Ceramides and metabolic profiles of patients with acute coronary disease: a cross-sectional study.

Metabolic Syndrome (MS) is a rapidly growing medical problem worldwide and is characterized by a cluster of age-related metabolic risk factors. The presence of MS increases the likelihood of developing atherosclerosis and significantly raises the morbidity/mortality rate of acute coronary syndrome (ACS) patients. Early detection of MS is crucial, and biomarkers, particularly blood-based, play a vital role in this process. This cross-sectional study focused on the investigation of certain plasma ceramides (Cer14:0, Cer16:0, Cer18:0, Cer20:0, Cer22:0, and Cer24:1) as potential blood biomarkers for MS due to their previously documented dysregulated function in MS patients. A total of 695 ACS patients were enrolled, with 286 diagnosed with MS (ACS-MS) and 409 without MS (ACS-nonMS) serving as the control group. Plasma ceramide concentrations were measured by LC-MS/MS assay and analyzed through various statistical methods. The results revealed that Cer18:0, Cer20:0, Cer22:0, and Cer24:1 were significantly correlated with the presence of MS risk factors. Upon further examination, Cer18:0 emerged as a promising biomarker for early MS detection and risk stratification, as its plasma concentration showed a significant sensitivity to minor changes in MS risk status in participants. This cross-sectional observational study was a secondary analysis of a multicenter prospective observational cohort study (Chinese Clinical Trial Registry, https://www.who.int/clinical-trials-registry-platform/network/primary-registries/chinese-clinical-trial-registry-(chictr), ChiCTR-2200056697), conducted from April 2021 to August 2022.

Diagnostic accuracy of noninvasive fractional flow reserve derived from computed tomography angiography in ischemia-specific coronary artery stenosis and indeterminate lesions: results from a multicenter study in China.

Background: To determine the diagnostic performance of a novel computational fluid dynamics (CFD)-based algorithm for in situ CT-FFR in patients with ischemia-induced coronary artery stenosis. Additionally, we investigated whether the diagnostic accuracy of CT-FFR differs significantly across the spectrum of disease and analyzed the influencing factors that contribute to misdiagnosis. Methods: Coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR were performed on 324 vessels from 301 patients from six clinical medical centers. Local investigators used CCTA and ICA to conduct assessments of stenosis, and CT-FFR calculations were performed in the core laboratory. For CCTA and ICA, CT-FFR ≤ 0.8 and a stenosis diameter ≥ 50% were identified as lesion-specific ischemia. Univariate logistic regression models were used to assess the effect of features on discordant lesions (false negative and false positive) in different CT-FFR categories. The diagnostic performance of CT-FFR was analyzed using an invasive FFR ≤ 0.8 as the gold standard. Results: The Youden index indicated an optimal threshold of 0.80 for CT-FFR to identify functionally ischemic lesions. On a per-patient basis, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for CT-FFR were 96% (91%-98%), 92% (87%-96%), 94% (90%-96%), 91% (85%-95%), and 96% (92%-99%), respectively. The diagnostic efficacy of CT-FFR was higher than that of CCTA without the influence of calcification. Closer to the cut point, there was less certainty, with the agreement between the invasive FFR and the CT-FFR being at its lowest in the CT-FFR range of 0.7-0.8. In all lesions, luminal stenosis ≥ 50% significantly affected the risk of reduced false negatives (FN) and false positives (FP) results by CT-FFR, irrespective of the association with calcified plaque. Conclusions: In summary, CT-FFR based on the new parameter-optimized CFD model has a better diagnostic performance than CTA for lesion-specific ischemia. The presence of calcified plaque has no significant effect on the diagnostic performance of CT-FFR and is independent of the degree of calcification. Given the range of applicability of our software, its use at a CT-FFR of 0.7-0.8 requires caution and must be considered in the context of multiple factors.

Diagnostic performance of a novel automated CT-derived FFR technology in detecting hemodynamically significant coronary artery stenoses: A multicenter trial in China.

BACKGROUND AND AIMS: Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. METHODS: 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." RESULTS: The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. CONCLUSIONS: The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD.

Remnant Cholesterol and the Risk of Coronary Artery Disease in Patients With Type 2 Diabetes.

Among statin-treated patients with type 2 diabetes mellitus (T2DM), there is still a great residual cardiovascular risk. Previous studies found that the level of remnant cholesterol (RC) could predict the coronary artery disease (CAD) risk. In the present study, we enrolled 4145 patients with T2DM; 2784 (67.2%) were male and their median age was 62 years. After multivariate logistic analyses, plasma RC level was significantly and independently associated with CAD [odds ratio (OR) 13.524, 95% confidence interval (CI) = 7.058-25.912, P < .001) after adjustment for conventional risk factors, such as age, gender, hypertension, and other lipid levels. Even in the presence of high high-density lipoprotein cholesterol (HDL-C) level, the elevated RC could still predict CAD in T2DM patients (OR 2.064, 95%CI 1.438-2.964, P < .001). Furthermore, RC had relationships with age, hypertension, and smoking status in promoting CAD progression in T2DM patients, with all p for interactive <.001. In conclusion, RC level was independently associated with CAD risk in patients with T2DM.

LncRNA-IMAT1 Promotes Invasion of Meningiomas by Suppressing KLF4/hsa-miR22-3p/Snai1 Pathway.

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

Stenting techniques for coronary bifurcation disease: a systematic review and network meta-analysis demonstrates superiority of double-kissing crush in complex lesions.

OBJECTIVE: This study was aimed to compare different stenting techniques for coronary bifurcation disease (CBD). BACKGROUND: Percutaneous coronary intervention (PCI) remains controversial for CBD; over the years, several stent techniques for bifurcation lesions have been used. Current guidelines recommend a provisional single-stent strategy as the preferred method for coronary artery bifurcation lesions. However, several randomized controlled trials (RCT) indicated that two-stent techniques showed better clinical outcomes. METHODS: We systematically searched Embase, PubMed, and Web of Science to include RCTs. The primary endpoint was the major adverse cardiovascular event (MACE). Secondary outcomes were cardiac death, myocardial infarction (MI), target-lesion or target-vessel revascularization (TLR or TVR), and definite or probable stent thrombosis (ST). Finally, we used 26 RCTs and a total of 7257 individuals were randomly assigned to one of the 6 stent techniques and included in this network meta-analysis. RESULTS: In our network meta-analysis, double-kissing (DK) crush was significantly more superior to other 5 stent techniques in MACEs: OR vs. provisional 0.40 (95% CI 0.28-0.55); vs. culotte 0.40 (95% CI 0.26-0.60). DK crush ranked the most effective treatment for MACE (100%), MI (75%), ST (83%), and TLR (100%) in the rank probabilities analysis. In patients with complex bifurcation lesion defined by DEFINITION criteria, DK crush was notably more efficacious than provisional, culotte, and T-stenting/T-stenting and protrusion (TAP) in MACEs (OR vs. provisional 0.26, 95% CI 0.13-0.52) and TLR (OR vs. provisional 0.24, 95% CI 0.10-0.58). CONCLUSION: Compared with other stenting techniques, DK crush had a lower incidence of MACEs in CBD. DK crush was significantly associated with a lower rate of MACEs in patients with complex bifurcation lesions defined by the DEFINITION criterion.

Association of Plasma MiRNA-204 and the Presence and Severity of Coronary Artery Calcification in Patients With Type 2 Diabetes.

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

Association between Neutrophil Percentage-to-Albumin Ratio and All-Cause Mortality in Critically Ill Patients with Coronary Artery Disease.

BACKGROUND: Neutrophil percentage-to-albumin ratio (NPAR) has been proved to be associated with clinical outcome of many diseases. This study was aimed at exploring the independent effect of NPAR on all-cause mortality of critically ill patients with coronary artery disease (CAD). METHOD: NPAR was calculated as neutrophil percentage numerator divided by serum albumin concentration. Clinical endpoints were 30-day, 90-day, and 365-day all-cause mortality. Multivariable Cox proportional hazard models were performed to confirm the association between NPAR and all-cause mortality. RESULT: 3106 patients with CAD were enrolled. All-cause mortality rates of 30 days (P < 0.001), 90 days (P < 0.001), and 365 days (P < 0.001) increased as NPAR tertiles increased. And after adjusting for possible confounding variables, NPAR was still independently associated with 30-day (third tertile group versus first tertile group: HR, 95% CI: 1.924, 1.471-2.516; P for trend < 0.001), 90-day (third tertile group versus first tertile group: HR, 95% CI: 2.053, 1.646-2.560; P for trend < 0.001), and 365-day (third tertile group versus first tertile group: HR, 95% CI: 2.063, 1.717-2.480; P for trend < 0.001) all-cause mortality in patients with CAD. Subgroup analysis did not find obvious interaction in most subgroups. CONCLUSION: NPAR was independently correlated with 30-day, 60-day, and 365-day all-cause mortality in critically ill patients with CAD.

Anion Gap Was Associated with Inhospital Mortality and Adverse Clinical Outcomes of Coronary Care Unit Patients.

BACKGROUND: Anion gap (AG) has been proved to be associated with prognosis of many cardiovascular diseases. This study is aimed at exploring the association of AG with inhospital all-cause mortality and adverse clinical outcomes in coronary care unit (CCU) patients. METHOD: All data of this study was extracted from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4) database. All patients were divided into four groups according to AG quartiles. Primary outcome was inhospital all-cause mortality. Lowess smoothing curve was drawn to describe the overall trend of inhospital mortality. Binary logistic regression analysis was performed to determine the independent effect of AG on inhospital mortality. RESULT: A total of 3593 patients were enrolled in this study. In unadjusted model, as AG quartiles increased, inhospital mortality increased significantly, OR increased stepwise from quartile 2 (OR, 95% CI: 1.01, 0.74-1.38, P = 0.958) to quartile 4 (OR, 95% CI: 2.72, 2.08-3.55, P < 0.001). After adjusting for possible confounding variables, this association was attenuated, but still remained statistically significant (quartile 1 vs. quartile 4: OR, 95% CI: 1.02, 0.72-1.45 vs. 1.49, 1.07-2.09, P = 0.019). Moreover, CCU mortality (P < 0.001) and rate of acute kidney injury (P < 0.001) were proved to be higher in the highest AG quartiles. Length of CCU (P < 0.001) and hospital stay (P < 0.001) prolonged significantly in higher AG quartiles. Maximum sequential organ failure assessment score (SOFA) (P < 0.001) and simplified acute physiology score II (SAPSII) (P < 0.001) increased significantly as AG quartiles increased. Moderate predictive ability of AG on inhospital (AUC: 0.6291), CCU mortality (AUC: 0.6355), and acute kidney injury (AUC: 0.6096) was confirmed. The interactions were proved to be significant in hypercholesterolemia, congestive heart failure, chronic lung disease, respiratory failure, oral anticoagulants, Beta-blocks, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), and vasopressin treatment subgroups. CONCLUSION: AG was an independent risk factor of inhospital all-cause mortality and was associated with adverse clinical outcomes in CCU patients.

Serum microRNA-204 levels are associated with long-term cardiovascular disease risk based on the Framingham risk score in patients with type 2 diabetes: results from an observational study.

BACKGROUND: Previous studies have demonstrated that microRNA-204 (miR-204) is involved in atherosclerosis and vascular calcification. However, the value of miR-204 as the predictive biomarker for cardiovascular disease (CVD) remains unclear. We aimed to evaluate the association between the circulating miR-204 level and ten-year CVD risk based on the Framingham risk score (FRS). METHODS: In this retrospective study, we enrolled 194 consecutive patients with type 2 diabetes mellitus (T2DM) without CVD in Beijing Anzhen Hospital between January 2015 and September 2016. We used the FRS to evaluate the risk of CVD for each patient. Circulating miR-204 levels were measured by quantitative real-time polymerase chain reaction. RESULTS: Circulating miR-204 levels were significantly lower in the group of patients (0.49 ± 0.13) at high risk of CVD (FRS > 20%) than in the low (FRS < 10%) and intermediate (FRS: 10%-20%) risk groups (0.87 ± 0.19 and 0.75 ± 0.25, respectively; P < 0.001). FRS was negatively correlated with miR-204 levels (r = -0.421, P < 0.001). According to multivariate logistic analyses, reduced miR-204 level was independently associated with an increased risk of CVD after adjusting for conventional risk factors (OR = 0.876, 95% CI: 0.807-0.950, P = 0.001). Receiver-operating characteristic curve analysis showed that the circulating miR-204 level can predict the high risk of CVD with higher specificity than the traditional risk factor of high systolic blood pressure or the protective factor of high-density lipoprotein cholesterol. CONCLUSIONS: Our study demonstrated that patients with lower circulating miR-204 levels were at high risk for CVD. After adjustment for potential confounders, miR-204 was independently associated with CVD in patients with T2DM.

Increased plasma lipoprotein-associated phospholipase A2 levels are associated with coronary slow flow.

OBJECTIVE: Coronary slow flow (CSF) is characterized by delayed opacification of distal epicardial coronary arteries without significant coronary stenosis. In addition, The changes of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a significant predictive factor for CSF remain controversial. The study aims to investigate the association between plasma Lp-PLA2 and CSF. METHODS: In this retrospective study, 170 consecutive patients who underwent coronary angiography were enrolled in Beijing Anzhen Hospital from January 2017 to September 2019, and were divided into CSF group and normal control groups. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC > 27. Serum Lp-PLA2 levels were measured in an enzyme-linked immunosorbent assay. RESULTS: Lp-PLA2 levels were higher in the CSF group than in the control group (288.6 ± 50.3 versus 141.9 ± 49.7, P < 0.001) and were significantly correlated with the mean coronary artery thrombolysis in myocardial infarction (TIMI) frame count (r = 0.790, P<0.001). Logistic regression analysis showed that high Lp-PLA2 was independently associated with CSF after adjustment for conventional risk factors (OR = 1.040, CI = 1.022-1.059, P<0.001). Male sex (OR = 2.192, CI = 1.161-4.140, P = 0.016) and hypertension (OR = 1.965, CI = 1.034-3.736, P = 0.039) were also CSF risk factors. Receiver-operating characteristic curve (ROC) analysis showed that Lp-PLA2 levels can predict CSF severity; the predictive power was higher than the other risk factors. CONCLUSION: Our study demonstrated that patients with CSF had higher circulating levels of Lp-PLA2 than normal controls. After adjustment for potential confounders, increased Lp-PLA2 was independently associated with presence of CSF.

Triptolide Attenuates Vascular Calcification by Upregulating Expression of miRNA-204.

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204. Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting. Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group. Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.