Prognostic nutritional index during hospitalization correlates with adverse outcomes in elderly patients with acute myocardial infarction: a single-center retrospective cohort study.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is one of the most prevalent illnesses endangering the elderly's health. The predictive nutritional index (PNI) has been shown in several studies to be a good predictor of nutritional prognosis. In this study, we explored the correlation between PNI during hospitalization and the outcome of elderly AMI patients. METHODS: Elderly AMI patients in the Cardiac Intensive Care Unit of Huadong Hospital from September 2017 to April 2020 were recruited for analysis. The clinical and laboratory examination data of subjects were retrieved. All enrolled patients were monitored following discharge. The primary clinical endpoints encompass major adverse cardiovascular events (MACEs) and Composite endpoint (MACEs and all-cause mortality). Survival analyses were conducted via the Kaplan-Meier and the log-rank analyses, and the Cox, proportional hazards model, was employed for hazard rate (HR) calculation. RESULTS: 307 subjects were recruited for analysis. The optimal PNI threshold is 40.923. Based on the Kaplan-Meier analysis, the elevated PNI group experienced better prognosis (P < 0.001). Cox analysis demonstrated that the PNI group was a stand-alone predictor for elderly AMI patient prognosis (HR = 1.674, 95% CI 1.076-2.604, P = 0.022). Subgroup analysis showed that the HR of the PNI group was the highest in the ST-segment elevation myocardial infarction (STEMI) subgroup (HR = 3.345, 95% CI 1.889-5.923, P = 0.05), but no discernible difference was observed in the non-ST-segment elevation myocardial infarction (NSTEMI) subgroup. CONCLUSION: Based on our analyses, the PNI during hospitalization can accurately predict the prognosis of elderly STEMI patients but not that of elderly NSTEMI patients.

Absence of a causal link between COVID-19 and deep vein thrombosis: Insights from a bi-directional Mendelian randomisation study.

Background: Several large-scale observational studies have found deep vein thrombosis (DVT) to be related with coronavirus disease 2019 (COVID-19). However, whether there is a clear causal connection between the two is unknown. Methods: Our primary analytical method was the inverse variance-weighted (IVW) approach, complemented by the Mendelian randomisation-Egger (MR-Egger) and weighted median methods. We also used MR-Egger to examine the presence of pleiotropy and the Mendelian randomisation pleiotropy residual sum and outlier (MR-PRESSO) approach to analyse for heterogeneity in the data. Results: We did not observe a direct causal relationship between COVID-19 susceptibility (odds ratio (OR) = 1.023; 95% confidence interval (CI) = 0.828-1.264, standard error (SE) = 0.108, P = 0.833), hospitalisation (OR = 1.030; 95% CI = 0.943-1.125, SE = 0.374, P = 0.720), severity (OR = 0.994; 95% CI = 0.923-1.071, SE = 0.038, P = 0.877), and DVT. The results of the reverse Mendelian randomisation (MR) for DVT and COVID-19 susceptibility exhibited heterogeneity and horizontal pleiotropy. Even after removing outliers, we detected no direct causal relationship between the two (OR = 1.015; 95% CI = 0.954-1.080, SE = 0.032, P = 0.630). Similarly, we found no direct causal relationship between DVT and COVID-19 hospitalisation (OR = 0.999; 95% CI = 0.907-1.102, SE = 0.050, P = 0.999) or severity (OR = 1.014; 95% CI = 0.893-1.153, SE = 0.065, P = 0.826). Conclusions: In this MR study, we identified no direct causal impact in a European population between DVT and the COVID-19 susceptibility, severity, or hospitalisation.

Ascending aortic perivascular adipose tissue inflammation associates with aortic valve disease.

BACKGROUND: Ascending aortic perivascular adipose tissue (AA-PVAT) mainly comprises brown adipose tissue (BAT), originates from neural crest cells that derive from ectoderm, and plays important role in angiotensin II-induced vascular inflammation and remodeling in mice. However, the characterization and function of human AA-PVAT remains highly unclear. METHODS: Patients with coronary artery disease (CAD) (n = 20) and aortic valve disease (AVD) (n = 23) who underwent cardiac surgery consented to take part in transcriptome and histological studies. Paired samples of AA-PVAT, epicardial adipose tissue (EAT), and subcutaneous adipose tissue (SAT) were obtained. RNA sequencing, histological analysis, quantitative reverse transcription polymerase chain reaction and western blot studies were performed on those samples. RESULTS: Human AA-PVAT exhibited smaller adipocyte morphology and high expression of brown adipocyte marker. Transcriptome analysis revealed that AA-PVAT showed unique transcriptome characteristics compared with EAT and SAT. While comparing CAD and AVD patients, AA-PVAT exhibited a decreasing brown phenotype and higher inflammatory response in AVD patients. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the differentially expressed genes in AA-PVAT between CAD and AVD patients were involved mainly in the processes of inflammation and metabolism regulation. CONCLUSIONS: Human AA-PVAT is a BAT-like adipose tissue with unique transcriptome characteristics, and exhibits a weakened brown phenotype and an enhanced inflammation response in AVD patients.

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study.

Background: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China. Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan-Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects. Results: Based on the first year of follow-up data analysis, the elevation of SUA levels (P<0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P<0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups. Conclusion: Taken together, the findings in this study indicate that high SUA levels (P<0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.

Association of Pericardiac Adipose Tissue With Coronary Artery Disease.

Background and Aim: Coronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD. Methods: We acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry. Results: A total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively. Conclusion: This study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD.

Disorders of sodium balance and its clinical implications in COVID-19 patients: a multicenter retrospective study.

BACKGROUND: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. METHODS AND RESULTS: A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. CONCLUSION: Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

NAD+ administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux.

Microvascular damage is a key pathological change in myocardial ischemia/reperfusion (I/R) injury. Using a rat model of myocardial I/R, our current study has provided the first evidence that nicotinamide adenine dinucleotide (NAD+) administration can significantly attenuate myocardial I/R-induced microvascular damage, including reduced regional blood perfusion, decreased microvessel density and integrity, and coronary microvascular endothelial cells (CMECs) injury. In studies with primary cultured CMECs under hypoxia/reoxygenation (HR) and a rat model of I/R, our results suggested that the protective effect of NAD+ on CMECs exposed to HR or I/R is at least partially mediated by the NAD+-induced restoration of autophagic flux, especially lysosomal autophagy: NAD+ treatment markedly induced transcription factor EB (TFEB) activation and attenuated lysosomal dysfunction in the I/R or HR-exposed cells. Collectively, our study has provided the first in vivo and in vitro evidence that NAD+ significantly rescued the impaired autophagic flux and cell apoptosis that was induced by I/R in rat CMECs, which is mediated in part through the action of TFEB-mediated lysosomal autophagy.

Coronary Computed Tomography (CT) Angiography Characteristics of High-Risk Plaque: Correlation with Stress Myocardial Perfusion Imaging in Patients with Moderate Coronary Stenosis.

BACKGROUND The aim of this study was to investigate the ability of coronary computed tomographic angiography (CCTA) characteristics of high-risk plaque (HRP) in moderate stenosis to improve differentiation of myocardial ischemia detected by stress CT perfusion (CTP) imaging. MATERIAL AND METHODS Sixty-two patients with coronary plaques and moderate stenosis confirmed by invasive coronary angiography (ICA) had stress CTP and 26 of these patients were found to have myocardial ischemia. The other 36 patients without myocardial ischemia were defined as controls. Characteristics of major plaques on CCTA images of the ischemia and non-ischemia groups were analyzed and compared. RESULTS Differences between the 2 groups were observed in plaque volume, burden and rough inner surface necrotic core volume, plaque-lipid interface and plaque length. In a multivariable analysis, plaque burden and necrotic core volume were significantly associated with myocardial ischemia: plaque burden odds ratio (OR) was 1.28 (95% confidence interval [CI], 1.12-1.48); necrotic core volume OR was 1.78 (95% CI, 1.03-1.34). Compared with other quantitative measurements, optimized thresholds for plaque burden (area under the curve was 0.852) and necrotic core volume (area under the curve was 0.730) showed significantly higher diagnostic performance for ischemia with threshold values of 60.8% and 11.25 mm³, respectively. CONCLUSIONS CCTA characteristics of major plaques may improve the discrimination of ACS patients with myocardial ischemia on stress CTP.

Isolation, Culture, and Adipogenic Induction of Neural Crest Original Adipose-Derived Stem Cells from Periaortic Adipose Tissue.

An excessive amount of adipose tissue surrounding the blood vessels (perivascular adipose tissue, also known as PVAT) is associated with a high risk of cardiovascular disease. ADSCs derived from different adipose tissues show distinct features, and those from the PVAT have not been well characterized. In a recent study, we reported that some ADSCs in the periaortic arch adipose tissue (PAAT) descend from the neural crest cells (NCCs), a transient population of migratory cells originating from the ectoderm. In this paper, we describe a protocol for isolating red fluorescent protein (RFP)-labeled NCCs from the PAAT of Wnt-1 Cre+/-;Rosa26RFP/+ mice and inducing their adipogenic differentiation in vitro. Briefly, the stromal vascular fraction (SVF) is enzymatically dissociated from the PAAT, and the RFP+ neural crest derived ADSCs (NCADSCs) are isolated by fluorescence activated cell sorting (FACS). The NCADSCs differentiate into both brown and white adipocytes, can be cryopreserved, and retain their adipogenic potential for ~3-5 passages. Our protocol can generate abundant ADSCs from the PVAT for modeling PVAT adipogenesis or lipogenesis in vitro. Thus, these NCADSCs can provide a valuable system for studying the molecular switches involved in PVAT differentiation.

Evaluation of a High Concentrated Contrast Media Injection Protocol in Combination with Low Tube Current for Dose Reduction in Coronary Computed Tomography Angiography: A Randomized, Two-center Prospective Study.

RATIONALE AND OBJECTIVES: The study aimed to prospectively evaluate the radiation dose reduction potential and image quality (IQ) of a high-concentration contrast media (HCCM) injection protocol in combination with a low tube current (mAs) in coronary computed tomography angiography. MATERIALS AND METHODS: Eighty-one consecutive patients (mean age: 62 years; 34 females; body mass index: 18-31) were included and randomized-assigned into two groups. All computed tomography (CT) examinations were performed in two groups with the same tube voltage (100 kV), flow rate of contrast medium (5.0 mL/s), and iodine dose (22.8 g). An automatic mAs and low concentration contrast medium (300 mgI/mL) were used in group A, whereas effective mAs was reduced by a factor 0.6 along with HCCM (400 mgI/mL) in group B. Radiation dose was assessed (CT dose index [CTDIvol] and dose length product), and vessel-based objective IQ for various regions of interest (enhancement, noise, signal-to-noise ratio, and contrast-to-noise ratio), subjective IQ, noise, and motion artifacts were analyzed overall and vessel-based with a 5-point Likert scale. RESULTS: The CT attenuation of coronary arteries and image noise in group B were significantly higher than those in group A (ranges: 507.5-548.1 Hounsfield units vs 407.5-444.5 Hounsfield units; and 20.3 ± 8.6 vs 17.7 ± 8.0) (P ≤ 0.0166). There was no significant difference between the two groups in signal-to-noise ratio, contrast-to-noise ratio, and subjective IQ of coronary arteries (29.4-31.7, 30.0-37.0, and medium score of 5 in group A vs 29.4-32.4, 27.7-36.3, and medium score of 5 in group B, respectively, P ≥ 0.1859). Both mean CTDIvol and dose length product in group B were 58% of those of group A. CONCLUSIONS: HCCM combined with low tube current allows dose reduction in coronary computed tomography angiography and does not compromise IQ.

Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs.

The present study investigated whether atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators in human coronary artery endothelial cells (HCAECs). Several analysis methods, such as reverse transcription-quantitative polymerase chain reaction, western blot analysis and H2DCFDA incubation, were used in the present study. The data showed that atorvastatin decreased the visfatin-induced expression of interleukin (IL)-6 and IL-8 in HCAECs. In addition, atorvastatin inhibited the visfatin-induced expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HCAECs. In addition, the present study found that atorvastatin inhibited the visfatin-activated nuclear factor-κB (NF-κB) signal pathway by preventing extracellular signal-regulated kinase phosphorylation in HCAECs. Atorvastatin significantly inhibited visfatin-induced NF-κB activity via the upregulation of reactive oxygen species production. Atorvastatin, a visfatin antagonist (FK866) and an NF-κB inhibitor (BAY11-7082) decreased the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs. These results suggest that atorvastatin may inhibit the visfatin-induced upregulation of inflammatory mediators through blocking the NF-κB signal pathway. The findings of the present study provide a potential use for atorvastatin and visfatin in the pathogenesis of HCAEC dysfunction. This knowledge may contribute to the development of novel therapies for atherosclerosis.

Diagnosis of Dissection of the Coronary Artery Dissection by Multidetector Computed Tomography: A Comparative Study With Coronary Angiology.

OBJECTIVES: This study was to assess the diagnostic performance of multidetector computed tomography (MDCT) angiographic protocol for dissection of the coronary artery (DCA) detection compared with coronary angiology (CAG). METHODS: Intravascular ultrasound was used as the gold standard for DCA diagnosis. Thirty-six DCA patients and 34 non-DCA (control) participants were retrospectively reviewed. The CAG and MDCT angiography images were separately reviewed by 4 independent observers, and a 5-point grading scale was used for DCA diagnosis. Diagnostic performance was compared using receiver operating characteristic analysis. Sensitivity, specificity, and negative predictive values were calculated. RESULTS: The MDCT performed significantly better than that of CAG (AZ = 0.9943 ± 0.0034 vs AZ = 0.8411 ± 0.0274, respectively) for DCA detection. The sensitivity (98.6%), specificity (89.7%), and negative predictive value (98.4%) of MDCT for DCA were higher than those of CAG (77.8%, 79.4%, and 77.1%, respectively). CONCLUSIONS: Multidetector computed tomography angiography was a more sensitive and specific technique for the diagnosis of DCA compared with CAG.