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In this multicenter, randomized trial, edoxaban monotherapy led to a lower risk of net clinical adverse events at 12 months than dual antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease.

Background Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). Methods This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m 2 ; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. Results The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P  < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026–2.166); especially non-calcified (OR 1.581, 95% CI 1.002–2.493) and mixed plaques (OR 2.419, 95% CI 1.051–5.569) (all P  < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P  < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. Conclusions TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients.

In the present study, we demonstrate the regulatory effects and mechanism of broussonin A and B, diphenylpropane derivatives isolated from Broussonetia kazinoki, on vascular endothelial growth factor‐A (VEGF‐A)–stimulated endothelial cell responses in vitro and microvessel sprouting ex vivo. Treatment with broussonin A or B suppressed VEGF‐A‐stimulated endothelial cell proliferation by regulating the expression of cell cycle–related proteins and the phosphorylation status of retinoblastoma protein. In addition, treatment with broussonin A or B abrogated VEGF‐A‐stimulated angiogenic responses including endothelial cell migration, invasion, tube formation and microvessel formation from rat aortic rings. These anti‐angiogenic activities of broussonin A and B were mediated through inactivation of VEGF‐A‐stimulated downstream signalling pathways, localization of vascular endothelial‐cadherin at cell‐cell contacts, and down‐regulation of integrin β1 and integrin‐liked kinase. Furthermore, treatment with broussonin A or B inhibited proliferation and invasion of non–small cell lung cancer and ovarian cancer cells. Taken together, our findings suggest the pharmacological potential of broussonin A and B in the regulation of angiogenesis, cancer cell growth and progression.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

This study sought to evaluate the association between the degree of hypertension and subclinical coronary atherosclerosis in asymptomatic subjects with and without diabetes mellitus (DM). We retrospectively analyzed 7,352 asymptomatic subjects (mean age 52.8 ± 7.8 years; 4,689 [63.8%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomography angiography as part of a general health examination. The classification of hypertension was adapted from the American College of Cardiology and American Heart Association 2017 guideline. Subclinical coronary atherosclerosis was defined as the presence of coronary plaque by coronary computed tomography angiography. In subjects without DM (n = 6,598), after the adjustment for cardiovascular risk factors, subclinical coronary atherosclerosis was significantly associated with both stage 1 hypertension (adjusted odds ratio [aOR] 1.356; 95% confidence interval [CI], 1.167 to 1.575; p <0.001) and stage 2 hypertension (aOR, 1.614; 95% CI, 1.329 to 1.961; p <0.001) groups compared with the normal group. In contrast, in subjects with DM (n = 754), there was no statistical difference in the aOR of the stage 1 hypertension group for the presence of coronary plaque (aOR, 1.449; 95% CI, 0.982 to 2.136; p = 0.061). However, the stage 2 hypertension group had a significant association with subclinical coronary atherosclerosis (aOR, 2.067; 95% CI, 1.287 to 3.322; p = 0.003). In subjects without DM, both stages 1 and 2 hypertension were associated with subclinical coronary atherosclerosis. However, in subjects with DM, stage 2 hypertension was only associated with an increased risk of subclinical coronary atherosclerosis.

The impact of pre-existing depression on mortality in individuals with established coronary artery disease (CAD) remains unclear. We evaluate the clinical implications of pre-existing depression in patients who underwent percutaneous coronary intervention (PCI). Based on National Health Insurance claims data in Korea, patients without a known history of CAD who underwent PCI between 2013 and 2017 were enrolled. The study population was divided into patients with angina (n = 50,256) or acute myocardial infarction (AMI; n = 40,049). The primary endpoint, defined as all-cause death, was compared between the non-depression and depression groups using propensity score matching analysis. After propensity score matching, there were 4262 and 2346 matched pairs of patients with angina and AMI, respectively. During the follow-up period, there was no significant difference in the incidence of all-cause death in the angina (hazard ratio [HR] of depression, 1.013; 95% confidence interval [CI] 0.893–1.151) and AMI (HR, 0.991; 95% CI 0.865–1.136) groups. However, angina patients less than 65 years of age with depression had higher all-cause mortality (HR, 1.769; 95% CI 1.240–2.525). In Korean patients undergoing PCI, pre-existing depression is not associated with poorer clinical outcomes. However, in younger patients with angina, depression is associated with higher all-cause mortality.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia—a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

The aim of the present study was to assess the intravascular ultrasound predictors for angiographic edge restenosis after newer generation drug-eluting stent implantation. A total of 820 patients (987 lesions) who underwent newer generation drug-eluting stent placement (236 Endeavor zotarolimus-eluting stents, 246 Resolute zotarolimus-eluting stents, and 505 everolimus-eluting stents) with 9 months of angiographic surveillance were enrolled. The post-stenting angiographic and intravascular ultrasound images of 1,668 reference segments (681 proximal and 987 distal) were analyzed. Overall, 37% of angiographically normal proximal reference segments and 21% of angiographically normal distal reference segments had plaque burden >50%. In the overall cohort of 1,668 reference segments, 47 (2.8%) had 9-month angiographic edge restenosis (diameter stenosis >50%). Edge restenosis was predicted by a post-stenting reference segment plaque burden >54.5% (sensitivity 81%, specificity 80%) and a reference segment minimum lumen area of 5.7 mm2 (sensitivity 72%, specificity 59%). The edge restenosis rate was 2.1% in the Endeavor zotarolimus-eluting stents, 2.4% in the Resolute zotarolimus-eluting stents, and 3.4% in the everolimus-eluting stents lesions (p = 0.311). The predictive cutoff of the reference plaque burden was 56.3% for Endeavor zotarolimus-eluting stents, 57.3% for Resolute zotarolimus-eluting stents, and 54.2% for everolimus-eluting stents. The criteria for residual plaque burden were similar between proximal and distal reference segments (56.4% vs 51.9%, respectively), but the minimum lumen area criteria were quite different (<7.1 mm2 for proximal vs <4.8 mm2 for distal reference segments). In conclusion, after newer drug-eluting stent implantation, edge restenosis was predicted by post-stenting reference segment plaque burden >55%.

Low-risk individuals still experience adverse cardiac events. We sought to evaluate long-term cardiac events and predictors for subclinical coronary atherosclerosis in subjects without indication for statin therapy. We analyzed 3,272 individuals without indication for statin therapy who voluntarily underwent coronary computed tomography angiography as part of a general health examination. A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. The prevalence of normal coronary arteries, nonobstructive coronary artery disease (CAD) (diameter stenosis < 50%), and obstructive CAD (diameter stenosis ≥50%) was 2,338 (71.5%), 809 (24.7%), and 125 (3.8%), respectively. During the follow-up period (median 5.3 [interquartile range, 4.3–6.3] years), the 6-year event-free survival rates were 99.2%±0.2% in subjects with normal coronary arteries, 98.2%±0.6% in those with nonobstructive CAD, and 90.2%±2.7% in those with obstructive CAD (log-rank p < 0.001). Multivariable regression analysis showed that low-density lipoprotein cholesterol (LDL-C, odds ratio [OR]: 1.012; 95% confidence interval (CI): 1.005–1.019) and high-density lipoprotein cholesterol (HDL-C, OR: 0.968; 95% CI: 0.952–0.984) levels were associated with subclinical obstructive CAD, together with age (OR: 1.080; 95% CI: 1.040–1.121) and male sex (OR: 3.102; 95% CI: 1.866–5.155) (all p < 0.05). In conclusion, LDL-C and HDL-C are significantly associated with the presence of subclinical obstructive CAD with a worse prognosis in subjects without indication for statin therapy. These findings suggest that stricter control of LDL-C and HDL-C levels may be necessary for primary prevention even in a relatively low-risk population.