iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.

BACKGROUND: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. METHODS: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. RESULTS: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. CONCLUSIONS: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

Development and validation of a risk score nomogram model to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension: A study based on NHANES data.

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999-2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan-Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73-0.79, p < 0.001) and 0.75 (95% confidence interval: 0.69-0.81, p < 0.001), respectively. The calibration curves indicated that the model had satisfactory consistency in the two cohorts. The risk of all-cause mortality gradually increased as the tertiles of the nomogram model score increased (log-rank test, p < 0.001). Conclusion: The newly developed nomogram model, a readily useable and efficient tool to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension, provides a novel risk stratification method for individualized intervention.

Distance between the lead-implanted site and tricuspid valve annulus in patients with left bundle branch pacing: Effects on postoperative tricuspid regurgitation deterioration.

BACKGROUND: Left bundle branch pacing (LBBP) is an alternative strategy for His-bundle pacing (HBP); however, little is known about tricuspid regurgitation (TR) deterioration after LBBP implantation. OBJECTIVES: The purpose of this study was to characterize the incidence of post-LBBP TR deterioration and identify predicting factors, especially lead position parameters. METHODS: Patients who received LBBP were continuously enrolled from January 2018 to August 2020. The progression of TR and the anatomic position of LBBP were characterized by echocardiography. RESULTS: A total of 89 patients were enrolled and assigned to 2 subgroups based on the degree of TR before LBBP implantation: 58 (65.2%) with relatively normal tricuspid valve (TV) function (grade 0/1 subgroup: with none/trivial or mild TR) and 31 (34.8%) with more severe TR (grade 2/3 subgroup: with moderate or severe TR). At 19.0 ± 6.5 months of follow-up, 29 patients (32.6%) had TR deterioration, and 23 of them were in the grade 0/1 subgroup. In the grade 0/1 subgroup, patients with TR deterioration had a shorter distance between the lead-implanted site and TV (Lead-TA-dist) than those without TR (19.0 ± 7.6 vs 23.9 ± 5.4; P = .006). The receiver operating characteristic (ROC) curve (area under the curve 0.721; 95% confidence interval [CI] 0.575-0.867; P = .005) indicated the favorable efficacy of Lead-TA-dist for predicting TR deterioration after LBBP. Lead-TA-dist ≤16.1 mm was independently associated with TR deterioration after LBBP (hazard ratio 0.20; 95% CI 0.06-0.76; P = .017). CONCLUSION: TR was a common complication of LBBP implantation. In patients with none/trivial or mild TR, Lead-TA-dist ≤16.1 mm was an independent predictor of TR deterioration after LBBP implantation.

Effect of glycemic control and glucose fluctuation on in-hospital adverse outcomes after on-pump coronary artery bypass grafting in patients with diabetes: a retrospective study.

BACKGROUND: The optimal glycemic control level in diabetic patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (On-Pump) remains unclear. Therefore, this study aimed to investigate the effect of different blood glucose control levels and glucose fluctuations on in-hospital adverse outcomes in diabetic patients undergoing on-pump CABG. METHOD: A total of 3918 patients with diabetes undergoing CABG were reviewed in this study. A total of 1638 patients were eligible for inclusion and were categorized into strict, moderate and liberal glucose control groups based on post-operative mean blood glucose control levels of < 7.8 mmol/L, from 7.8 to 9.9 mmol/L and ≥ 10.0 mmoL/L, respectively. The primary endpoint was defined as a composite endpoint including in-hospital all-cause mortality and major cardiovascular complications. The secondary endpoint was defined as major cardiovascular complications including acute myocardial infarction, strokes and acute kidney injuries. To determine the associations between blood glucose fluctuations and adverse outcomes, patients with different glycemic control levels were further divided into subgroups according to whether the largest amplitude of glycemic excursion (LAGE) was ≥ 4.4 mmol/L or not. RESULTS: A total of 126 (7.7%) patients had a composite endpoint. Compared with moderate control, strict glucose control was associated with an increased risk of the primary endpoint (adjusted OR = 2.22, 95% CI 1.18-4.15, p = 0.01) and the secondary endpoint (adjusted OR = 1.95, 95% CI 1.01-3.77, p = 0.049). Furthermore, LAGE ≥ 4.4 mmol/L was significantly associated with the primary endpoint (adjusted OR = 1.67, 95% CI 1.12-2.50, p = 0.01) and the secondary endpoint (adjusted OR = 1.75, 95% CI 1.17-2.62, p = 0.01),respectively. Patients with LAGE ≥ 4.4 mmol/L had significantly higher rates of the composite endpoint and major vascular complications in both the strict-control (the primary endpoint, 66.7% vs 12.4%, p = 0.034, the secondary endpoint, 66.7% vs 10.3%, p = 0.03) and moderate-control groups (the primary endpoint, 10.2% vs 6.0%, p = 0.03, the secondary endpoint, 10.2% vs 5.8%, p = 0.02). CONCLUSIONS: After On-Pump CABG patients with diabetes, strict glucose control (< 7.8 mmol/L) and relatively large glucose fluctuations (LAGE ≥ 4.4 mmol/L) were independently associated with in-hospital adverse outcomes.

Higher Serum Lysophosphatidic Acids Predict Left Ventricular Reverse Remodeling in Pediatric Dilated Cardiomyopathy.

Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.

A scoring system to predict the occurrence of very late stent thrombosis following percutaneous coronary intervention for acute coronary syndrome.

We aimed to derive and validate an effective risk score to identify high-risk patients of very late stent thrombosis (VLST), following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Stepwise multivariable Cox regression was used to build the risk model using data from 5,185 consecutive ACS patients treated with PCI (derivation cohort) and 2,058 patients from the external validation cohort. Eight variables were independently associated with the development of VLST: history of diabetes mellitus, previous PCI, acute myocardial infarction as admitting diagnosis, estimated glomerular filtration rate <90 ml/min/1.73 m2, three-vessel disease, number of stents per lesion, sirolimus-eluting stent, and no post-dilation. Based on the derived score, patients were classified into low- (≤7), intermediate- (8-9), and high- (≥10) risk categories. Observed VLST rates were 0.5%, 2.2%, and 8.7% and 0.45%, 2.3%, and 9.3% across the 3 risk categories in the derivation and validation cohorts, respectively. High discrimination (c-statistic = 0.80 and 0.82 in the derivation and validation cohorts, respectively) and excellent calibration were observed in both cohorts. VLST risk score, a readily useable and efficient tool to identify high-risk patients of VLST after PCI for ACS, may aid in risk-stratification and pre-emptive decision-making.

Association of Soluble ST2 Serum Levels With Outcomes in Pediatric Dilated Cardiomyopathy.

BACKGROUND: Prognosis in patients with pediatric dilated cardiomyopathy (PDCM) is urgently required to identify high-risk patients. Elevated soluble ST2 (sST2) is associated with prognosis in adult patients with heart failure. This study aimed to assess the prognostic value of sST2 in PDCM. METHODS: Ninety-four patients with PDCM were enrolled after admission from 2 centres in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). B-type natriuretic peptide (BNP) and sST2 levels were measured. RESULTS: Over a median of 678 (interquartile range [IQR]: 533-785) days, 28 (29.8%) adverse events occurred. Patients in the highest tertile of sST2 levels had increased risk of short-term (< 6 months) (adjusted hazard ratio [HR]: 8.36, 95% confidence interval [CI], 1.02-73.52; P < 0.05) and long-term adverse events (2 years) (adjusted HR: 4.23; 95% CI, 1.32-13.60; P < 0.01) than those in lower tertiles. The C-statistic was increased with addition of sST2 to BNP from 0.697 (95% CI, 0.541-0.852) to 0.812 (95% CI, 0.697-0.939) for short-term and from 0.712 (95% CI, 0.604-0.819) to 0.798 (95% CI, 0.697-0.899) for prediction of long-term adverse events. An intermediate-risk subgroup was identified, and 24% had adverse events. When serial measurements were taken in a nested case-control subgroup, sST2 levels were constantly high in patients with late adverse events (> 6 months) but gradually decreased in nonadverse-event controls compared with 3-month and 6-month baseline levels. CONCLUSIONS: In patients with PDCM, serum sST2 levels are associated with adverse events and have robust prognostic value. Serial measurements of sST2 could help in managing patients for monitoring outcomes of treatment.

Increased branched-chain amino acid levels are associated with long-term adverse cardiovascular events in patients with STEMI and acute heart failure.

AIMS: The long-term prognosis of ST-segment elevation myocardial infarction (STEMI) with acute heart failure (AHF) is poor. Identification of metabolic changes could provide understanding of the underlying pathological progress associated with adverse events in patients with STEMI and AHF. Therefore, the study aimed to identify new plasm metabolites associated with long-term adverse cardiovascular events in patients with STEMI and AHF. MATERIALS AND METHODS: Mass spectrometry measurements of 26 amino acids were performed in 138 patients with STEMI and AHF. Endpoints were adverse cardiac events (composite of death and heart failure hospitalization). Survival analysis was performed to determine independent predictors of amino acids. KEY FINDINGS: During a 3-year follow-up, there were 32 deaths and 21 hospitalizations for heart failure (HF). Multivariable Cox regression analysis showed that branched-chain amino acid (BCAA) levels were independent predictors for adverse cardiovascular events in patients with STEMI and AHF (adjusted HR: 2.67, p < 0.001). The prognostic value of BCAA was better than that of N-terminal pro-B-type natriuretic peptide (area under the curve: 0.77 vs. 0.72) and Kaplan-Meier curves for adverse cardiac events (log-rank: 14.91 vs. 10.05). The combination of BCAAs and NT-proBNP yielded a stronger predictive value (area under the curve: 0.81, log-rank: 27.14). Importantly, addition of BCAAs and NT-pro BNP to the Global Registry of Acute Coronary Events score increased the C-statistic from 0.707 to 0.813, with a net reclassification improvement of 0.714. SIGNIFICANCE: Our study shows that increased plasma BCAA levels are associated with long-term adverse cardiovascular events in patients with STEMI and AHF. These findings suggest that dysregulated BCAA metabolism pathways affect clinical outcome after STEMI with AHF.

Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI.

The incidence of in-hospital cardiovascular adverse events (AEs) in patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) is relatively high. Identification of metabolic markers could improve our understanding of the underlying pathological changes in these patients. We aimed to identify associations between concentrations of plasma metabolites on admission and development of in-hospital AEs in post-PCI patients with STEMI. We used targeted mass spectrometry to measure plasma concentrations of 26 amino acid metabolites on admission in 96 patients with STEMI who subsequently developed post-PCI AEs and in 96 age- and sex-matched patients without post-PCI cardiovascular AEs. Principal component analysis (PCA) revealed that PCA-derived factors, including branched chain amino acids (BCAAs), were associated with increased risks of all three pre-specified outcomes: cardiovascular mortality/acute heart failure (AHF), cardiovascular mortality, and AHF. Addition of BCAA to the Global Registry of Acute Coronary Events risk score increased the concordance C statistic from 0.702 to 0.814 (p < 0.001), and had a net reclassification index of 0.729 (95% confidence interval, 0.466-0.992, p < 0.001). These findings demonstrate that high circulating BCAA concentrations on admission are associated with subsequent in-hospital AEs after revascularization in patients with STEMI.

Circulating microRNA signature for the diagnosis of childhood dilated cardiomyopathy.

Circulating miRNAs are proposed as a biomarker of heart disease. This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12). The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated. Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects. Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction. This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.