The glycemic gap as a prognostic indicator in cardiogenic shock: a retrospective cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: Absolute GG was associated with 30-day all-cause mortality in CS patients (HRadjusted: 1.779 95% CI: 1.137-2.783; HRPSM: 1.954 95% CI: 1.186-3.220; HRIPTW: 1.634 95% CI: 1.213-2.202). The higher the absolute GG level, the higher the lactic acid level (ßadjusted: 1.448 95% CI: 0.474-2.423). A similar trend existed in relative GG (HRadjusted: 1.562 95% CI: 1.003-2.432; HRPSM: 1.790 95% CI: 1.127-2.845; HRIPTW: 1.740 95% CI: 1.287-2.352; ßadjusted:1.294 95% CI: 0.369-2.219). Subgroup analysis showed that the relationship existed irrespective of DM. The area under the curve of GG combined with the Glasgow Coma Scale (GCS) for 30-day all-cause mortality was higher than that of GCS (absolute GG: 0.689 vs. 0.637; relative GG: 0.688 vs. 0.633). GG was positively related to the triglyceride-glucose index. Kaplan-Meier curves revealed that groups of higher GG with DM had the worst outcomes. The outcomes differed among races and GG levels (all P < 0.05). CONCLUSIONS: Among patients with CS, absolute and relative GGs were associated with increased 30-day all-cause mortality, regardless of DM. The relationship was stable after multivariate Cox regression analysis, PSM, and IPTW analysis. Furthermore, they reflect the severity of CS to some extent. Hyperlactatemia and insulin resistance may underlie the relationship between stress-induced hyperglycemia and poor outcomes in CS patients. They both improve the predictive efficacy of the GCS.

Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy.

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.

Stress hyperglycemia ratio linked to worse prognosis in Cardiac Intensive Care Unit patients: A retrospective observational study.

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.

3,4-benzo[a]pyrene aggravates myocardial infarction injury by activating NLRP3-related pyroptosis through PINK1/Parkin-mitophagy-mPTP opening axis.

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.

The Ratio of Red Blood Cell Distribution Width to Albumin Is Correlated With All-Cause Mortality of Patients After Percutaneous Coronary Intervention - A Retrospective Cohort Study.

Objectives: The 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). Methods: Clinical 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). Results: A 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. Conclusion: RA 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.

Machine Learning for Prediction of Outcomes in Cardiogenic Shock.

Objective: The 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. Methods: We 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. Results: A 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. Conclusion: In 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.

Low-Density Lipoprotein Cholesterol is Inversely Associated with All-Cause Mortality of Patients in the Coronary Care Unit.

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.

The Association Between Left Ventricular Hypertrophy and the Occurrence and Prognosis of Atrial Fibrillation: A Meta-Analysis.

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.

Cardiovascular Alterations and Management of Patients With White Coat Hypertension: A Meta-Analysis.

A large and growing body of literature has focused on the association between "white coat hypertension" (WCH) and the underlying target organ damage. The evidence suggests that WCH is may not an entirely benign phenomenon. However, whether patients with WCH should receive antihypertensive drugs is unresolved. Therefore, we performed a meta-analysis to fully determine the ability of WCH to alter cardiovascular structure and to determine whether patients with WCH could benefit from drug intervention. Medline, EMBASE, and the Cochrane Library were searched from inception through 21 Oct 2019. A total of 25 studies (8,100 individuals) were included. In participants with WCH, values of aortic pulse wave velocity, augmentation index, intima-media thickness, interventricular septum thickness, left ventricular posterior wall thickness, and left ventricular mass index were lower than those with sustained hypertension, but greater than those in the normotensive group. Of note, antihypertensive drug therapy did not reduce the risk of cardiovascular events in patients with WCH. WCH is accompanied by alterations of cardiovascular structure; however, the benefits from antihypertensive therapy are limited.

Association between neutrophil-to-albumin ratio and mortality in patients with cardiogenic shock: a retrospective cohort study.

OBJECTIVES: To investigate the prognostic value of neutrophil-to-albumin ratio (NAR) in critically ill patients with cardiogenic shock (CS). DESIGN: A retrospective cohort study. SETTING: A single centre in Boston, USA. PARTICIPANTS: 475 patients with CS were included, among which 272 (57.3%) were men and 328 (69.1%) were white. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 90-day mortality and the secondary outcomes were 30-day and 365-day mortality. RESULTS: A significant positive correlation between NAR levels and 90-day, 30-day or 365-day mortality was observed. For 90-day mortality, the adjusted HR (95% CI) values given NAR levels 23.54-27.86 and >27.86 were 1.71 (1.14 to 2.55) and 1.93 (1.27 to 2.93) compared with the reference (NAR<23.47). Receiver operator characteristic curve analysis showed that NAR had a certain prognostic value in predicting 90-day mortality of CS, which was more sensitive than the neutrophil percentage or the serum albumin level alone (0.651 vs 0.509, 0.584). For the secondary outcomes, the upward trend remained statistically significant. CONCLUSIONS: NAR level was associated with the mortality of CS patients. The prognostic value of NAR was more sensitive than the neutrophil percentage or the serum albumin level alone, but not as good as Sequential Organ Failure Assessment or Simplified Acute Physiology Score.

Prognostic Value of Neutrophil-Lymphocyte Ratio in Cardiogenic Shock: A Cohort Study.

BACKGROUND Inflammation plays an important part in the pathogenesis of cardiogenic shock (CGS). Whether the neutrophil-lymphocyte ratio (NLR), an integrated biomarker of inflammation, is associated with the outcome of CGS patients remains unknown. This retrospective cohort study was performed to identify the utility of using NLR among patients with CGS. MATERIAL AND METHODS Data were extracted from the MIMIC database. We applied smooth curve fitting to define the NLR cutoff values. The primary outcome was 30-day mortality. Cox proportional hazards models, subgroup analysis, and receiver operator characteristic (ROC) curve analysis were performed. RESULTS A total of 1470 CGS patients were extracted, among which 801 (54.5%) were men. The mean age of the population was 70.37 years. An inverse U-shaped relationship was observed between NLR and mortality in CGS patients, with the highest risk being at values ranging from 9.4 to 15. For the primary outcome of 30-day mortality, the adjusted HR (95% CI) values of the middle tertile (NLR 9.4-15) and the upper tertile (NLR >15) were 1.47 (1.14, 1.88) and 1.22 (0.94, 1.57) compared with the reference of lower tertile (NLR <9.4). ROC curve analysis showed that NLR had a more sensitive prognostic value in predicting 30-day mortality of CGS than the neutrophil or lymphocyte percentage alone (0.660 vs. 0.540, 0.549). CONCLUSIONS An inverse U-shaped curve was presented between NLR and the mortality of CGS. NLR seemed to be a readily available and independent prognostic biomarker for patients with CGS. The prognostic value of NLR was more sensitive than the neutrophil or lymphocyte percentage alone, but not as good as SOFA or SAPSII score.

The neutrophil-lymphocyte ratio: A promising predictor of mortality in coronary care unit patients - A cohort study.

BACKGROUND: Severe inflammation causes poor outcomes in coronary care unit (CCU) patients. The neutrophil-lymphocyte ratio (NLR), a biomarker used to monitor inflammation and the immune response, can predict a poor prognosis in various diseases. However, it remains unclear whether the NLR is associated with all-cause mortality in CCU patients. This study investigated the association between the NLR and CCU outcomes. METHODS: Clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database, which contains health data for over 50,000 patients. The primary outcome was 30-day mortality and the secondary outcome was 90-day mortality. Cox proportional hazard models were used to reveal the associations between NLR and outcomes. Multivariate analyses were used to control for confounders. RESULTS: We enrolled 3563 CCU patients. For 30-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) for the second (NLR 4.80-10.08) and the third (NLR ≥ 10.09) tertiles were 1.57 (1.24, 1.97) and 2.76 (2.23, 3.41), respectively, compared to the first tertile (NLR < 4.80). In the model adjusted for multiple confounders, the fifth quintile (NLR ≥ 14.17) showed a slightly lower mortality risk [HR (95% CI) 1.44 (1.07, 1.94)] compared to the fourth (NLR 8.82-14.16) [HR (95% CI) 1.55 (1.15, 2.10)]. A similar trend was observed for 90-day mortality. The interactions between the acute kidney injury, respiratory failure, and pneumonia subgroups and 30-day mortality were significant. CONCLUSIONS: The NLR was an independent predictor of 30- and 90-day mortality for CCU patients. The NLR is a promising clinical biomarker as an integrated, readily available predictor of CCU mortality.