Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague-Dawley rats through coronary artery ligation. The MI rats were randomly assigned to two groups: one received a vehicle, and the other received 100 mg/kg/day of irbesartan for 5 weeks. Cardiac function and myocardial fibrosis were assessed using echocardiography and Masson's trichrome staining, respectively. The impact of angiotensin II (Ang II) stimulation on cardiac microvascular endothelial cells (CMECs) from commercial sources was determined using ELISA, real-time PCR, and Western blotting. Irbesartan reduced left ventricular mass index, collagen composition, and aldosterone levels while enhancing cardiac function in MI rats. In vitro, Ang II time-dependently stimulated aldosterone secretion and CYP11B2 mRNA expression in CMECs (p < 0.05). Additionally, Ang II significantly upregulated p-CREB protein levels. However, these effects were abrogated by irbesartan and partially attenuated by CaMK inhibitor KN93 (p < 0.05). In conclusion, our study demonstrated that improvement in VR by irbesartan coincided with reduced CREB phosphorylation in CMECs and reduced aldosterone synthesis in the non-infarcted tissue. These effects may be mediated by blocking the AT1 receptor.

BACKGROUND:Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies.HYPOTHESIS:A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients.METHODS:We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included.RESULTS:A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years).CONCLUSION:Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

Background: The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non-CKD population and its associated risks with cardiovascular outcomes. Methods and Results: The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group-based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow-up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01-1.23), 1.27 (95% CI, 1.14-1.40), and 1.56 (95% CI, 1.38-1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39-2.21] and 2.19 [95% CI, 1.68-2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected. Conclusions: In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high-risk population and inspire future studies on individualized risk management.

IntroductionDifferent studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke.MethodsWe performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsA total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 & mu;g daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years.ConclusionsAdministration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

Although fibronectin has been associated with the pathogenesis of atherosclerosis, little is currently known about the relationship between plasma fibronectin and coronary heart disease (CHD). This retrospective study aimed to determine the predictive value of plasma fibronectin for CHD and its severity. A total of 1644 consecutive patients who underwent selective coronary angiography were recruited into the present study. The characteristics and results of the clinical examination of all patients were collected. Logistic regression analyses were performed to determine the predictive value of plasma fibronectin for the presence and severity of CHD. Compared with non-CHD patients, the CHD patients showed significantly higher plasma levels of troponin I and creatine kinase isoenzyme, along with lower plasma levels of fibronectin. However, no significant differences were detected in plasma fibronectin among patients with different grades of CHD. The logistic regression model showed that plasma fibronectin remained an independent predictor of CHD after adjustment with a 1.39-fold increased risk for every 1 SD decrease in plasma fibronectin. Nevertheless, plasma fibronectin could not predict the severity of CHD determined by the number of stenosed vessels and the modified Gensini score. This study demonstrated that lower plasma fibronectin might be an independent predictor of CHD, but it may be of no value in predicting the severity of CHD.

Summary: The reported incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) after cancer varies.Methods: We performed a meta-analysis to define the incidence of thromboembolism (TE) in cancer patients. Articles were searched in PubMed and Embase from inception to April 1, 2022. Studies reporting the incidence data or data from which incidence could be estimated among patients with cancer and the explicit follow-up duration were included. Articles were excluded if they were cross-sectional studies, review articles, commentaries, case reports or editorials. Studies involving a population receiving a specific or single treatment and primary studies with a small sample size (<100 participants) were also excluded. This meta-analysis was conducted in accordance with the Meta-analyses and Systematic reviews of Observational Studies (MOOSE). Data were abstracted by two investigators from included studies. The primary outcome of this analysis was the incidence of TE events, including ATE and VTE. The incidence of ATE and VTE in cancer patients was expressed as per 1000 person-years of follow-up. (PROSPERO CRD42021272276)Findings: Seventy-four studies involving 5059134 cancer patients were identified. The incidence rate per 1000 person-years was 11·66 (95% CI 7·68-15·64) for ATE, 26·32 (95% CI 24·46-28·18) for VTE. In addition, the highest incidence of ATE was observed in patients with gastrointestinal cancer, while patients with pancreatic cancer had the highest incidence of VTE. The risk of ATE and VTE increased at the initial stage of cancer, and then declined and became non-significant.Interpretation: This meta-analysis provided overall estimates of ATE and VTE incidence in cancer patients, adding an important insight into the trajectory of the development of TE in cancer patients, which could help reduce the risk of TE in cancer patients in the future.Funding: None to declare. Declaration of Interest: We declare no competing interests.

Erasure coding (EC) has been widely used in cloud storage systems to provide both high reliability and low storage cost. Previous literatures show that the cross-rack update operations are prevalent for many applications in erasure-coded cloud storage systems, which introduces significant I/O amplification, load imbalance and high latency. Several existing methods have been proposed to mitigate these problems. However, they ignore the correlations among chunks when performing data placement. Thus numerous stripes and racks participate in the update leading to extra I/Os and cross-rack traffic. Moreover, they don't take into account the parallelism of network transmission which loses the potential update performance gains. To address the issues, we propose a novel Graph-based cross-Rack Parallel Update (GRPU) scheme to improve the update performance for erasure-coded cloud storage systems. The key idea of GRPU is to place the correlated chunks in the same stripe and rack, and transmit the chunks in parallel based on the network distance. The data placement and transmission paths selection are guided by two kinds of graphs. To demonstrate the effectiveness of GRPU, we conduct several experiments in a local cluster. The results show that, compared to the state-of-the-art methods, GRPU reduces the cross-rack traffic by up to 34.66% and the average response time by up to 61.69%, respectively.

Erasure Codes (ECs) have widely been used in distributed storage systems to ensure data availability because of its low storage cost and high reliability. However, the update operations in erasure coded storage systems can bring extremely high I/O latency and load imbalance due to the complexity of relationships between data and parity blocks. Although several methods such as Parity Logging (PL) and Log-Structured Array (LSA) have been proposed to improve the performance of updates, they either bring extra I/O operations or decrease the performance of file access. To address the above problems, we propose a novel Graph-assisted Out-of-place Update (GOOD) scheme to improve the performance of the update, which avoids extra I/O operations and maintains the parallelism of the file access. The key idea of GOOD is to write the updated blocks into new places while maintaining blocks of the same file distribute among different nodes. The update and garbage collection processes are guided by the graphs constructed in advance. To demonstrate the effectiveness of GOOD, we conduct several experiments in a Hadoop cluster. The results show that GOOD reduces the average response time by up to 55.33% and number of I/O operations by up to 20.28% compared to the existing methods.