The association between serum uric acid / serum creatinine ratio and in-hospital outcomes in elderly patients with acute myocardial infarction.

BACKGROUND: The role of Serum uric acid (SUA) in acute myocardial infarction (AMI) was controversial, which might be influenced by the renal clearance function of the patients. The present study aimed to explore the association between serum uric acid to serum creatinine ratio (SUA/Scr), reflecting a net production of SUA, and the in-hospital outcomes of elderly patients with AMI. METHODS: In this retrospective study, a total of 330 elderly AMI patients (≥ 75 years) were enrolled. Data of SUA and Scr on admission were collected to calculate SUA/Scr ratio. Logistic regression analysis and receiver-operating curves were performed to assess the association between SUA/Scr ratio and in-hospital major adverse cardiovascular events (MACEs) and all-cause death. RESULTS: Among the 330 patients, 68 patients had MACEs and 44 patients died. Patients with MACEs or died had lower SUA/Scr values compared with those without MACEs or survival (P < 0.05). Univariate logistic analysis showed that a lower value of SUA/Scr (< 3.45) was significantly associated with in-hospital MACEs (odd ratios (OR): 2.359, 95% confidential interval (CI): 1.369-4.065, P = 0.002) and death (OR: 2.424, 95% CI: 1.275-4.608, P = 0.007). After correcting for confounding factors, a lower SUA/Scr value was still independently associated with in-hospital MACEs (OR: 2.144, 95% CI: 1.169-3.934, P = 0.014) and death (OR: 2.125, 95% CI: 1.050-4.302, P = 0.036). Subgroup analysis showed that the association between a lower SUA/Scr ratio and increased risk of in-hospital outcomes could observed only in males (OR: 2.511, 95%CI: 1.211-5.207, P = 0.013 for MACEs; OR: 2.730, 95% CI: 1.146-6.502, P = 0.023 for death). CONCLUSIONS: A lower SUA/Scr ratio was associated with an increased risk of in-hospital adverse events in elderly patients with AMI, especially in males, which maybe a marker of poor outcomes for elderly AMI patients.

Genetic analysis using targeted next-generation sequencing of sporadic Chinese patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Inherited dilated cardiomyopathy (DCM) contributes to approximately 25% of idiopathic DCM cases, and the proportion is even higher in familial DCM patients. Most studies have focused on familial DCM, whereas the genetic profile of sporadic DCM in Chinese patients remains unknown. METHODS: Between June 2018 and September 2019, 24 patients diagnosed with idiopathic DCM without a family history were included in the present study. All patients underwent genetic screening for 80 DCM-related genes using targeted next-generation sequencing. RESULTS: By in silico analysis, 10 of 99 detected variants were considered pathogenic or likely-pathogenic, including seven TTN truncating variants (TTNtv), one in-frame deletion in TNNT2, one missense mutation in RBM20, and one frameshift deletion variant in FLNC. Of these variants, eight are reported for the first time. CONCLUSIONS: Using targeted next-generation sequencing, potential genetic causes of idiopathic DCM were identified. Sarcomere mutations remained the most common genetic cause of inherited DCM in this cohort of sporadic Chinese DCM.

The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome.

BACKGROUND AND AIMS: Glucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS). METHODS AND RESULTS: A total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013). CONCLUSION: After adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.

Lnc-Ang362 is a pro-fibrotic long non-coding RNA promoting cardiac fibrosis after myocardial infarction by suppressing Smad7.

BACKGROUND: Cardiac fibrosis following myocardial infarction (MI) leads to cardiac remodeling and dysfunction. Dysregulation of Smad7 which negatively regulates the profibrotic transforming growth factor-ß1 (TGF-ß1)/Smad signaling promotes cardiac fibrosis. However, the molecular mechanisms underlying TGF-ß1/Smad7 dysregulation remain elusive. Long non-coding RNAs (lncRNAs) are recently emerging as important regulators of cardiac diseases. Here, we report lnc-Ang362 is a novel lncRNA mediating MI-induced fibrosis through TGF-ß1/Smad7 signaling pathway. METHODS AND RESULTS: The MI model was established by artificial coronary artery occlusion in rats. Microarray analysis identified 215 lncRNAs (fold change > 2.0, P < 0.05) differentially expressed between MI hearts and the sham group 4 weeks after MI. Lnc-Ang362 had the highest fold upregulation and the change was validated by reverse transcription polymerase chain reaction. Also, MI caused a marked increase in TGF-ß1 and collagen I/III expression, but significantly downregulated Smad7 expression. Adult rat cardiac fibroblasts (RCFs) treated with TGF-ß1 showed increased lnc-Ang362 expression and decreased Smad7 expression. Moreover, overexpression and knockdown of lnc-Ang362 by small interfering RNAs reduced and increased Smad7 expression, respectively. Importantly, this result was negatively correlated with the expression of collagen I/III in RCFs. Furthermore, the luciferase reporter assays confirmed that Smad7 was a validated lnc-Ang362 target. Further silencing Smad7 attenuated the effects of lnc-Ang362 knockdown on decreasing collagen I/III expression in RCFs. CONCLUSIONS: These results suggested lnc-Ang362 promoted cardiac fibrosis after MI via directly suppressing Smad7, which may decrease the inhibitory feedback regulation of TGF-ß1/Smad signaling pathway. Thus, lnc-Ang362 may be a novel profibrotic lncRNA in the regulation of cardiac fibrosis post MI.

LncRNA CRNDE regulates the proliferation and migration of vascular smooth muscle cells.

Restenosis after angioplasty or stent is a major clinical problem. While long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their role in restenosis is not well understood. This study aims to investigate how dysregulated lncRNAs and messenger RNAs (mRNAs) contribute to restenosis. By microarray analysis, we identified 202 lncRNAs and 625 mRNAs (fold change > 2.0, p < 0.05) differentially expressed between the balloon-injured carotid artery and uninjured carotid artery in the rats. Among differentially expressed lncRNAs, LncRNA CRNDE had the highest fold change and the change was validated by reverse transcription polymerase chain reaction. We found that LncRNA CRNDE was significantly upregulated in injured rat carotid artery and vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth factor-BB (PDGF-BB). Knockdown of LncRNA CRNDE by small interference RNA significantly inhibited PDGF-BB stimulated proliferation and migration of VSMCs. Moreover, knockdown of LncRNA CRNDE attenuated PDGF-BB-induced phenotypic change of VSMCs. Taken together, our study reveals a novel mechanoresponsive LncRNA CRNDE which may be a therapeutic target for restenosis.

Corrigendum to "Cardiac rehabilitation improved oxygen uptake measured by cardiopulmonary exercise test in patients after aortic valve surgery" (Rev. Cardiovasc. Med. 2019, 20(1):47-52).

The support statement for Song F. et al., "Cardiac rehabilitation improved oxygen uptake measured by cardiopulmonary exercise test in patients after aortic valve surgery" Rev. Cardiovasc. Med. 2019 vol. 20(1), 47-52, was incorrectly attributed. This study was supported by the Medical Scientific Research Foundation of Guangdong Province, China (Grant No. A2017257) and the National Science Foundation for Young Scientists of China (Grant No. 81600255). The corrected article appears overleaf with its original pagination. This corrects the article DOI: 10.31083/j.rcm.2019.01.3183.

Cardiac rehabilitation improved oxygen uptake measured by cardiopulmonary exercise test in patients after aortic valve surgery.

Evidence for cardiac rehabilitation after valve surgery remains scarce. We retrospectively enrolled consecutive patients undergoing aortic valve surgery. The intervention group consisted of physical exercise for 3 months after surgery, while the control group underwent usual care without physical exercise. It was observed that cardiac rehabilitation has a beneficial effect on the peak oxygen uptake compared to the control group (24.2 ml/kg/min vs. 20.6 ml/kg/min) as measured by cardiopulmonary exercise testing 3 months after surgery. There was no significant difference observed in New York Heart Association class I or II between groups. Conversely, the intervention group underperformed the SF-36 Mental Component Scale at 3 months (50.3 vs. 53.8 points).

Atorvastatin attenuates contrast-induced nephropathy by modulating inflammatory responses through the regulation of JNK/p38/Hsp27 expression.

This study aimed to investigate whether atorvastatin reduce the contrast-induced nephropathy inflammatory response and apoptosis of renal tubular epithelial cells and the relationship with MAPK signaling pathway. We utilized the iopamidol-induced contrast-induced nephropathy (CIN) rat model which was induced by a single dose of iopamidol (2.9 g iodine/kg) and a cell model in which human embryonic proximal tubular (HK2) cells were treated with iopamidol. The rats were divided into five groups: (1) control rats (CR); (2) atorvastatin (CA); (3) iopamidol (CM); (4) iopamidol and atorvastatin (20 mg/kg d) (CMA2); (5) iopamidol and atorvastatin (40 mg/kg d) (CMA4). On days 1, 2 and 6 after iopamidol injection, the urea nitrogen and cystatin C increased in CM compared with CR but decreased in CMA compared with CM. Inflammatory parameters and the percentage of apoptotic cells were increased in CM compared with CR and CA, but they were decreased in CMA compared with CM. We also found that atorvastatin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function in a dose dependent manner (P < 0.05). Furthermore, in vivo, both of SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor) could decrease the expression of Bax and caspase-3, but increase Bcl-2 levels in HK2 cells treated with iopamidol. Our study demonstrates that high-dosage atorvastatin treatment attenuates both the inflammatory processes and apoptosis in contrast-induced acute kidney injury, and that the JNK/p38 MAPK pathway participates in the contrast-induced apoptosis of renal tubular cells. Finally, atorvastatin reduces CIN by suppression of apoptosis, which may be through inhibition of JNK/p38 MAPK pathways.

Rapid atrial pacing induces myocardial fibrosis by down-regulating Smad7 via microRNA-21 in rabbit.

Tachycardia-induced atrial fibrosis is a hallmark of the structural remodeling of atrial fibrillation (AF). The mechanisms underlying tachycardia-induced atrial fibrosis remain unclear. In our previous study, we found that Smad7-downregulation promoted the development of atrial fibrosis in AF. Fibroblasts are enriched in microRNA-21 (miR-21), which contributes to the development of fibrosis and heart failure in the cardiovascular system. Our study was designed to test the hypothesis that miR-21 reinforces the TGF-ß1/Smad signaling pathway in AF-induced atrial fibrosis by down-regulating Smad7. Rapid atrial pacing (RAP, 1000 ppm) was applied to the left atrium of the rabbit heart to induce atrial fibrillation and fibrosis. qRT-PCR and northern blot analysis revealed that RAP caused a marked increase in the expression of miR-21. Transfection with a miR-21 inhibitor significantly increased the expression of Smad7, while the expression of collagen I/III significantly decreased. These changes were implicated in the AF-induced release of miR-21 and down-regulation of Smad7. Adult rat cardiac fibroblasts treated with TGF-ß1 showed increased miR-21 expression and decreased Smad7 expression. Pretreatment with a TGF-ß1 inhibitor reduced the TGF-ß1-induced up-regulation of miR-21. Pretreatment with pre-miR-21 and a miR-21 inhibitor significantly decreased and increased Smad7 expression, respectively. This result was negatively correlated with the expression of collagen I/III in fibroblasts. Moreover, the results of a luciferase activity assay suggest that Smad7 is a validated miR-21 target in CFs. Our results provide compelling evidence that the miR-21 specific degradation of Smad7 may decrease the inhibitory feedback regulation of TGF-ß1/Smad signaling and serves as a new insight of the mechanism of atrial fibrosis in atrial fibrillation.

Efficacy and safety of sacubitril/valsartan in chronic Type B aortic dissection combined with mild hypertension.

BACKGROUND: Optimal antihypertensive medication for chronic Type B aortic dissection remains undecided. This study compared the efficacy and safety of sacubitril/valsartan with valsartan to determine suitable antihypertensive drug combinations. METHODS: In this single-center, open-label, randomized, controlled trial, patients with chronic Stanford type B aortic dissection and mild hypertension were randomized to receive sacubitril/valsartan 100/200 mg or valsartan 80/160 mg. The primary endpoint was the reduction in mean sitting systolic blood pressure (msSBP) at Week 8 in patients with sacubitril/valsartan versus valsartan. Key secondary endpoints included changes in 1) mean sitting diastolic blood pressure (msDBP); 2) pulse pressure; and 3) mean ambulatory blood pressure for 24-hour, daytime, and nighttime. Safety assessments included adverse events and serious adverse events. This trial was registered with the Chinese Clinical Trial Registry, identifier: ChiCTR2300073399. RESULTS: A total of 315 patients completed the study. Sacubitril/valsartan provided a significantly greater reduction in msSBP than valsartan at Week 8 (between-treatment difference: -5.1 mm Hg [95% confidence interval (CI) -5.8 to -4.5], P < 0.001). Reductions in msSBP, msDBP, and pulse pressure as well as the mean ambulatory blood pressure for 24-hour, daytime, and nighttime, were significantly greater in sacubitril/valsartan compared with valsartan (all P < 0.001). No excessive episodes of adverse events occurred in the sacubitril/valsartan group. CONCLUSION: Sacubitril/valsartan and valsartan reduced BP compared with baseline values. However, sacubitril/valsartan improved blood pressure control to a greater extent than valsartan. It may offer a new treatment option for patients with mild hypertension and chronic Type B aortic dissection.

Changes in cell autophagy and apoptosis during age-related left ventricular remodeling in mice and their potential mechanisms.

Cardiac structures and functions change with advanced age, but the underlying mechanisms are not well understood. Autophagy and apoptosis play important roles in the process of cardiac remodeling. This study was designed to explore changes in cell autophagy and apoptosis during age-related left ventricular remodeling and to determine whether the mitogen-activated protein kinase (MAPK) pathway is an underlying mechanism. Eight 5-month-old (adult group) and eight 24-month-old male C57bl/6 mice (aged group) were studied. The heart mass index, left ventricular mass index and hydroxyproline content of both groups were compared. Western Blotting was used to quantitate the protein expression of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, caspase-3, B-cell leukemia-2 (Bcl-2) and MAPKs in the left ventricles of adult and aged mice. Our results showed that the heart mass index, left ventricular mass index and hydroxyproline content in the left ventricles of the aged mice were increased significantly compared with the adult mice, indicating that left ventricular remodeling occurs with aging. The expression of LC3 and Beclin-1 in the left ventricles of aged mice were decreased significantly compared to adult mice. Meanwhile, the level of myocardial caspase-3 in adult mice remained the same in aged mice, and the level of myocardial Bcl-2 increased significantly in aged mice. There were no differences in the expression level of myocardial extracellular signal-regulated kinase 1/2 (ERK1/2), activated/phospho-ERK1/2, c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 between aged and adult mice. However, the expression of myocardial activated/phospho-JNK1/2 increased significantly in aged mice, while activated/phospho-p38 decreased significantly. These findings indicate that autophagy decreases without a concurrent change in apoptosis during age-related left ventricular remodeling in mice. The MAPK pathway may be involved in the regulation of age-related left ventricular remodeling by modulating autophagy.

Atrial fibrillation induces myocardial fibrosis through angiotensin II type 1 receptor-specific Arkadia-mediated downregulation of Smad7.

RATIONALE: Tachycardia-induced atrial fibrosis is a hallmark of structural remodeling of atrial fibrillation (AF). The molecular mechanisms underlying the AF-induced atrial fibrosis remain unclear. OBJECTIVE: To determine the role of angiotensin II (Ang II)/Ang II type 1 (AT(1)) receptor-coupled transforming growth factor (TGF)-ß(1)/Smad signaling pathway in the AF-induced atrial fibrosis. METHODS AND RESULTS: Rapid atrial pacing (1000 ppm) was applied to the left atrium of rabbit heart to induce atrial fibrillation and fibrosis. Quantitative PCR and Western blot analysis revealed that rapid atrial pacing caused a marked increase in the expression of Ang II, TGF-ß(1), phosphorylated Smad2/3 (P-Smad2/3), Arkadia, and hydroxyproline synthesis. However, the expression of Smad7, a key endogenous antagonist of the TGF-ß(1)/Smad-mediated fibrosis, was significantly decreased. These changes were dose-dependently reversed by AT(1) receptor antagonist losartan, implicating the involvement of AF-induced release of Ang II and activation of AT(1) receptor-specific pathway. In the adult rabbit cardiac fibroblasts, Ang II increased the expression of TGF-ß(1), P-Smad2/3, Smad4, Arkadia, and collagen I synthesis and significantly reduced Smad7 expression. These effects of Ang II were reversed by losartan but not by the AT(2) antagonist (PD123319). In addition, extracellular signal-regulated kinase inhibitor and anti-TGF-ß(1) antibody also blocked the Ang II-induced downregulation of Smad7. Silencing of Smad7 gene by small interfering RNA abolished the antagonism of losartan on the fibrogenic effects of Ang II on cardiac fibroblasts, whereas overexpression of Smad7 blocked Ang II-induced increase in collagen I synthesis. CONCLUSIONS: Ang II/AT(1) receptor-specific activation of Arkadia-mediated poly-ubiquitination and degradation of Smad7 may decrease the inhibitory feedback regulation of TGF-ß(1)/Smad signaling and serves as a key mechanism for AF-induced atrial fibrosis.

Protocol for the PORT study: short-term perioperative rehabilitation to improve outcomes in cardiac valvular surgery - a randomised control trial.

INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.

The Prognostic Significance of Chronic Kidney Disease on the All-Cause Death of Ischemic Heart Failure in the Chinese Population: A Prospective Cohort Study.

OBJECTIVE: Our team tried to explore the impact of chronic kidney disease (CKD) on all-cause death among ischemic heart failure (IHF) patients. METHODS: From December 2015 to June 2019, IHF patients were continuously recruited in the Department of Cardiology, Guangdong Provincial People's Hospital. Participants were tracked through telephone interviews until October 15, 2020, or until the clinical endpoints appeared. The clinical endpoints were defined as all-cause death. The date of death or the last follow-up date minus the discharge date was used to calculate the follow-up time. RESULTS: A total of 1568 IHF patients (mean age 63.5 ± 11.0 years old, 85.8% male) were included in this study. Using the estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 as the dividing line, IHF patients were divided into non-CKD group (n = 1,134) and CKD group (n = 434). After a median follow-up of 2.1 years, the all-cause death of non-CKD and CKD patients was 6.1/100 person-years and 13.7/100 person-years, respectively, and the incidence rate ratio was 2.24 (95% CI: 1.75-2.88; p value <0.001). The cumulative all-cause death of non-CKD and CKD patients were 19.4% and 40.7%, respectively (p value <0.001). CKD was an independent predictor of all-cause death in IHF patients (HR: 1.35, 95% CI: 1.03-1.76, p value = 0.029). Among IHF patients, in 8 subgroups, the all-cause death of CKD patients was consistently higher than that of non-CKD patients. Among IHF patients, the risk of all-cause death gradually increased when eGFR gradually decreased. CONCLUSION: Among IHF patients, CKD is a significant risk factor for all-cause death.

Stress Induced Hyperglycemia in the Context of Acute Coronary Syndrome: Definitions, Interventions, and Underlying Mechanisms.

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.

Identification of Biomarkers Related to Atrial Fibrillation With Mitral Regurgitation.

BACKGROUND: We aimed to explore the biomarkers associated with atrial fibrillation (AF) with mitral regurgitation (MR). METHODS: The gene expression profile data GSE115574 were downloaded from Gene Expression Omnibus database, which were obtained from patients with degenerative MR with AF and sinus rhythm (SR). The differentially expressed genes (DEGs) in samples of AF with MR compared with those of SR with MR were selected, followed by functional enrichment analysis, protein-protein interaction (PPI) network analysis, transcription factor (TF) prediction, and drug-gene interaction prediction. RESULTS: By comparing the genes' expression profiles between AF with MR and SR with MR, 379 DEGs were obtained. The upregulated genes, such as NMNAT2, LDHB, and hexosaminidase subunit beta (HEXB), were significantly enriched in metabolic pathways. Hub genes, such as amyloid beta precursor protein (APP), CDH2, SPP1, and STC2, were significantly associated with functions related to extracellular matrix organization and vitamin D response. Additionally, two TFs, PRDM3 and LSM6, were predicted for the key module genes. APP predicted the most drug molecules, that is, 22 molecules, and SPP1 predicted 10 drug molecules. CONCLUSIONS: Dysregulation of the metabolic pathway may play a critical role in AF with MR. Changes in functions related to the extracellular matrix and vitamin D response may also be associated with AF progression in patients with MR. Furthermore, APP, STC2, and SPP1 may serve as potential therapeutic targets of AF.

Association Between Stress Hyperglycemia Ratio and In-hospital Outcomes in Elderly Patients With Acute Myocardial Infarction.

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI. Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding. Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (n = 69) or death (n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626-5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428-5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281-5.762], P = 0.009; all-cause death: 2.394 [1.040-5.507], P = 0.040), but the association was not significant in diabetic patients. Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.

Gene expression profile of THZ1-treated nasopharyngeal carcinoma cell lines indicates its involvement in the inhibition of the cell cycle.

BACKGROUND: The aim of this study was to identify downstream target genes and pathways regulated by THZ1 in nasopharyngeal carcinoma (NPC). METHODS: The gene expression profile of GSE95750 in two NPC cell lines, untreated group and treated with THZ1 group, was analyzed. Differentially expressed genes (DEGs) were compared using the R-software. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) was analyzed using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Cytoscape was used for protein-protein interaction (PPI) analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verified the gene expression. RESULTS: We identified 25 genes with increased expression and 567 genes with decreased expression in THZ1-treated NPC cells. The top 10 significantly DEGs between untreated group and THZ1 treated group were identified by qRT-PCR and the results were in agreement with RNA-seq. The total 592 DEGs were found enriched in 1,148 GO terms and 38 KEGG pathways. The most important enriched pathways identified were cell cycle related, and several related node genes were identified, such as CDC6, CDC34, CDK7, CDK9, CCNA2, CCNB1, CDT1, KIF11, LIN9, PLK1, and POLR family, which consistent with RNA-seq. CONCLUSIONS: Our results emphasize the differential genes and pathways occurring in THZ1-treated NPC cells, which increases our understanding of the anti-tumor mechanisms of THZ1.

Association of anaemia and all-cause mortality in patients with ischaemic heart failure varies by renal function status.

AIMS: The aims of the current study were to evaluate the association between anaemia and all-cause mortality according to chronic kidney disease (CKD) status and to explore at what level of haemoglobin concentration would the all-cause mortality risk increase prominently among CKD and non-CKD patients, respectively. METHODS AND RESULTS: This is a prospective cohort study, and 1559 patients with ischaemic heart failure (IHF) were included (mean age of 63.5 ± 11.0 years, 85.8% men) from December 2015 to June 2019. Patients were divided into the CKD (n = 481) and non-CKD (n = 1078) groups based on the estimated glomerular filtration rate of 60 mL/min/1.73 m2 . In the CKD group, the incidence rate of all-cause mortality in anaemic and non-anaemic patients was 15.4 per 100 person-years and 10.8 per 100 person-years, respectively, with an incidence rate ratio of 1.42 (95% confidence interval: 1.00-2.02; P-value = 0.05). In the non-CKD group, the incidence rate of all-cause mortality in anaemic and non-anaemic patients was 9.8 per 100 person-years and 5.5 per 100 person-years, respectively, with an incidence rate ratio of 1.78 (95% confidence interval: 1.20-2.59; P-value = 0.005). After a median follow-up of 2.1 years, the cumulative incidence rate of all-cause mortality in anaemic and non-anaemic patients was 41.5% and 44.1% (P-value = 0.05) in the CKD group, and 30.9% and 18.1% (P-value < 0.0001) in the non-CKD group. In the CKD group, cumulative incidence rate of all-cause mortality increased prominently when haemoglobin concentration was below 100 g/L, which was not observed in the non-CKD group. CONCLUSIONS: Results of the current study indicated that among IHF patients, the association between anaemia and all-cause mortality differed by the renal function status. These findings underline the importance to assess mortality risk and manage anaemia among IHF patients according to the renal function status.

Shock Index-C: An Updated and Simple Risk-Stratifying Tool in ST-Segment Elevation Myocardial Infarction.

Background: Shock index (heart rate/systolic blood pressure, SI) is a simple scale with prognostic value in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The present study introduces an updated version of SI that includes renal function. Methods: A total of 1,851 consecutive patients with STEMI undergoing PCI were retrospectively included at Cardiac Care Unit in Guangdong Provincial People's Hospital and divided into two groups according to their admission time: derivation database (from January 2010 to December 2013, n = 1,145) and validation database (from January 2014 to April 2016, n = 706). Shock Index-C (SIC) was calculated as (SI × 100)-estimated CCr. Calibration was evaluated using the Hosmer-Lemeshow statistic. The predictive power of SIC was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The predictive value and calibration of SIC for in-hospital death was excellent in derivation [area under the curve (AUC) = 0.877, p < 0.001; Hosmer-Lemeshow chi-square = 3.95, p = 0.861] and validation cohort (AUC = 0.868, p < 0.001; Hosmer-Lemeshow chi-square = 5.01, p = 0.756). SIC exhibited better predictive power for in-hospital events than SI (AUC: 0.874 vs. 0.759 for death; 0.837 vs. 0.651 for major adverse clinical events [MACEs]; 0.707 vs. 0.577 for contrast-induced acute kidney injury [CI-AKI]; and 0.732 vs. 0.590 for bleeding, all p < 0.001). Cumulative 1-year mortality was significantly higher in the upper SIC tertile (log-rank = 131.89, p < 0.001). Conclusion: SIC was an effective predictor of poor prognosis and may have potential as a novel and simple risk stratification tool for patients with STEMI undergoing PCI.