Association between aspirin and mortality in critically ill patients with atrial fibrillation: a retrospective cohort study based on mimic-IV database.

Background: Atrial fibrillation (AF) is a prevalent issue among critically ill patients, and the availability of effective treatment strategies for AF is limited. Aim: The objective of this study was to evaluate the mortality rate associated with AF in critically ill patients who were either aspirin or non-aspirin users. Methods: This cohort study incorporated critically ill patients with AF from the Medical Information Mart for Intensive Care database. The study compared incidences of 28-day mortality, 90-day mortality, and 1-year mortality between patients with and without aspirin prescriptions. To assess the association between aspirin and the endpoints, Kaplan-Meier analysis and Cox proportional hazards regression analyses were conducted. Results: In this study, a total of 13,330 critically ill patients with atrial fibrillation (AF) were included, of which 4,421 and 8,909 patients were categorized as aspirin and non-aspirin users, respectively. The 28-day, 90-day, and 1-year mortality rates were found to be 17.5% (2,330/13,330), 23.9% (3,180/13,330), and 32.9% (4,379/13,330), respectively. The results of a fully-adjusted Cox proportional hazard model indicated that aspirin use was negatively associated with the risk of death after adjusting for confounding factors (28-day mortality, HR 0.64, 95% CI 0.55-0.74; 90-day mortality, HR 0.65, 95% CI 0.58-0.74; 1-year mortality, HR 0.67, 95%CI 0.6∼0.74). The results of the subgroup analysis indicate a more robust correlation, specifically among patients under the age of 65 and those without a history of congestive heart failure or myocardial infarction. Conclusions: The utilization of aspirin may exhibit a correlation with a reduction in risk-adjusted mortality from all causes in critically ill patients diagnosed with atrial fibrillation. However, additional randomized controlled trials are necessary to elucidate and confirm this potential association.

Nonlinear Relationship Between Interleukin-6 and NT-proBNP at Admission in Hospitalized COVID-19 Patients.

Purpose: Elevated levels of the inflammatory marker interleukin-6 (IL-6) and cardiac injury marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been observed in patients with coronavirus disease 2019 (COVID-19). However, the relationship between IL-6 and NT-proBNP levels remains unclear. Therefore, we investigated the relationship between IL-6 and NT-proBNP levels in patients with COVID-19. Patients and Methods: This was a cross-sectional study. Consecutive patients with COVID-19 were included herein. The independent and dependent target variables were the IL-6 and NT-proBNP levels, respectively, measured at baseline. Univariate and multivariate linear regression analyses and curve fitting were also performed. Results: The average age of the 121 selected participants was 49.8 ± 15.8 years old, and 48.8% (59/121) were male. The estimated ß value between Ln-transformed IL-6 and NT-proBNP was 0.28 (95% confidence interval [CI] 0.12-0.44, P = 0.001) in univariate logistic regression analysis and 0.09 (95% CI -0.04-0.21, P = 0.176) in the fully adjusted model. This relationship was nonlinear, with a point of 2.7, and the ß values (and CIs) for the left (<2.7) and right (≥2.7) sides of the inflection point were -0.06 (95% CI -0.23-0.12, P = 0.534) and 0.77 (95% CI 0.18-1.37, P = 0.016) in the fully adjusted model, respectively. Conclusion: Our results suggest a nonlinear association between IL-6 and NT-proBNP levels. Higher IL-6 levels are associated with NT-proBNP in patients with COVID-19.

Identification of atrial fibrillation-associated lncRNAs and exploration of their functions based on WGCNA and ceRNA network analyses.

Atrial fibrillation (AF) is a common cardiac arrhythmia that induces serious complications. However, pharmacological treatments of AF remain challenging. This study aimed to screen crucial long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) for AF using the microarray datasets (lncRNAs and mRNAs: GSE79768, GSE115574; miRNAs: GSE68475) collected from the Gene Expression Omnibus database. Weighted correlation network analysis of GSE79768 and GSE115574 datasets identified five modules were highly related to AF status. Among 118 module-related differentially expressed mRNAs, FBXW7, EGFR, CXCR2, ROCK1 and UBE2D1 were considered as hub genes according to the gene significance, module membership and the topological characteristics for the nodes in the protein-protein interaction network. lncRNA MIR100HG and LINC01105 may function by co-expressing with (MIR100HG-ROCK1/FBXW7/UBE2D1, LINC01105-EGFR) mRNAs or sponging miRNAs to regulate mRNAs (LINC01105-miR-125a-3p-EGFR, MIR100HG-miR-200b-3p- FBXW7, MIR100HG-miR-561-3p-CXCR2, MIR100HG-miR-548z-UBE2D1). Connectivity Map and Comparative Toxicogenomics Database searches predicted dexamethasone may treat AF by reversing the expression of MIR100HG; artemisinin may reverse the expression of hub DEGs. In conclusion, our results may provide novel molecular mechanisms and potential therapeutic targets and drugs for AF.

Probucol Protects Against Contrast-Induced Acute Kidney Injury via the Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2)/JNK-Caspase 3 Pathway in Diabetic Rats.

BACKGROUND Contrast-induced acute kidney injury is an important clinical problem, yet its pathogenic mechanisms are incompletely understood. In this study we explored the potential beneficial effects of probucol as treatment of contrast-induced acute kidney injury in diabetic rats. MATERIAL AND METHODS Rats were divided into 3 groups: i) diabetic control, ii) diabetic with contrast, and iii) probucol treatment groups. Probucol was administered by gavage and the contrast diatrizoate (60%) was injected via femoral vein. After 24 h, the rats were sacrificed and samples were taken to measure biochemical indicators. Pathological damage of renal tubules was evaluated by HE staining. Expression of Bcl-2, Bax, p-ERKs, and p-JNK proteins in the kidneys was examined by Western blotting, whereas expression level of caspase-3 in kidneys was detected by immunohistochemistry. RESULTS Compared to the probucol treatment group, the diabetes with contrast group showed higher serum creatinine and lower creatinine clearance. The pathological changes of kidneys in the probucol treatment group were improved compared with the contrast group. Moreover, Western blot analyses revealed that use of contrast agent led to lower p-ERK1/2, higher p-JNK, lower Bcl-2, and higher Bax levels, which were reversed by probucol. Finally, immunohistochemical findings revealed higher caspase-3 after contrast use, which was partially reversed by probucol. CONCLUSIONS Probucol exerts protective effects on contrast-induced acute kidney injury in diabetic rats by inhibition of renal cell apoptosis. This is achieved by reducing mitochondrial caspase-3 expression through increasing and decreasing the expression of the upstream mediators p-ERK1/2 and p-JNK, respectively.

Adjunctive loading dose of cilostazol in preventing periprocedural myocardial infarction.

INTRODUCTION: Periprocedural myocardial infarction (PMI) is a common complication of percutaneous coronary intervention (PCI). This study evaluated the safety and efficacy of adjunctive loading dose of cilostazol in preventing PMI in patients with acute coronary syndrome (ACS). METHODS: A total of 113 patients with ACS undergoing PCI were randomized to receive loading doses of dual (aspirin plus clopidogrel; DAPT group; n=57) or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT group; n=56). The loading and maintenance doses were 100 and 50 mg bid for cilostazol. Patients in the TAPT group received adjunctive cilostazol for 1 week. Cardiac biomarkers were measured before PCI, 8 and 24 hours after PCI to determine the incidence of PMI. RESULTS: There was no significant difference in the incidence of PMI between the TAPT and DAPT groups (32.1% vs 47.4%, P=.098). However, in the antiplatelet-naïve subgroup, TAPT significantly lowered the incidence of PMI compared to DAPT (17.9% vs 42.9%, P=.042). In the antiplatelet-treated subgroup, the incidences of PMI were comparable (46.4% vs 51.7%, P=.698). Multivariable logistic analysis showed that antiplatelet-treated (vs antiplatelet-naïve) (hazard ratio [HR]: 2.45; 95% confidence interval [CI]: 1.09-5.52; P=.030) subgroup was independently associated with PMI. However, TAPT (vs DAPT) (HR: 0.51; 95% CI: 0.23-1.14; P=.102) was not an independent protective factor of PMI. CONCLUSIONS: The present single-center, randomized study indicates that TAPT with adjunctive cilostazol was not associated with lower incidence of PCI-related PMI in patients with ACS. Further study with large study population is needed to get definite conclusions.

Cardioprotective effects of traditional Chinese medicine Guanmaitong on acute myocardial infarction.

Guanmaitong (GMT) is a traditional Chinese herbal compound that has been used for the treatment of coronary heart disease (CHD) and other cardiovascular diseases. However, the efficacy of GMT in treating cardiovascular diseases remains unclear. The aim of the present study was to investigate the protective mechanisms and identify the targeted proteins and signaling networks associated with the physiological activity of GMT in a rat model of acute myocardial infarction (AMI). Sprague-Dawley rats were randomly allocated into five groups: Control group (sham-operated), the model group, and small, medium, and large dosage GMT groups. The rat model of AMI was established via ligation of the coronary artery. The results indicate that GMT was able to reduce myocardial infarction size and improve the activities of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule 1 (ICAM-1) and interleukin-1. Furthermore, the reduced apoptotic index of the GMT-treated cardiocytes (P<0.05 vs. model group) was in accordance with the downregulated expression of Bax and the upregulated expression of Bcl-2. In conclusion, GMT may exert a protective potential against myocardial infarction injury by inhibiting apoptosis and inflammation of cardiomyocytes, and may offer a promising adjunct treatment for CHD.

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys.

BACKGROUND: The risk of contrast-induced acute kidney injury (CIAKI) is significantly increased in patients with diabetes mellitus. This study aimed to investigate molecular mechanisms of contrast media-induced apoptosis in diabetic rat kidneys, especially the involvement of ERK1/2 and JNK signal pathways. METHODS: Diabetic Sprague-Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered high-osmolar contrast media (HOCM; meglumine diatrizoate) or normal saline (10 mL/kg) injection for 2 consecutive days. At 24 h after the operation, the rats were sacrificed, the blood samples were collected for examining serum creatinine and the kidneys were collected for determining the expression of caspase-3 by immunohistochemistry and the expression of Bcl-2, Bax, upstream signal molecule p-JNK, and p-ERK1/2 by western blotting. RESULTS: The serum creatinine was significantly increased in diabetes + contrast media group (DC group) after operation compared with in the diabetic group (D group; 103.89 ± 9.01 µmol/L vs. 71.52 ± 7.03 µmol/L, p < 0.05). While creatinine clearance rate (Ccr) was significantly decreased in DC group after operation (1.49 ± 0.33 mL/min vs. 2.60 ± 0.54 mL/min, p < 0.05). Especially, in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection of HOCM compared with normal saline. The expression level of upstream signal molecule p-JNK protein was apparently increased, but p-ERK1/2 protein was significantly decreased (both p < 0.05). CONCLUSIONS: The ionic HOCM-induced renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway, which might be mediated by upstream MAPK (inhibiting p-ERK1/2 expression and promoting p-JNK expression) signal pathways.

Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials.

BACKGROUND: The objective of this study was to examine the association between administration route and relative renal safety of contrast agents. METHODS: We searched all published articles indexed in Embase, Medline and the Cochrane Central Register of Controlled Trials, from January 1980 to November 2010, to identify relevant studies. Of the 1,047 initially identified studies, 11 randomized controlled trials (RCTs) including 2,210 patients with intra-arterial route and 7 RCTs including 919 patients with intravenous route were finally analyzed. RESULTS: With regard to intra-arterial route, our meta-analysis showed that iodixanol significantly decreased the risk of contrast-induced acute kidney injury (CI-AKI) when compared with a pool of low-osmolar contrast media (LOCM; risk ratio [RR] = 0.68; 95% confidence interval [95% CI], 0.50-0.92; Z=2.47; p=0.01), with no significant heterogeneity between individual studies (p=0.14, I2=32.4%). However, iodixanol was not associated with a reduction in CI-AKI compared with the LOCM pooled together (RR=0.75; 95% CI, 0.44-1.26; Z=1.10; p=0.27) with intravenous application, again with no significant heterogeneity between individual studies (p=0.40, I2=3.6%). CONCLUSIONS: Our meta-analysis suggests that administration route may affect the renal safety of contrast agents. Specifically, iodixanol may be a better choice for patients in the interventional cardiology setting.

[Effects and potential mechanisms of short-term use of simvastatin on myocardial no-reflow after ischemia-reperfusion in rats].

OBJECTIVE: The main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms. METHODS: Adult male Wistar rats were randomized into sham group (n = 12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and arteriole. RESULTS: The NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/- 6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS and MPO, the contents of NO and MDA were significantly lower while eNOS activity was significantly higher in I/R plus sim group than those in I/R group (5.02 +/- 1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43 vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs. 3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5 vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05). CONCLUSION: Simvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.