[This corrects the article DOI: 10.3389/fphar.2021.642925.].

Systemic inflammation is associated with the outcomes of coronary care unit (CCU) patients. We sought to assess the prognostic implication of the prognostic nutritional index (PNI), a surrogate marker of inflammation in CCU patients. The study included 1,158 participants from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and 342 from the Second Affiliated Hospital of Wenzhou Medical University (WMU), participants were subsequently grouped based on the PNI threshold. Key endpoints were 30-day mortality and major adverse cardiovascular events (MACEs) at 1-year follow-up and were examined with propensity score matching (PSM) and Cox regression analysis. The prognostic implications of PNI and other inflammatory markers were compared using an area under the curve (AUC). A total of 285 participants in the MIMIC-IV cohort developed 30-day mortality, and 139 developed MACEs in WMU, of which 103 (30.12

Objective: This study was found to demonstrate whether red blood cell distribution width -to-al-bumin ratio (RA) cah effectively evaluate the prognosis of Cardiogenic shock (CS) patients and to explore the relationship between RA vs. inflammation and water retention. Methods: This cohort study included only adults (age >= 18) with CS. Data were obtained from the Medical Information Mart for Intensive Care III III) database and the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (2016-2021). Cox proportional hazard regression was used to assess the relationship between RA and all-cause mortality. Logistic segression was used to assess the relationship between RA and sepsis occur-rence and renal replacement therapy (RRT). Receiver operator characteristic (ROC) curve anal-ysis and general linear correlation analysis were used to assess the deeper relationship between RA and CS. Results: A total of 720 CS patients were included. Cox proportional hazard regression showed that the HR (95 % Cls) for all-cause mortality in 30-day in the higher RA groups (4.79-5.84 ml/g and >5.84 ml/g) in qualtile was 1.99 (1.32, 2.98) and 2.04 (1.36, 3.06), respectively, in the unad-justed model. The same correlation existed in model 2 and model 3 after further adjustment of possible covariates. Similar relationships were also observed for 90-day and one-year all-cause mortality. ROC curve analysis indicated that the predictive ability of RA on mortality risk of CS patients was similar to that of sequential organ failure assessment score (SOFA) and simplified acute physiology seore II (SAPS II) (P > 0.05) The area under the curve (AUC) of RA, SOFA, and SAPS II were not statistically different (0.612, 0.615, and 0.656, respectively). Logistic regression showed that RA and renal replacement therapy occurred, and the prevalence of Sepsis was closely related. General lintar correlation analysis indicated a linear correlation between RA and C-reactive protein, brlin natriuretic peptide. Conclusion: The resdits shown that RA is an independent risk factor for CS patients. Besides, the predictive ability of RA on mortality risk of CS patients was similar to SOFA and SAPS II scores. This prediction ability may be related to inflammation and water retention.

Background: Sepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and lifethreatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70-90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. Materials and methods: In vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 mu M phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, coimmunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. Results: In vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1 alpha/Bnip3 axis), promoting the formation and degradation of autophagosomes. Conclusion: We indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1 alpha/Bnip3 axis.

Aims: This study aimed to delineate correlation between stress hyperglycemia ratio (SHR) and clinical outcomes among patients in the cardiac intensive care unit (CICU). Methods: Participants were categorized based on their SHR threshold values. Key outcomes were short-term mortality and major adverse cardiovascular events (MACEs) at 1-year follow-up. The association between SHR and outcomes was estimated using inverse probability of treatment weighting (IPTW) and Kaplan-Meier analyses. The C-statistic was used to gauge the predictive capability of SHR. Results: The study included 1,133 patients from the Medical Information Mart for Intensive Care IV and 412 from the Second Affiliated Hospital of Wenzhou Medical University. Kaplan-Meier curves revealed that individuals with elevated SHR exhibited higher 90-day mortality and MACEs. When considering SHR levels and diabetes status simultaneously, those with increased SHR but non-diabetes had the highest 90-day mortality and MACEs. SHR was associated with short-term mortality and MACEs (HRadjusted 1.63 95%CI 1.15-2.30; HRIPTW 1.47 95%CI 1.05-2.05). Upon integrating SHR into the foundational model, the C-statistic was 0.821, outperforming other hyperglycemia metrics. Conclusion: SHR is a valuable indicator for predicting poor outcomes in CICU patients. Its utility spans potential risk stratification and offers insights for tailoring prognostic treatments to CICU patients.

Stress-induced hyperglycemia (SIH) is associated with poor outcomes in cardiogenic shock (CS), and there have been inconsistent results among patients with or without diabetes mellitus (DM). The glycemic gap (GG) is derived by subtracting A1c-derived average glucose from blood glucose levels; it is a superior indicator of SIH. We aimed to explore the role of GG in the outcomes of patients with CS. Data on patients diagnosed with CS were extracted from the MIMIC-IV v2.0 database to investigate the relationship between GG and 30-day mortality (Number of absolute GG subjects = 359; Number of relative GG subjects = 357). CS patients from the Second Affiliated Hospital of Wenzhou Medical University were enrolled to explore the correlation between GG and lactic acid (Number of absolute GG subjects = 252; Number of relative GG subjects = 251). Multivariate analysis, propensity score-matched (PSM) analysis, inverse probability treatment weighting (IPTW), and Pearson correlation analysis were applied. Absolute GG was associated with 30-day all-cause mortality in CS patients (HRadjusted: 1.779 95

Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia–reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation–reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53–BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53–BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants. However, the exact mechanism by which Bap can worsen the condition of patients with AAA and increase the mortality of patients with AAA remains unknown. This research aims to investigate the role of Bap in inducing pyroptosis in AAA. In vitro experiments, we revealed that pyroptosis-Gasdermin D (GSDMD) increased when Bap was used. Additionally, the release of inflammatory factors, such as IL-1β and IL-18 were also rising. An mRNA sequencing analysis revealed that macrophages expressed a high level of the endothelin gene when cells were stimulated by Bap. It seemed that smooth muscle cells pyroptosis was related to macrophages. Experiments revealed that endothelin could increase the calcium ion concentration in smooth muscle cells, resulting in a large amount of ROS and activation of NLRP3 inflammasomes. We discovered that treatment with endothelin receptor antagonist (ABT-546) in vivo and calcium ion chelator (BAPTA) in vitro decreased AAA diameter, downregulated NLRP3 inflammasomes and ROS, and significantly reduced the number of activated GSDMD. Inflammatory mediators were released at a lower level. These findings suggest that Bap-induced pyroptosis may be mediated by the ET-1-Ca2+-inflammasome pathway, providing a new way to reduce mortality in AAA patients.

Objective:The present study aimed to evaluate the relationship between all-cause mortality and the neutrophil percentage-to-albumin ratio (NPAR) in patients with atrial fibrillation (AF).Methods:We obtained clinical information from patients with AF from the Medical Information Mart for Intensive Care-IV version 2.0 (MIMIC-IV) database and the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (WMU). The clinical endpoints were all-cause death measured at 30-day, 90-day, and one-year intervals. For endpoints associated with the NPAR, logistic regression models were used to calculate odds ratios (OR) with 95% confidence intervals (CI). Receiver operating characteristic (ROC) curves and area under the curve (AUC) were developed to compare the ability of different inflammatory biomarkers to predict 90-day mortality in patients with AF.Results:Higher NPAR was associated with a higher risk of 30-day (OR 2.08, 95% CI 1.58-2.75), 90-day (OR 2.07, 95% CI 1.61-2.67), and one-year mortality (OR 1.60, 95% CI 1.26-2.04) in patients with AF in 2813 patients from MIMIC-IV. The predictive performance of NPAR (AUC = 0.609) for 90-day mortality was better than that of neutrophil-to-lymphocyte ratio (NLR) (AUC = 0.565, P < 0.001), and platelet-to-lymphocyte ratio (PLR) (AUC = 0.528, P < 0.001). When NPAR and sequential organ failure assessment (SOFA) were combined, the AUC increased from 0.609 to 0.674 (P < 0.001). Higher NPAR was associated with a higher risk of 30-day mortality (OR 2.54, 95% CI 1.02-6.30) and 90-day mortality (OR 2.76, 95% CI 1.09-7.01) in 283 patients from WMU.Conclusion:An increased 30-day, 90-day, and one-year mortality risk among patients with AF were linked to a higher NPAR in MIMIC-IV. NPAR was thought to be a good predictor of 90-day all-cause mortality. Higher NPAR was associated with a higher risk of 30-day and 90-day mortality in WMU.

BACKGROUND:Air pollution is an important and interventionable risk factor for cardiovascular disease. Air pollution exposure, even for a short-term exposure, is conspicuously relevant to increased risk of myocardial infarction (MI) mortality and clinical evidence has shown that air pollution particulate matter (PM) induces the aggravation of AMI. 3,4-benzo[a]pyrene (BaP), an extremely toxic polycyclic aromatic hydrocarbon (PAH) and a common component of PM, is listed as one of the main objects of environmental pollution monitoring. Both epidemiological and toxicological studies suggest that BaP exposure may be associated with cardiovascular disease. Since PM is significantly associated with the increased risk of MI mortality, and BaP is an important component of PM associated with cardiovascular disease, we intend to investigate the effect of BaP on MI models.METHODS:The MI mouse model and the oxygen and glucose deprivation (OGD) H9C2 cell model were used to investigate the effect of BaP in MI injury. The involvement of mitophagy and pyroptosis in regulating deterioration of cardiac function and aggravation of MI injury induced by BaP was comprehensively evaluated.RESULTS:Our study shows that BaP exacerbates MI injury in vivo and in vitro, a result based on BaP-induced NLRP3-related pyroptosis. In addition, BaP can inhibit PINK1/Parkin dependent mitophagy through the aryl hydrocarbon receptor (AhR), thus the mitochondrial permeability transition pore (mPTP) was induced to open.CONCLUSION:Our results suggest a role for the BaP from air pollution in MI injury aggravation and reveal that BaP aggravates MI injury by activating NLRP3-related pyroptosis via the PINK1/Parkin-mitophagy-mPTP opening axis.

Systemic inflammation is closely associated with the development and progression of heart failure (HF), increasing vulnerability to thromboembolic events. This retrospective cohort study assessed the potential of the fibrinogen‐to‐albumin ratio (FAR), a new inflammatory biomarker, as a prognostic indicator for HF risk.

Background Abdominal aortic aneurysm (AAA) is a fatal disease characterized by high morbidity and mortality in old population. Globally, effective drugs for AAA are still limited. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine (TCM) formula with a high medical value, was reported to be successfully used in an old AAA patient. Thus, we reason that SMYAD may serve as a potential anti-AAA regime. Objective The exact effects and detailed mechanisms of SMYAD on AAA were explored by using the experimental study and bioinformatics analysis. Methods Firstly, C57BL/6N mice induced by Bap and Ang II were utilized to reproduce the AAA model, and the effects of SMYAD were systematically assessed according to histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Then, network pharmacology was applied to identify the biological processes, pathways, and hub targets of SMYAD against AAA; moreover, molecular docking was utilized to identify the binding ability and action targets. Results In an animal experiment, SMYAD was found to effectively alleviate the degree of pathological expansion of abdominal aorta and reduce the incidence of Bap/Ang II-induced AAA, along with reducing the damage to elastic lamella, attenuating infiltration of macrophage, and lowering the circulating IL-6 level corresponding to the animal study, and network pharmacology revealed the detailed mechanisms of SMYAD on AAA that were related to pathways of inflammatory response, defense response, apoptotic, cell migration and adhesion, and reactive oxygen species metabolic process. Then, seven targets, IL-6, TNF, HSP90AA1, RELA, PTGS2, ESR1, and MMP9, were identified as hub targets of SMYAD against AAA. Furthermore, molecular docking verification revealed that the active compounds of SMYAD had good binding ability and clear binding site with core targets related to AAA formation. Conclusion SMYAD can suppress AAA development through multicompound, multitarget, and multipathway, which provides a research direction for further study.

ObjectiveThe management of cardiogenic shock (CS) in the elderly remains a major clinical challenge. Existing clinical prediction models have not performed well in assessing the prognosis of elderly patients with CS. This study aims to build a predictive model, which could better predict the 30-day mortality of elderly patients with CS.MethodsWe extracted data from the Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III) as the training set and the data of validation sets were collected from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Three models, including the cox regression model, the Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and the CoxBoost model, were established using the training set. Through the comparison of area under the receiver operating characteristic (ROC) curve (AUC), C index, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and median improvement in risk score, the best model was selected. Then for external validation, compared the best model with the simplified acute physiology score II (SAPSII) and the CardShock risk score.ResultsA total of 919 patients were included in the study, of which 804 patients were in the training set and 115 patients were in the verification set. Using the training set, we built three models: the cox regression model including 6 predictors, the LASSO regression model including 4 predictors, and the CoxBoost model including 16 predictors. Among them, the CoxBoost model had good discrimination [AUC: 0.730; C index: 0.6958 (0.6657, 0.7259)]. Compared with the CoxBoost model, the NRI, IDI, and median improvement in risk score of other models were all<0. In the validation set, the CoxBoost model was also well-discriminated [AUC: 0.770; C index: 0.7713 (0.6751, 0.8675)]. Compared with the CoxBoost model, the NRI, IDI, and median improvement in risk score of SAPS II and the CardShock risk score were all < 0. And we constructed a dynamic nomogram to visually display the model.ConclusionIn conclusion, this study showed that in predicting the 30-day mortality of elderly CS patients, the CoxBoost model was superior to the Cox regression model, LASSO regression model, SAPS II, and the CardShock risk score.

Background: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. Materials and methods: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 mu g/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. Results: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pymptosis, inhibited oxidative stress, reduced IL-1 beta and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. Conclusion: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.

ObjectivesThe purpose of this study was to investigate the independent effect of the ratio of red blood cell distribution width (RDW) to albumin (RA) on all-cause mortality in patients after percutaneous coronary intervention (PCI).MethodsClinical data were obtained from the Multiparameter Intelligent Monitoring in Intensive Care-III (MIMIC-III) database version 1.4 and the database of Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University. We used the MIMIC-III database for model training, and data collected from the Second Affiliated Hospital of Wenzhou Medical University for validation. The primary outcome of our study was 90-day mortality. Cox proportional hazards regression model was used to estimate hazard ratio (HR) for the association between RA and all-cause mortality in patients after PCI. Pearson correlation analysis was conducted to assess the relationship between RA and Gensini score or cardiac troponin I (cTnI).ResultsA total of 707 patients were eligible in MIMIC-III database, including 432 males, with a mean age of 70.29 years. For 90-day all-cause mortality, in the adjusted multivariable model, the adjusted HRs [95% confidence intervals (CIs)] for the second (RA: 3.7–4.5 ml/g) and third (RA >4.5 ml/g) tertiles were 2.27 (1.11, 4.64) and 3.67 (1.82, 7.40), respectively, compared to the reference group (RA <3.7 ml/g) (p < 0.05). A similar relationship was also observed for 30-day all-cause mortality and 1-year all-cause mortality. No significant interaction was observed in subgroup analysis. Receiver operating characteristic (ROC) curve analysis proved that the ability of RA to predict the 90-day mortality was better than that of RDW or albumin alone. The correlation coefficient between Gensini score and RA was 0.254, and that between cTnI and RA was 0.323.ConclusionRA is an independent risk factor for all-cause mortality in patients after PCI. The higher the RA, the higher the mortality. RA has a good predictive ability for all-cause mortality in patients after PCI, which is better than RDW or albumin alone. RA may be positively correlated with the severity of coronary artery disease (CAD) in patients with CAD.

Background Neutrophils and albumin had been shown to be independent predictors of mortality from various diseases. Purpose of this study was to investigate the effect of neutrophil-to-albumin ratio (NPAR) as an independent predictor of mortality in heart failure (HF) patients. Methods Data were extracted from Medical Information Mart for Intensive Care-III database. Primary outcome was 30-day mortality, secondary outcomes were in-hospital, 90-day, 365-day mortality, length of stay (LOS) in hospital. Cox proportional hazards regression model and receiver operating characteristic (ROC) curve analysis and Pearson correlation analysis were used. Results The HR (95% CI) values of the mid-tertile and the upper tertile were 1.27 (1.01 to 1.59) and 2.29 (1.87 to 2.81) in 30-day mortality compared with the reference. The trend continued after adjusted for demographic and clinical variables. In the secondary outcomes were the same trends. The data of the Second Affiliated Hospital of Wenzhou Medical University showed the correlation coefficient between hospital LOS with NPAR. Conclusion NPAR was an independent factor of mortality in HF patients, which was correlated with hospital LOS. Our results need to be verified by prospective studies.

Aims: The aim of this study was to perform a meta-analysis of studies of the association of left ventricular hypertrophy (LVH) and atrial fibrillation (AF), especially the predictive and prognostic role of LVH. Methods and Results: We searched Medline, Embase, and the Cochrane Library from inception through 10 April 2020. A total of 16 cohorts (133,091 individuals) were included. Compared with the normal subjects, patients with LVH were more susceptible to AF (RR = 1.46, 95% CI, 1.32–1.60). In patients with AF and LVH, there was a higher risk of all-cause mortality during 3.95 years (RR = 1.60, 95% CI, 1.42–1.79), and these patients were more likely to progress to persistent or paroxysmal AF (RR = 1.45, 95% CI, 1.20–1.76) than were patients without LVH. After catheter ablation of AF, patients with LVH were more likely to recur (RR = 1.58, 95% CI, 1.27–1.95). Conclusion: LVH is strongly associated with AF and has a negative impact on outcome in patients with AF.

OBJECTIVE:The aims of this study were to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in coronary care unit (CCU) patients, adjusting for a wide range of potential confounding factors, to examine the potential of LDL-C in predicting the prognostic value of CCU patients.METHODS:Clinical data were extracted from Medical Information Mart for Intensive Care-III database (MIMIC-III database version v.1.4). Baseline data were collected within 24 hours after the patient was first admitted to the hospital. The primary endpoint of our study is 30-day all-cause mortality. The secondary endpoints are 90-day and one-year all-cause mortality and infections. Cox proportional hazard regression and propensity score-matched (PSM) analysis were used to analyze the association between LDL-C levels and prognostic value of CCU patients.RESULTS:We included a total of 1476 patients with an average age of 66.7 ± 14.1 years (66% male). For 30-day all-cause mortality, the hazard ratio (95% confidence interval) of high LDL-C level group (≥ 55 mg/dl) was 0.42 (0.29, 0.62), which was compared with low LDL-C level group (< 55 mg/dl) in unadjusted model. After adjusting for age, gender and race, the association still existed (P < 0.05), and the HR (95% CI) was 0.49 (0.33, 0.72). Further adjustment of possible covariates showed similar correlation (P < 0.05), and HR (95% CI) was 0.65 (0.43, 0.97). Similar correlations were observed for 90-day and one-year all-cause mortality. The relationship between all-cause mortality and LDL-C levels in CCU patients was further verified by propensity score-matched (PSM) analysis. In addition, the higher the LDL-C level, the lower the risk of infection, odds ratio (OR) values in the three models were less than 1 (P < 0.05).CONCLUSION:Our data suggest that high LDL-C level is associated with a reduced risk of 30-day, 90-day, and one-year mortality of patients in the CCU. And this result is still stable in the PSM model. The results need to be verified in prospective trials.

Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O2·−) and hydrogen peroxide (H2O2), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O2·− was upregulated in H2O2-induced H9C2 cardiac myocyte injury in vitro and myocardial I/R injury in vivo, while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O2·− by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O2·− was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.