Factor Receptor Superfamily Member 21 Induces Endothelial-Mesenchymal Transition in Coronary Artery Endothelium of Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is an increasing threat to human health and regarded as an important public issue. Coronary artery disease is one of the main causes of death in type 2 DM patients. However, the effect of hyperglycemia on coronary artery endothelial cells (CAECs) and the pathophysiologic mechanisms are still not well-explored. This study aims to explore the signal pathway and novel biomarkers of injury of CAECs in DM in understanding the microenvironment changes and mechanisms of diabetic heart disease. Next-generation sequence (NGS) and bioinformatics analysis to analyze the CAECs of one type 2 DM patient and one normal individual was performed, and it was found that tumor necrosis factor receptor superfamily member 21 (TNFRSF21) was a soluble factor in circulating system. Further experiments confirmed that advanced glycation end products (AGEs), the metabolite derived by hyperglycemia, increased the expression of TNFRSF21 in CAECs. TNFRSF21 induced endothelial-mesenchymal transition (EndoMT) in CAECs, resulting in increased permeability of CAECs. In addition, levels of serum TNFRSF21 were higher in type 2 DM patients with left ventricular hypertrophy (LVH) than those without LVH. Serum TNFRSF21 levels were also positively correlated with the LV mass index and negatively with LV systolic function. Serum TNFRSF21 levels were associated with changes in cardiac structure and function in patients with type 2 DM. In conclusion, TNFRSF21 plays a pathogenic role in heart disease of type 2 DM, and can be used as a biomarker of the impairment of cardiac structure and function in type 2 DM patients.

Carbon Dioxide-Derived Biodegradable and Cationic Polycarbonates as a New siRNA Carrier for Gene Therapy in Pancreatic Cancer.

Pancreatic cancer is an aggressive malignancy associated with poor prognosis and a high tendency in developing infiltration and metastasis. K-ras mutation is a major genetic disorder in pancreatic cancer patient. RNAi-based therapies can be employed for combating pancreatic cancer by silencing K-ras gene expression. However, the clinical application of RNAi technology is appreciably limited by the lack of a proper siRNA delivery system. To tackle this hurdle, cationic poly (cyclohexene carbonate) s (CPCHCs) using widely sourced CO2 as the monomer are subtly synthesized via ring-opening copolymerization (ROCOP) and thiol-ene functionalization. The developed CPCHCs could effectively encapsulate therapeutic siRNA to form CPCHC/siRNA nanoplexes (NPs). Serving as a siRNA carrier, CPCHC possesses biodegradability, negligible cytotoxicity, and high transfection efficiency. In vitro study shows that CPCHCs are capable of effectively protecting siRNA from being degraded by RNase and promoting a sustained endosomal escape of siRNA. After treatment with CPCHC/siRNA NPs, the K-ras gene expression in both pancreatic cancer cell line (PANC-1 and MiaPaCa-2) are significantly down-regulated. Subsequently, the cell growth and migration are considerably inhibited, and the treated cells are induced into cell apoptotic program. These results demonstrate the promising potential of CPCHC-mediated siRNA therapies in pancreatic cancer treatment.

Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration.

Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation.

Effects of Trans, Trans-2,4-decadienal on the Ions Currents of Cardiomyocytes: Possible Mechanisms of Arrhythmogenesis Induced by Cooking-oil Fumes.

Household air pollution has adverse effects on cardiovascular health. One of the major sources of household air pollutants is the combustion of cooking oils during cooking. Trans, trans-2,4-decadienal (tt-DDE) is a type of dienaldehyde that is present in a wide range of food and food products. It is a byproduct of the peroxidation of linoleic acid following the heating of oil during cooking. The mechanisms of the associations between household air pollution and cardiac arrhythmias are currently unclear. The purpose of this study was to determine effects of tt-DDE on the ion currents in H9c2 cells. The IK and ICa,L in H9c2 cells treated with and without tt-DDE were measured using the whole-cell patch clamp method. Expressions of Kv2.1 and Cav1.2 in H9c2 cells treated with and without tt-DDE were measured by western blot analysis. After the H9c2 cells had been exposed to tt-DDE, the IK and ICa,L were significantly decreased. The expression of Kv2.1, unlike that of Cav1.2, was also significantly decreased in these cells. These changes in IK and ICa,L that were induced by tt-DDE may help to explain the association between cardiac arrhythmogenesis and cooking-oil fumes.

Epicardial adipose tissue thickness is not associated with adverse cardiovascular events in patients undergoing haemodialysis.

In non-haemodialysis (HD) patients, increased epicardial adipose tissue (EAT) thickness was significantly associated with adverse cardiovascular (CV) events. This study was designed to investigate whether EAT thickness was a useful parameter in the prediction of adverse CV events in HD patients. In addition, we also evaluated the major correlates of EAT thickness in these patients. In 189 routine HD patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV death, non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease, and hospitalization for heart failure. The follow-up period for CV events was 2.5 ± 0.7 years. Thirty-one CV events were documented. The multivariable analysis demonstrated that older age, smoking status, the presence of diabetes mellitus and coronary artery disease, and low albumin levels were independently correlated with adverse CV events. However, increased EAT thickness was not associated with adverse CV events (P = 0.631). Additionally, older age, female sex, low haemoglobin, and low early diastolic mitral annular velocity were correlated with high EAT thickness in the univariable analysis. In the multivariable analysis, older age and female sex were still correlated with high EAT thickness. In conclusion, high EAT thickness was associated with older age and female sex in the multivariable analysis in our HD patients. However, EAT thickness was not helpful in predicting adverse CV events in such patients. Further large-scale studies are necessary to verify this finding.

Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction.

BACKGROUND: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting. OBJECTIVE: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. METHODS: In the experimental group, a radio transmitter was implanted during the first sterile surgery to record nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. RESULTS: In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 µV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 µV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 µV (P<.039) and 2.14±0.50 µV (P<.001) at 4 and 8 weeks, respectively, after MI. In comparison, aSGNA at 4 and 8 weeks in dogs with MI but no ScNS was 8.26±6.31 µV (P=.005) and 10.82±7.86 µV (P=0002), respectively. Immunostaining showed confluent areas of remodeling in bilateral stellate ganglia and a high percentage of tyrosine hydroxylase-negative ganglion cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling was positive in 26.61%±11.54% of ganglion cells in the left stellate ganglion and 15.94%±3.62% of ganglion cells in the right stellate ganglion. CONCLUSION: ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac nerve sprouting after acute MI.

Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs.

BACKGROUND: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. OBJECTIVE: We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. METHODS: We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 µV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. CONCLUSION: Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

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 10(3) 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.

Acute reversal of phospholamban inhibition facilitates the rhythmic whole-cell propagating calcium waves in isolated ventricular myocytes.

Phospholamban (PLB) inhibits the activity of cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a). Phosphorylation of PLB during sympathetic activation reverses SERCA2a inhibition, increasing SR Ca(2+) uptake. However, sympathetic activation also modulates multiple other intracellular targets in ventricular myocytes (VMs), making it impossible to determine the specific effects of the reversal of PLB inhibition on the spontaneous SR Ca(2+) release. Therefore, it remains unclear how PLB regulates rhythmic activity in VMs. Here, we used the Fab fragment of 2D12, a monoclonal anti-PLB antibody, to test how acute reversal of PLB inhibition affects the spontaneous SR Ca(2+) release in normal VMs. Ca(2+) sparks and spontaneous Ca(2+) waves (SCWs) were recorded in the line-scan mode of confocal microscopy using the Ca(2+) fluorescent dye Fluo-4 in isolated permeabilized mouse VMs. Fab, which reverses PLB inhibition, significantly increased the frequency, amplitude, and spatial/temporal spread of Ca(2+) sparks in VMs exposed to 50 nM free [Ca(2+)]. At physiological diastolic free [Ca(2+)] (100-200 nM), Fab facilitated the formation of whole-cell propagating SCWs. At higher free [Ca(2+)], Fab increased the frequency and velocity, but decreased the decay time of the SCWs. cAMP had little additional effect on the frequency or morphology of Ca(2+) sparks or SCWs after Fab addition. These findings were complemented by computer simulations. In conclusion, acute reversal of PLB inhibition alone significantly increased the spontaneous SR Ca(2+) release, leading to the facilitation and organization of whole-cell propagating SCWs in normal VMs. PLB thus plays a key role in subcellular Ca(2+) dynamics and rhythmic activity of VMs.

MicroRNA-21-3p, a berberine-induced miRNA, directly down-regulates human methionine adenosyltransferases 2A and 2B and inhibits hepatoma cell growth.

Methionine adenosyltransferase (MAT) is the cellular enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM), the principal biological methyl donor and a key regulator of hepatocyte proliferation, death and differentiation. Two genes, MAT1A and MAT2A, encode 2 distinct catalytic MAT isoforms. A third gene, MAT2B, encodes a MAT2A regulatory subunit. In hepatocellular carcinoma (HCC), MAT1A downregulation and MAT2A upregulation occur, known as the MAT1A:MAT2A switch. The switch is accompanied with an increasing expression of MAT2B, which results in decreased SAM levels and facilitates cancer cell growth. Berberine, an isoquinoline alkaloid isolated from many medicinal herbs such as Coptis chinensis, has a wide range of pharmacological effects including anti-cancer effects. Because drug-induced microRNAs have recently emerged as key regulators in guiding their pharmacological effects, we examined whether microRNA expression is differentially altered by berberine treatment in HCC. In this study, we used microRNA microarrays to find that the expression level of miR-21-3p (previously named miR-21*) increased after berberine treatment in the HepG2 human hepatoma cell line. To predict the putative targets of miR-21-3p, we integrated the gene expression profiles of HepG2 cells after berberine treatment by comparing with a gene list generated from sequence-based microRNA target prediction software. We then confirmed these predictions through transfection of microRNA mimics and a 3' UTR reporter assay. Our findings provide the first evidence that miR-21-3p directly reduces the expression of MAT2A and MAT2B by targeting their 3' UTRs. In addition, an overexpression of miR-21-3p increased intracellular SAM contents, which have been proven to be a growth disadvantage for hepatoma cells. The overexpression of miR-21-3p suppresses growth and induces apoptosis in HepG2 cells. Overall, our results demonstrate that miR-21-3p functions as a tumor suppressor by directly targeting both MAT2A and MAT2B, indicating its therapeutic potential in HCC.

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.

Predictor of poor coronary collaterals in elderly population with significant coronary artery disease.

BACKGROUND: Coronary collateral circulation plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. Advanced age might be associated with poor coronary collateral development and cardiovascular outcome. However, limited studies investigate the predictors for collateral development in the elderly population. METHODS: The authors evaluated 950 consecutive patients undergoing coronary angiography and finally analyzed 207 patients of 65 years or more. The collateral scoring system developed by Rentrop was used to classify patients into those with poor or good collateral formation. RESULTS: The patients with poor collateral were older age, had lower incidence of smoking, more male sex, had fewer diseased vessels and had a trend to be diabetic. Multivariate analysis showed age (odds ratio (OR) = 1.068; P = 0.019), diabetes (OR = 2.681; P = 0.003) and diseased vessels numbers (OR = 0.337; P < 0.001) were significant predictors of poor collaterals development. Furthermore, age and diabetes have a synergistic effect on poor collateral development (P = 0.041 for interaction). CONCLUSIONS: Even in the elderly population, age and diabetes might negatively influence the coronary collaterals development.

Chewing areca nut increases the risk of coronary artery disease in Taiwanese men: a case-control study.

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.