Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation. The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes, which is involved in atherogenesis.

The effect of preoperative statin treatment on acute kidney injury in elderly patients undergoing valve replacement surgery.

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.

The prognostic nutritional index might predict clinical outcomes in patients with idiopathic dilated cardiomyopathy.

BACKGROUND AND AIMS: The prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM. METHODS AND RESULTS: A total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7-47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626-0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64-4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11-2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001). CONCLUSION: The PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.

Risk prediction in infective endocarditis by modified MELD-XI score.

The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤ 10 (n = 588) and MELD-XI > 10 (n = 270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p < 0.001) and major adverse clinical events (33.3 vs. 18.4%, p < 0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR] = 1.06, 95% CI, 1.02-1.10, p = 0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein > 9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p < 0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score > 13 than those without (log-rank = 25.30, p < 0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio = 1.08, 95% CI, 1.04-1.12, p < 0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.

[Relationship between hyperuricemia and adverse events in patients aged 40 years or older receiving rheumatic aortic valve replacement].

OBJECTIVE: To explore the prognostic value of hyperuricemia for adverse events in patients >40 years old receiving valve replacement surgery for rheumatic aortic valve disease. METHDS: Consecutive middle-aged and elderly patients receiving aortic valve replacement surgery for rheumatic aortic valve disease between March, 2009 and July, 2013 were recruited in this study. The patients were divided into hyperuricemic group and normouricemic group based on their serum levels of uric acid, and the clinical data and adverse events within 1 year after the surgery were compared between the 2 groups. RESULTS: A total of 632 consecutive patients were recruited, including 381 patients with hyperuricemia and 251 with normouricemia. The in-hospital mortality rate was significantly higher in hyperuricemic group than in normouricemic group (7.6% vs 2.0%, P=0.002). Serum uric acid levels were negatively correlated with eGFR (r=-0.421, P<0.001) and positively correlated with C-reactive protein level (r=0.093, P=0.025). Multivariate analysis showed that hyperuricemia was independently associated with the in-hospital mortality (OR=3.07, 95%CI: 1.13-8.37, P=0.028) and mortality at 1 year after the surgery (HR=3.14, 95%CI: 1.30-7.62, P=0.011) after adjusting for potential risk factors including age, NYHA III-IV and postoperative acute kidney injury (AKI). Kaplan-Meier analysis showed that the cumulative rate of 1-year mortality after surgery was significantly higher in patients with hyperuricemia (Log-rank=11.73, P=0.001). CONCLUSION: Hyperuricemia is a predictor of in-hospital and one-year mortality in middle-aged and elderly patients following aortic valve replacement surgery for rheumatic aortic valve disease.